JP2025500080A - Synthesis of amphiphilic block copolymers and polymer nanofibers produced therefrom - Google Patents

Abstract

This disclosure relates to the field of synthesis of block copolymers and polymeric nanofibers having core-shell morphology produced therefrom. This disclosure relates to the field of synthesis of block copolymers, where one block is more hydrophobic than the other block and is of different composition. This disclosure also relates to the use of these polymeric nanofibers in various applications, such as for reinforcing polymer matrices and for coating applications.

Description

RELATED APPLICATIONS This application claims priority from Australian Provisional Patent Application No. 2021903943, filed on December 6, 2021, the entire contents of which are incorporated herein by reference.

The present invention relates to the field of synthesis of block copolymers and polymeric nanofibers having a core-shell morphology produced therefrom. The invention also relates to the use of these polymeric nanofibers in various applications, such as for reinforcing polymer matrices and for coating applications. However, it will be understood that the invention is not limited to these particular fields of use.

The following discussion of the prior art is provided to place the present invention in its proper technical context and to provide a more complete understanding of the advantages of the present invention. It should be understood, however, that any discussion of the prior art throughout this specification should not be construed as an explicit or implicit admission that such prior art is widely known or forms part of the common general knowledge in the art.

Polymerization-induced self-assembly (PISA) has recently attracted great interest for the synthesis of amphiphilic block copolymer nanoparticles with complex morphology at high solids contents (up to 50%). PISA can in principle be carried out using any reversible deactivation radical polymerization (RDRP) technique, but reversible addition fragmentation chain transfer (RAFT)-mediated PISA is by far the most commonly used method. It is also worth noting that PISA can be carried out using addition fragmentation chain transfer (AFCT) polymerization, i.e., a "non-living" polymerization technique. RAFT PISA can be practiced as both a dispersion polymerization and an aqueous emulsion polymerization.

In RAFT-mediated PISA, a solvent-philic macro-RAFT agent is chain-extended with a solvent-phobic core-forming monomer(s). As polymerization proceeds, the increasing insolubility of the core-forming blocks drives in situ self-assembly resulting in block copolymer nanoparticles. Morphology is determined by several factors, but can be largely rationalized based on the relative molecular weights of the solvent-philic block (i.e., the "corona" or shell-forming block) and the solvent-phobic block (core-forming block). Morphology typically varies from spheres, fibers, and vesicles with increasing length of the solvent-phobic block.

Polymeric materials are ubiquitous in today's society. The use of various so-called fillers (additives) to tailor and improve the performance of polymeric materials is a common strategy and often a requirement. However, traditionally used fillers, e.g., carbon black and glass fibers, are associated with significant drawbacks, such as high density of the final reinforced polymeric material, the requirement of relatively high weight fractions of the filler, and/or lack of transparency. In addition, traditional fillers tend to offer only limited material improvements in terms of high breaking strain and extensibility. Furthermore, current fillers are typically difficult to disperse in the polymer matrix and surface modification is typically required, adding cost to the process.

The prior art teaches the use of high T _g core-forming blocks in amphiphilic block copolymers and the formation of nanofibers prepared by PISA in RAFT aqueous emulsion polymerization. The conventional view is that a "hard" core is necessary to form nanofibers and also to provide mechanical properties as a filler. In particular, PISA has been performed using a second block (core-forming block) of high T _{g monomers} such as styrene (T _g ≈100° C.), methyl methacrylate (MMA) (T _g ≈105° C.), and 2-hydroxypropyl methacrylate (HPMA) (T _g ≈72° C.). In other studies, only low-order spherical morphology resulted from the use of low T _g core-forming blocks in aqueous emulsion RAFT PISA. These include the statistical copolymerization of MMA and n-butyl acrylate (nBA), the homopolymerization of nBA (T _g ≈-54°C) and benzyl methacrylate (BzMA) (T _g ≈54°C), and copolymers formed by the copolymerization of nBA and MMA with a poly(ethylene oxide) macro RAFT agent. In addition to these studies, there have been reports of copolymers of poly(acrylic acid)-b-poly(nBA) diblock copolymer nanoparticles, poly(glycerol monomethacrylate)-poly(BzMA) diblock copolymers, poly(2-(diethylamino)ethyl methacrylate)-poly(methacrylic acid-stat-BzMA), and poly(acrylic acid)-b-poly(nBA)-co-poly(styrene) triblock copolymer nanoparticles. However, in all of the previous studies, only spherical nanoparticles were obtained.

The object of the present invention is to overcome or ameliorate one or more of the shortcomings of the prior art, or at least to provide a useful alternative.

Disclosed herein is the synthesis of self-assembled nanofibers formed via the RAFT-PISA process. In particular, in one aspect of the invention, an amphiphilic block copolymer is disclosed, in which the core is a copolymer having a Tg of about 75°C (or less). In another aspect of the invention, an amphiphilic block copolymer is disclosed, in which the core is a homopolymer and has a Tg of about 16°C (or less). In another aspect of the invention, a nanofiber is disclosed, in which the core is a copolymer or homopolymer having a Tg of up to 16°C. Additionally, in a further aspect of the invention, a block copolymer is disclosed, in which the core and shell are prepared from a hydrophobic copolymer or homopolymer.

The present invention is a significant advance over the prior art. The copolymers of the present invention disclosed herein can efficiently self-assemble to form high concentrations of stable nanofibers that can be used in a variety of applications. The present invention provides one or more of the following advantages: composites comprising the nanofibers of the present invention that are tougher and/or have higher impact resistance; lower density composites comprising the nanofibers of the present invention; nanofiber reinforced composites that have higher stiffness and are relatively light weight (weight loss as low as about 10-20%, which is a significant reduction; in some embodiments, the weight loss is 5-40%); nanofiber reinforced composites that exhibit higher elongation to break; nanofiber reinforced composites that are substantially transparent by matching the refractive index of the nanofibers of the present invention disclosed herein to the polymer matrix in which they are dispersed; and/or improved control of the rheological properties (thixotropy) of emulsions through the use of the nanofibers of the present invention. In addition, as discussed above, current fillers for composites can be difficult to disperse in polymer matrices and surface modification is typically required, adding cost to the process. However, the nanofibers of the present invention do not require surface modification because the outer surface or shell is solvent-philic and can be wetted by polar polymers, solvents, or other matrices, and they can be dispersed relatively easily in polymer matrices. Furthermore, it is possible to prepare surface coatings and films that are substantially or entirely formed from the nanofibers of the present invention.

According to a first aspect, the present invention provides a polymeric nanofiber having a core-shell morphology, the shell being hydrophilic and the core being
A polymeric nanofiber is provided, comprising: a) a hydrophobic copolymer; or b) a hydrophobic homopolymer having a Tg of less than 16°C.

According to a second aspect, the present invention provides a method for producing a method for treating a pulmonary circulation comprising the steps of:
A block [A] containing a hydrophilic homopolymer or copolymer;
a) a hydrophobic copolymer having a Tg of less than about 75° C.; or b) a hydrophobic homopolymer having a Tg of less than about 16° C.; and
and optionally a crosslinker.

In preferred embodiments of the first and second aspects of the invention, the hydrophobic homopolymer has a Tg in the range of about -70°C to at most or about 16°C. In preferred embodiments of the first and second aspects of the invention, the hydrophobic copolymer has a Tg in the range of about -70°C to at most or about 75°C.

According to a third aspect, the present invention provides a method for producing an amphiphilic block copolymer of the second aspect, the method comprising:
a) reacting at least one hydrophilic monomer using RDRP to form a hydrophilic block [A];
b) adding a hydrophobic block [B] comprising at least one hydrophobic monomer to the hydrophilic block [A] using RDRP;
c) optionally adding a cross-linking agent in step b).

According to a fourth aspect, the present invention provides nanofibers when self-assembled from amphiphilic block copolymers produced by the method of the third aspect.

According to a fifth aspect, the present invention provides the use of nanofibers of the first or fourth aspect for at least partially producing a film or coating.

According to a sixth aspect, the present invention provides a method of forming a film or coating of the fifth aspect, the method comprising:
dispersing the nanofibers of the first or fourth aspect in a solvent to form a dispersion;
applying the dispersion to a surface;
and c. allowing or causing the solvent to substantially or completely evaporate, thereby forming the film.

According to a seventh aspect, the present invention provides a method for producing a composition comprising:
A matrix or binder;
There is provided use of the nanofibers of the first or fourth aspect to prepare a composite material comprising: the nanofibers of the first or fourth aspect dispersed throughout a matrix or binder.

According to an eighth aspect, the present invention provides nanofibers of the first or fourth aspect for modifying or improving the mechanical properties of a matrix or binder.

According to a ninth aspect, the present invention provides a method for producing a composite material, the method comprising:
Providing a polymer dispersion;
dispersing the nanofibers of the first or fourth aspect in the polymer dispersion to form a mixture;
and drying the mixture to form a composite material.

According to a tenth aspect, the present invention provides a method for producing a composite material comprising a polymer and a nanofiber of the first or fourth aspect by melt extrusion, the method comprising:
heating the polymer and the nanofibers to a temperature above the melting temperature of the polymer;
mixing a polymer with nanofibers;
and extruding the mixture to form a composite material.

According to an eleventh aspect, the present invention provides the use of a polymer nanofiber as a viscosity or rheology modifier, the polymer nanofiber comprising a core-shell morphology, the shell being hydrophilic and the core comprising a hydrophobic homopolymer or copolymer.

According to a twelfth aspect, the present invention provides the use of a polymer nanofiber according to the first or fourth aspect as a viscosity or rheology modifier.

According to a thirteenth aspect, the present invention provides a method for producing a block copolymer, the method comprising:
a) reacting at least one hydrophobic monomer using RDRP to form a substantially hydrophobic block [A], the block [A] being substantially soluble in a 20/80% by volume water/ethanol mixture;
b) adding a hydrophobic block [B] comprising at least one hydrophobic monomer to hydrophobic block [A] using RDRP in the presence of at least one polar solvent, wherein block [B] is more hydrophobic than block [A] and is of a different composition than block [A];
c) optionally adding a cross-linking agent in step b).

The block copolymers produced by the thirteenth aspect can self-assemble into nanofibers having a core-shell morphology.

In a preferred embodiment of the thirteenth aspect, block [A] is substantially insoluble in water.

The nanofibers of the present invention are formed from polymers. The monomer units can be of a single type (homopolymer) or of different types (copolymer). The physical behavior of a polymer is determined by several characteristics, including the total molecular weight, the composition of the polymer (e.g., the relative concentrations of different monomers), the chemical identity of each monomer unit and its interaction with the solvent, and the architecture of the polymer (e.g., whether it is single-chain or branched).

In one aspect, the present invention provides a compound comprising blocks [A] and [B],
Block [A] is a hydrophilic homopolymer or copolymer,
Block [B] is a hydrophobic homopolymer having a Tg of less than or about 16° C., or a hydrophobic copolymer having a Tg of the hydrophobic block of less than about 75° C.,
The process comprises obtaining blocks [A] and [B] by RDRP, preferably via RAFT of ethylenically unsaturated monomers,
A process for preparing amphiphilic block copolymers, optionally including a crosslinking agent, is provided.

In another aspect, the present invention provides a compound comprising blocks [A] and [B],
Block [A] is a hydrophobic homopolymer or copolymer,
Block [B] is a hydrophobic homopolymer or copolymer,
The process comprises obtaining blocks [A] and [B] by RDRP, preferably via RAFT of ethylenically unsaturated monomers,
A process for preparing a block copolymer, optionally including a crosslinking agent, is provided.

The block copolymers of the present invention will be understood to self-assemble into nanofibers.

According to a fourteenth aspect, the present invention provides a block copolymer comprising a hydrophobic block [A], the block [A] being substantially soluble in a 20/80% by volume water/ethanol mixture, a hydrophobic block [B], the block [B] being more hydrophobic than the block [A] and comprising at least one hydrophobic monomer having a different composition from the block [A], and optionally a crosslinker.

According to a fifteenth aspect, the present invention provides a polymer nanofiber having a core-shell morphology, the shell being hydrophobic, the shell comprising a polymer that is substantially soluble in a 20/80% by volume water/ethanol mixture, and the core being hydrophobic, the core comprising a polymer that is more hydrophobic than the shell polymer and is of a different composition than the shell polymer.

Use of the block copolymer of the 14th aspect or the polymer nanofiber of the 15th aspect to at least partially produce a film or coating.

Use of the block copolymer of the 14th aspect or the polymer nanofiber of the 15th aspect to prepare a composite material comprising a matrix or binder and the block copolymer of the 14th aspect or the polymer nanofiber of the 15th aspect dispersed throughout the matrix or binder.

Use of the block copolymer of the 14th aspect or the polymer nanofiber of the 15th aspect to modify or improve the mechanical properties of a matrix or binder.

Use of the block copolymer of the 14th aspect or the polymer nanofiber of the 15th aspect as a viscosity or rheology modifier.

RAFT Polymerization RAFT polymerization is one of the most robust and versatile methods for providing living character to radical polymerization. With the appropriate choice of chain transfer agent (RAFT agent) for the monomer and reaction conditions, it is applicable to the majority of monomers amenable to radical polymerization. This process can be used to synthesize well-defined homo-, gradient, diblock, triblock and star polymers, as well as more complex architectures including microgels and polymer brushes.

For example, when preparing a block copolymer in the presence of a chain transfer agent (RAFT agent), the terminals of the growing blocks are provided with specific functional groups by RDRP that control the growth of the blocks. The functional groups at the terminals of the blocks are of such a nature that the growth of the blocks in the second and/or third stages of the polymerization process can be reactivated, for example, by other ethylenically unsaturated monomers providing a covalent bond between the first and second blocks [A] and [B], and by any further optional blocks.

Further details on the chemistry of the synthesis of block copolymers by the RAFT process can be found in the following publications, each of which is incorporated herein by reference in its entirety: Polymer, 2008, volume 49, 1079-1131; Chemical Society Reviews, 2014, volume 43, 496-505; Macromolecules, 1998, volume 31, 55
59-5562; and Polymer, 2013, volume 54, 2011-20
19.

In one non-limiting embodiment, the block copolymers according to the disclosed and/or claimed inventive concepts are obtained by RAFT polymerization.

Radical Initiator The radical initiator is selected to have an appropriate half-life at the polymerization temperature sufficient to initiate polymerization.

Non-limiting examples of radical initiators suitable for the present invention include one or more of the following compounds: 2,2'-azobis(isobutyronitrile), 2,2'-azobis(2-cyanobutane), dimethyl 2,2'-azobis(isobutyrate), 4,4'-azobis(4-cyanovaleric acid), 4,4'-azobis-(4-cyanopentanoic acid), 2,2'-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride, 1,1'-azobis(cyclohexanecarbonitrile), 2-(t-butyl azo)-2-cyanopropane, 2,2'-azobis{2-methyl-N-[1,1-bis(hydroxymethyl)-2-hydroxyethyl]propionamide}, 2,2'-azobis[2-methyl-N-(2-hydroxyethyl)propionamide], 2,2'-azobis(N,N'-dimethyleneisobutylamidine) dihydrochloride, 2,2'-azobis(2-amidinopropane) dihydrochloride, 2,2'-azobis(N,N'-dimethyleneisobutylamidine), 2,2'-azobis{2-methyl -N-[1,1-bis(hydroxymethyl)-2-hydroxyethyl]propionamide}, 2,2'-azobis{2-methyl-N-[1,1-bis(hydroxymethyl)-2-ethyl]propionamide}, 2,2'-azobis[2-methyl-N-(2-hydroxyethyl)propionamide], 2,2'-azobis(isobutylamide) dihydrate, 2,2'-azobis(2,2,4-trimethylpentane), 2,2'-azobis(2-methylpropane), t-butylperoxyacetate peroxydibenzoate, t-butyl peroxyneodecanoate, t-butyl peroxyisobutyrate, t-amyl peroxypivalate, t-butyl peroxypivalate, diisopropyl peroxydicarbonate, dicyclohexyl peroxydicarbonate, dicumyl peroxide, dibenzoyl peroxide, dilauroyl peroxide, potassium peroxydisulfate, ammonium peroxydisulfate, di-t-butyl hyponitrite, dicumyl hyponitrite, etc. Other suitable initiating systems are described in the literature, for example Moad and Solomon "The Initiating System of the Invention" (1999).
Chemistry of Free Radical Polymerization”, Pergamon, London, 1995, pp 53-95.

