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Sulfonamide-based sequence-defined polymer with modular architecture and post-synthetic modification: Design, synthesis and its biological and material applications via experimental and in-silico approaches

Implementing Organization

Principal Investigator
Dr. Mintu Porel
Indian Institute Of Technology Palakkad  
mintu@iitpkd.ac.in
CO-Principal Investigator
Dr. Prasun Kumar
Indian Institute Of Technology Palakkad  , Po, Kanjikode-Malampuzha Road, West Kanjikode, Pudusserry West, Kanjikode,Kerala,Palakkad-678623

Project Overview

A recent trend in polymer chemistry is to manipulate material’s property to lead its on-demand structure and function. Primary structure of a polymer is generated from the precise arrangement of its monomer sequence. While natural biopolymers (proteins, nucleic acids) exhibit precise monomer sequences, it is still challenging in synthetic polymers. Compared to biopolymers, synthetic sequence-defined polymer (SDP) has an even wider scope of unlimited side chains and backbone diversity. Motivated by this, we propose a novel class of synthetic SDPs featuring sulfonamide backbone, an organo-sulfur group reported in many therapeutic and functional materials. To overcome the limitation of two conventional methods (supported and one-pot synthesis), we introduce a novel support-free iterative strategy for sulfonamide-SDP (SN-SDP) that allows precise control over not only sequence but also architecture (linear vs. hyperbranched). SN-SDPs will be employed for antibacterial agents and tunable hydrogels, broadening their use in biomedical and material sciences. Firstly, a support-free, iterative strategy will be established for synthesis of SN-SDPs. Individual scheme has been proposed for two architectures: (i)Linear SN-SDP (SN-SDP-L) and (ii)Hyperbranched SN-SDP (SN-SDP-HB) with tunable side-chain in both cases. Next, synthetic platform will be advanced for strategic post-synthetic modification of SN-SDP to meet the requirement for multiple applications. To facilitate the reaction of post-synthetic modification, we strategically designed the synthesis of SN-SDP such a way that it will end with either terminal hydroxy (nucleophile) or chloro (leaving group). This proposal is focused on post-synthetically modifying SN-SDP-L/SN-SDP-HB with three different systems: (i) dye, (ii) peptide, (iii) surface. Thereafter, SN-SDP with tunable side-chain, architecture and post-synthetic modification will be equipped with wide-range of biological and material applications. This proposal will focus on two applications which are briefly explained here. (i) Developing antibacterial drugs to combat antibacterial resistance: inspired by the presence of sulfonamide group in several FDA approved drugs (Sulfamethazine, Sulfadiazine), we strongly believe SN-SDP to be potential antibacterial platform. By incorporating cationic and hydrophobic side-chains, SN-SDPs can target bacterial membranes via electrostatic (cationic monomer and anionic phosphate of membrane) and hydrophobic (hydrophobic monomer and hydrophobic lipid) interactions. A library of SN-SDP-Ls/SN-SDP-HBs will be synthesized by changing sequence and number of cationic/hydrophobic monomers to enhance antibacterial efficacy and reduce cytotoxicity. (ii) Developing hydrogel with tunable properties: Hydrogels are highly valued for their water content, porosity, and soft texture. This project aims to tune hydrogel properties by modifying functional groups within SN-SDP-L/SN-SDP-HB. Mechanical properties will be studied by varying either polymer architecture or functional groups (hydrogen bonding, π–π interactions, disulfide bonding) independently. Functional groups will be strategically selected to adjust pH (acidic: carboxyl, phenol; basic: aliphatic and aromatic amine, hydroxy) and temperature (hydrophobic and hydrophilic) responsiveness. Fluorophore attached SN-SDP will be employed to make fluorescent hydrogel. A diverse library of SN-SDPs will be synthesized and characterized, enabling the design of hydrogels with tailored, application-specific properties using a single SN-SDP platform. Computational modeling will complement experiments to predict SN-SDPs behavior and accelerate the discovery of optimal sequences. Taken together, this proposal lays the foundation for novel sulfonamide-based SDPs with extensive molecular diversity, enabling the emergence of distinctive properties. These advanced materials hold strong potential for a wide range of applications in material and biomedical sciences.
Funding Organization
Quick Information
Area of Research
Chemical Sciences
Focus Area
Organic Chemistry
Start Date
16 Mar 2026
End Date
15 Mar 2029
Status
ongoing
Output
No. of Research Paper
00
Technologies (If Any)
00
No. of PhD Produced
00
Publications
00
No. of Patents
Filed : 00
Grant : 00
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