Thermosensitive noncovalently bonded block copolymerlike micelles from interpolymer complexes

Interpolymer complexes between polystyrene‐b‐poly(2‐vinylpyridine), (PS‐P2VP), and poly(methacrylic acid) (PMAA), have been studied in dioxane. Dioxane is a good solvent for PS‐P2VP copolymers but it is a nonsolvent for PMAA at room temperature. In this way noncovalent bonded micelles are formed after mixing the solutions of the polymers at 60 °C and then allowing them to cool at room temperature. Static and dynamic light scattering as well as viscosity measurements have been used to study the dependence of aggregate mass and size as a function of the molar ratio of functional groups in PS‐P2VP/PMAA mixtures, as well as temperature. Plots of apparent average molecular weight and hydrodynamic radius of the aggregates versus amine to carboxyl group ratio show a maximum at a ratio close to one. The size of the aggregates decreases at higher ratios because of the formation of more stable micelles with smaller cores. In all cases rather compact structures were formed, as evidenced by viscometry. The mass of the aggregates was found to decrease by an increase in temperature while hydrodynamic radii were increased. This was attributed to the increase of the thermodynamic quality of the solvent toward PMAA as temperature increases. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 6230–6237, 2004     

Preparation of polymeric vesicles through ultrasonic treatment of poly(styrene‐block‐2‐vinylpyridine) micelles under alkaline conditions

An approach for the preparation of block copolymer vesicles through ultrasonic treatment of polystyrene‐block‐poly(2‐vinyl pyridine) (PS‐b‐P2VP) micelles under alkaline conditions is reported. PS‐b‐P2VP block copolymers in toluene, a selective solvent for PS, form spherical micelles. If a small amount of NaOH solution is added to the micelles solution during ultrasonic treatment, organic‐inorganic Janus‐like particles composed of the PS‐b‐P2VP block copolymers and NaOH are generated. After removal of NaOH, block copolymer vesicles are obtained. A possible mechanism for the morphological transition from spherical micelles to vesicles or Janus‐like particles is discussed. If the block copolymer micelles contain inorganic precursors, such as FeCl₃, hybrid vesicles are formed, which may be useful as biological and chemical sensors or nanostructured templates. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 953–959     

Morphological transitions in aggregates of thermosensitive poly(ethylene oxide)‐b‐poly(N‐isopropylacrylamide) block copolymers prepared via RAFT polymerization

Double hydrophilic poly(ethylene oxide)‐b‐poly(N‐isopropylacrylamide) (PEO‐b‐PNIPAM) block copolymers were synthesized via reversible addition‐fragmentation chain transfer (RAFT) polymerization, using a PEO‐based chain transfer agent (PEO‐CTA). The molecular structures of the copolymers were designed to be asymmetric with a short PEO block and long PNIPAM blocks. Temperature‐induced aggregation behavior of the block copolymers in dilute aqueous solutions was systematically investigated by a combination of static and dynamic light scattering. The effects of copolymer composition, concentration (C_p), and heating rate on the size, aggregation number, and morphology of the aggregates formed at temperatures above the LCST were studied. In slow heating processes, the aggregates formed by the copolymer having the longest PNIPAM block, were found to have the same morphology (spherical “crew‐cut” micelles) within the full range of C_p. Nevertheless, for the copolymer having the shortest PNIPAM block, the morphology of the aggregates showed a great dependence on C_p. Elongation of the aggregates from spherical to ellipsoidal or even cylindrical was observed. Moreover, vesicles were observed at the highest C_p investigated. Fast heating leads to different characteristics of the aggregates, including lower sizes and aggregation numbers, higher densities, and different morphologies. Thermodynamic and kinetic mechanisms were proposed to interpret these observations, including the competition between PNIPAM intrachain collapse and interchain aggregation. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4099–4110, 2009     

Dimensional Control of Block Copolymer Nanofibers with a π‐Conjugated Core: Crystallization‐Driven Solution Self‐Assembly of Amphiphilic Poly(3‐hexylthiophene)‐b‐poly(2‐vinylpyridine)

