Rational design of cisplatin and carboplatin complexes for enhanced anticancer efficacy based on DFT QTAIM and docking analyses

Abstract

Abstract Cisplatin (CP) and carboplatin (CBP), two key platinum‑based anticancer drugs, face clinical limitations that prompt the search for new strategies to enhance efficacy and reduce toxicity. This study applies density functional theory (DFT), quantum theory of atoms in molecules (QTAIM), molecular docking, and spectroscopic analyses to explore possible synergistic effects of cisplatin–carboplatin [CP–CBP] complexes in breast and cervical cancers. Structural optimizations show small bond‑length adjustments in the [CP–CBP] complexes, which strengthen intermolecular interactions and overall stability. Thermodynamic analyses confirm their exothermic nature (ΔH < 0), indicating thermodynamic stability, while adsorption energies (Ead = − 14.69, − 12.47, − 14.27 kcal/mol for States I, II, III) suggest enhanced bioavailability and controlled release in aqueous environments, though higher gas-phase energies indicate stronger interactions. Quantum descriptors, including electrophilicity index (ω) and chemical potential (μ), reveal increased reactivity and improved drug-target interactions, supporting enhanced anticancer potential. Spectroscopic analyses (UV–Vis, IR) confirm altered electronic transitions, reinforcing stability and reactivity changes. Molecular docking indicates that [CP–CBP] complexes outperform individual CP and CBP, with State III achieving − 3.75 kcal/mol (Ki = 1.78 μM) for aromatase and State II − 5.48 kcal/mol (Ki = 96.86 μM) for HER2. CBP stabilizes CP, preventing degradation, enhancing solubility, and enabling controlled release, reducing toxicity. These findings highlight [CP–CBP] complexes as a promising platinum‑based chemotherapeutic strategy with potentially improved pharmacokinetics, warranting further in vitro and in vivo validation for targeted cancer therapy.