Novel platinum-based anti­cancer drug: a complete vibrational study

The introduction of cisplatin to oncology, in the 1970s, marked the onset of the search for novel and improved metal-based anti­cancer drugs. Polynuclear Pt^II and Pd^II complexes with linear alkyl­amines as bridging ligands are a class of potential anti­neoplastic agents that have shown promising cytotoxicity against low-prognosis human cancers, such as metastatic breast adenocarcinoma and osteosarcoma. The present study reports an analysis of [μ-N,N′-bis­(3-amino­prop­yl)butane-1,4-di­amine-κ⁴N,N′:N′′,N′′′]bis­[di­chlorido­platinum(II)], [Pt₂Cl₄(C₁₀H₂₆N₄)], denoted Pt₂Spm (Spm is spermine), by vibrational spectroscopy coupled to theoretical calculations. Within the latter, the Density Functional Theory (DFT – mPW1PW/6-31G*) and Effective Core Potential (ECP – LANL2DZ) approaches were used, in order to ensure the most accurate representation of the mol­ecule and achieve a maximum agreement with the experimental data. The solid-state geometry of Pt₂Spm corresponds to C_i symmetry, displaying 132 vibrational modes. A complete assignment of the experimental vibrational profile of the system was attained through the com­bined application of complementary Raman, FT–IR and Inelastic Neutron Scattering (INS) techniques. INS allowed an unequivocal identification of the CH₂ and NH₂ rocking modes, not clearly detected by the optical techniques, while Raman measurements led to a clear discrimination of the Pt—N stretching frequencies from the two distinct Pt—N moieties within the chelate. The metal-to-metal distances calculated for the mol­ecule under study were found to allow the establishment of effective inter- and intra­strand crosslinks with DNA. These results will hopefully help to clarify the mode of action of the compound, at the mol­ecular level, contributing to the development of improved cisplatin-like chemotherapeutic drugs having a higher efficacy and specificity coupled to lower acquired resistance and deleterious side effects.