In one embodiment, the radical initiator is 4,4'-azobis-(4-cyanopentanoic acid).

Chain transfer agents Chain transfer agents are generally selected taking into consideration the type of monomer to be polymerized. Suitable chain transfer agents for use in the present invention include chain transfer agents for nitroxide mediated radical polymerization (NMP), atom transfer radical polymerization (ATRP), and RDRP, including RAFT. Other chain transfer agents will be known to those skilled in the art.

の構造を有し、式中、Ｚは、Ｃ＝Ｓ部分の反応性を増強する基であり、
Ｒは、ラジカル重合を開始することができるホモロイティック（ｈｏｍｏｌｏｙｔｉｃ）脱離基である。 Examples of chain transfer agents suitable for the present invention are (I)

where Z is a group that enhances the reactivity of the C=S moiety;
R is a homoloytic leaving group capable of initiating radical polymerization.

In one embodiment of the invention, R is selected from the group consisting of secondary cyanoalkyl, such as cyanomethyl, 1-cyanoethyl, 2-cyanopropan-2-yl, primary and secondary alkoxycarbonylalkyl, such as ethoxycarbonylmethyl, 1-ethoxycarbonylethyl, and primary and secondary carboxyalkyl, tertiary cyanoalkyl, such as 2-cyanobutan-2-yl, 1-cyanocyclohexyl, 2-cyano-4-methylpentan-2-yl, 2-cyano-4-methoxy-4-methylpentan-2-yl, 2-cyano-4-carboxybutan-2-yl, 2-cyano-5-hydroxypentan-2-yl, secondary cyano(aryl)alkyl, such as cyano(phenyl)methyl, tertiary alkoxycarbonylalkyl, such as 2-alkoxycarbonylprop ... 1-cyanocyclohexyl, 2-cyano-4-methylpentan-2-yl, 1-cyanocyclohexyl, 2-cyano-4-methylpentan-2-yl, 1-cyanocyclohexyl, 2-cyano-4-methoxy-4-methylpentan-2-yl, 1- -(butylamino)-2-methyl-1-oxopropan-2-yl, tertiary carboxyalkyl, secondary aryl(alkoxylcarbonyl)alkyl such as phenyl(ethoxycarbonyl)methyl, and other tertiary radicals such as 1-(cyclohexylamino)-2-methyl-1-oxopropan-2-yl, 1-(2-hydroxyethylamino)-2-methyl-1-oxopropan-2-yl, 1-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-ylamino)-2-methyl-1-oxopropan-2-yl, 2-(4,5-dihydro-1H-imidazol-2-yl)propan-2-yl, and 2-(1-(2-hydroxyethyl)-4,5-dihydro-1H-imidazol-2-yl)propan-2-yl;
Z is selected from the group consisting of aryl, C _1-30 alkyl, -S-C alkyl, -O-aryl, -N(C _1-6 alkyl) ₂ , -N(aryl)(C _1-6 alkyl), -heteroaryl, -heterocyclyl, -OC 1-30 alkyl, heterocyclyl, and phosphate, wherein -aryl, -C _{1-30 alkyl, -heteroaryl, and -heterocyclyl may each be optionally substituted 1 to 4 times with substituents independently selected from the group consisting of C 1-30 alkyl ,} ═O, -CN, aryl, and -COOC _1-6 alkyl.

の構造を有し、式中、Ｒ、Ｚ_１、Ｚ_２、及びＺ_３は、式（Ｉ）で定義される通りである。 In other embodiments of the present invention, the chain transfer agent is (II), (III), or (IV).

wherein R, Z ₁ , Z ₂ , and Z ₃ are as defined in formula (I).

In one embodiment, the chain transfer agent is a RAFT agent.

In non-limiting embodiments, the chain transfer agent can be one or more compounds selected from the group consisting of dithiobenzoates, dithioesters, thioether-thiones, trithiocarbonates, dithiocarbamates, xanthates, and mixtures thereof.

In one embodiment, the RAFT agent is a macro RAFT agent.

As used herein, the term "macroRAFT" or "macroRAFT agent" refers to a RAFT agent that includes one or more monomers.

In certain embodiments, the macro RAFT agent is prepared by a process that includes polymerizing one or more unsaturated monomers under the control of the RAFT agent to form the macro RAFT agent.

In one embodiment, the macroRAFT agent is of the general formula (Block [A])-RAFT, where Block [A] is a hydrophilic polymer or copolymer as defined herein, and RAFT is a RAFT agent as described herein. In other words, the macroRAFT agent consists of a RAFT agent bound to a hydrophilic block of the present invention.

In one embodiment, the macroRAFT agent is P(AA-stat-PEGA)-DDMAT.

In another embodiment, the macroRAFT agent is P(AA-stat-PEGA)-TTC.

Monomer Suitable polymers for the present invention include those prepared by any polymerization process. If desired, the monomer should also be capable of polymerizing with other monomers (e.g., copolymers). The factors that determine the copolymerizability of various monomers are well documented in the art. See, for example, Greenlee, R. Z., Polymer Handbook 4th Edition (Brandup, J. and Immergut. E.H., Grulke, E.A., John Wiley & Sons Ltd., Hoboken, 1999).

のものを含み、式中、Ｕ及びＷは、－ＣＯ_２Ｈ、－ＣＯ_２Ｒ^１、－ＣＯＲ^１、－ＣＳＲ^１、－ＣＳＯＲ^１、－ＣＯＳＲ^１、－ＣＯＮＨ_２、－ＣＯＮＨＲ^１、－ＣＯＮＲ^１ _２、水素、ハロゲン、及び任意選択的に置換されたＣ_１～Ｃ_４アルキルから独立的に選択されるか、又はＵ及びＷは、それ自体が任意選択的に置換され得るラクトン、無水物、又はイミド環を一緒になって形成し、任意選択的な置換基は、ヒドロキシ、－ＣＯ_２Ｈ、－ＣＯ_２Ｒ^１、－ＣＯＲ^１、－ＣＳＲ^１、－ＣＳＯＲ^１、－ＣＯＳＲ^１、－ＣＮ、－ＣＯＮＨ_２、－ＣＯＮＨＲ^１、－ＣＯＮＲ^１ _２、－ＯＲ^１、－ＳＲ^１、－Ｏ_２ＣＲ^１、－ＳＣＯＲ^１、及びＯＣＳＲ^１から独立的に選択され、
Ｖは、水素；Ｒ^１、－ＣＯ_２Ｈ、－ＣＯ_２Ｒ^１、－ＣＯＲ^１、－ＣＳＲ^１、－ＣＳＯＲ^１、ＣＯＳＲ^１、－ＣＯＮＨ_２、－ＣＯＮＨＲ^１、－ＣＯＮＲ^１ _２、－ＯＲ^１、－ＳＲ^１、－Ｏ_２ＣＲ^１、－ＳＣＯＲ^１、及び－ＯＣＳＲ^１から選択され、
各Ｒ^１は、任意選択的に置換されたアルキル、任意選択的に置換されたアルケニル、任意選択的に置換されたアルキニル、任意選択的に置換されたアリール、任意選択的に置換されたヘテロアリール、任意選択的に置換されたカルボシクリル、任意選択的に置換されたヘテロシクリル、任意選択的に置換されたアリールアルキル、任意選択的に置換されたヘテロアリールアルキル、任意選択的に置換されたアルキルアリール、任意に置換されたアルキルヘテロアリール、及び任意選択的に置換されたポリマー鎖から独立的に選択される。 Suitable monomers that may be used according to the present invention are represented by formula (V):

wherein U and W are independently selected from _-CO2H , _-CO2R1 , ^-COR1 , ^-CSR1 , ^-CSOR1 , ^-COSR1 , ^-CONH2 , _-CONHR1 , ^-CONR12 , hydrogen, _halogen , and optionally substituted _C1 - _C4 ^alkyl ; or U and W together form a lactone, anhydride, or imide ring which itself may be optionally substituted, the optional substituents being hydroxy, _-CO2H , _-CO2R1 , ^-COR1 , ^-CSR1 , ^-CSOR1 , ^-COSR1 , ^-CN , _-CONH2 , ^-CONHR1 , -CONR12, _-OR1 ^{, -SR1 , -O2} _. is independently selected from CR ¹ , -SCOR ¹ , and OCSR ¹ ;
V is selected from hydrogen; R ¹ , —CO ₂ H, —CO ₂ R ¹ , —COR ¹ , —CSR ¹ , —CSOR ¹ , COSR ¹ , —CONH ₂ , —CONHR ¹ , —CONR ¹ ₂ , —OR ¹ , —SR ¹ , —O ₂ CR ¹ , —SCOR ¹ , and —OCSR ¹ ;
Each ^R1 is independently selected from optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted alkylaryl, optionally substituted alkylheteroaryl, and optionally substituted polymer chains.

Examples of optional substituents for R ¹ include those selected from alkyleneoxydyl (epoxy), hydroxy, alkoxy, acyl, alkylcarbonyl, carboxy, sulfonic acid, isocyanato, cyano, silyl, halo, amino, including salts and derivatives thereof.

Examples of polymer chains include those selected from polyalkylene oxides, polyarylene ethers, and polyalkylene ethers.

Non-limiting examples of monomers include maleic anhydride, N-alkylmaleimides, N-arylmaleimides, dialkylfumarates and cyclopolymerizable monomers, acrylate and methacrylate esters, acrylic and methacrylic acid, styrene, acrylamide, methacrylamide, and methacrylonitrile, mixtures of these monomers, methyl methacrylate, ethyl methacrylate, propyl methacrylate (all isomers), butyl methacrylate (all isomers), 2-ethylhexyl methacrylate, isobornyl methacrylate, methacrylic acid, benzyl methacrylate, phenyl methacrylate, methacrylonitrile, alpha-methylstyrene, methyl acrylate, ethyl acrylate, propyl acrylate (all isomers), butyl acrylate (all isomers, e.g., n-butyl acrylate), 2-ethylhexyl acrylate, isobornyl acrylate, acrylic acid, benzyl acrylate, phenyl acrylate, acrylonitrile, styrene,
Functional methacrylates, glycidyl methacrylate, 2-hydroxyethyl methacrylate, hydroxypropyl methacrylate (all isomers), hydroxybutyl methacrylate (all isomers), N,N-dimethylaminoethyl methacrylate, N,N-diethylaminoethyl methacrylate, triethylene glycol methacrylate, itaconic anhydride, itaconic acid, glycidyl acrylate, 2-hydroxyethyl acrylate, hydroxypropyl acrylate (all isomers), hydroxybutyl acrylate (all isomers), N,N-dimethylaminoethyl acrylate, N,N-diethylaminoethyl acrylate, triethylene glycol acrylate acrylates selected from the group consisting of acrylates, methacrylamide, N-methylacrylamide, N,N-dimethylacrylamide, N-tert-butyl methacrylamide, N-n-butyl methacrylamide, N-methylol methacrylamide, N-ethylol methacrylamide, N-tert-butyl acrylamide, N-n-butyl acrylamide, N-methylol acrylamide, N-ethylol acrylamide, vinyl benzoic acid (all isomers), diethylaminostyrene (all isomers), alpha-methylvinyl benzoic acid (all isomers), diethylamino-alpha-methylstyrene (all isomers), p-vinylbenzene sulfonic acid, p-vinylbenzene sulfonic acid Sodium salt, trimethoxysilylpropyl methacrylate, triethoxysilylpropyl methacrylate, tributoxysilylpropyl methacrylate, dimethoxymethylsilylpropyl methacrylate, diethoxymethylsilylpropyl methacrylate, dibutoxymethylsilylpropyl methacrylate, diisopropoxymethylsilylpropyl methacrylate acrylate, dimethoxysilylpropyl methacrylate, diethoxysilylpropyl methacrylate, dibutoxysilylpropyl methacrylate, diisopropoxysilylpropyl methacrylate, trimethoxysilylpropyl acrylate, triethoxysilylpropyl acrylate, tributoxysilyl propyl acrylate, dimethoxymethylsilylpropyl acrylate, diethoxymethylsilylpropyl acrylate, dibutoxymethylsilylpropyl acrylate, diisopropoxymethylsilylpropyl acrylate, dimethoxysilylpropyl acrylate, diethoxysilylpropyl acrylate, dibutoxysilylpropyl acrylate, diisopropoxysilylpropyl acrylate, vinyl acetate, vinyl butyrate, vinyl benzoate, vinyl chloride, vinyl fluoride, vinyl bromide, maleic anhydride, N-phenylmaleimide, N-butylmaleimide, N-vinylpyrrolidone, N-vinylcarbazole, butadiene, ethylene, and chloroprene.

