Helical Superstructures from the Hierarchical Self-Assembly of Coil-Coil Block Copolymer Guided by Side Chain Amyloid-ß(17-19) LVF Peptide.

The rational design of precisely controlled hierarchical chiral nanostructures from synthetic polymers garnered inspiration from sophisticated biological materials. Since chiral peptide motifs induce helix formation in macromolecules, herein we report the synthesis of a novel type of hybrid polymer consisting of a ß-sheet forming a LVF [L = leucine, V = valine, and F = phenylalanine] tripeptide pendant polymethacrylate block and a poly[poly(ethylene glycol) methyl ether methacrylate] (PPEGMA) block. The designed block copolymer self-organized into helical superstructures with a left-handed twisting sense, as visualized by field emission scanning electron microscopy, transmission electron microscopy, and atomic force microscopy. This intriguing hierarchical self-assembly is driven by the minimalistic peptide motif that itself has a high propensity to adopt an antiparallel ß-sheet conformation. We also report the generation of a diverse array of nanostructures, including spherical micelles, spindle micelles, rod-like micelles, vesicles, helical supramolecular fibers, and helical toroids via self-assembly of the designed block copolymer in tetrahydrofuran/water mixed solvents. To realize the observable helical superstructure, a twisted two-dimensional core-shell tape is proposed as a structure model in which the peptide segments form an antiparallel ß-sheet with a polymer shell. The findings contribute to the advancement of a helical polymer or the superhelical self-assembly of polymers, paving the way for diverse applications in materials science and related fields.

Inhibition and eradication of bacterial biofilm using polymeric materials.

Biofilms, ubiquitous in nature, are three-dimensional complex microbial communities sheathed in a self-secreted extracellular polymeric matrix. Infections caused by these communities have sprouted as serious threats to global healthcare systems due to their intrinsic tolerance toward conventional antibiotics. There is a huge demand for alternative "cutting-edge" materials featuring strong antibiofilm abilities to mitigate and/or exterminate pre-matured biofilms. Natural or synthetic macromolecule-based compounds have evolved as one of the most sought-after materials because of their unique stimulus-directed selective targeting efficiency to the bacterial cell, antibiotic-encapsulation ability endowing them with a synergistic effect, and highly dense embedded cationic functionalities that promote accumulation within the biofilm. In this comprehensive review, we aim to highlight the progress made in inhibiting or eradicating bacterial biofilms using various forms of polymeric material including cationic and charge-switchable macromolecules, conjugated polymers, polymeric metal nanocomposites, hydrogels, and supramolecular polymers. We particularly emphasize understanding the underlying antibiofilm mechanisms of each presented example ushered in by state-of-the-art synthetic strategies. Lastly, focusing on bench-to-bedside, the review is concluded by providing some forthcoming aspects and possible future development directions to expand polymer-based antibiofilm research, keeping their clinical translations in mind.

Stimuli-Responsive Aggregation-Induced Emission (AIE)-Active Polymers for Biomedical Applications.

At high concentration or in the aggregated state, most of the traditional luminophores suffer from the general aggregation-caused quenching (ACQ) effect, which significantly limits their biomedical applications. On the contrary, a few fluorophores exhibit an aggregation-induced emission (AIE) feature which is just the opposite of ACQ. The luminophores with aggregation-induced emission (AIEgens) have exhibited noteworthy advantages to get tunable emission, excellent photostability, and biocompatibility. Incorporating AIEgens into polymer design has yielded diversified polymer systems with fascinating photophysical characteristics. Again, stimuli-responsive polymers are capable of undergoing chemical and/or physical property changes on receiving signals from single or multiple stimuli. The combination of the AIE property and stimuli responses in a single polymer platform provides a feasible and effective strategy for the development of smart polymers with promising biomedical applications. Herein, the advancements in stimuli-responsive polymers with AIE characteristics for biomedical applications are summarized. AIE-active polymers are first categorized into conventional π-π conjugated and nonconventional fluorophore systems and then subdivided based on various stimuli, such as pH, redox, enzyme, reactive oxygen species (ROS), and temperature. In each section, the design strategies of the smart polymers and their biomedical applications, including bioimaging, cancer theranostics, gene delivery, and antimicrobial examples, are introduced. The current challenges and future perspectives of this field are also stated at the end of this review article.

AIE-active non-conjugated poly(N-vinylcaprolactam) as a fluorescent thermometer for intracellular temperature imaging.

Since temperature is one of the most significant physiological parameters that dictate the cellular status of living organisms, accurate intracellular temperature measurement is crucial and a valuable biomarker for the diagnosis and treatment of diseases. Herein, we introduce the foremost example of a non-conjugated polymer as a next generation fluorescent thermometer which is capable of addressing the key shortcomings including toxicity and thermal-induced fluorescence quenching associated with π-π conjugated system-based thermometers developed so far. We revealed, for the first time, the unique photophysical and aggregation-induced emission (AIE) characteristics of well-known thermoresponsive poly(N-vinylcaprolactam) (PNVCL) devoid of any classical fluorophore entity. PNVCL underwent a coil to globular conformational transition in an aqueous medium and appeared to be fluorescent above its lower critical solution temperature (LCST) near body temperature (38 °C). Eventually, this intriguing aspect enabled higher cellular uptake of PNVCL at the LCST boundary. By virtue of the AIE effect, the thermo-induced aggregation phenomenon has been ingeniously utilized to apply PNVCL as a novel fluorescent thermometer for intracellular temperature determination.

