Post-polymerization Modification Research Articles

Cysteine Conjugation: An Approach to Obtain Polymers with Enhanced Muco- and Tissue Adhesion

The modification of polymers towards increasing their biocompatibility gathers the attention of scientists worldwide. Several strategies are used in this field, among which chemical post-polymerization modification has recently been the most explored. Particular attention revolves around polymer-L-cysteine (Cys) conjugates. Cys, a natural amino acid, contains reactive thiol, amine, and carboxyl moieties, allowing hydrogen bond formation and improved tissue adhesion when conjugated to polymers. Conjugation of Cys and its derivatives to polymers has been examined mostly for hyaluronic acid, chitosan, alginate, polyesters, polyurethanes, poly(ethylene glycol), poly(acrylic acid), polycarbophil, and carboxymethyl cellulose. It was shown that the conjugation of Cys and its derivatives to polymers significantly increased their tissue adhesion, particularly mucoadhesion, stability at physiological pH, drug encapsulation efficiency, drug release, and drug permeation. Conjugates were also non-toxic toward various cell lines. These properties make Cys conjugation a promising strategy for advancing polymer applications in drug delivery systems and tissue engineering. This review aims to provide an overview of these features and to present the conjugation of Cys and its derivatives as a modern and promising approach for enhancing polymer tissue adhesion and its application in the medical field.

Post-Functionalization of Fluorinated Dibenzosulfone-Based Conjugated Polymer for Smart 'Turn-off' Sensing of Cu2+ Ions.

Post-functionalization of conjugated polymeric backbone with various N-containing heterocycles through nucleophilic aromatic substitution reaction (SNAr) demonstrates crucial tailoring of their photophysical properties. This study explores an approach of post-polymerization modification of a fluorinated dibenzosulfone-based conjugated polymer aiming to incorporate functional groups having coordinating sites to bind metal ions. The resulting polymers, namely BDT-DBTS-IM, BDT-DBTS-TR, and BDT-DBTS-PY revealed successful substitution reactions with imidazole, triazole, and pyridine respectively, and showed significant changes in their absorption and emission properties. Notably, BDT-DBTS-IM demonstrated exceptional performance as a chemosensor, exhibiting a dramatic fluorescence turn-off response specifically to copper ions (Cu2+) with the limit of detection of 26 nM and Stern-Volmer quenching constant (KSV) of 8.2×105 Lmol-1. This high selectivity and sensitivity are attributed to the ability of the imidazole group to form a stable complex with Cu2+, resulting in both static and dynamic quenching efficiently. Our findings underscore the potential of post-polymerization modifications to significantly enhance the functionality of conjugated polymers. The ability of BDT-DBTS-IM to detect trace levels of copper ions with high precision highlights its practical utility in environmental and biological monitoring. This research not only demonstrates an approach for post-polymeric modification through SNAr reaction but also opens new avenues for developing sensors.

End-Group Dye-Labeled Poly(hemiacetal ester) Block Copolymers: Enhancing Hydrolytic Stability and Loading Capacity for Micellar (Immuno-)Drug Delivery.

Polymers with hemiacetal esters integrated in their backbone provide beneficial degradation profiles for (immuno-) drug delivery. However, their fast hydrolysis and low drug loading capacity have limited their applications so far. Therefore, this study focuses on the stability and loading capacity of hemiacetal ester polymers. The hydrophobicity of the micellar core has a tremendous effect on the hemiacetal ester stability. For that purpose, we introduce a new monomer with a phenyl moiety for stabilizing the micellar core and improving drug loading. The carrier functionality can further be expanded by post-polymerization modifications via activated ester groups at the polymer chain end. This allows for covalent dye labeling, which provides substantial insights into the polymers' in vitro performance. Flow cytometric analyses on RAW dual macrophages revealed intact micelles exhibiting significantly higher cellular uptake compared to degraded species, thus, highlighting the potential of end group functionalized poly(hemiacetal ester)s for (immuno)drug delivery purposes.