Non-limiting examples of acrylate monomers include methyl acrylate, methyl alpha-bromoacrylate, methyl 2-(bromomethyl)acrylate, methyl 2-(chloromethyl)acrylate, methyl 2-(trifluoromethyl)acrylate, ethyl acrylate, 2-(2-ethoxyethoxy)ethyl acrylate, 2-phenoxyethyl acrylate, alkoxylated phenol acrylate, alkoxylated tetrahydrofurfuryl acrylate, dicyclopentadienyl acrylate, 3,3,5-trimethylcyclohexyl acrylate, ethoxylated hydroxyethyl acrylate, ethoxylated nonylphenol acrylate, methoxypolyethylene glycol acrylate, polypropylene glycol acrylate, triethylene glycol ethyl ether acrylate, ethyl ethyl 2-(bromomethyl)acrylate, ethyl cis-(beta-cyano)acrylate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate, diacetone acrylate, mono-2-acryloyloxyalkyl succinate, mono-2-acryloyloxyethyl succinate, mono-2-acryloyloxyalkyl phthalate, mono-2-acryloyloxyethyl phthalate, ethylene glycol dicyclopentenyl ether acrylate, ethylene glycol methyl ether acrylate, ethylene glycol phenyl ether acrylate, ethyl 2-ethyl acrylate, 2-ethylhexyl acrylate, ethyl 2-propyl acrylate, 4-acetoxyphenethyl acrylate, [2-(acryloyloxy)ethyl]trimethylammonium chloride, 2-(4-
Benzoyl-3-hydroxyphenoxy)ethyl acrylate, benzyl 2-propyl acrylate, n-propyl acrylate, isopropyl acrylate, n-butyl acrylate, isobutyl acrylate, sec-butyl acrylate, tert-butyl acrylate, tert-butyl 2-bromoacrylate, 4-tert-butylcyclohexyl acrylate, 2-carboxyethyl acrylate, 2-chloroethyl acrylate, di(ethylene glycol) ethyl ether acrylate, di(ethylene glycol) 2-ethylhexyl ether acrylate, cyclohexyl acrylate, n- Pentyl acrylate, n-hexyl acrylate, cyclohexyl acrylate, 4-hydroxybutyl acrylate, 2-hydroxyethyl acrylate, 2-hydroxy-3-phenoxypropyl acrylate, hydroxypropyl acrylate, benzyl acrylate, phenethyl acrylate, isobornyl acrylate, isooctyl acrylate, tert-octyl acrylate, n-decyl acrylate, isodecyl acrylate, undecyl acrylate, 10-undecenyl acrylate, dodecyl acrylate, lauryl acrylate, myristyl acrylate, stearyl acrylate , palmityl acrylate, octadecyl acrylate, n-eicosyl acrylate, isonorbornyl acrylate, pentabromobenzyl acrylate, pentabromophenyl acrylate, pentafluorophenyl acrylate, poly(ethylene glycol) methyl ether acrylate, poly(propylene glycol) acrylate, tetrahydrofurfuryl acrylate, 3,5,5-trimethylhexyl acrylate, acetonyl acrylate, 2-carboxyethyl acrylate, carboxymethyl acrylate, oxazolidinyl ethyl acrylate, methoxyethoxyethyl acrylate , cyclohexyloxymethyl acrylate, methoxymethoxyethyl acrylate, benzyloxymethyl acrylate, 2-butoxyethyl acrylate, 2-ethoxyethoxymethyl acrylate, 2-ethoxyethyl acrylate, allyloxymethyl acrylate, 2,3-dibromopropyl acrylate, 4-bromophenyl acrylate, 1,3-dichloro-2-propyl acrylate, 2-bromoethyl acrylate, 2-iodoethyl acrylate, chloromethyl acrylate, 2-isocyanatoethyl acrylate, 2-acetoacetoxyethyl acrylate, dialkylaminoalkyl acrylate Acrylates, such as 2-(dimethylamino)ethyl acrylate, 2-(diethylamino)ethyl acrylate, 3-(dimethylamino)propyl acrylate, 3-(diethylamino)propyl acrylate, etc.; quaternary ammonium salts of dialkylaminoalkyl acrylates, such as acryloyloxyethyl trimethyl ammonium chloride, acryloyloxypropyl trimethyl ammonium chloride, acryloyloxypropyl lauryl dimethyl ammonium chloride, acryloyloxyethyl ethyl dimethyl ammonium ethyl sulfate, acryloyloxyethyl trimethyl ammonium ammonium sulfate, and acryloyloxyethyl trimethylammonium methosulfate; phosphorus-containing acrylates, such as diethyl[(acryloyloxy)methyl]phosphonate, diethyl[(acryloyloxy)ethyl]phosphonate, diethyl(acryloyloxy)methyl phosphate, and diethyl(acryloyloxy)ethyl phosphate; sulfur-containing acrylates, such as 4-thiocyanatobutyl acrylate, thiocyanatomethyl acrylate, 2-methylthioethyl acrylate, 2-methylsulfonylethyl acrylate, 2-ethylthioethyl acrylate, 2-ethyl ... butyl acrylate, 2,3-bis(methylthio)propyl acrylate, 2,3-bis(methylsulfonyl)propyl acrylate, 2,3-bis(ethylthio)propyl acrylate, 2,3-bis(butylsulfonyl)propyl acrylate, and 2-methylthio-3-ethylthiopropyl acrylate; silicon-containing acrylates, for example, 2-(trimethylsilyloxy)ethyl acrylate, trimethylsilylmethyl acrylate, diphenylmethylsilylmethyl acrylate, ethyl 2-(trimethylsilylmethyl ) acrylate, 3-[tris(trimethylsiloxy)silyl]propyl acrylate, and 3-(trimethoxysilyl)propyl acrylate, methyl methacrylate, methyl alpha-bromo methacrylate, methyl 2-(bromomethyl) methacrylate, methyl 2-(chloromethyl) methacrylate, methyl 2-(trifluoromethyl) methacrylate, ethyl methacrylate, 2-(2-ethoxyethoxy)ethyl methacrylate, 2-phenoxyethyl methacrylate, alkoxylated phenol methacrylate, alkoxylated tetrahydrofurfuryl methacrylate, dicyclopentadienyl methacrylate, Acrylate, 3,3,5-trimethylcyclohexyl methacrylate, ethoxylated hydroxyethyl methacrylate, ethoxylated nonylphenol methacrylate, methoxypolyethylene glycol methacrylate, polypropylene glycol methacrylate, triethylene glycol ethyl ether methacrylate, ethyl 2-(bromomethyl)methacrylate, ethyl cis-(beta-cyano)methacrylate, 2-ethylhexyl 2-cyano-3,3-diphenyl methacrylate, diacetone methacrylate, mono-2-methacryloyloxyethyl succinate, mono-2-methacryloyloxya alkyl succinate, mono-2-methacryloyloxyethyl phthalate, mono-2-methacryloyloxyalkyl phthalate, ethylene glycol dicyclopentenyl ether methacrylate, ethylene glycol methyl ether methacrylate, ethylene glycol phenyl ether methacrylate, ethyl 2-ethyl methacrylate, 2-ethylhexyl methacrylate, ethyl 2-propyl methacrylate, 4-acetoxyphenethyl methacrylate, [2-(methacryloyloxy)ethyl]trimethylammonium chloride, 2-(4-benzoyl 1-3-hydroxyphenoxy)ethyl methacrylate acrylate, benzyl 2-propyl methacrylate, n-propyl methacrylate, isopropyl methacrylate, n-butyl methacrylate, isobutyl methacrylate, sec-butyl methacrylate, tert-butyl methacrylate, tert-butyl 2-bromo methacrylate, 4-tert-butylcyclohexyl methacrylate, 2-carboxyethyl methacrylate, 2-chloroethyl methacrylate, di(ethylene glycol) ethyl ether methacrylate, di(ethylene glycol) 2-ethylhexyl ether methacrylate, cyclohexyl methacrylate, dialkylamino alkylene Methacrylates, such as 2-(dimethylamino)ethyl methacrylate, 2-(diethylamino)ethyl methacrylate, 3-(dimethylamino)propyl methacrylate, and 3-(diethylamino)propyl methacrylate; quaternary ammonium salts of dialkylaminoalkylene methacrylates, such as methacryloyloxyethyl trimethyl ammonium chloride, methacryloyloxypropyl trimethyl ammonium chloride, methacryloyloxypropyl lauryl dimethyl ammonium chloride, methacryloyloxyethyl ethyl dimethyl ammonium ethyl sulfate, methacryloyloxyethyl ... methacryloyloxyethyltrimethylammonium sulfate, and methacryloyloxyethyltrimethylammonium methosulfate, n-pentyl methacrylate, n-hexyl methacrylate, cyclohexyl methacrylate, 4-hydroxybutyl methacrylate, 2-hydroxyethyl methacrylate, 2-hydroxy-3-phenoxypropyl methacrylate, hydroxypropyl methacrylate, benzyl methacrylate, phenethyl methacrylate, isobornyl methacrylate, isooctyl methacrylate, tert-octyl methacrylate, n-decyl methacrylate, isodecyl methacrylate, methacrylate, undecyl methacrylate, 10-undecenyl methacrylate, dodecyl methacrylate, lauryl methacrylate, myristyl methacrylate, stearyl methacrylate, palmityl methacrylate, octadecyl methacrylate, n-eicosyl methacrylate, iso-norbornyl methacrylate, pentabromobenzyl methacrylate, pentabromophenyl methacrylate, pentafluorophenyl methacrylate, poly(ethylene glycol) methyl ether methacrylate, poly(propylene glycol) methacrylate, tetrahydrofurfuryl methacrylate, ethyl 2-(trimethylsilyl) ... (phenylsilylmethyl) methacrylate, 3,5,5-trimethylhexyl methacrylate, acetonyl methacrylate, 2-carboxyethyl methacrylate, carboxymethyl methacrylate, oxazolidinyl ethyl methacrylate, methoxyethoxyethyl methacrylate, cyclohexyloxymethyl methacrylate, methoxymethoxyethyl methacrylate, benzyloxymethyl methacrylate, 2-butoxyethyl methacrylate, 2-ethoxyethoxymethyl methacrylate, 2-ethoxyethyl methacrylate, allyloxymethyl methacrylate, 2,3-dibromopropyl methacrylate, 4-methyl ... -bromophenyl methacrylate, 1,3-dichloro-2-propyl methacrylate, 2-bromoethyl methacrylate, 2-iodoethyl methacrylate, chloromethyl methacrylate, 2-isocyanatoethyl methacrylate, 2-acetoacetoxyethyl methacrylate, phosphorus-containing methacrylates such as diethyl[(acryloyloxy)methyl]phosphonate, diethyl[(acryloyloxy)ethyl]phosphonate, diethyl(acryloyloxy)methyl phosphate, and diethyl(acryloyloxy)ethyl phosphate, sulfur-containing methacrylates such as 4-thiocyanatobutyl methacrylate,

acrylates, thiocyanatomethyl methacrylate, 2-methylthioethyl methacrylate, 2-methylsulfonylethyl methacrylate, 2-ethylthioethyl methacrylate, 2-ethylsulfonylethyl methacrylate, 2-propylthioethyl methacrylate, 4-methylthiobutyl methacrylate, 2,3-bis(methylthio)propyl methacrylate, 2,3-bis(methylsulfonyl)propyl methacrylate, 2,3-bis(ethylthio)propyl methacrylate, 2,3-bis(butylsulfonyl)propyl methacrylate, and 2-methylthio-3-ethylthiopropyl methacrylate; silicon-containing methacrylates, such as 2-(trimethylsilyloxy)ethyl methacrylate, trimethylsilylmethyl methacrylate, diphenylmethylsilylmethyl methacrylate, ethyl 2-(trimethylsilylmethyl)methacrylate, 3-[tris(trimethylsiloxy)silyl]propyl methacrylate, 3-(trimethoxysilyl)propyl methacrylate, and combinations thereof.

A more extensive list of exemplary methacrylate monomers, acrylate monomers, methacrylamide monomers, acrylamide monomers, styrenic monomers, diene monomers, vinyl monomers, monomers with reactive functional groups, and crosslinking monomers suitable for use as radically polymerizable monomers herein is set forth in Moad et al., "Living Radical Polymerization by the RAFT Process-a Third Update," Australian Journal of Chemistry 65:985-1076 (2012), which is incorporated herein by reference in its entirety.

In a first embodiment, the present invention provides a block copolymer comprising blocks [A] and [B],
Block [A] is a hydrophilic homopolymer or copolymer,
Block [B] is a hydrophobic homopolymer having a Tg of less than 16° C. or a hydrophobic copolymer having a Tg of the hydrophobic block of less than about 75° C.,
The present invention provides a process for preparing an amphiphilic block copolymer, the process comprising obtaining blocks [A] and [B] by RDRP, preferably via RAFT polymerization of ethylenically unsaturated monomers.

In this first embodiment, block [A] is a hydrophilic polymer or copolymer formed by polymerization of one or more monomers as described herein.

In one example of the first embodiment, block [A] is prepared from one or more of poly(ethylene glycol) methyl ether acrylate (PEGA), poly(ethylene glycol) methyl ether methacrylate (PEGMA), and acrylic acid.

In this first embodiment, block [B] is a hydrophobic polymer or copolymer formed by polymerization of one or more monomers as described herein.

In one example of the first embodiment, block [B] is prepared from one or more of n-butyl acrylate (nBA), tert-butyl acrylate (tBA), and styrene.

In a second embodiment, the present invention provides a process for preparing a block copolymer comprising blocks [A] and [B], comprising:
Block [A] is a hydrophobic homopolymer or copolymer,
Block [B] is a hydrophobic homopolymer or copolymer,
The process comprises obtaining blocks [A] and [B] by RDRP, preferably via RAFT polymerization of ethylenically unsaturated monomers.

In one example of the second embodiment, block [A] is prepared from poly(methyl methacrylate) (PMMA).

In one example of the second embodiment, block [B] is prepared from one or more of benzyl methacrylate, ethylhexyl methacrylate, and methyl methacrylate, preferably PMMA70-b-PBzMA40 or PMMA70-b-P(EHMA90-stat-MMA10).

Glass Transition Temperature As will be appreciated by those skilled in the art, the glass transition temperature (Tg) of a polymer is defined as the temperature at which both the long range segmental motion of the polymer chain and the coiling and uncoiling of the chain segments are "frozen" and the polymer behaves like a "solid glass" or has crystalline properties. Below its Tg, the polymer does not flow or exhibit rubbery elasticity, but above its Tg, the polymer does. In other words, a polymer at a temperature below its Tg is harder and less elastic than the same polymer at a temperature above its Tg. The Tg of a polymer can be determined by any standard method known in the art, for example, using differential scanning calorimetry (DSC) and dynamic mechanical thermal analysis (DMTA).

In an embodiment, block [B] comprises a hydrophobic copolymer selected to have a Tg of the hydrophobic block less than about 75°C, preferably in the range of -70°C to 75°C.

In another embodiment, block [B] comprises a hydrophobic homopolymer selected to have a Tg of less than 16°C, preferably in the range of -70°C to 16°C.

Reaction Conditions Conventional techniques, conditions, and reagents used for the preparation of polymers by RAFT polymerization can be advantageously used according to the present invention. As a general guideline in selecting conditions for polymerization, the concentration of initiator(s), monomer, and other reaction conditions (solvent(s), if present, reaction temperature, reaction pressure, surfactants, if present, other additives) should be selected to optimize polymer properties, e.g., narrow dispersion polymer (good control/livingness based on a satisfactory RDRP (RAFT) process).

Suitable ratios for the monomers of block [A] (M1:M2) include 1:100 to 100:1, or about 1:100 to 1:1, or about 1:1 to 1:100, or about 5.
It may be between 0:1 and 1:50, or may be about 1:100, 1:95, 1:90, 1:85, 1:80, 1:75, 1:70, 1:65, 1:60, 1:55, 1:50, 1:45, 1:40, 1:35, 1:30, 1:25, 1:20, 1:15, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1: It may be 1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 15:1, 20:1, 25:1, 30:1, 35:1, 40:1, 45:1, 50:1, 55:1, 60:1, 65:1, 70:1, 75:1, 80:1, 85:1, 90:1, 95:1 or 100:1, or any range therein.

Suitable ratios (M1:M2) for the monomers of block [B] include 1:100 to 100:1, or may be about 1:100 to 1:1, or about 1:1 to 1:100, or about 50:1 to 1:50, or may be about 1:100, 1:95, 1:90, 1:85, 1:80, 1:75, 1:70, 1:65, 1:60, 1:55, 1:50, 1:45, 1:40, 1:35, 1:30, 1:25, 1:20, 1:15, It may be 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 15:1, 20:1, 25:1, 30:1, 35:1, 40:1, 45:1, 50:1, 55:1, 60:1, 65:1, 70:1, 75:1, 80:1, 85:1, 90:1, 95:1 or 100:1, or any range therein.

The chain transfer agent can be present in any suitable concentration, for example, from about 1 mmol·L ⁻¹ to about 1000 mmol·L ⁻¹ , or from about 10 mmol·L ⁻¹ to about 1000 mmol·L ⁻¹ , for example, from about 5 mmol·L ⁻¹ to 20 mmol·L −1 , or from about 7 mmol·L ⁻¹ to about 13 mmol·L ⁻¹ , or about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 ^, 17, 18, 19 or 20 mmol·L ⁻¹ , or any range therein.

In one embodiment, the ratio of [hydrophobic monomer]:[chain transfer agent] ranges from about 10 to about 400, or from about 100 to about 150, or from about 75 to about 100, or it can be about 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, or 200, or any range therein. In one preferred embodiment, the ratio ranges from about 40 to about 200.

The polymerization temperature may be optimized by one of ordinary skill in the art taking into account the particular monomer(s) being polymerized and other components of the polymerization or reaction medium.

The polymerization is generally carried out at a temperature in the range of 20 to 100°C, for example, about 0 to 180°C, or about 50 to 150°C, or about 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100°C, or any range therein, preferably in the range of 40 to 100°C.

The reaction time can be from 1 to 48 hours, e.g., from 1 to 20 hours, from 1 to 12 hours, or from 1 to 8 hours, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours, or any range therein.

The polymerization can be carried out at any suitable pH range. In one embodiment, the pH ranges from 3 to 8, or it can be from about 3.5 to about 6, or from about 4 to about 7, or about 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, or 8, or any range therein.

In one embodiment, the polymerization was carried out at 80°C in an oil bath with an agitation speed of 350 rpm for 6 hours.

The reaction medium may be selected from a wide range of media to suit the monomer(s) being used. For example, water and alcohols such as methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, n-pentanol, and mixtures thereof.

The reaction medium may further include one or more of an acid, a base, a catalyst, a surfactant, and/or a coupling agent, or any other suitable components.

Hydrophobicity and Hydrophilicity Those skilled in the art will appreciate that the terms "hydrophilic" and "hydrophobic" as used herein are not intended to define the absolute properties of a particular substance, but rather are indicators of favorable or unfavorable interactions (i.e., attractive or repulsive interactions). In other words, the terms "hydrophilic" and "hydrophobic" are used herein as primary indicators to define properties such as what attracts and what repels each other.

