Metal-Based Anticancer Drugs: Integrating Pharmaceutical Perspectives with DFT-Based Quantum Chemical Topology (QTAIM and ELF)

Anticancer metal drugs are presented with mechanistically different opportunities in therapeutic use that are not limited by conventional organic chemotherapeutics. Molecular structure not only regulates their clinical behaviour but also their electronic structure, coordination dynamics and metal speciation in complex biological conditions. Rational design of such agents is, nevertheless, a challenging task, even with the long-term interest given, because standard structure–activity relationships are not that effective at revealing such attributes. This review critically studies metal-based anticancer therapeutics in an integrated framework, with a combination of pharmaceutical sciences, density functional theory (DFT), and quantum chemical topology. Following the analysis of significant classes of platinum and non-platinum metal complexes in a structure–reactivity–limitation perspective, the main aspects of pharmacology, such as pharmacokinetics, cellular absorption, resistance, and toxicity, are discussed. The importance of DFT in the explanation of electronic structure is evaluated in addition to the conceptualisations and uses of the Quantum Theory of Atoms in Molecules and the Electron Localisation Function. The focus is on topology-supported relationships between structures and activities that can be integrated into pharmacological results according to electronic and topological measures. Through applications of computational and pharmaceutical knowledge, this review suggests a mechanistically based, multidisciplinary approach to the rational design of next-generation metal-based anticancer drugs.