With the aim of accessing colloidally stable, fiberlike, π‐conjugated nanostructures of controlled length, we have studied the solution self‐assembly of two asymmetric crystalline–coil, regioregular poly(3‐hexylthiophene)‐b‐poly(2‐vinylpyridine) (P3HT‐b‐P2VP) diblock copolymers, P3HT₂₃‐b‐P2VP₁₁₅ (block ratio=1:5) and P3HT₄₄‐b‐P2VP₁₁₅ (block ratio=ca. 1:3). The self‐assembly studies were performed under a variety of solvent conditions that were selective for the P2VP block. The block copolymers were prepared by using Cu‐catalyzed azide–alkyne cycloaddition reactions of azide‐terminated P2VP and alkyne end‐functionalized P3HT homopolymers. When the block copolymers were self‐assembled in a solution of a 50 % (v/v) mixture of THF (a good solvent for both blocks) and an alcohol (a selective solvent for the P2VP block) by means of the slow evaporation of the common solvent; fiberlike micelles with a P3HT core and a P2VP corona were observed by transmission electron microscopy (TEM). The average lengths of the micelles were found to increase as the length of the hydrocarbon chain increased in the P2VP‐selective alcoholic solvent (MeOH<iPrOH<nBuOH). Very long (>3 μm) fiberlike micelles were prepared by the dialysis of solutions of the block copolymers in THF against iPrOH. Furthermore the widths of the fibers were dependent on the degree of polymerization of the chain‐extended P3HT blocks. The crystallinity and π‐conjugated nature of the P3HT core in the fiberlike micelles was confirmed by a combination of UV/Vis spectroscopy, photoluminescence (PL) measurements, and wide‐angle X‐ray scattering (WAXS). Intense sonication (iPrOH, 1 h, 0 °C) of the fiberlike micelles formed by P3HT₂₃‐b‐P2VP₁₁₅ resulted in small (ca. 25 nm long) stublike fragments that were subsequently used as initiators in seeded growth experiments. Addition of P3HT₂₃‐b‐P2VP₁₁₅ unimers to the seeds allowed the preparation of fiberlike micelles with narrow length distributions (L_w/L_n <1.11) and lengths from about 100‐300 nm, that were dependent on the unimer‐to‐seed micelle ratio.     

Biocompatibility evaluation of self‐assembled micelles prepared from poly(lactide‐co‐glycolide)‐poly(ethylene glycol) diblock copolymers

In this work, a series of PLGA‐PEG diblock copolymers were synthesized by ring‐opening polymerization of L‐lactide and glycolide using mPEG as macroinitiator and stannous octoate as catalyst. Spherical micelles were obtained from the various copolymers by using co‐solvent evaporation method. The biocompatibility of micelles was evaluated with the aim of assessing their potential in the development of drug delivery systems. Various aspects of biocompatibility were considered, including MTT assay, agar diffusion test, release of cytokines, hemolytic test, dynamic clotting time, protein adsorption in vitro, and zebrafish embryonic compatibility in vivo. The combined results revealed that the micelles present good cytocompatibility and hemocompatibility in vitro. Moreover, the cumulative effects of micelles throughout embryos developing stages have no toxicity in vivo. It is thus concluded that micelles prepared from PLGA‐PEG copolymers present good biocompatibility as potential drug carrier.     

Aggregation behavior of poly(γ‐benzyl‐L‐glutamate)‐b‐polyisoprene‐b‐poly(γ‐benzyl‐L‐glutamate) rod‐coil‐rod triblock copolymer in N,N‐dimethylformamide