Merely as a convenient reference point, one skilled in the art may consider a "hydrophilic" liquid to have a solubility in water of at least 5 g/L at 25° C. and a "hydrophobic" liquid to have a solubility in water of less than 5 g/L at 25° C. From the perspective of solids, the terms "hydrophilic" and "hydrophobic" may be considered by one skilled in the art to refer to solids that may be capable of being wetted (i.e., not repelled) by hydrophilic and hydrophobic liquids, respectively.

Molecular Weight and Dispersity Index Those skilled in the art will understand that polymers exist as a distribution of chain lengths and molecular weights, therefore the molecular weight of a polymer must be stated as the average molecular weight calculated from the molecular weights of all the chains in a sample.

In the present invention, the molecular weight (MW) of block [A] or block [B] may be in the range of 5000 to 100,000, or it may be about 10,000 to 100,000, or about 25,000 to about 75,000, or it may be about 5000, 5500, 6000, 6500, 7000, 7500, 8000, 8500, 9000, 9500, 10000, 11000, 12000, 13000, 14000, 15000, 1 6000, 17000, 18000, 19000, 20000, 25000, 30000, 35000, 40000, 45000, 50000, 60000, 70000, 80000, 90000, 100000, 125000, 150000, 175000, 200000, 225000, 250000, 275000, 300000, 350000, 400000, 450000, or 500000, or any range therein. In a preferred embodiment, the molecular weight of block [A] or block [B] is in the range of 5000 to 40,000.

In the present invention, the average degree of polymerization (DP) of the block copolymers as described herein ranges from about 10 to about 1000, or from about 20 to about 500, or from about 50 to 750, or from about 300 to about 800, or about 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, or 200, or any range of values therein. In a preferred embodiment, the degree of polymerization (DP) of the block copolymers ranges from about 50 to about 300.

Polymers prepared according to the present invention may advantageously exhibit well-defined molecular architecture, predetermined molecular weight, weight, and narrow molecular weight distribution, or low polydispersity (D).

Nanofiber Dimensions As will be appreciated by one of ordinary skill in the art, nanofibers of the present invention are defined as having a length that is greater than or significantly greater than the width of the nanofiber. The ratio of length to width of a nanofiber can be greater than 5:1, or greater than 10:1, or greater than 25:1, or greater than 50:1, or greater than 100:1, or greater than 250:1, or greater than 500:1, or greater than 1000:1, or it can be from 5:1 to 200,000:1, or from 100:1 to 10,000:1, or from 500:1 to 5,000:1, or any range therein.

The width of the nanofibers is about 1 nm to about 250 nm, or about 3 nm to about 100 nm, or about 5 nm to about 50 nm, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 55, 60, 65, 70, It may be 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245 or 250 nm, or any range therein.

The length of each of the nanofibers is about 5 nm to 2 mm, or about 10 nm to about 1 mm, or about 50 nm to about 500 μm, or about 20 nm to about 100 μm, or about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 250, 300, 350, 400, 450, 500, 600, 700, 8 00, 900 or 1000 nm, or 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900 or 1000 μm, or about 1.5 or 2 mm, or any range therein.

Crosslinking Agents In certain embodiments, the amphiphilic block copolymers may be crosslinked to durably stabilize the resulting nanofibers and thus provide them with long-term stability. The crosslinking agent may provide a covalent crosslink between two different polymer chains. Any suitable crosslinking agent may be used. As one skilled in the art will appreciate, the crosslinking agent should have two end groups that are capable of radical polymerization and thus incorporation into the polymer chains of the present invention. Examples of suitable crosslinking agents include, but are not limited to, ethylene glycol diacrylate esters (e.g., ethylene glycol dimethyl acrylate) when the monomeric material is an acrylate ester, or ethylene glycol diacrylic acid (e.g., ethylene glycol dimethacrylic acid) when the monomeric material is an acrylic acid. In embodiments in which a crosslinking agent is present, the ratio of monomeric material to crosslinking agent in the solvent may be from 10:1 to 50:1, for example, from 20:1 to 40:1.

Non-limiting examples of crosslinking agents include divinyl ethers of compounds selected from the group consisting of (meth)acrylic anhydride, ethylene glycol, ethylene glycol diacrylate, poly(ethylene glycol) diacrylate, 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, 1,8-octanediol, 1,9-nonanediol, 1,10-decanediol, 1,11-undecanediol, 1,12-dodecanediol, and combinations thereof; divinyl ethers of diethylene glycol, triethylene glycol, tetraethylene glycol, pentaethylene glycol, hexaethylene glycol, heptaethylene glycol, octaethylene glycol, nonaethylene glycol, decaethylene glycol, and polyalkylene glycols; methylene bis(meth)acrylamide; ethylene glycol di(meth)acrylate; butanediol di(meth)acrylate; tetraethylene glycol di(meth)acrylamide; Acrylates; polyethylene glycol di(meth)acrylate; polyethylene glycol di(meth)acrylamide; dipropylene glycol diallyl ether; polyglycol diallyl ether; hydroquinone diallyl ether; trimethylolpropane tri(meth)acrylate; trimethylolpropane diallyl ether; pentaerythritol triallyl ether; allyl (meth)acrylate; triallyl cyanurate; diallyl maleate, polyallyl ester; tetraallyloxyethane; 1,13-tetradecadiene; divinylbenzene; diallyl phthalate; triallyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione; N,N'-divinylimidazolidone, 1-vinyl-3(E)-ethylidenepyrrolidone; 2,4,6-triallyloxy-1,3,5-triazine; and combinations thereof.

In one non-limiting embodiment, the crosslinker is selected from the group consisting of (meth)acrylic anhydride, methylene bis(meth)acrylamide, ethylene glycol di(meth)acrylate, butanediol di(meth)acrylate, tetraethylene glycol di(meth)acrylate, polyethylene glycol di(meth)acrylate, polyethylene glycol di(meth)acrylate, polyethylene glycol di(meth)acrylamide, dipropylene glycol diallyl ether, polyglycol diallyl ether, hydroquinone diallyl ether, trimethylolpropane tri(meth)acrylate, trimethylolpropane diallyl ether, pentaerythritol triallyl ether, and combinations thereof.

In the present invention, the crosslinker can be added at any time during the polymerization of the second block, including at the beginning, middle, or end. In one embodiment, the crosslinker is added at t=0 hours. In another embodiment, the crosslinker is added at t=2 hours. It is expected that one skilled in the art can optimize the timing of the addition of the crosslinker depending on the effect desired, for example, adding the crosslinker later in the polymerization process may have less effect on the final morphology, and vice versa.

In one non-limiting embodiment, the crosslinker(s) can be present in an amount of about 0.001% to about 20% by weight of the block copolymer. In another non-limiting embodiment, the crosslinker(s) can be present in an amount of about 0.001% to about 10% by weight of the block copolymer. In yet another non-limiting embodiment, the crosslinker(s) can be present in an amount of about 0.001% to about 5% by weight of the block copolymer. The crosslinker may be present at about 0.001, 0.01, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20% by weight, or any range therein.

In one embodiment, the crosslinker is ethylene glycol diacrylate (EGDA) or ethylene glycol dimethacrylate (EGDMA).

In another embodiment, the crosslinker is poly(ethylene glycol) diacrylate (PEGDA).

Uses of the Nanofibers of the Invention The nanofibers disclosed herein may be used as vehicles for active agents. In other words, the nanofibers may further include an active agent encapsulated in the nanofiber. As used herein, the term "encapsulated" refers to the inclusion of an active agent within the core of the body of the nanofibers described herein. For example, in embodiments of the invention where the nanofiber has a solid core, the active agent will be held within the polymer matrix of the nanofiber within the core of the nanofiber.

In embodiments of the present invention, the nanofiber composition further comprising an active agent may contain 0.01-50 wt.% of the active agent based on the weight of the nanofiber as a whole. For example, the active agent may be present in an amount of 1-30 wt.%, such as 5-10 wt.%, based on the weight of the nanofiber as a whole. The active agent may be selected from one or more of the group consisting of vitamin C, peptides, glycerol, dyes, flavors, perfume oils, citronellal, silicon oils, organosilicons, pesticides, beta-carotene, and pharmacologically active agents.

The term "pharmacologically active agent" as used herein may refer to a substance useful for the treatment or prevention of a condition affecting a human or other animal. The condition may be a disease, disorder, or physiological condition. It will be understood that an active agent may not directly affect the underlying condition, but may be used as an adjuvant with an additional active agent to enhance the effectiveness of the other active agent. Thus, the term "pharmacologically active agent" as used herein includes all classes of pharmacologically active agents, whether adjuvant or therapeutic, that may be provided to a subject through oral administration. As used herein, the terms "pharmacologically active agent" and "drug" may be used interchangeably, and therefore the term "drug" may be interpreted based on the definition of "active agent." Examples of pharmacologically active agents include, but are not limited to, ibuprofen, fenofibrate, and isotrencinoin.

Further active agents that may be mentioned herein may include, but are not limited to, carbon metabolites (e.g., glucose, fructose, fumarate, etc.), electron acceptors (e.g., nitrates, peroxides, etc.), and vitamins, such as vitamins A, B1, B2, B3, B6, B12, D, E, biotin, folate, and pantothenate; minerals, such as calcium, magnesium, selenium, and zinc; amino acids, such as asparagine, carnitine, glutamine, and serine; antioxidants selected from coenzyme Q10, glutathione, and cysteine; or metabolites, such as lipoic acid, oleic acid, choline, inositol, fructose, glucose, insulin, epigallocatechin gallate, and mixtures thereof.

In an embodiment of the invention, the nanofibers may have a core region that may include an active agent. The nature of the active agent in the core will be determined by the nature of the nanofiber formed. For example, a nanofiber formed such that the hydrophilic blocks of the amphiphilic block copolymer are disposed at the surface of the nanofiber may be suitable for encapsulating a hydrophobic active agent (as described above). Alternatively, a nanofiber formed such that the hydrophobic blocks of the amphiphilic block copolymer are disposed at the surface of the nanofiber may be suitable for encapsulating a hydrophilic active agent (as described above). Nanofibers of the invention may have an average diameter of 50-200 nm, e.g., 70-150 nm.

In some materials, the hydrophobic repeat units form the surface of the nanofiber and the hydrophilic repeat units form the core. In other embodiments having the opposite arrangement, the hydrophilic repeat units form the surface of the nanofiber and the hydrophobic repeat units form the core. In still further embodiments, the hydrophobic repeat units form the surface of the nanofiber and the hydrophobic repeat units also form the core.

Other uses of the nanofibers of the present invention relate to sun care compositions, face care compositions, lip care compositions, eye care compositions, skin care compositions, after-sun compositions, body care compositions, nail care compositions, anti-aging compositions, insect repellents, oral care compositions, deodorant compositions, hair care compositions, conditioning compositions, color cosmetic compositions, color protection compositions, self-tanning compositions, and foot care compositions.

The nanofibers disclosed herein may also be used as fillers and/or reinforcing agents for composite materials. In other words, the nanofibers may be encapsulated in or dispersed throughout a matrix material. The nanofibers may modify the physical properties of the composite material formed. The nanofibers may be added to or dispersed throughout a matrix during the manufacture of a composite material, such as when the matrix is dissolved or dispersed throughout a solvent, such as water, or when melted. In one example, the matrix may include a polymer as described herein to form a composite polymer material, such as a film, or coating, or formed article. The polymer matrix may preferably be hydrophilic or formed from an aqueous dispersion, such that the hydrophilic shell of the nanofibers is wetted by the matrix during production. If the polymer matrix is formed from an aqueous dispersion (i.e., a latex), the nanofibers may be mixed with the aqueous dispersion prior to curing. If the polymer matrix is melted, the nanofibers may be added to an extruder along with the polymer pellets and mixed during or after melting of the polymer matrix material.

In another example, the matrix may include a hydraulic binder such as cement (e.g., Portland cement) or fly ash, where the nanofibers can be added to and then mixed with the hydraulic binder before, after, or consecutively with the addition of water to produce a cementitious material containing the nanofibers of the present invention.

In another example, the matrix may include mineral materials such as calcium sulfate (i.e., gypsum) in the production of gypsum-based articles such as gypsum board/drywall.

In yet another example, the matrix can be any material that benefits from modification of the matrix viscosity and/or rheology. In other words, the nanofibers can be used as viscosity modifiers for a range of liquid or semi-solid materials, such as gels, hydraulic fluids, etc.

As will be appreciated by those skilled in the art, the nanofibers of the present invention may be used to replace fillers and/or reinforcing agents in other known materials where the effects of the low Tg core may have beneficial effects.

Preferred features, embodiments, and variations of the present invention can be identified from the following detailed description, which provides sufficient information for one skilled in the art to practice the present invention. The detailed description should not be construed in any way as limiting the scope of the foregoing summary of the invention. The detailed description makes reference to several drawings, as follows:

Total monomer conversions for RAFT aqueous emulsion polymerizations of styrene and nBA in the presence of P(AA-stat-PEGA)-TTC macroRAFT agent at pH 3.5, pH 5, and pH 7 (see also Table 1). Molecular weight distributions (w(log M) vs. log M) of RAFT aqueous emulsion polymerizations of styrene and nBA in the presence of P(AA-stat-PEGA)-TTC macroRAFT agent at pH 3.5, pH 5, and pH 7 (see also Table 1). TEM images of RAFT aqueous emulsion polymerizations of styrene and nBA in the presence of P(AA-stat-PEGA)-TTC macroRAFT agent ([styrene]/[nBA]=70/30, [hydrophobic monomer] ₀ /[macroRAFT] ₀ =200) carried out at pH 3.5, pH 5, and pH 7 (see also Table 1). Scale bars: A-1=500 nm, A-2=2 μm, A-3=500 nm. Molecular weight distributions (w(logM) vs. logM) of RAFT aqueous emulsion polymerizations of styrene and nBA in the presence of P(AA-stat-PEGA)-TTC macroRAFT agent with different [hydrophobic monomer] ₀ /[macroRAFT] ₀ (macroRAFT agents, from left to right: [hydrophobic monomer] ₀ /[macroRAFT] ₀ = 50 (B-1), 100 (B-2), 130 (B-3), 150 (B-4), 170 (B-5), 200 (B-6)) (see also Table 2). TEM images of RAFT aqueous emulsion polymerizations of styrene and nBA in the presence of P(AA-stat-PEGA)-TTC macroRAFT agent with different [hydrophobic monomer] ₀ /[macroRAFT] ₀ ([hydrophobic monomer] ₀ /[macroRAFT] ₀ = 50 (B-1), 100 (B-2), 130 (B-3), 150 (B-4), 170 (B-5), 200 (B-6)) (see also Table 2). Scale bars: B-1 = 200 nm, B-2 = 1 μm, B-3 = 1 μm, B-4 = 2 μm, B-5 = 2 μm, B-6 = 2 μm. TEM images of nanoparticles synthesized via RAFT aqueous emulsion polymerization of styrene and nBA in the presence of P(AA-stat-PEGA)-TTC macroRAFT agent at pH 5 with EGDA or PEGDA in method (i) at t=0 h (entries C-x and D-x; top panel) and method (ii) at t=2 h (entries E-x and F-x; bottom panel) ([hydrophobic monomer] ₀ /[macroRAFT] ₀ =100). Scale bars: B-2=1 μm, C-1=1 μm, C-2=1 μm, D-1=1 μm, D-2=1 μm, D-3=100 nm, E-1=1 μm, E-2=1 μm, F-1=1 μm, F-2=1 μm, F-3=500 nm. EGDA or PEGDA crosslinked P(AA-stat-PEGA)-b-P(S-stat-nBA) nanoparticles dissolved in THF: (a) no crosslinker added, 1 mol% PEGDA added at t = 0 h, and 2.5 mol% PEGDA added at t = 0 h (top left to right); (b) no crosslinker added, 0.5 mol% EGDA added at t = 0 h, 1 mol% EGDA added at t = 0 h, and 10 mol% EGDA added at t = 0 h (top left to right); (c) no crosslinker added, 1 mol% PEGDA added at t = 2 h, and 10 mol% PEGDA at t = 2 h (bottom left to right); (d) No crosslinker added, 3 mol % EGDA added at t = 2 hours, 5 mol % EGDA added at t = 2 hours, 10 mol % EGDA added at t = 2 hours (bottom left to right). TEM images of nanoparticles synthesized via RAFT aqueous emulsion polymerization of styrene and nBA ([styrene] ₀ /[nBA] ₀ =20/80) in the presence of P(AA-stat-PEGA)-TTC macroRAFT agent at pH 5 with 5 mol % EGDA (relative to macroRAFT agent) at different solid contents ([hydrophobic monomer] ₀ /[macroRAFT] ₀ =130, solid contents 15.2% (H-1), 24.7% (H-2), 32.7% (H-3)) after 2 h polymerization. Scale bars: H-1=200 nm, H-2=200 nm, H-3=200 nm. Molecular weight distribution (w(logM) vs. logM) of P(AA-stat-PEGA)-TTC macroRAFT agent (M _n =13,400 g/mol; D=1.20). Figure 2 TEM images of nanoparticles synthesized via RAFT aqueous emulsion polymerization of styrene and _nBA ([styrene] ₀ /[nBA] ₀ =20/80) in the presence of P(AA-stat-PEGA)-TTC macroRAFT agent at pH 5 with 5 mol % EGDA (relative to macroRAFT _agent ) at different [hydrophobic monomer] 0 /[macroRAFT] 0 ([hydrophobic monomer] 0 /[macroRAFT] 0 =80 (G-1), 100 (G-2), 115 (G-3), 130 (G-4), 150 (G-5), 180 (G-6), 200 (G-7), 250 (G-8) _{, 300 (} G-9)) after 2 h polymerization. Scale bars: G-1 = 200 nm, G-2 = 1 μm, G-3 = 100 nm, G-4 = 1 μm, G-5 = 1 μm, G-6 = 1 μm, G-7 = 2 μm, G-8 = 1 μm, G-9 = 2 μm. FIG. 1 is a schematic diagram of a block copolymer having a first hydrophilic block and a second hydrophobic block self-assembled into a nanofiber having a hydrophilic outer "shell" portion and a hydrophobic inner "core" portion used in the preparation of a nanofiber-reinforced nanocomposite polymer material. (A) TEM micrograph of PMMA-b-P(EHMA-stat-MMA) and (B) SEM micrograph of PMMA-b-PBzMA.

