Importance of Metal–Ligand Bond Stretching Frequency in Cancer Drug Activity of Ru and Os Metal Clusters

Tri-ruthenium (0) carbonyl cluster derivatives have demonstrated significant anticancer and anti-angiogenic activities, making them promising candidates for novel chemotherapy agents. These clusters exhibit moderate water solubility and stability in aqueous environments, preventing hydrolysis and decomposition within biologically relevant timeframes. This stability sets them apart from conventional ruthenium (II) and ruthenium (III) complexes, indicating their potential for enhanced therapeutic efficacy. In this study, we investigate the molecular-level interactions of tri-ruthenium carbonyl clusters functionalized with glucose-modified bicyclophosphite ligands to elucidate key factors contributing to their anticancer properties.Our findings reveal that metal-ligand bond stretching frequency, particularly CO bond vibrational characteristics, plays a crucial role in modulating the drug-like properties of these complexes. Through computational and in-silico analyses, we evaluate the corresponding osmium analogs to determine their comparative efficacy. The results highlight that osmium-based derivatives exhibit significantly higher anticancer potency, attributed to differences in metal-ligand electronic interactions. This study employs a property-based drug design (PBDD) framework, utilizing quantum mechanical approaches to predict IC50 values, LogP, and other key pharmacological parameters. By leveraging theoretical modeling and computational chemistry techniques, we provide insights into how molecular properties influence drug efficacy. Our results suggest that a systematic approach to designing transition metal-based drugs, particularly through rational ligand modifications, can enhance anticancer activity. This research opens avenues for the development of next-generation metal cluster-based chemotherapeutics with improved stability, specificity, and therapeutic performance.