Synthesis and characterization of thiophene based C-S coupled aldehydes and comparison of anti-microbial activity of aliphatic and aromatic derivatives

Abstract

The synthesis and characterisation of novel thiophene-based C-S coupled aldehydes derived from both aromatic thiols and aliphatic thiols has been carried out, along with a comparative analysis of anti-microbial activity of aromatic and aliphatic derivatives. The carbon-sulphur (C-S) bond was constructed using transition metal-catalysed cross-coupling reaction, specifically copper-catalysed reaction. The authenticity of synthesized compounds was established using ¹H NMR, ¹³C NMR and HRMS. Their antimicrobial activities were tested against E. coli, P. aeruginosa as well as S. aureus. Density functional theory (DFT) studies were conducted to explore the quantum chemical data, which was further utilized to analyse activity trend and their correlation with experimental results. The findings revealed that aromatic thiols exhibit significant antimicrobial activity, whereas aliphatic thiols lack such activity due to the presence of an alkyl group in the aldehyde unit. Calculations of chemical potential, chemical hardness, and electrophilicity suggested that aromatic thiols are stable, while aliphatic thiols are rigid and less stable. Hence, this study contributes to the growing field of organo-sulphur chemistry and provides insights into the development of novel synthetic pathways for potential drug candidates.