Solid-state solvatochromism of oxazolidine in multi-functionalized copolymer nanoparticles: Development of advanced materials with multi-color fluorescence

Investigating the solvatochromism of stimuli-chromic compounds such as oxazolidine in polymer matrices with various polarities or functionalities is a unique approach to developing advanced materials for anticounterfeiting, sensor, optoelectronic, and displayers. In a novel strategy, multi-functionalized copolymer nanoparticles were synthesized by copolymerization of methyl methacrylate (MMA) with various functional comonomers in emulsion media for post-polymerization modification with oxazolidine and investigation of its solvatochromism in both colloidal solution and solid phase. The particle size and morphology of nanoparticles were influenced significantly by the polarity of functional groups, and the morphology evolution from sphere to anisotropic shapes was observed by increasing the polarity of functional groups. Investigation of oxazolidine solvatochromism in colloidal solution and solid polymer powders indicated different mechanisms for solvatochromism, in which the polarity of media is the main effective parameter in colloidal solution and the polarity of functional groups in the polymer structure is the main effective parameter in solid polymer phase. The solvatochromism of oxazolidine was confirmed by observed red shift and blue shift in UV–Vis and fluorescence spectra, in which the intensity of absorbance and emission peaks was changed as a function of the polarity of functional groups. Solvatochromic photoluminescent polymer nanoparticles were used for several advanced applications such as solid anticounterfeiting inks to information encryption, dual-mode visualization of latent fingerprints, and also development of organic light-emitting diodes (OLEDs). For the first time, the results indicate a significant effect of polymer chain local polarity induced by functional groups on the tuning of optical properties of the oxazolidine by the solid-state solvatochromic phenomenon. Solvatochromism of oxazolidine in functionalized polymer nanoparticles is an interesting approach to developing novel intelligent materials that have advanced applications in different fields such as anticounterfeiting and information encryption, optoelectronic, polarity sensor, and visualization of latent fingerprints.

Modification of polyolefins utilizing C–H insertion of azides: Azidoformate end-functionalized polystyrene for modifying polypropylene

Polyolefins dominate the global plastics industry, constituting roughly 60% of all commercial plastics. However, their limited chemical functionality restricts their applicability in adhesion, printability, and compatibility-dependent applications. To overcome these limitations, this study investigated metal-free, melt-process post-polymerization modification of polypropylene (PP) via C-H insertion of azidoformate (AF) groups. We investigated grafting of AF end-functionalized polystyrene (PS) onto PP and demonstrated the successful preparation of novel PP hybrids with interesting properties, including enhanced compatibility between PP and PS components due to grafting, smaller PP crystallite size, high Young's modulus, and elastic rheological behaviors likely attributable to the presence of PS branches. Importantly, the presented approach avoids chain scission of PP and undesirable coloration of the product, offering a promising avenue for industrial transformations of conventional polyolefins. This research paves the way for developing polyolefin-based hybrid materials with enhanced properties and environmental benefits.

Bio-sourced tartaric acid-derived tartarimides as diol counterparts towards renewable polyurethanes

The depletion of petroleum-based fossil resources and ever-increasing environmental problems are serious issues in the production of polymeric materials. An increasingly important approach is to obtain the building blocks used in the production of these materials from renewable sources of natural origin. In the present study, bio-sourced tartaric acid-based tartarimides were evaluated as monomeric diol compounds to synthesize polyurethane polymers. Structurally diverse tartarimides were conveniently obtained from the condensation reactions of tartaric acid with various primary amine compounds. The diol structure of the generated tartarimides allowed to access polyurethanes along with the polymerizations of diisocyanate monomers. Copolymers in the range of 22.9 kDa to 29.3 kDa molecular weights were obtained with moderately high total monomer conversions (up to 96%). Depending on the tartarimide and diisocyanate monomers employed during polymerization, copolymers with different physical and thermal properties were generated. By utilizing tartarimides carrying furan and alkene functionalities, side chain reactive polyurethanes were synthesized. These reactive polymers were evaluated in post-polymerization modification and crosslinking processes by using radical thiol-ene and Diels-Alder based click reactions. The results obtained in this study demonstrated that the bio-sourced tartarimides could provide a convenient access to structurally tailorable polyurethane polymers that are important materials in various applications.

Multifunctional Polymer Synthesis via Sequential Postpolymerization Modification Using a Single Aldehyde Repeat Unit: Allylation and Orthogonal Esterification and Thiol-ene Reaction.

Herein, we present a highly efficient method for synthesizing multifunctional polymers. This method involves the sequential postpolymerization modification (PPM) of a highly reactive aldehyde polymer. We introduce an allylic alcohol functionality into the polymer backbone via Barbier-type allylation, a process facilitated by easy-to-handle indium(0) powder. This step enables the formation of orthogonal pendants, secondary alcohol, and terminal alkene, which can be further functionalized through esterification and thiol-ene click reactions. All of these processes are carried out under mild conditions, ensuring high efficiency and a wide range of functional groups. Our study underscores PPM's operational simplicity and versatility in developing advanced polymer materials and expanding the scope of multifunctional polymer design.

C-H Functionalization of Poly(ethylene oxide) - Embracing Functionality, Degradability, and Molecular Delivery.