Solution property of poly(γ‐benzyl‐L ‐glutamate)‐b‐polyisoprene‐b‐poly(γ‐benzyl‐L ‐glutamate) (GIG copolymer) was studied by using dynamic light scattering and static light scattering for N,N‐dimethylformamide (DMF) solution and DMF/toluene mixed solutions. GIG copolymer proved to aggregate in DMF and under DMF‐rich condition, that is, high‐polar region. The aggregate decreased in size, and completely disappeared under toluene‐rich condition, that is, low‐polar region. The correlation between solubility parameter and aggregate size of GIG copolymer in the DMF/toluene solution systems quantitatively demonstrated how strongly polarity caused by hydrogen bond made an impact on the aggregation behavior. Because the main driving force to the aggregation under DMF‐rich condition originates with polyisoprene (PIP) blocks, the aggregate in DMF is considered to be a core‐shell micelle consisting of flexible PIP core surrounded by rigid poly(γ‐benzyl‐L ‐glutamate) (PBLG) shell. The values of dimensionless parameter ρ, defined as the ratio of radius of gyration 〈S²〉^1/2 to hydrodynamic radius R_H, revealed that a single chain of GIG copolymer had the form of rigid rod with flexibility, that is, once‐broken rod, caused by the incorporation of a flexible PIP chain between two rigid PBLG rods in the DMF/toluene solution system. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1740–1748, 2010     

Noncovalently connected micelles based on a β‐cyclodextrin‐containing polymer and adamantane end‐capped poly(ε‐caprolactone) via host–guest interactions

New random copolymers, poly(N‐vinyl‐2‐pyrrolidone‐co‐mono‐6‐deoxy‐6‐methacrylate ethylamino‐β‐cyclodextrin) (PnvpCD) bearing pendent β‐cyclodextrin (CD) groups were synthesized. PnvpCD formed soluble graft‐like polymer complex with adamantane (AD) end‐capped poly(ε‐caprolactone) (PclAD) in their common solvent N‐methyl‐2‐pyrrolidone driven by the inclusion interactions between the CD and AD groups. The formation of the graft complex has been confirmed by viscometry, dynamic light scattering (DLS), and isothermal titration calorimeter. The graft complex self‐assembled further into noncovalently connected micelles in water, which is a selective solvent for the main chain PnvpCD. Transmission electron microscopy, DLS, and atomic force microscopy have been used to investigate the structure and morphology of the resultant micelles. A unique “multicore” structure of the micelles, in which small PclAD domains scattered within the micelles, was obtained under nonequilibrium conditions in the preparation. However, the micelles prepared in a condition close to equilibrium possess an ordinary core‐shell structure. In both cases, the core and shell are believed to be connected by the AD‐CD inclusion complexation. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4267–4278, 2009     

Supramolecular complexes of poly(3‐Hexylthiophene)‐block (and random)‐poly[3‐(2‐(6‐carboxyhexyl)methyl)thiophene] copolymers with perylene bisimide

Block and random copolymers of poly(3‐hexylthiophene) and poly[3‐(2‐(6‐carboxyhexyl)methyl)thiophene] with side‐chain carboxylic functionality ((P3HT‐b‐P3COOH) and (P3HT‐r‐P3COOH) were developed by Grignard Metathesis (GRIM) polymerization. The carboxylic functionality was introduced in the side chain via the oxazoline route. Both the block and random polythiophene copolymers were complexed with pyridine functionalized perylene bisimide to obtain supramolecular block and random polymer complexes. The complex formation in both systems was confirmed by ¹H NMR, WXRD and SAXS studies. An expansion of d spacing upon complex formation was observed in both the block and random copolymer, which could be traced by WXRD. Hole and electron mobilities measured for the supramolecular complexes indicated values which were higher by an order of magnitude for the supramolecular block complex (μ_h ≈ 2.9 × 10⁻⁴ cm²/Vs; μ_e ≈ 3.1 × 10⁻⁶ cm²/Vs) as compared to the random (μ_h ≈ 1.4 × 10⁻⁵ cm²/Vs; μ_e ≈ 4.7 × 10⁻⁷ cm²/Vs) copolymer. These results are indicative of the higher degree of disorder prevailing in the films of random copolymer system compared to the block copolymer. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1574–1583     

Synthesis and characterization of pH sensitive poly(glycidol)‐b‐poly(4‐vinylpyridine) block copolymers

