Functionalization of Ferrocenyl Molecules for Bridged Architectures: Synthesis, Structure, Sensing and Amyloid Inhibition

Abstract

Ferrocene-based organometallic derivatives stand out as exceptionally versatile molecular entities in the field of organometallic chemistry owing to its unique structural architecture properties, redox behavior and diversity in functionalization. In the last two-three decades, ferrocenyl chemistry has undergone remarkable advancement, positioning itself as a highly versatile building block with applications spanning medicinal chemistry, material science, catalysis, sensing and electronic communication. Recent studies indicate that the meticulous design and functionalization of ferrocenyl analogues across various structural levels can significantly tune their electronic, structural and biological properties. Among the widely known ferrocenyl derivatives, mono-functionalized ferrocenyl derivatives are extensively investigated, whereas research on bi-functionalized ferrocenyl frameworks remains limited. Moreover, the synthesis of symmetrical and unsymmetrical 1, 1’-bifunctionalized bridged ferrocenyl architectures with rotational flexibility led to molecular systems endowed with exceptional biological, sensor-based and catalytic properties, with a range of different conformational orientations. The immense potentials of functionalized bridged ferrocene-based organometallic derivatives and the scarcity of suitable reaction conditions prompted us to adopt a solid-supported reaction methodology to synthesize a diverse range of flexible and rigid heterocycle and carbocycle linked bridged ferrocenyl derivatives, along with di and tri ferrocenyl molecular architectures. The thesis, with six chapters, bridges these gaps by pioneering a solid-supported reaction methodology to synthesize a diverse array of multifunctional ferrocene-based organometallic systems encompassing, heterocycle and carbocycle tethered ferrocenyl molecules, heterocycle functionalized diastereomeric carba[3]ferrocenophanes, azine bridged di- and tri ferrocenyl molecular frameworks and enone bridged tri ferrocenyl system along with their characterization and structural evaluation. The synthesized heterocycle tethered ferrocenyl conjugates demonstrate significant advancements in amyloid inhibition study, effectively inhibiting bovine serum albumin (BSA) and hen egg white lysozyme (HEWL) amyloid fibrillation, along with the disaggregation of matured fibrils. Furthermore, the bridged di and tri ferrocenyl architectures exhibit high selectivity in sensing chemical warfare agents (CWAs) like picric acid (PA) and phosgene gas. In addition, an Arduino-based electrochemical device has also been fabricated with the azine bridged diferrocenyl receptor for detecting toxic phosgene gas.