This study presents an organocatalytic C-H functionalization approach for postpolymerization modification (PPM) of poly(ethylene oxide) (PEO). Most of PEO PPM is previously processed at the end hydroxy group, but recent advances in C-H functionalization open a way to modify the backbone position. Structurally diverse carboxylic acids are attached to PEO through a cascade process of radical generation by peroxide and oxidation to oxocarbenium by tertiary butylammonium iodide. Attaching carboxylic acids yields a series of functionalize PEO with acetal units (2-5 mol%) in a backbone, which is not accessible via conventional copolymerization of epoxides. The optimized conditions minimizes the uncontrolled degradation or crosslinking from the highly reactive radical and oxocarbenium intermediate. The newly introduced acetal units bring degradability of PEO as well as delivery of carboxylic acid molecules. Hydrolysis studies with high molecular weight functionalization PEO (Mn = 13.0kgmol-1) confirm the steady release of fragmented PEO (Mn ∼ 2.0kgmol-1) and carboxylic acid over days and the process rate is not sensitive to pH variation between pH 5 and 9. The presented method offers a versatile and efficient way to modify PEO with potential energy and medical applications.

Catalytic Installation of Primary Amines Onto Polyolefins for Oligomer Valorization.

Polymerization of primary amine-containing monomers is challenging because the amine inhibits polymerization catalyst activity. An alternative approach to access primary amine functionalized polymers is postpolymerization modification. To this end, the hydroaminoalkylation of vinyl-terminated polyolefins with N-(trimethylsilyl)benzylamine is used to prepare primary amine-terminated polyolefins, with the free primary amine substituent being revealed upon hydrolytic work up. These materials are spectroscopically characterized, and an investigation of thermal properties by differential scanning calorimetry and thermogravimetric analysis is completed. These results show that the primary amine substituent increases the glass transition temperature and improves thermal stability. The reactive primary amine functionality is used in the photo-oxidative dimerization of polyolefins to demonstrate how this elusive functionality can be applied in oligomer valorization.

Undergraduate Laboratory Experiment Examining Free-Radical and Copper(0)-Mediated Polymerization and Postpolymerization Modification

Undergraduate Laboratory Experiment Examining Free-Radical and Copper(0)-Mediated Polymerization and Postpolymerization Modification

Catechol- and Phenolic Hydroxyl-Functionalized Partially Bio-Based (Co)poly(ether sulfone)s with Multifarious Applicability

A largely bio-based new bisphenol, namely, 4,4′-((3,4-dimethoxyphenyl)methylene)-bis(2-methoxyphenol) (DMBM) was synthesized by the reaction of veratraldehyde with guaiacol. DMBM and varying compositions of DMBM and bisphenol A were polycondensed with bis(4-fluorophenyl) sulfone to afford reasonably high molecular weight film-forming (co)poly(ether sulfone)s possessing built-in methoxyl groups. T10 and Tg values of (co)poly(ether sulfone)s were in the range 382–478 °C and 171–187 °C, respectively indicating their good thermal stability and the values decreased with increase in mol % incorporation of DMBM. The methoxyl groups present in (co)poly (ether sulfone)s were quantitatively de-blocked resulting in the formation of corresponding polymers possessing pendant catechol moieties and free phenolic hydroxyl groups. By virtue of the presence of these functional moieties, (co)poly(ether sulfone)s are amenable for post-polymerization modifications, and exhibited properties such as antimicrobial (23 mm against Staphylococcus aureus and 18 mm against Escherichia coli)), antioxidant (72 % scavenger of free radicals), adhesive (2.24 MPa lap shear strength) and usefulness as redox-active agent in zinc-ion batteries. These data underscore the promise of DMBM as a versatile monomer of wider utility for the synthesis of functional (co)poly(ether sulfone)s capable of expanding their applicability beyond the conventional ones.

Installing a Trigger to Upcycle High-Density Polyethylene.

Creating C═C bonds as "weak" sites in the stable C-C chains of polyethylene (PE) is an appealing strategy to promote sustainable development of the polyolefin industry. Compared to methods, such as dehydrogenation and postpolymerization modification, the copolymerization of ethylene (E) and butadiene (BD) should be a convenient and direct approach to introduce C═C bonds in PE, whereas it encounters problems in controlling the composition and regularity of the copolymer due to the mismatched activities and mechanisms between the two monomers. Herein, we report by employing the amidinate gadolinium complex, controllable E/BD copolymerization was achieved, where BD was incorporated in the uniformly discrete 1,4 mode. The obtained copolymer possesses the same physical, mechanical, processing, and antioxygen (aging at 100 °C for 28 days) properties as commercial high-density-PE, which, strikingly, were degraded by C═C bonds into α,ω-telechelic oligomers with narrow distribution. These degraded functional products were transferred to compatibilizers via atom-transfer radical polymerization or immortal ring-opening polymerization, achieving upcycling.