Block copolymers of poly(glycidol)‐b‐poly(4‐vinylpyridine) were obtained by ATRP of 4‐vinylpyridine initiated by ω‐(2‐chloropropionyl) poly(glycidol) macroinitiators. By changing the monomer/macroinitiator ratio in the synthesis polymers with varied P4VP/PGl molar ratio were obtained. The obtained block copolymers showed pH sensitive solubility. It was found that the linkage of a hydrophilic poly(glycidol) block to a P4VP influenced the pK_a value of P4VP. DLS measurements showed the formation of fully collapsed aggregates exceeding pH 4.7. Above this pH values the collapsed P4VP core of the aggregates was stabilized by a surrounding hydrophilic poly(glycidol) corona. The size of the aggregates depended significantly upon the composition of the block copolymers. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1782–1794, 2009     

Aggregation behavior of amphiphilic random copolymer of 2‐(acrylamido)‐2‐methylpropanesulfonic acid and tris(trimethylsiloxy)silylpropylmethacrylate in aqueous solution

Aggregation behavior including dilute solution property and surface‐activity of the amphiphilic random copolymer composed of 2‐(acrylamido)‐2‐methylpropanesulfonic acid and tris(trimethylsiloxy)silylpropylmethacrylate (AMPS/TRIS copolymer) in aqueous solution were studied by static light scattering (SLS), dynamic light scattering (DLS), surface tension measurement, and transmission electron microscopy (TEM). The surface tension measurement made it clear that AMPS/TRIS copolymer exhibited weaker surface‐activity than a typical low‐molecular weight surfactant sodium dodecyl sulfate in water, that is, there were no plateau of surface tension γ versus concentration and no critical micelle concentration (CMC) in the whole concentration studied. SLS and DLS analyses, and TEM revealed that AMPS/TRIS copolymer self‐associated into imperfect core‐shell micelles having hydrophobic TRIS core surrounded by hydrophilic AMPS shell in water. AMPS shell was considered as a hard shell due to the stiffness of AMPS chain in water. TRIS chain could not densely aggregate in water due to the large steric hindrance between bulky trimethylsiloxy groups despite its hydrophobic nature, thereby providing TRIS core with less‐dense structure. The balance between the spreading force of stiff AMPS chain and the cohesion force of bulky TRIS chain provides the driving force for forming the unique micelle having less‐dense TRIS core and hard AMPS shell. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

Dispersion of polystyrene inside polystyrene‐b‐poly(N‐isopropylacrylamide) micelles in water

The addition of mixture of polystyrene‐b‐poly(N‐isopropylacrylamide) (PS‐b‐PNIPAM) and polystyrene homopolymer (h‐PS) in tetrahydrofuran dropwise into water leads to nanoparticles with a PS core and a thermally sensitive PNIPAM shell. The effects of the ratio of the homopolymer to copolymer and temperature on the formation and stabilization of the dispersion were investigated by using a combination of static and dynamic laser light scattering. PNIPAM shell continuously collapses as temperature increases in the range 20–40 °C. Such formed particles are stable even at temperatures much higher than lower critical solution temperature (LCST ～ 32 °C) of PNIPAM. Our results reveal that the area occupied per hydrophilic PNIPAM chain on the hydrophobic PS core remains nearly a constant regardless of the amount of h‐PS in the polymer mixture. This clearly indicates that the surface area occupied per hydrophilic group is a critical parameter for stabilizing particles dispersed in water. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 749–755, 2010     

β‐Lactam functionalized poly(isoprene‐b‐ethylene oxide) amphiphilic block copolymers