Polyisobutylene-Based pH-Responsive Self-Healing Polymeric Gels.

This work demonstrates the successful application of dynamic covalent chemistry for the construction of self-healing gels from side-chain primary amine leucine pendant diblock copolymers of polyisobutylene (PIB) ((P(H2N-Leu-HEMA)-b-PIB)) in the presence of PIB based dialdehyde functionalized cross-linker (HOC-PIB-CHO) through imine (-HC═N-) bond formation without aiding any external stimuli. Gels were synthesized in 1,4-dioxane at room temperature at varied wt % of gelator concentration, [H2N]/[CHO] ratios and molecular weight of the block segments. The mechanical property of gels was examined by rheological measurements. We observed higher value of storage modulus (G') than the loss modulus (G″) within the linearity limits of deformation, indicating the rheological behavior in the gel is dominated by an elastic property rather than a viscous property. The G' values significantly depend upon the extent of cross-linking in the gel network. To establish self-healing property of the gels, rheology analysis through step-strain measurements (strain = 0.1 to 200%) at 25 °C was performed. The polymeric gel network shows reversible sol-gel transition for several cycles by adjusting the pH of the medium with the help of hydrochloric acid (HCl) and triethylamine (Et3N) triggers. FT-IR spectroscopy established formation of imine bonds in the gel network and these gels showed poor swelling behavior in various organic solvents because of the small interstitial porosity, confirmed by field emission-scanning electron microscopy (FE-SEM).

Specific counterion repercussions on the thermal, pH-response, and electrochemical properties of side-chain leucine based chiral polyelectrolytes.

Effects of counterions of side chain amino acid based polyelectrolytes (PEs) on the solubility in aqueous medium, pH responsiveness, thermal properties, and ionic conductivities have been appraised. Deprotection of the tert-butyl carbamate (Boc) group from poly(Boc-l-leucine methacryloyloxyethyl ester) [P(Boc-l-Leu-HEMA)] was carried out to produce PE with trifluoroacetate as an associative counteranion (1a). PEs with bis(trifluoromethylsulfonyl)imide and hexafluorophosphate counteranion were prepared through anion exchange reactions of 1a. Protonation of the neutralized polymer (2) obtained from 1a, followed by anion exchange, leads to the production of miscellaneous PEs bearing different counteranions, such as tetrafluoroborate, trifluoromethanesulfonate, chloride, and nitrate. Differential scanning calorimetry traces of the PEs reveal that the comparatively larger and weakly coordinated counteranions require less thermal energy to dissociate, and thus, the glass transition temperature (Tg) of the PEs fall off with an increase in the size of the counteranion. A remarkable conductivity of 2.1 mS/cm was obtained in deionized water when Cl(-) acted as the counteranion. Steric and electronic factors of the counteranion induce a change of transition pH in different PEs, although the chiroptical nature was retained, as confirmed by circular dichroism spectroscopy.

Controlled synthesis of amino acid-based pH-responsive chiral polymers and self-assembly of their block copolymers.

Leucine/isoleucine side chain polymers are of interest due to their hydrophobicity and reported role in the formation of α-helical structures. The synthesis and reversible addition-fragmentation chain transfer (RAFT) polymerization of amino acid-based chiral monomers, namely Boc-L-leucine methacryloyloxyethyl ester (Boc-L-Leu-HEMA, 1a), Boc-L-leucine acryloyloxyethyl ester (Boc-L-Leu-HEA, 1b), Boc-L-isoleucine methacryloyloxyethyl ester (Boc-L-Ile-HEMA, 1c), and Boc-L-isoleucine acryloyloxyethyl ester (Boc-L-Ile-HEA, 1d), are reported. The controlled nature of the polymerization of the said chiral monomers in N, N-dimethylformamide (DMF) at 70 °C is evident from the formation of narrow polydisperse polymers, the molecular weight controlled by the monomer/chain transfer agent (CTA) molar ratio and the linear relationship between molecular weight and monomer conversion. The resulting well-defined polymers were used as macro-CTAs to prepare corresponding diblock copolymers by RAFT polymerization of methyl (meth)acrylate monomers. Deprotection of Boc groups in the homopolymers and block copolymers under acidic conditions produced cationic, pH-responsive polymers with primary amine moieties at the side chains. The optical activity of the homopolymers and block copolymers were studied using circular dichroism (CD) spectroscopy and specific rotation measurements. The self-assembling nature of the block copolymers to produce highly ordered structures was illustrated through dynamic light scattering (DLS) and atomic force microscopy (AFM) studies. The side chain amine functionality instills pH-responsive behavior, which makes these cationic polymers attractive candidates for drug delivery applications, as well as for conjugation of biomolecules.