High-Shear Enhancement of Biginelli Reactions in Macromolecular Viscous Media.

Chemical reactions and transformations in non-traditional vessels have gained significant interest in recent years. Flow chemistry, with its advantages in mixing, mass transfer, scalability, and automation, is a driving force behind this paradigm shift. In particular, the Vortex Fluidic Device (VFD) has emerged as a versatile tool across various applications, from organic synthesis to materials science. In this study, the role of the VFD in performing the Biginelli reaction, a multicomponent reaction widely used in pharmaceutical and polymer science, for a post-polymerization modification is explored. By conducting the Biginelli reaction in the VFD, rapid product formation with low catalyst loading and without the need for high temperatures is achieved. However, the critical need to understand and know solution viscosity, especially within the context of modifying macromolecules is highlighted.

An Expedient Route to Bio-Based Polyacrylate Alternatives with Inherent Post-Chemical Modification and Degradation Capabilities by Organic Catalysis for Polymerization of Muconate Esters.

The quest for polymers that would be at the same time bio-based and degradable after usage, in addition to offering chemical post-modification options, remains a daunting challenge in contemporary polymer science. Despite advances in polymer chemistry, attempts at controlling the chain-growth polymerization of muconate esters remain unexplored. Here we show that dialkyl muconates can be rapidly polymerized by organocatalyzed group transfer polymerization (O-GTP). O-GTP is conducted to completion at room temperature in toluene within a few minutes, using 1-ethoxy-1-(trimethylsiloxy)-1,3-butadiene (ETSB) as initiator and 1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)-phosphoranylidenamino]-2 5,4 5 catenadi(phosphazene) (P4-t-Bu) as catalyst. Chain extension experiments and synthesis of all muconate-type block copolymers can also be achieved. Furthermore, polymuconates are amenable to facile post-polymerization modification reactions. This is showcased through the hydrolysis of the ester side chains leading to well-defined poly(muconic acid), and by epoxidation of the C=C double bonds of the main chain. Last but not least, these internal alkene groups can be selectively cleaved by ozonolysis, demonstrating the upcyclability of polymuconates under oxidative conditions. This work demonstrates that polymuconates constitute a unique platform of bio-based polymers, easily modifiable in addition to being chemically degradable under user friendly experimental conditions.

Zwitterionic Amino‐Acid‐Derived Polyacrylamides with a Betaine Twist – Synthesis and Characterization

AbstractAmino‐acid‐derived polyzwitterions and polybetaines (PBs) are two promising alternatives to non‐ionic polymers, for example, to increase tumor permeability. In this study, amino‐acid‐derived polyzwitterions are synthesized and a strategy to quarternize the amine in the side chain functional group is developed to combine the advantages of both types. The functional monomer is polymerized via reversible addition−fragmentation chain‐transfer polymerization for which a kinetic study is performed. Further, the impact of the permanent positive charge on amino‐acid‐derived polyzwitterions is studied based on two zwitterionic polymers obtained via post‐polymerization modification (PPM) of Poly(N‐acryloxysuccinimide) to allow good comparison between methylated and non‐methylated polymers. Circular dichroism shows that the stereocenter remains intact during PPM. pH titration and ζ‐potential measurements show that the methylated polymer has a negative ζ‐potential over the measured pH range and, therefore, the polymer remains zwitterionic over a broader pH range than its non‐methylated equivalent. Both polymers are well tolerated by mammalian cells up to concentrations of 1 mg mL−1. The study introduces a path to a new polymer class that combines the advantages of both PBs and amino‐acid‐derived polyzwitterions and highlights the impact a permanent charge has on the physiochemical properties.