Amphiphilic block copolymers containing β‐lactam groups on the polyisoprene block were synthesized from poly(isoprene‐b‐ethylene oxide) (IEO) diblock copolymer precursors, prepared by anionic polymerization. β‐Lactam functionalization was achieved via reaction of the polyisoprene (PI) block with chlorosulfonyl isocyanate and subsequent reduction. The resulting block copolymers were molecularly characterized by SEC, FTIR, and NMR spectroscopies and DSC. Functionalization was found to proceed in high yields, altering the solubility properties of the PI block and those of the functionalized diblocks. Hydrogen bond formation is assumed to be responsible for the decreased crystallinity of the poly(ethylene oxide) block (PEO) in the bulk state as indicated by DSC measurements. The self‐assembly behavior of the β‐lactam functionalized poly(isoprene‐b‐ethylene oxide) copolymers (LIEO) in aqueous solutions was studied by dynamic light scattering (DLS), static light scattering (SLS), fluorescence spectroscopy, and atomic force microscopy (AFM). Nearly spherical loose aggregates were formed by the LIEO block copolymers, having lower aggregation numbers and higher cmc values compared to the IEO precursors, as a result of the increased polarity of the β‐lactam rings incorporated in the PI blocks. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 24–33, 2010     

Reversibly light‐responsive biodegradable poly(carbonate) micelles constructed via CuAAC reaction

Light‐responsive poly(carbonate)s PEG₁₁₃‐b‐PMPC_n‐SP were synthesized via copper catalyzed azide‐alkyne cycloaddition reaction between azide‐modified spiropyran (SP‐N₃) and amphiphilic copolymer PEG₁₁₃‐b‐PMPC_n. PEG₁₁₃‐b‐PMPC₂₅‐SP can self‐assemble to biocompatible micelles with an average diameter of ～96 nm and a critical aggregation concentration of 0.0148 mg mL^?1. Under 365 nm UV light irradiation, the characteristic absorption intensity of merocyanine (MC) progressively increased and most of the micellar aggregations were disrupted within 10 min, suggesting the completion of the transformation of hydrophobic SP to hydrophilic MC. Subsequent exposuring the micelles to 620 nm visible light, spherical micelles aggregated again. The light‐controlled release and re‐encapsulation behaviors of coumarin 102‐loaded micelles were further investigated by fluorescence spectroscopy. This study provides a convenient way to construct smart poly(carbonate)s nanocarriers for controlled release and re‐encapsulation of hydrophobic drugs. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 750–760     

Microphase segregation and selective chain scission of poly(2‐methyl‐2‐oxazoline)‐block‐polystyrene

Herein, we report the design and synthesis of a block copolymer (BCP) with a high Flory–Huggins interaction parameter to access 10 nm feature sizes for potential lithographic applications. The investigated BCP is poly[(2‐methyl‐2‐oxazoline)‐block‐styrene] (PMeOx‐b‐PS), where the PMeOx segment functions as a hydrophilic segment. Two BCPs with different molecular weights were prepared using PMeOx as macroinitiator for copper(0) mediated controlled radical polymerization. The thin film self‐assembly of the obtained PMeOx‐b‐PS was performed by solvent annealing and investigated by atomic force microscopy. Both polymers formed PMeOx cylinders in a PS matrix with an average cylinder diameter of 10.5 nm. Additionally, the ability of the PMeOx domains to selectively degrade under ultraviolet irradiation was explored. It was shown that scission of the PMeOx block does occur selectively, and furthermore that the degraded domains can be removed while leaving the PS matrix intact. By combining synthetic accessibility, small feature sizes, and a selectively cleavable domain, this new BCP system holds significant promise as a lithographic mask for patterning surfaces with high precision. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1349–1357     

Synthesis,characterization, and electrical properties of nanostructural polyaniline doped with novel sulfonic acids (4‐{n‐[4‐(4‐nitrophenylazo)phenyloxy]alkyl}aminobenzene sulfonic acid)

4‐{n‐[4‐(4‐Nitrophenylazo)phenyloxy]alkyl}aminobenzene sulfonic acid (Cn‐ABSA, where n = 2, 4, 6, 8, or 10) as a novel dopant for conducting polymers of polyaniline (PANI) was designed and synthesized. The molecular structure of Cn‐ABSA was characterized with ¹H NMR, Fourier transform infrared, and secondary‐ion mass spectrometry. Nanostructures (nanotubes or nanorods) of PANI–(Cn‐ABSA) were successfully synthesized with a self‐assembly process in the presence of Cn‐ABSA as the dopant. The morphology (shape and size) and conductivity of the resulting nanostructures strongly depended on the number of alkyl groups (n) and, in particular, the addition of water before polymerization. The formed micelles of aniline/Cn‐ABSA/water were proposed to be templatelike in forming PANI–(Cn‐ABSA) nanostructures on the basis of the emulsion properties measured by dynamic light scattering. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3485–3497, 2001     

