Chemical Engineering Seminar Series : Prof. Nirmalya Bachhar

Effect of Alkylation on Small Molecule Aggregation and its Transport.

The contemporary drug design process is characterized by high costs and lengthy timelines, commencing with the identification of biological targets followed by an extensive search for suitable ligands. Traditional hit-and-trial methodologies often dominate this phase, which can be less efficient. In an effort to streamline drug discovery, a more targeted strategy focusing on interfacial interactions—specifically through methylation and alkylation of drug candidates—has emerged as a promising avenue. This study aims to exploit these modifications to enhance the potency of orphan drugs and other low-efficacy molecules. Our research aims to clarify the effects of alkylation on the aggregation and transport dynamics of methylated rhodamine dyes in aqueous environments, supported by analyses of hydrogen bonding interactions. Our findings indicate that increased hydrophobicity resulting from alkylation promotes greater self-aggregation while also enhancing transport characteristics in semi-dilute polymer solutions. We demonstrate that position-specific alkylation improves the diffusive transport of these molecules in semi-dilute polymer solutions by increasing their hydrophobicity. This enhancement may have applications in drug delivery for respiratory and gastrointestinal tract therapies. This investigation incorporates a variety of theoretical and experimental methodologies, including molecular dynamics simulations using GROMACS and diffusion studies performed through Fluorescence Correlation Spectroscopy (FCS).