DEFINITIONS In describing and claiming the present invention, the following terminology will be used in accordance with the definitions set out below. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments of the invention only, and is not intended to be limiting.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention pertains.

Unless the context clearly requires otherwise, throughout the specification and claims, the terms "comprise," "comprising," and the like are intended to be construed in an inclusive sense, i.e., "including, but not limited to," as opposed to an exclusive or exhaustive sense. For example, a composition, mixture, process, or method that includes a list of elements is not necessarily limited to only those elements and may include other elements not expressly listed or inherent to such composition, mixture, process, or method.

The transitional phrase "consisting of" excludes any element, step, or ingredient not specified. When present in a claim, such would close the claim to the inclusion of materials other than those recited, except for impurities normally associated therewith. When the phrase "consisting of" appears in a section in the body of a claim rather than immediately following a preamble, it limits only the elements recited in that section and does not exclude other elements from the claim as a whole.

The transitional phrase "consisting essentially of" is used to define a composition, process, or method that includes materials, steps, features, components, or elements in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristic(s) of the claimed invention. The term "consisting essentially of" occupies a compromise between "comprising" and "consisting of."

It should be readily understood that where applicants have defined an invention or portions thereof using open-ended terms such as "comprising," the specification should also be construed (unless otherwise stated) as describing such invention using the terms "consisting essentially of" or "consisting of." In other words, with respect to the terms "comprising,""consistingof," and "consisting essentially of," where one of these three terms is used herein, the presently disclosed and claimed subject matter may also include the use of either of the other two terms. Thus, in some embodiments not expressly stated otherwise, any instance of "comprising" may be replaced with "consisting of" or alternatively "consisting essentially of."

Furthermore, unless expressly stated to the contrary, "or" refers to an inclusive or, not an exclusive or. For example, a condition "A or B" is satisfied by any one of the following: A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), and both A and B are true (or exist).

Additionally, the indefinite articles "a" and "an" preceding an element or component of the invention are intended to be non-restrictive with respect to the number of instances (i.e., occurrences) of the element or component. Thus, "a" or "an" should be read to include one or at least one, and the singular form of an element or component also includes the plural, unless a numerical value is clearly intended to be in the singular.

Except in the operating examples or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood in all instances as modified by the term "about." The examples are not intended to limit the scope of the invention. Hereinafter, or where otherwise indicated, "%" means "% by weight," "ratio" means "ratio by weight," and "parts" means "parts by weight."

As used herein, the terms "majority" and "substantially" shall mean including greater than 50% by weight, unless otherwise indicated.

As used herein, the terms "about," "approximately," and "substantially," in connection with a range of numerical values, are understood to refer to a range of -10% to +10% of the referenced numerical value, preferably -5% to +5% of the referenced numerical value, more preferably -1% to +1% of the referenced numerical value, and most preferably -0.1% to +0.1% of the referenced numerical value. Furthermore, in connection with numerical ranges, these terms should be interpreted as providing support for a claim regarding any number or subset of numbers within that range. For example, a disclosure of 1 to 10 should be interpreted as supporting ranges of 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, 8 to 10, etc.

As used herein, weight percent refers to the weight of a particular component relative to the total weight of the reference composition.

The term "and/or" used in the context of "X and/or Y" should be interpreted as "X", or "Y", or "X and Y". Similarly, "at least one of X or Y" should be interpreted as "X", or "Y", or "both X and Y".

The terms "preferred" and "preferably" refer to embodiments of the invention that may provide certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the invention.

The complete disclosures of the patents, patent documents, and publications cited herein are incorporated by reference in their entirety as if each was incorporated individually.

As used herein, the term "nanofiber" refers to a solid nanoparticle material that is similar to a micelle in that it has a solid core and a solid shell/corona (i.e., the cylindrical interior portion is not hollow). In other words, the core and shell are formed from a polymeric material, with the hydrophilic block on the outer surface of the nanofiber (to form the shell) and the hydrophobic block forming the core of the nanofiber (or vice versa). In another embodiment, the hydrophobic block is on the outer surface of the nanofiber, and the hydrophobic block also forms the core of the nanofiber. While the shell is solid, these nanofibers may have the ability to be used as carriers, since other molecules (e.g., active agents) can still be dispersed (e.g., by diffusion or other suitable means) into the core of the cylindrical nanofiber, thereby allowing the cylindrical nanofiber to function as a carrier for the active agent.

The term "each independently selected from the group consisting of" means that when a group occurs more than one time in a structure, the group may be independently selected at each occurrence.

The term "alkyl" refers to a functionalized or non-functionalized, monovalent, straight, branched, or cyclic C ₁ -C ₆₀ hydrocarbyl group, optionally with one or more heteroatoms. In one non-limiting embodiment, the alkyl is a C ₁ -C ₄₅ hydrocarbyl group. In another non-limiting embodiment, the alkyl is a C ₁ -C ₃₀ hydrocarbyl group. Non-limiting examples of alkyl include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, n-heptyl, n-octyl, 2-ethylhexyl, tert-octyl, iso-norvomyl, n-dodecyl, tert-dodecyl, n-tetradecyl, n-hexadecyl, n-octadecyl, n-eicosyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like. The definition of "alkyl" also includes groups resulting from a combination of linear, branched, and/or cyclic structures.

The term "aryl" refers to a functionalized or unfunctionalized monovalent aromatic hydrocarbyl group, optionally having one or more heteroatoms. The definition of aryl includes carbocyclic and heterocyclic aromatic groups. Non-limiting examples of aryl groups include phenyl, naphthyl, indenyl, indanyl, azulenyl, fluorenyl, anthracenyl, furyl, thienyl, pyridyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, 2-pyrazolinyl, pyrazolidinyl, isoxazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,3-triazolyl, 1,3,4-thiadiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazinyl, 1,3,5-trithianyl, indolizinyl, indolyl, isoinyl, and the like. These include dolyl, 3H-indolyl, indolinyl, benzo[b]furanyl, 2,3-dihydrobenzofuranyl, benzo[b]thiophenyl, 1H-indazolyl, enzimidazolyl, benzothiazolyl, purinyl, 4H-quinolizinyl, isoquinolinyl, cinnolinyl, phthalazinyl group, quinazolinyl, quinoxalinyl, 1,8-naphthridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxyazinyl, and pyrazolo[1,5-c]triazinyl.

The term "alkylene" refers to a functionalized or non-functionalized divalent, straight, branched, or cyclic C ₁ -C ₄₀ hydrocarbyl group, optionally having one or more heteroatoms. In one non-limiting embodiment, the alkylene is a C ₁ -C ₃₀ group. In another non-limiting embodiment, the alkylene is a C ₁ -C ₂₀ group. Non-limiting examples of alkylene groups include the following:

The term "heteroatom" refers to oxygen, nitrogen, sulfur, silicon, phosphorus, or halogen. The heteroatom(s) may be present as part of one or more heteroatom-containing functional groups. Non-limiting examples of heteroatom-containing functional groups include ether, hydroxy, epoxy, carbonyl, carboxamide, carboxylate, carboxylic acid, imine, imide, amine, sulfone, sulfonamide, phosphone, and silane groups. The heteroatom(s) may also be present as part of a ring, such as in heteroaryl and heteroarylene groups.

As used herein, the term "alkenyl" refers to a group formed from a straight-chain, branched, or cyclic hydrocarbon residue containing at least one carbon-carbon double bond, including an ethylenically mono-, di-, or polyunsaturated alkyl or cycloalkyl group as defined above, preferably a _C2-20 alkenyl (e.g., _C2-10 or _C2-6 ). Examples of alkenyl include vinyl, allyl, 1-methylvinyl, butenyl, iso-butenyl, 3-methyl-2-butenyl, 1-pentenyl, cyclopentenyl, 1-methyl-cyclopentenyl, 1-hexenyl, 3-hexenyl, cyclohexenyl, 1-heptenyl, 3-heptenyl, 1-octenyl, cyclooctenyl, 1-nonenyl, 2-nonenyl, 3-nonenyl, 1- Examples of alkenyl groups include decenyl, 3-decenyl, 1,3-butadienyl, 1,4-pentadienyl, 1,3-cyclopentadienyl, 1,3-hexadienyl, 1,4-hexadienyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, 1,3-cycloheptadienyl, 1,3,5-cycloheptatrienyl, and 1,3,5,7-cyclooctatetraenyl. Alkenyl groups may be optionally substituted by one or more optional substituents as defined herein.

As used herein, the term "alkynyl" denotes a group derived from a straight-chain, branched, or cyclic hydrocarbon residue containing at least one carbon-carbon triple bond, including an ethylenically mono-, di-, or polyunsaturated alkyl or cycloalkyl group as defined above. Unless the number of carbon atoms is specified, the term preferably refers to a C _2-20 alkynyl (e.g., C _2-10 or C _2-6 ), examples include ethynyl, 1-propynyl, 2-propynyl, and butynyl isomers, and pentynyl isomers. Alkynyl groups may be optionally substituted by one or more optional substituents as defined herein.

The term "carbocyclyl" refers to a non-aromatic monocyclic, polycyclic, fused, or conjugated hydrocarbon residue, preferably C _3-20 (e.g., C _3-10 or C _3-8 ). The ring may be saturated, e.g., cycloalkyl, or may have one or more double bonds (cycloalkenyl) and/or one or more triple bonds (cycloalkynyl). Particularly preferred carbocyclyl moieties are 5-6 membered or 9-10 membered ring systems. Suitable examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cyclopentenyl, cyclohexenyl, cyclooctenyl, cyclopentadienyl, cyclohexadienyl, cyclooctatetraenyl, indanyl, decalinyl, and indenyl. A carbocyclyl group may be optionally substituted by one or more optional substituents as defined herein. The term "carbocyclylene" is intended to indicate the divalent form of carbocyclyl.

The term "heterocyclyl" refers to a stable 3- to 18-membered ring (radical) consisting of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. The heterocycle may be a monocyclic or polycyclic ring system, which may include fused, bridged, or spiro ring systems, the nitrogen, carbon, or sulfur atoms in the heterocycle may be optionally oxidized, the nitrogen atom may be optionally quaternized, and the ring may be partially or fully saturated. Examples of such heterocycles include, but are not limited to, azepinyl, azocanyl, pyranyl, dioxanyl, dithianyl, 1,3-dioxolanyl, tetrahydrofuryl, dihydropyrrolidinyl, decahydroisoquinolyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, oxazolidinyl, oxiranyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, thiazolidinyl, tetrahydropyranyl, thiamorpholinyl, thiamorpholinyl sulfoxide, and thiamorpholinyl sulfone.

The term "heteroaryl" means an aromatic monocyclic or polycyclic ring system of about 5 to about 19 ring atoms, or about 5 to about 10 ring atoms, in which one or more of the atoms in the ring system is an element(s) other than carbon, such as nitrogen, oxygen, or sulfur. In the case of polycyclic ring systems, only one of the rings must be aromatic for the ring system to be defined as a "heteroaryl". Certain heteroaryls contain about 5 to 6 ring atoms. The prefix aza, oxa, thia, or thio before heteroaryl, respectively, means that at least one nitrogen, oxygen, or sulfur atom is present as a ring atom. The nitrogen, carbon, or sulfur atom in a heteroaryl ring may be optionally oxidized and the nitrogen may be optionally quaternized. Representative heteroaryls include pyridyl, 2-oxo-pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, furanyl, pyrrolyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, indolyl, isoindolyl, benzofuranyl, benzothiophenyl, indolinyl, 2-oxoindolinyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, indazolyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzoisoxazolyl, benzoisothiazolyl, benzotriazolyl, benzo[1,3]dioxolyl, quinolinyl, isoquinolinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, and the like.

The term "acyl" refers to a group containing the moiety C=O, such as C(O)-R ^e , which is also bonded through an oxygen atom -C(O)O-R ^e , such as a carboxylic acid, ester, amide, etc. Preferred acyl groups include those in which R ^e is hydrogen or an alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl or heterocyclyl residue. Examples of acyl include formyl, straight-chain or branched alkanoyl (e.g., C _1-20 ), such as acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2,2-dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, undecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyl, and icosanoyl; cycloalkylcarbonyl, such as cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, and and cyclohexylcarbonyl; aroyl, for example, benzoyl, toluoyl, and naphthoyl; aralkanoyl, for example, phenylalkanoyl (e.g., phenylacetyl, phenylpropanoyl, phenylbutanoyl, phenylisobutyryl, phenylpentanoyl, and phenylhexanoyl), and naphthylalkanoyl (e.g., naphthylacetyl, naphthylpropanoyl, and naphthylbutanoyl); aralkenoyl, for example, phenylalkenoyl (e.g., phenylpropenoyl, phenylbutenoyl, , phenylmethacryloyl, phenylpentenoyl, and phenylhexenoyl), and naphthylalkenoyl (e.g., naphthylpropenoyl, naphthylbutenoyl, and naphthylpentenoyl); aryloxyalkanoyl, for example, phenoxyacetyl and phenoxypropionyl; arylthiocarbamoyl, for example, phenylthiocarbamoyl; arylglyoxyloyl, for example, phenylglyoxyloyl and naphthylglyoxyloyl; arylsulfonyl, for example, phenylsulfonyl and naphthylsulfonyl; Heterocyclic alkanoyl, such as thienylacetyl, thienylpropanoyl, thienylbutanoyl, thienylpentanoyl, thienylhexanoyl, thiazolylacetyl, thiadiazolylacetyl, and tetrazolylacetyl; heterocyclic alkenoyl, such as heterocyclic propenoyl, heterocyclic butenoyl, heterocyclic pentenoyl, and heterocyclic hexenoyl; and heterocyclic glyoxyloyl, such as thiazolyglyoxyloyl and thienylglyoxyloyl. ^{R e} residues can be optionally substituted as described herein.

The term "sulfoxide" refers to the group -S(O) _Rf , where _Rf is selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, carbocyclyl, and aralkyl. Preferred examples of R include _C1-20 alkyl, phenyl, and benzyl.