Post-Polymerization Modification of Polystyrene through Mn-Catalyzed Phosphorylation of Aromatic C(sp2)–H Bonds

Post-Polymerization Modification of Polystyrene through Mn-Catalyzed Phosphorylation of Aromatic C(sp²)–H Bonds

Efficient and facile dual post-polymerization modification using acetoacetate-acrylate Michael addition

Post-polymerization modification (PPM) is a valuable strategy for achieving diversified functional polymers; nonetheless, the pursuit of achieving mild and efficient dual modification along the polymeric backbone remains as a challenge. In this work, the Michael addition reaction of acetoacetates and acrylates have been demonstrated as a robust PPM technique. The reversible addition-fragmentation chain transfer polymerization of commercially available 2-(acetoacetoxy)ethyl methacrylate provides a polymer scaffold with controlled molecular weight and acetoacetate groups. These pendant groups are capable of undergoing efficient double addition reactions with acrylates, leading to an increased density of functional moieties within the polymeric backbone. This PPM reaction exhibits unique advantages such as mild reaction conditions (at 40 °C), rapid kinetics (completion within 1 h), and high atom economy. Consequently, a series of polymers with tunable thermal stability, glass transition temperature, and hydrophilicity have been successfully synthesized. Applications have been demonstrated for both the synthesis of polymers exhibiting aggregation-induced luminescence and the preparation of luminescent materials with adjustable mechanical properties. This pioneering work unveils a robust post-polymerization modification technique, significantly advancing the synthesis of innovative functional polymers.

Aromatic (Co)polycarbonates bearing pendant norbornenyl groups: Synthesis, characterization and post-polymerization modification

A homo- and three co-polycarbonates (PC-NBs) bearing pendant norbornenyl groups were synthesized via solution polycondensation of triphosgene with 4, 4'-(bicyclo (2.2.1) hept-5-en-2 yl methylene) bis (2-methoxyphenol) (BPA-NB) or various mol % compositions of BPA-NB and bisphenol-A, respectively. 1H-NMR spectroscopy confirmed the chemical structure and composition of PC-NBs. Inherent viscosity and number-average molecular weight (Mn) values of PC-NBs were in the range 0.44 – 0.64 dL g−1 and 21,800 – 34,100 g mol−1, respectively, indicating the formation of polymers of medium to reasonably high molecular weights. Tough, transparent, and flexible films of PC-NBs could be cast from chloroform solution. X-Ray diffraction studies indicated the amorphous nature of PC-NBs. Glass transition temperature (Tg) values, determined by DSC analysis, of PC-NBs were in the range 154 – 175°C and Tg values increased with the increase in mol % of BPA-NB. The post-polymerization modification of a representative PC-NB was demonstrated using 3,6-diphenyl-1,2,4,5-tetrazine via tetrazine-ene reaction.

Alternating Graft Copolymer Carrying PLA Graft Chains at Every Other Unit: Sequence Impacts on Crystallization Behaviors.

Alternating graft copolymers were precisely synthesized via selective cyclopolymerization of pendant-transformable divinyl monomer (1), post-polymerization modification via aminolysis with alkylamine, and ring-opening polymerization of l-lactide (LLA) from the hydroxy pendant group in alternating sequence. The poly(LLA) (PLLA) graft chain on the alternating copolymer gave a higher crystallization degree on the isothermal treatment than that on the random counterpart likely because of the periodic sequence. The comonomer pendant group from alkylamine in the aminolysis reaction in the alternating sequence affected the crystallization behaviors, and the oligoethylene glycol (OEG) group promoted the crystallization thanks to the larger free volume effect. As for the stereocomplex formation of the racemic mixture of enantiomeric PLLA and poly(d-lactide) (PDLA) chains, the alternating graft copolymer gave a higher degree of stereocomplex crystallization in the mixture with the enantiomer homopolymer than the random analogue.

Rapid synthesis and post-polymerization modification of poly(vinylene sulfide) via sequential nucleophilic thiol-yne/ene click reactions

Click chemistry has emerged as a versatile and robust polymerization technique for the construction of functional polymers. In this work, organocatalyst-mediated consecutive thiol-yne and thiol-ene click reactions were performed for the synthesis and modification of the electron-deficient poly(vinylene sulfide) (PVS) structure. PVS was prepared within an hour in the presence of 1,4-diazabicyclo[2.2.2] octane (DABCO) and in an anti-Markovnikov fashion, with a high molecular weight (M n = 12.9 kDa) and high stereoregularity (88% E-isomer). Following various optimization studies using 1-propanethiol as the model thiol, the obtained PVS was modified with various thiols in chloroform for 10 min using 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as the catalyst, resulting in thioacetal main chain polymers. The scope of thiols used in the modification studies spans from alkyl and cycloalkyl to aromatic and allylic, and the polymers were obtained with varying efficiencies. Primary alkyl and aromatic thiols exhibited high efficiencies ranging from 87% to 100%. Similar high efficiencies were found for secondary mercaptans (70% and 92%); however, a very low efficiency (5%) was found for a tertiary mercaptan due to steric hindrance. It is believed the proposed indirect polythioacetal synthesis method holds the potential to be utilized in bio-related applications and material science.