Atropisomers are stereoisomers that principally arise due to the constrained rotation of single bonds flanked by a pair of hindered planar groups; the stereogenicity of these molecules originates from the concept of axial chirality. These optically active molecules allow the stable and specific presentation of functional groups in space and are widely employed in applications such as medicinal chemistry, molecular devices, electrochemical polymerization, spectrochemical and photophysical investigations, asymmetric catalysis, and organic dyes. The biological activities, toxicities and pharmacokinetics of an individual atropisomer may fluctuate in biological environment due to significant diastereomeric interactions. However, major problems associated with their practical applications is their chiral instability over long periods of time because of insufficient activation barrier to racemization. Previous studies suggest that an axially chiral molecule can retain optical purity over time only if they possess about >24kcal/mol activation barrier to rotation along their chiral axes.
Considering medicinal chemistry applications, I am working on developing stable atropisomer. In support with density functional theory (DFT) calculations, I am designing synthetic strategies to induce axial chirality in heterobiaryl molecular system. Using different analytical techniques and thermodynamic calculations, the axial chiral bond rotation dynamics of these molecules will also be investigated to determine their significantly higher activation barrier to racemization.