The term "sulfonyl" refers to the group S(O) ₂ -R _f , where R _f is selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, carbocyclyl, and aralkyl. Preferred examples of R _f include C _1-20 alkyl, phenyl, and benzyl.

The term "sulfonamide" refers to the group S(O)NR _f R _f , where each R _f is independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclyl, carbocyclyl, and aralkyl. Preferred examples of R _f include C _1-20 alkyl, phenyl, and benzyl. In one embodiment, at least one R _f is hydrogen. In another embodiment, both R _f are hydrogen.

Here, the term "amino" is used in its broadest sense as understood in the art and includes groups of formula NR ^a R ^b , where R ^a and R ^b can be independently selected from hydrogen, alkyl, alkenyl, alkynyl ^, aryl, carbocyclyl, heteroaryl, heterocyclyl, arylalkyl, and ^acyl .
Together with the nitrogen to which they are attached, they may form a monocyclic or polycyclic ring system, for example a 3-10 membered ring, particularly 5-6 and 9 membered ring systems. Examples of "amino" include _NH2 , NHalkyl (e.g., _C1-20 alkyl), NHaryl (e.g., NHphenyl), NHaralkyl (e.g., NHbenzyl), NHacyl (e.g., NHC(O) _C1-20 alkyl, NHC(O)phenyl), Nalkylalkyl (wherein each alkyl, e.g., _C1-20 , may be the same or different), and 5- or 6-membered rings optionally containing one or more of the same or different heteroatoms (e.g., O, N, and S).

The term "amide" herein is used in its broadest sense as understood in the art and includes groups having the formula C(O)NR ^a R ^b , where R ^a and R ^b are as defined above. Examples of amides include C(O)NH ₂ , C(O)NH alkyl (e.g., C _1-20 alkyl), C(O)NH aryl (e.g., C(O)NH phenyl), C(O)NH aralkyl (e.g., C(O)NH benzyl), C(O)N acyl (e.g., C(O)NHC(O)C _1-20 alkyl, C(O)NHC(O) phenyl), C(O)N alkyl alkyl (where each alkyl, e.g., C _1-20 , can be the same or different), and 5- or 6-membered rings optionally containing one or more of the same or different heteroatoms (e.g., O, N, and S). The term "halogen" or "halo" refers to Cl, Br, I, or F.

The term written "[group A][group B]" refers to group A when linked through the divalent form of group B. For example, "[group A][alkyl]" refers to a particular group A (e.g., hydroxy, amino, etc.) when linked through a divalent alkyl, i.e., alkylene (e.g., hydroxyethyl is intended to refer to HO-CH ₂ -CH-). Thus, the term written "[group]oxy" refers to a particular group when linked through an oxygen, and for example, the terms "alkoxy" or "alkyloxy", "alkenoxy" or "alkenyloxy", "alkynoxy" or "alkynyloxy", "aryloxy", and "acyloxy" refer to alkyl, alkenyl, alkynyl, aryl, and acyl groups as defined above, respectively, when linked through an oxygen. Similarly, the term "thio" refers to that particular group when linked through a sulfur, for example, the terms "alkylthio", "alkenylthio", "alkynylthio", and "arylthio" represent alkyl, alkenyl, alkynyl, and aryl groups, as defined above, respectively, when linked through a sulfur.

The terms "substituted" or "optionally substituted" are used to indicate that a group may have a substituent at each substitutable atom of the group (including more than one substituent on a single atom), provided that the normal valence of the designated atom is not exceeded and the identity of each substituent is independent of the others. Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds. The terms "stable compound" or "stable structure" refer to a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture and formulation into an effective drug.

The term "functionalized" in relation to any moiety refers to the presence of one or more functional groups on the moiety. Various functional groups can be introduced to a moiety by one or more functionalization reactions known to those skilled in the art. Non-limiting examples of functionalization reactions include alkylation, epoxidation, sulfonation, hydrolysis, amidation, esterification, hydroxylation, dihydroxylation, amination, ammonolysis, acylation, nitration, oxidation, dehydration, elimination, hydration, dehydrogenation, hydrogenation, acetalization, halogenation, dehalogenation, Michael addition, aldol condensation, Cannizzaro reaction, Mannich reaction, Classien condensation, Suzuki coupling, and the like. In one non-limiting embodiment, the term "functionalized" in relation to any moiety refers to the presence of one or more functional groups selected from the group consisting of alkyl, alkenyl, hydroxyl, carboxyl, halogen, alkoxy, amino, imino, and combinations thereof.

The term "monomer" refers to a small molecule that chemically bonds to one or more monomers of the same or different type during polymerization to form a polymer.

The term "polymer" refers to a large molecule that contains one or more types of monomer residues (repeating units) connected by covalent chemical bonds. By this definition, polymers encompass compounds in which the number of monomer units can range from very few (which may be more commonly called oligomers) to very many. Non-limiting examples of polymers include homopolymers, copolymers, terpolymers, tetrapolymers, and more advanced analogs. Polymers can have random, block, and/or alternating architectures.

The term "homopolymer" refers to a polymer composed of a single monomer type.

The term "copolymer" refers to a polymer that contains at least two different monomer types.

The term "terpolymer" refers to a copolymer that contains three different monomer types.

The term "branched" refers to any non-linear polymer structure. The term includes both branched and hyperbranched structures.

The term "block copolymer" refers to a polymer that contains at least two blocks of polymerized monomers. Any block may be derived from either a single monomer resulting in a homopolymeric subunit, or from two or more monomers resulting in a copolymeric (or non-homopolymeric) subunit within the block copolymer. Block copolymers may be diblock copolymers (i.e., polymers containing two blocks of monomers), triblock copolymers (i.e., polymers containing three blocks of monomers), multiblock copolymers (i.e., polymers containing more than three blocks of monomers), and combinations thereof. Block copolymers may be linear, branched, star-shaped, or comb-shaped and may have structures such as [A][B], [A][B][A], [A][B][C], [A][B][A][B], [A][B][C][B], etc. An exemplary representation of a block copolymer is [A]x[B]y or [A]x[B]y[C]z, where x, y, and z are the degrees of polymerization (DP) of the corresponding blocks [A], [B], and [C]. Further insight into the chemistry, properties, and applications of block copolymers can be found in the book 'Block Copolymers: Synthetic Strategies, Physical Properties, and Applications', by Nikos Hadjichristidis, Stergios Pispas, and George Floudas, John Wiley and Sons (2003), the contents of which are incorporated herein by reference in their entirety.

The terms "reversible deactivation radical polymerization" (RDRP), "controlled radical polymerization" or "controlled/living radical polymerization" refer to a specific radical polymerization process, also denoted by the term "living radical polymerization", in which a control agent is used so that the polymer chains being formed are functionalized with end groups that can be reactivated in the form of free radicals by reversible transcription or termination reactions, thus allowing, for example, the synthesis of block copolymers.

The term "addition-fragmentation" refers to a two-step chain transfer mechanism during polymerization in which radical addition is followed by fragmentation to generate new radical species.

The term "residue of at least one crosslinker" refers to one or more crosslinking moieties that become part of the polymer backbone after polymerization. The residues can be monovalent, divalent, or multivalent.

The term "radical addition polymerization initiator" refers to a compound used in catalytic amounts to initiate radical addition polymerization. The choice of initiator depends primarily on its solubility and its decomposition temperature.

The term "alkyl acrylate" refers to an alkyl ester of acrylic acid or alkylacrylic acid.

The term "alkylacrylamide" refers to an alkylamide of acrylic acid or alkylacrylic acid.

The term "moiety" refers to a part or functional group of a molecule.

The term "pharmaceutical composition" refers to any composition containing at least one pharma- ceutical active ingredient, as well as any product that results directly or indirectly from the combination, complexation, or aggregation of any two or more ingredients, or from the dissociation of one or more ingredients, or from any other type of reaction or interaction of one or more ingredients.

The term "coating composition" refers to an aqueous or solvent-based liquid composition that can be applied to a substrate and then solidified (e.g., by radiation, air curing, post-crosslinking, or ambient temperature drying) to form a cured coating on the substrate.

As used herein, the term "degree of polymerization" (DP) generally refers to the average number average degree of polymerization, as would be readily understood by one of ordinary skill in the art.

Those skilled in the art will appreciate that the present invention includes the embodiments and features disclosed herein, and all combinations and/or permutations of the disclosed embodiments and features.

The present invention will now be described with reference to the following examples, which should be considered in all respects as illustrative and non-limiting.

Materials Acrylic acid ("AA", 99%, Sigma-Aldrich), poly(ethylene glycol) methyl ether acrylate ("PEGA", with an average of 9 ethylene glycol units, M _n =480 gmol ^-1 , Sigma-Aldrich), 4,4'-azobis-(4-cyanopentanoic acid) ("ACPA", 98%, Aesar), sodium bicarbonate ("NaHCO ₃ ", Sigma-Aldrich), 1,3,5-trioxane (99%, Sigma-Aldrich), diethyl ether (100%, Chem Supply), ethanol (EtOH, 100%, Chem Supply), tetrahydrofuran ("THF", 100%, RCL Labscan), poly(ethylene glycol) diacrylate ("PEGDA", with an average of 3 ethylene glycol units, M _n =250 gmol ^-1 , Sigma-Aldrich), and ethylene glycol diacrylate ("EGDA", 90%, Sigma-Aldrich) were used as received. Inhibitors in styrene ("S", 99%, Sigma-Aldrich), n-butyl acylate ("nBA", 99%, Sigma-Aldrich), methyl methacrylate ("MMA", 99%, Sigma-Aldrich), benzyl methacrylate ("BzMA", 99%, Sigma-Aldrich), and 2-ethylhexyl methacrylate ("EHMA", 99%, Sigma-Aldrich) were removed by passage through an aluminum oxide column prior to use. Azobis(isobutyronitrile) in acetone ("AIBN", Sigma-Aldrich) was precipitated in water. Water was deionized (milli-Q water) prior to use. The RAFT agents 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid ("DDMAT") and 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid ("CPADB") were synthesized according to the literature.

Two-Step Synthesis of P(AA-stat-PEGA)-b-P(S-stat-nBA) Amphiphilic Block Copolymers Experiments are labeled A-x, B-x, C-x, D-x, Ex, and F-x (x is the experiment number). Entry A-x is the RAFT aqueous emulsion polymerization of styrene and nBA carried out at different pH. Entry B-x is the RAFT aqueous emulsion polymerization of styrene and nBA carried out at pH 5 with different molar ratios [hydrophobic monomer]:[macroRAFT] (Scheme 1). Entry C-x, D-x, Ex, and F-x refer to the synthesis of crosslinked P(AA-stat-PEGA)-b-P(S-stat-nBA) nanofibers (Scheme 2).

Synthesis of P(AA-stat-PEGA)-DDMAT macro RAFT agent. The macro RAFT agent was prepared by solution copolymerization of AA (0.8882 g, 12.3 mmol) and PEGA (5.9164 g, 12.3 mmol) (molar ratio=50/50) in the presence of DDMAT RAFT agent (0.2 g, 0.55 mmol) (monomer/RAFT agent molar ratio=44), ACPA (0.0154 g, 0.055 mmol) and EtOH (5.0309 g) as solvent. Additionally, 1,3,5-trioxane (0.1650 g, 1.8 mmol) was added to the polymerization mixture as an internal standard for ¹ H NMR analysis. The solution was mixed in a 25 mL glass vial at ambient temperature for 10 minutes, followed by purging with nitrogen in an ice bath for 30 minutes. The polymerization was carried out at 70° C. in an oil bath with a stirring speed of 500 rpm for 3 hours. The final total conversion of AA and PEGA was 95% as determined by ¹ H NMR. The resulting final polymerization mixture was added dropwise to 35 mL of diethyl ether in a 50 mL centrifuge tube and centrifuged at 7000 rpm for 5 minutes. After centrifugation, the product was precipitated in diethyl ether and the supernatant was discarded. It was then refilled with 35 mL of fresh diethyl ether and mixed thoroughly before centrifugation. This process was repeated three times. The purified sample was dried overnight in a vacuum oven at 50° C.

RAFT Aqueous Emulsion Polymerization of Styrene and nBA ([Styrene] ₀ /[nBA] ₀ =70/30) (Items A-x and B-x)
P(AA-stat-PEGA)-b-P(S-stat-nBA) amphiphilic block copolymers were prepared by RAFT-mediated aqueous emulsion polymerization of styrene and nBA ([styrene] ₀ /[nBA] ₀ =70/30). In this example, ACPA, NaHCO ₃ , P(AA-stat-PEGA)-DDMAT, and milli-Q water were added to a 25 mL glass vial. The solution was mixed using a sonication bath for 10 minutes. To observe the effect of pH, different amounts of 1 M NaOH were added in items A-x. For A-1, the pH of the solution was not adjusted (0 μL of 1 M NaOH). For A-2 and A-3, 1 M NaOH solution was added to adjust the pH (A
For A-2, 290 μL of 1 M NaOH was added, and for A-3, 930 μL was added). To the solution, styrene and nBA ([hydrophobic monomer] ₀ /[macroRAFT] ₀ =200) were added after pH adjustment. The effect of DP on the hydrophobic block was studied in section B-x. The pH of the solution was adjusted to pH 5 by adding 290 μL of 1 M NaOH. After adjusting the pH, styrene and nBA with different [hydrophobic monomer] ₀ /[macroRAFT] ₀ were added to the solution. The polymerization was carried out at 80° C. in an oil bath with a stirring speed of 350 rpm for 6 h (section A-x) and 4 h (section B-x). The polymerization mixture was subsequently quenched by placing the flask in an ice bath. The conversion of styrene and nBA was determined by gravimetric analysis. All experiments are summarized in Table 1 (sections Ax) and Table 2 (sections Bx).

によって決定し、式中、Ｍ_{マクロＲＡＦＴ}、Ｍ_Ｓ、Ｍ_ｎＢＡは、それぞれ、マクロＲＡＦＴ剤、スチレン、及びｎＢＡのモル質量であり、［マクロＲＡＦＴ］_０、［スチレン］_０、［ｎＢＡ］_０は、それぞれ、マクロＲＡＦＴ剤、スチレン、及びｎＢＡの初期濃度であり、Ｘ_変換は、重量測定によって決定される総モノマー変換を示す。 The theoretical number average molecular weight (M _n,th ) is calculated according to formula (1):

where _MmacroRAFT , _Ms , _MnBA are the molar masses of the macroRAFT agent, styrene, and nBA, respectively, [macroRAFT] ₀ , [styrene] ₀ , and [nBA] ₀ are the initial concentrations of the macroRAFT agent, styrene, and nBA, respectively, and _Xconversion denotes the total monomer conversion determined gravimetrically.

Synthesis of Crosslinked P(AA-stat-PEGA)-b-P(S-stat-nBA) Nanofibers ([styrene] ₀ /[nBA] ₀ =70/30) (sections C-x, D-x, E-x, and F-x)
Crosslinked P(AA-stat-PEGA)-b-P(S-stat-nBA) nanofibers were synthesized by in situ chemical crosslinking using EGDA (170.16 gmol ^-1 ) or PEGDA ( _Mn = 250 gmol ^-1 ) as crosslinkers. Two different approaches were used. The first approach was to introduce EGDA before the RAFT aqueous emulsion polymerization of styrene and nBA, and the second approach was to introduce EGDA after 2 h of polymerization (conversion > 90%). The ratio [hydrophobic monomer] ₀ /[macroRAFT] ₀ was fixed at 100. After polymerization, 120 μL of latex was added to 1 mL of THF (volume ratio ≈ 10/90) to observe whether the polymer particles were dissolved in THF. Insolubility indicates that crosslinking has been achieved.