Synthesis and aggregation of poly(valine)‐poly (ethylene glycol) block copolymers

The solubility nature of many medicines presents a challenge for successful delivery of these drugs to the body. Polymeric carriers are potentially viable as vessels for both the protection and transport of these medicinal substances. In an effort to generate polymeric materials for this desired application, A‐B‐A triblock copolymers have been synthesized with a central block composed of hydrophilic poly (ethylene glycol) (PEG) and flanking hydrophobic sequences composed of five valine units terminated with end groups of varying hydrophobicity. These copolymers were constructed by adding amino acids stepwise to the hydrophilic block using solution phase chemistry. The self‐assembly behavior of all polymers was investigated using fluorimetry with a pyrene probe. In general, copolymers with more hydrophobic end groups exhibited lower critical aggregation concentrations (CACs). Fmoc‐terminated copolymers displayed the lowest CAC of 0.032 mg/mL and demonstrated little cytotoxicity when exposed to SW620 colorectal cancer cells. Transmission electron micrographs show the presence of multiple compartments within these spherical assemblies, which may prove useful in encapsulating medicinal substances. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5381–5389, 2008     

Molecular captain: A light‐sensitive linker molecule in poly(ethylene glycol)‐poly(L‐alanine)‐poly(ethylene glycol) triblock copolymer directs molecular nano‐assembly,conformation, and sol‐gel transition

We report a poly(ethylene glycol)‐poly(L ‐alanine)‐azobenzene‐poly(L ‐alanine)‐poly(ethylene glycol) (PEG‐PA‐Z‐PA‐PEG) as a temperature and light sensitive polymer. The poly(ethylene glycol)‐poly(L ‐alanine) diblock copolymers with a flexible‐rigid block structure were coupled by an azobenzene group that undergoes a reversible configurational change between “trans” and “cis” upon exposure to UV and vis light. The single azobenzene molecule embedded in the middle of a block copolymer with a flexible (shell)‐rigid (core) structure significantly affected molecular assembly, micelle size, polypeptide secondary structure, and sol‐to‐gel transition temperature of the polymer aqueous solution, depending on its exposure to UV or vis light. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Exploring the synthesis and impact of end‐functional poly(3‐hexylthiophene)

In recent years, end‐functional poly(3‐hexylthiophene) (P3HT) has proven to be instrumental in the continued development and innovation within the broad conjugated polymer arena, enabling a variety of applications, particularly in organic electronics. The availability of P3HT with controlled molecular weights, low polydispersity, and importantly, a wide range of reactive end‐groups not only serves as a key building block for the preparation of conjugated block copolymers but also facilitates the development of hybrid nanocomposite materials via inorganic surface modification strategies. This Highlight focuses on the synthetic approaches to end‐functional P3HT and the impact of these systems in emerging technologies. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 831–841     

Simulation of the self‐assembly of poly(α‐glutamate) and dodecyltrimethylammonium: Diffusive role of the surfactant cations

The self‐assembly process of stoichiometric complexes formed by poly(α‐glutamate) and dodecyltrimethylammonium molecular cations has been studied at the atomistic by molecular dynamics simulations. The results presented in this work depict a time‐dependent succession of events. Among them, the formation of the assembled complex is an extraordinarily fast event. On the other side, the surfactant units do not influence the kinetics of the polypeptide folding process, showing that the characteristic independent organization experimentally detected for the charged groups and aliphatic tails has its reflection during the assembly process. Through these results, it is possible to infer new strategies to engineer the final nano‐organization that these stoichiometric complexes can adopt. The instantaneous assembly of the oppositely charged components allows a further kinetic control over the polypeptide folding process, which is expected to take place in time scales that are between 10 and 100 times larger than those explored in this work. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 917–924, 2008