Broad-spectrum anticancer properties, DFT calculations and macromolecular binding potential of a novel thiolato-bridged fac-Mn(CO)3-core-based CO-releasing molecule.

The present study investigates the anticancer potential, density functional theory (DFT) calculations and biological target interactions of a novel, hetero-ligated horse-stirrup-shaped thiolato-bridged fac-Mn(CO)3-core-based CO-releasing compound (S-MnC). The S-MnC exhibited selective, broad-spectrum cytotoxicity against ovarian (SKOV-3), breast (MDA-MB-231), pancreatic (PANC-1), and prostate (PC-3) cancer cells. The macromolecular binding potential of S-MnC with DNA and human serum albumin (HSA) was elucidated using spectroscopic and molecular docking studies. The S-MnC interacts with ctDNA through a combination of partial intercalation and groove binding, causing structural changes and exhibiting hydrolytic DNA cleavage, suggesting its potential to induce oxidative DNA damage. Furthermore, DFT calculation confirmed a redox-active MnS core and ligand centred LUMO, supporting the oxidative DNA cleavage and cytotoxic potential of S-MnC. The structural framework of S-MnC contains an ester-functionalized ligand that exhibits a strong binding potential towards human serum albumin (HSA). The flexibility of the ether and ester groups permits the coordinating ligand to embrace different conformations and provides the stability to ligand complexes. The binding process was spontaneous, entropy-driven interactions, indicated by positive ∆H° and ∆S° values and negative ∆G° values. These dynamic binding interactions induced conformational changes in the secondary structure of HSA. Reported results established the structure-activity relationships and biological insights of S-MnC as a potent, selective, Mn-based therapeutic scaffold.