Synthesis of crosslinked P(AA-stat-PEGA)-b-P(S-stat-nBA) nanofibers ([styrene] ₀ /[nBA] ₀ =20/80) (items Gx and Hx)
The synthesis was carried out for RAFT aqueous emulsion polymerization of styrene and nBA as above, except that the molar ratio of styrene to nBA was 20/80 ([styrene] ₀ /[nBA] ₀ =20/80), and the nanoparticles were crosslinked by adding 5 mol % (relative to macroRAFT agent) EGDA after 2 hours of polymerization. The pH of the solution was adjusted to pH 5 by adding 290 μL of 1 M NaOH for item G-x (Table SI-1), and 290 μL, 580 μL, and 870 μL of 1 M NaOH for items H-1, H-2, and H-3 (Table SI-2). After adjusting the pH for item G-x, styrene and nBA with different [hydrophobic monomer] ₀ /[macroRAFT] ₀ were added to the solution. Styrene and nBA with fixed ([hydrophobic monomer] ₀ /[macroRAFT] ₀ =130) and different solids contents were carried out for sections H-x. The conversions of styrene and nBA were determined by gravimetric analysis. The theoretical M _n,th was determined by equation (SI-1). All experiments are summarized in Table SI-1 (sections G-x) and Table SI-2 (sections H-x).

Gravimetric Analysis The total conversion of styrene and nBA was determined by gravimetric analysis. Latex was sampled at different time intervals to observe the progress of monomer conversion over time. 950 μL of latex was weighed into a pre-weighed aluminum pan and dried overnight in a vacuum oven at 50 °C.

nuclear magnetic resonance (NMR)
The final total conversion of AA and PEGA at t=3 hours was determined by ¹ H NMR spectroscopy using a Bruker Avance III 300 MHz NMR with 1,3,5-trioxane as an internal standard. Samples were prepared by dissolving the mixtures (t=0 h and t=3 h) in 600 μL of deuterated dimethylsulfoxide (d ₆ -DMSO).

Gel Permeation Chromatography (GPC)
Number-average (M _n ) and weight-average (M _w ) molecular weights and dispersities (D) were determined by gel permeation chromatography (GPC) using a Shimadzu modular system equipped with a SIL-10AD autoinjector, LC-10AT pump, DGU-12A degasser, CTO-10A column oven, and RID-10A refractive index detector. A column configuration consisting of a Polymer Laboratories 5.0 μm bead size guard column (50×7.8 mm), followed by four linear PL columns (300×7.8 mm, 500, 10 ³ , 10 ⁴ , and 10 ⁵ Å, 5 μm pore size) was used for the analysis. N,N-Dimethylacetamide (DMAc, 0.03% w/v LiBr, 0.05% w/v 2,6-dibutyl-4-methylphenol (BHT)) was used as the mobile phase at 50°C and a flow rate of 1 mL min- ¹ . The SEC system was calibrated using linear polystyrene standards ranging from 500 to 10 ⁶ gmol ^-1 (Polymer Laboratories). Chromatograms were processed using Cirrus 2.0 software (Polymer Laboratories). Samples were methylated to modify the carboxylic acid groups in the acrylic acid to reduce interaction with the column. The dried latex (10 mg) was added to 1 mL of milli-Q water in a 25 mL glass vial and HCl was added to adjust the pH to 3-4. 20 mL of THF was then added to the mixture. Trimethylsilyldiazomethane methylating agent was added dropwise to the vial. The mixture was stirred at room temperature for 4 hours. After methylation, the solution was dried overnight at ambient temperature in an aluminum pan. It was further dried at 35°C using a high vacuum oven for 1 hour to remove water. The sample was dissolved in DMAc and filtered using a syringe filter (0.45 μm) before injection into the GPC system.

Transmission electron microscope (TEM)
TEM samples were prepared by dropping 10 μL of diluted latex (10 μL latex in 1 mL milli-Q water) onto glow-discharged formvar-coated copper grids, which were allowed to dry at ambient temperature. The grids were glow-discharged to modify the grid surface from hydrophobic to hydrophilic to avoid accumulation of block copolymer nanoparticles around the grid. TEM images were obtained using a JEOL 1400 transmission electron microscope under an accelerating voltage of 100 kV.

Effect of pH PISA was carried out as an aqueous emulsion polymerization at 80° C. using the macro-RAFT agent P(AA-stat-PEGA)-TTC (hydrophilic block; M _n =13,400 g/mol; D=1.20) and ACPA as initiator (Scheme 1). In this example, the macro-RAFT agent was prepared by solution polymerization in EtOH at 70° C. (Scheme 1, FIG. 9; M _n =13,400 g/mol; D=1.20). Copolymerization of styrene and nBA in a weight ratio of 65.5:34.5 (corresponding to a theoretical T _g value of 27.1° C. at full conversion based on the Fox equation) in RAFT aqueous emulsion polymerization (sections A-x) was carried out at three different pHs (3.5, 5, and 7) to determine the most suitable pH for the formation of nanofibers. The target degree of polymerization (DP) was fixed at [hydrophobic monomer] ₀ /[macroRAFT] ₀ =200 (Table 1).

スキーム１。Ｐ（ＡＡ－ｓｔａｔ－ＰＥＧＡ）－ＴＴＣマクロＲＡＦＴ剤の存在下でのスチレン及びｎＢＡのＲＡＦＴ水性エマルション重合
３つのｐＨ値全てについて、６時間後の全モノマー変換は、９０％超に達し、最高変換は、ｐＨ３．５で達した（表１、図１）。理論に縛られることを望むものではないが、自己組織化挙動自体は、ｐＨによって影響を受け得ると考えられる。

Scheme 1. RAFT aqueous emulsion polymerization of styrene and nBA in the presence of P(AA-stat-PEGA)-TTC macro RAFT agent. For all three pH values, the total monomer conversion after 6 hours reached over 90%, with the highest conversion reached at pH 3.5 (Table 1, Figure 1). Without wishing to be bound by theory, it is believed that the self-assembly behavior itself may be influenced by pH.

At pH 3.5, the molecular weight distribution (MWD) shifted toward higher molecular weights with low dispersity (D = 1.18), indicating good control/living properties (Table 1, Figure 2). However, at pH 5 (Figure 2.A-2) and pH 7 (Figure 2.A-3), there was a significant low molecular weight shoulder, consistent with residual unreacted macro-RAFT agent.

TEM images show that only spherical morphology was obtained at pH 3.5 (Fig. 3.A-1) and pH 7 (Fig. 3.A-3), with particle diameters of about 50 nm and 120 nm, respectively. However, a mixture of nanofibers and vesicles was obtained at pH 5 (Fig. 3.A-2). It is believed that at pH 3.5, due to the protonation of the AA units of the macroRAFT, this block could not drive the reorganization into higher-order morphology because the segments became hydrophobic enough to be buried within the particle. Furthermore, the reduced separation strength between the macroRAFT agent (hydrophilic block) and the core-forming block (hydrophobic block) due to the absence of charges on the macroRAFT agent could lead to the preferred spherical morphology. The formation of spherical micelles without higher-order morphology has also been previously reported for the copolymerization of styrene and MMA using poly(methacrylic acid-stat-poly(ethylene oxide) methyl ether methacrylate) at pH 3.5. At pH 5, partial ionization of the hydrophilic block leads to the formation of AA molecules buried within the particle.
It is believed that the hydrophobic block length was long enough to minimize the occurrence of moieties, thus resulting in the transformation into nanofibers/vesicles. Without wishing to be bound by theory, the spherical morphology obtained at pH 7 can possibly be rationalized by the negative charges generated by the deprotonation of AA, which prevents the reorganization of the spheres into higher order morphologies due to electrostatic repulsion.

Effect of DP of the hydrophobic block Polymerizations were subsequently carried out at a fixed macroRAFT agent concentration (entry B-x, Table 2) and at pH 5 with varying [hydrophobic monomer] ₀ /[macroRAFT] ₀ with the aim of obtaining pure nanofibers as opposed to mixed forms (Figure 3.A-2). The target DP was varied from 50 to 200 and the solids content increased as a result from 10 wt% to 17.5 wt%. The color of the final dispersion changed from yellow to white as the amount of hydrophobic monomer increased. The experimental M _n values were similar to M _n,th , D = 1.54 to 1.93 (Table 2). A low molecular weight shoulder in the MWD was present in all cases demonstrating the presence of unreacted macroRAFT for the reasons discussed above (Figure 4).

TEM imaging revealed that the morphology changed from spheres (Fig. 5.B-1) to nanofibers (Fig. 5.B-2 and B-3) and finally to vesicles (Fig. 5.B-4, B-5, and B-6) with the expected increase in target DP. Without wishing to be bound by theory, this is believed to occur due to an increase in the packing parameter (P) due to the increase in the length of the core-forming blocks. The viscosity of the latex increased as nanofibers were obtained. All latexes remained stable without coagulation and sedimentation. Nanofibers were observed over a wide range of DP from 100 to 200, but the parameter window corresponding to relatively pure nanofibers was narrow. In most cases, nanofibers were present along with a small amount of spheres (Fig. 5.B-2) or vesicles (Fig. 5.B-3 to B-6). The amount of vesicles increased as the DP increased from 130 to 200. Relatively pure nanofibers were obtained at DP = 100 (Figure 5.B-2) and 130 (Figure 5.B-3).

A narrower MWD was achieved with decreasing target DP, when spheres (Fig. 5.B-1, D = 1.54) or relatively pure nanofibers (Fig. 5.B-2, D = 1.56) (Table 2 and Fig. 4) were obtained. Higher dispersity was achieved with a mixture of nanofibers and vesicles (Figs. 5.B-3 to B-6).
), resulting in a broader MWD. Previous reports have reported similar results for the homopolymerization of styrene in the presence of hydrophilic macro-RAFT agents in RAFT aqueous emulsion polymerizations.

Synthesis of Crosslinked Nanofibers ([styrene] ₀ /[nBA] ₀ =70/30) Polymer nanofibers prepared by PISA can be crosslinked using various approaches. In one example, we utilized the divinyl crosslinkers EGDA and PEGDA to crosslink the core cross-section of nanofibers (Scheme 2). Two simple in situ crosslinking methods were investigated: (i) addition of crosslinker at the beginning of emulsion polymerization (items C-x and D-x), and (ii) addition of crosslinker after 2 hours of polymerization (conversion >90%) (items E-x and F-x). Depending on the crosslinking method, different crosslinked structures can be expected. The entire core-forming block is crosslinked based on method (i), while the core-forming block is only partially crosslinked using method (ii) (only the part of the block forming at the highest conversion range, i.e., the segment of the chain closest to the RAFT end group).

スキーム２。ＥＧＤＡ又はＰＥＧＤＡを架橋剤として使用した、Ｐ（ＡＡ－ｓｔａｔ－ＰＥＧＡ）－ＴＴＣマクロＲＡＦＴ剤の存在下でのスチレン及びｎＢＡのＲＡＦＴ水性エマルション重合の概略図での架橋ステップ（［疎水性モノマー］_０／［マクロＲＡＦＴ］_０＝１００、ｐＨ５）。
架橋剤なしの塩基条件は、ＴＥＭ画像Ｂ－２（図５）に対応し、これは、架橋剤の不在下で比較的純粋なナノ繊維を生成した（［疎水性モノマー］_０／［マクロＲＡＦＴ］_０＝１００）。重合の開始時に添加される場合（方法（ｉ））、ＥＧＤＡ及びＰＥＧＤＡ（項目Ｃ－ｘ、及びＤ－ｘ）は、ＰＩＳＡプロセスに干渉し、最終的な形態に影響を与えた。ＰＥＧＤＡの場合、より薄い（図６；Ｃ－２）及びより短い（図６；Ｃ－３）ナノ繊維が、１又は２．５ｍｏｌ％のＰＥＧＤＡで得られた。ＥＧＤＡ（項目Ｄ－ｘ）の場合、比較的純粋なナノ繊維（図６；Ｄ－１、及びＤ－２）が、０．５又は１ｍｏｌ％のＥＧＤＡで得られ、その一方で、球状ミセルが、１０ｍｏｌ％のＥＧＤＡを導入したときに得られた（図６；Ｄ－３）。理論に縛られることを望むものではないが、架橋が、最終的な形態に影響を与えると考えられる。

Scheme 2. Schematic representation of the crosslinking step of the RAFT aqueous emulsion polymerization of styrene and nBA in the presence of P(AA-stat-PEGA)-TTC macroRAFT agent using EGDA or PEGDA as crosslinkers ([hydrophobic monomer] ₀ /[macroRAFT] ₀ =100, pH 5).
Basic conditions without crosslinker correspond to TEM image B-2 (FIG. 5), which produced relatively pure nanofibers in the absence of crosslinker ([hydrophobic monomer] ₀ /[macroRAFT] ₀ =100). When added at the beginning of the polymerization (method (i)), EGDA and PEGDA (items C-x and D-x) interfered with the PISA process and influenced the final morphology. In the case of PEGDA, thinner (FIG. 6; C-2) and shorter (FIG. 6; C-3) nanofibers were obtained with 1 or 2.5 mol% PEGDA. In the case of EGDA (item D-x), relatively pure nanofibers (FIG. 6; D-1 and D-2) were obtained with 0.5 or 1 mol% EGDA, while spherical micelles were obtained when 10 mol% EGDA was introduced (FIG. 6; D-3). Without wishing to be bound by theory, it is believed that crosslinking affects the final morphology.

EGDA and PEGDA (items E-x and F-x) had relatively less effect on the final morphology than in method (i) when added 2 hours after polymerization (method (ii)), except for 10 mol% EGDA. Again, almost pure nanofibers were obtained without crosslinker (Fig. 6. B-2). In the case of PEGDA, nanofibers and small amounts of vesicles were obtained for 1 and 10 mol% PEGDA (Fig. 6; E-2 and E-3). Relatively pure nanofibers were obtained for 3 and 5 mol% EGDA (Fig. 6; F-1 and F-2). However, 10 mol% EGDA led to the formation of vesicles (Fig. 6; F-3). Crosslinked nanofibers/vesicles can be obtained by introducing the crosslinker at the beginning of the polymerization (method (i)) and delaying the introduction of the crosslinker once the desired morphology has been formed (method (ii)).

Crosslinking was confirmed by mixing the nanoparticle latexes with THF. THF is a good solvent for linear diblock copolymers, i.e., a clear solution indicates minimal (if any) crosslinking, while a cloudy solution is consistent with significant crosslinking. Nearly pure nanofibers were obtained when 3 and 5 mol % of EGDA were introduced at t = 2 h (method (ii)) (Figure 6; F-1 and F-2). Addition of THF to these latexes resulted in a cloudy solution (Figure 7; (d)), confirming successful crosslinking. When added at t = 0 h (method (i)), crosslinking was successful in all cases for both EGDA and PEGDA, since cloudy solutions (Figure 7; (a) and (b)) were observed in all cases. When added at t = 2 hours (method (ii)), cross-linking was successful with EGDA (Figure 7; (d)), whereas PEGDA did not result in significant cross-linking, as evidenced by a clear solution upon addition of THF (Figure 7; (c)).

EGDA and PEGDA behaved differently, as determined by dissolving the final dispersion in THF (FIG. 7). Crosslinking was successful with EGDA when added at t=0 or t=2 hours (methods (i) and (ii)), whereas PEGDA only led to successful crosslinking when added at t=0 hours (method (i)). Without wishing to be bound by theory, a possible explanation could be the difference in hydrophobicity between these crosslinkers. The crosslinker is initially present as droplets in the continuous phase and, as the polymerization proceeds, gradually diffuses into the polymer particles following an emulsion polymerization mechanism. Due to the higher hydrophilicity (higher water solubility) of PEGDA, excessive partitioning into the aqueous phase could limit the degree of crosslinking.

Overall, it can be concluded that 1 mol% EGDA added at t=0 hours by using method (i) or 3 and 5 mol% EGDA added at t=2 hours by using method (ii) are the best methods to achieve crosslinked nanofibers.

Synthesis of crosslinked nanofibers ([styrene] ₀ /[nBA] ₀ =20/80) Polymer nanoparticles with a T _g of the core-building block below 0° C. were synthesized by copolymerization of styrene and nBA in a weight ratio of 16.9:83.1 (corresponding to a theoretical T _g value of −37.6° C. at full conversion based on the Fox equation) based on the methods of Schemes 1 and 2. Crosslinking was achieved by introducing 5 mol % EGDA (method (ii)) after 2 h of polymerization (conversion >90%). Despite the low T _g of the base polymer, structural stability was achieved by crosslinking, thereby enabling TEM imaging without the need for cryo-TEM.

