Oxalamide-Bridged Ferrocenes: Conformational and Gelation Properties and In Vitro Antitumor Activity

Abstract

The N-termini of the constitutional isomeric ferrocene peptides Boc–NH–Fn–CO–Ala–OMe (1) and Boc–Ala–NH–Fn–COOMe (2) were deprotected in the acidic milieu and subjected to oxalyl chloride-mediated dimerization to afford the oxalamides −(CO–NH–Fn–CO–Ala–OMe)2 (3) and −(CO–Ala–NH–Fn–COOMe)2 (4), respectively. The goal compounds were evaluated for their conformational properties, toluene gelation ability, and effect on cell viability of tumor (HeLa, MCF7, HepG2) and normal (HEK293T) cell lines. Detailed spectroscopic analysis in solution revealed the different conformational behavior of constitutional isomers 3 and 4, and oxalamide 3 was found to have a higher degree of chiral organization due to its involvement in stronger intramolecular hydrogen bonds. Crystallographic analysis showed the presence of two symmetry-independent conformers of compound 3 stabilized by stronger intramolecular hydrogen bonds. The tested compounds self-assemble in toluene to provide supramolecular nanostructures but were unable to form a stable gel. Interestingly, the formation of a stable gel was observed when the toluene solution of 4 was sonicated. Cytotoxic evaluation of 3 and 4 revealed a weaker growth-inhibitory effect on tumor cell lines compared to cisplatin. Oxalamide 3 appeared to be more cytotoxic to HeLa and MCF7 cancer cell lines than to normal HEK293T cells, indicating its potential for drug development as an anticancer agent.