First, polymerizations were performed by varying [hydrophobic monomer] ₀ /[macroRAFT] ₀ at a fixed macroRAFT agent concentration ([macroRAFT] ₀ =6.2 mmol/L) at pH 5 targeting nanofibers (entries G-x, Table SI-1). The target DP was varied from 80 to 300, and the solids content increased from 12.2% to 23.5%. In all cases, monomer conversion was greater than 90% (Table SI-2). With increasing target DP, the morphology changed from spheres (Figure 10; G-1, G-2, and G-3) to nanofibers (Figure 10; G-4), and finally to vesicles (Figure 10; G-8 and G-9). Nanofibers were observed over a range of target DPs from 130 to 180 (Figure 10). In most cases, nanofibers were present along with vesicles, and the amount of vesicles increased with increasing DP (Figure 10; G-5, G-6, G-7, G-8, and G-9). Nanofibers with a small amount of spheres and vesicles were obtained at DP = 130 (Figure 10; G-4). The final dispersion was stable without settling or coagulation, and the viscosity increased with increasing amount of nanofibers, as expected. Dissolution of the final dispersions (items G-x) in THF gave in all cases a cloudy solution indicating successful crosslinking.

When the solid content was 15.2% ([macroRAFT] ₀ =6.2 mmol/L), nanofibers with spheres and vesicles were obtained at DP=130 (FIG. 10; G-4) as described above. The solid content was then further increased to 24.7% ([macroRAFT] ₀ =11.5 mmol/L) and 32.7% ([macroRAFT] ₀ =17.7 mmol/L) and the target DP was fixed at 130 (entries H-x, Table SI-2). The monomer conversion was above 90% in all cases (Table SI-2) and the obtained latex was stable. When the solid content was 24.7%, almost pure nanofibers were formed (FIG. 8.H-2), whereas at 32.7%, a large amount of spheres with almost no nanofibers were obtained (FIG. 8.H-3). A cloudy solution was obtained in THF (entries Hx), indicating successful cross-linking.

Conclusions As demonstrated herein, PISA practiced as aqueous RAFT emulsion polymerization has been utilized to synthesize low _Tg nano-sized polymer fibers using the macro RAFT agent P(AA-stat-PEGA)-TTC. However, it will be understood that different types of macro RAFT agents can be used as alternatives. As shown above, two types of nanofibers were prepared using core building blocks consisting of different molar ratios of S:nBA, i.e., 70:30 and 20:80, corresponding to theoretical glass transition temperatures of 27.1°C (S:nBA=70:30) and -37.6°C (S:nBA=20:80). In the preferred embodiment that produced high yields of nanofibers, the pH was 5. Additionally, preferred embodiments utilized cross-linking of the core block using the divinyl monomers poly(ethylene glycol) diacrylate (PEGDA) and ethylene glycol diacrylate (EGDA), respectively, introduced either at the beginning of the PISA process or late in the growth of the core-forming block. The nature of the cross-linking agent and the time of addition can affect the nanofiber morphology. In preferred embodiments, addition of the cross-linking agent at the beginning or late in the polymerization successfully cross-linked while maintaining the nanofiber morphology.

Supplementary Information

The theoretical number average molecular weight (M _n,th ) was determined by formula (SI-1).

Example SI-1. In this example, block copolymers containing hydrophobic monomers were prepared by dispersion polymerization. Previous work has shown that PISA can be carried out in non-polar solvents such as dodecane and mineral oil using hydrophobic monomers. However, such non-polar solvents usually have high boiling points and are difficult to remove. Herein, the preparation of hydrophobic block copolymers in mixtures of water and alcohol is described. In a preferred embodiment, the hydrophobic monomers are substantially insoluble in water and/or substantially soluble in an 80/20 vol.% ethanol/water mixture.

Synthesis of PMMA-CPADB macro RAFT agent The macro RAFT agent was prepared by solution polymerization of MMA (6.0926 g; 60.8 mmol) in the presence of CPADB RAFT agent (0.2 g; 0.72 mmol; monomer/RAFT agent molar ratio=85), AIBN (0.0117 g; 0.07 mmol; CPADB/AIBN molar ratio=10.0) using toluene (6.0 g) as the solvent. The solution was mixed in a 25 mL glass vial at ambient temperature for 10 min, followed by purging with nitrogen in an ice bath for 30 min. The polymerization was carried out at 70° C. in an oil bath with a stirring speed of 500 rpm for 20 h. The final conversion of MMA was 78% as determined by ¹ H NMR. The final polymerization mixture was added dropwise to 35 mL of diethyl ether in a 50 mL centrifuge tube and centrifuged at 7000 rpm for 5 min. After centrifugation, the precipitated product was collected and the supernatant was discarded. After precipitation, the product was redissolved in toluene and subsequently added dropwise to 35 mL of fresh diethyl ether and mixed thoroughly before centrifugation. This process was repeated three times. The purified sample was dried overnight in a vacuum oven at 50° C. THF GPC analysis using a refractive index detector and poly(methyl methacrylate) standards showed a M _n of 8,200 gmol ⁻¹ and a M _w /M _n of 1.17.

RAFT Dispersion Polymerization of EHMA and MMA ([EHMA] ₀ /[MMA] ₀ =90/10)
PMMA-b-P (EHMA-stat-MMA) block copolymers were prepared by RAFT-mediated dispersion polymerization of EHMA and MMA ([EHMA] ₀ /[MMA] ₀ =90/10) in EtOH and milli-Q water mixture (EtOH/water = 80/20 v/v). PMMA-b-P (EHMA
The following example of PMMA-CPADB (-stat-MMA) is representative and is performed as follows: PMMA-CPADB (0.2624 g; 0.04 mmol), 1,3,5-trioxane (0.0477 g; 0.53 mmol), EtOH (6.3120 g), and milli-Q water (2.0 g) were weighed into a 25 mL glass vial. 1,3,5-trioxane was added as an internal standard to determine monomer conversion by ¹ H NMR. The solution was stirred in a preheated oil bath at 70° C. for 10 min. EHMA (0.6299 g; 3.18 mmol), MMA (0.0353 g; 0.35 mmol), and AIBN (0.0029 g; 0.02 mmol; macroRAFT/AIBN=2.0) were then added to the solution, followed by purging with nitrogen in an ice bath for 30 minutes. The polymerization was carried out at 70° C. in an oil bath with a stirring speed of 300 rpm for 21 hours.

RAFT Dispersion Polymerization of BzMA PMMA-b-PBzMA block copolymer was prepared by dispersion polymerization of BzMA in the presence of PMMA-CPADB macro RAFT agent and AIBN in an EtOH/water mixture. In this example, BzMA (0.4603 g, 2.6 mmol), PMMA-CPADB macro RAFT agent (0.4650 g, 0.065 mmol), AIBN (5.4 mg, 0.033 mmol), and 10 ml of an EtOH/water mixture (80/20 by volume) were mixed in a 25 ml glass vial to give a [BzMA]:[RAFT]:[AIBN] molar ratio of 40:1:0.5. The mixture was purged with nitrogen gas in an ice bath for 30 minutes and then placed in a 70° C. oil bath with magnetic stirring. After 18 hours, the polymerization was stopped by removal from oil and opening to air. Monomer conversion was determined to be about 98% via ¹ H NMR in d ₆ -DMSO. The as-synthesized block copolymers were analyzed by TEM/SEM.

スキームＳＩ－１．ＰＭＭＡマクロＲＡＦＴ剤の存在下での疎水性モノマー（複数可）のＲＡＦＴ分散重合 Polymer nanofibers containing hydrophobic corona and core were synthesized via dispersion polymerization of hydrophobic monomers in EtOH and water mixtures. The block polymers self-assembled into nanofibers and the morphology were confirmed by TEM/SEM (Figure 12).

Scheme SI-1. RAFT dispersion polymerization of hydrophobic monomer(s) in the presence of PMMA macro RAFT agent

Although the present invention has been described with reference to specific examples, it will be understood by those skilled in the art that the present invention may be embodied in many other forms, and in particular that a particular feature of any one of the various described examples may be provided in any combination of any of the other described examples. Various modifications and alterations to the present invention will become apparent to those skilled in the art without departing from the scope and spirit of the present invention. It should be understood that the present invention is not intended to be unduly limited by the illustrative embodiments and examples set forth herein, and that such examples and embodiments are presented only as examples with respect to the scope of the present invention, which is intended to be limited only by the scope of the claims set forth herein below.

Claims (39)

A polymeric nanofiber having a core-shell morphology, the shell being hydrophilic and the core being:
1. A polymeric nanofiber comprising: a) a hydrophobic copolymer; or b) a hydrophobic homopolymer having a Tg of less than 16°C. A block [A] containing a hydrophilic homopolymer or copolymer;
a) a hydrophobic copolymer having a Tg of less than about 75° C.; or b) a hydrophobic homopolymer having a Tg of less than 16° C.; and
and optionally a crosslinker. The amphiphilic block copolymer of claim 2 when self-assembled into nanofibers. 3. A method for producing the amphiphilic block copolymer of claim 2, said method comprising:
a) reacting at least one hydrophilic monomer using RDRP to form a hydrophilic block [A];
b) adding a hydrophobic block [B] comprising at least one hydrophobic monomer to the hydrophilic block [A] using RDRP;
c) optionally adding a cross-linking agent in step b). The method of claim 4, further comprising the step of causing the block copolymer to self-assemble into the nanofibers of claim 1. The method according to claim 4 or 5, wherein the polymerization is carried out as RAFT, ATRP, or NMP. The polymer nanofiber of claim 1, the amphiphilic block copolymer of claim 2 or 3, or the method of any one of claims 4 to 6, wherein the hydrophilic block [A] is prepared from one or more of poly(ethylene glycol) methyl ether acrylate (PEGA), poly(ethylene glycol) methyl ether methacrylate (PEGMA), and acrylic acid. The polymer nanofiber according to claim 1, the amphiphilic block copolymer according to claim 2 or 3, or the method according to any one of claims 4 to 7, wherein the hydrophobic block [B] is prepared from one or more of styrene, n-butyl acrylate, methyl acrylate, and methyl methacrylate, preferably styrene, n-butyl acrylate (nBA), and tert-butyl acrylate (tBA). The polymer nanofiber of claim 1, the amphiphilic block copolymer of claim 2 or 3, or the method of any one of claims 4 to 6, wherein the hydrophobic block [B] comprises a hydrophobic copolymer selected to have a Tg of the hydrophobic block less than about 75°C, preferably in the range of -70°C to 75°C. The polymer nanofiber according to claim 1, the amphiphilic block copolymer according to claim 2 or 3, or the method according to any one of claims 4 to 6, wherein the hydrophobic block [B] comprises a hydrophobic homopolymer selected to have a Tg of less than 16°C, preferably in the range of -70°C to 16°C. The method according to any one of claims 4 to 10, wherein the cross-linking agent is ethylene glycol diacrylate (EGDA) or poly(ethylene glycol) diacrylate (PEGDA). The method according to any one of claims 4 to 11, wherein the crosslinking agent in step c) is introduced either at the beginning of the polymerization or at the end of the polymerization. The method according to any one of claims 4 to 12, wherein the polymerization is carried out at a pH in the range of about 3 to about 8, preferably about 5. The method according to any one of claims 4 to 13, wherein the average degree of polymerization (DP) of the block copolymer is from about 50 to about 300. The polymer nanofiber of claim 1, the amphiphilic block copolymer of claim 2 or 3, or the method of any one of claims 4 to 14, wherein the nanofiber has a width of about 1 nm to about 100 nm. The polymer nanofiber of claim 1, the amphiphilic block copolymer of claim 2 or 3, or the method of any one of claims 4 to 15, wherein the nanofiber has a length of about 5 μm to about 1000 μm. Nanofibers when self-assembled from the amphiphilic block copolymer produced by the method according to any one of claims 4 to 16. Use of nanofibers according to any one of claims 1, 3 or 5 to 17 for at least partially producing a film or coating. 20. A method of forming the film or coating of claim 18, said method comprising:
Dispersing the nanofibers of any one of claims 1, 3, or 5-17 in a solvent to form a dispersion;
applying the dispersion to a surface;
allowing or causing the solvent to substantially or completely evaporate;
Thereby forming said film. A matrix or binder;
18. Use of the nanofibers of any one of claims 1, 3, or 5 to 17 to prepare a composite material comprising: and the nanofibers of any one of claims 1, 3, or 5 to 17 dispersed throughout said matrix or binder. Use of the nanofibers according to any one of claims 1, 3 or 5 to 17 to modify or improve the mechanical properties of a matrix or binder. 1. A method of producing a composite material, the method comprising:
Providing a polymer dispersion;
dispersing the nanofibers of any one of claims 1, 3, or 5-17 in the polymer dispersion to form a mixture;
and drying the mixture to form the composite material. 18. A method for producing a composite material comprising a polymer and a nanofiber according to any one of claims 1, 3 or 5-17 by melt extrusion, the method comprising:
heating the polymer and the nanofibers to a temperature above the melting temperature of the polymer;
mixing the polymer with the nanofibers;
and extruding the mixture to form the composite material. The use of polymer nanofibers as viscosity or rheology modifiers, wherein the polymer nanofibers comprise a core-shell morphology, the shell being hydrophilic and the core comprising a hydrophobic homopolymer or copolymer. 1. A method for producing a block copolymer, the method comprising:
a) reacting at least one hydrophobic monomer using RDRP to form a substantially hydrophobic block [A], the block [A] being substantially soluble in a 20/80% by volume water/ethanol mixture;
b) adding a hydrophobic block [B] comprising at least one hydrophobic monomer to hydrophobic block [A] using RDRP, wherein block [B] is more hydrophobic than block [A] and is of a different composition than block [A];
c) optionally adding a cross-linking agent in step b). 26. The method of claim 25, further comprising a step of causing the block copolymer to self-assemble into nanofibers having a core-shell morphology. The method of claim 25 or 26, wherein the hydrophobic block [A] is substantially insoluble in water. The method according to any one of claims 25 to 27, wherein the polymerization is carried out as RAFT, ATRP, or NMP. The method of any one of claims 26 to 28, wherein the block copolymer is prepared from one or more of benzyl methacrylate, ethylhexyl methacrylate, and methyl methacrylate. The method of claim 29, wherein the block copolymer is prepared from one or more of poly(methyl methacrylate) (PMMA), poly(benzyl methacrylate) (PBzMA), and poly(2-ethylhexyl methacrylate) (PEHMA). The method according to any one of claims 26 to 30, wherein the polar solvent is selected from the group consisting of water, methanol, ethanol, n-propanol, isopropyl alcohol, n-butanol, n-pentanol, and mixtures thereof. The method of any one of claims 26 to 31, wherein the nanofibers have a width of about 1 nm to about 100 nm. The method of any one of claims 26 to 32, wherein the nanofibers have a length of about 0.5 μm to about 1000 μm. a hydrophobic block [A], wherein the block [A] is substantially soluble in a 20/80% by volume water/ethanol mixture;
a hydrophobic block [B] containing at least one hydrophobic monomer, the block [B] being more hydrophobic than the block [A] and having a different composition from the block [A];
A block copolymer, optionally comprising a crosslinker. A polymer nanofiber having a core-shell morphology, the shell being hydrophobic and comprising a polymer that is substantially soluble in a 20/80% by volume water/ethanol mixture, and the core being hydrophobic and comprising a polymer that is more hydrophobic than the polymer of the shell and is of a different composition than the polymer of the shell. Use of the block copolymer of claim 34 or the polymer nanofiber of claim 35 to at least partially produce a film or coating. A matrix or binder;
36. Use of the block copolymer of claim 34 or the polymeric nanofiber of claim 35 to prepare a composite material comprising the block copolymer of claim 34 or the polymeric nanofiber of claim 35 dispersed throughout said matrix or binder. Use of the block copolymer of claim 34 or the polymer nanofiber of claim 35 to modify or improve the mechanical properties of a matrix or binder. Use of the block copolymer of claim 34 or the polymer nanofiber of claim 35 as a viscosity or rheology modifier.

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