Density functional theory characterization and descriptive analysis of cisplatin and related compounds.

Quantum and nonquantum descriptors clearly related to physicochemical features and predictors of the trends to evolve along different stages of a known mechanism of action were determined for a set of square-planar compounds of general formula [M(II)A(1)A(2)L(1)L(2)] (M(II) = Pt(II)/Pd(II); A(i)/L(i) = carrier/labile ligands), structurally related to the anticancer agent Cisplatin. Selected compounds have been sorted and classified by Ward's Cluster Analysis and Principal Components Analysis data-mining techniques using seventeen 1D and two 3D of such theoretical descriptors calculated at the DFT level (PCM-B3LYP/LANL2DZ/6-31G*). A rationale emerging from the study is that whereas most significant differences come from substitution of Cisplatin ligands, cis/trans isomerism, and exchange of M(II) introduce minor alterations in the electronic/geometrical structure. This provides theoretical support to the assay of transplatinum compounds as potential anticancer drugs, a fact already pointed out by empirical evidence. Similarly, the little geometrical/electronic differences triggered by switching M(II) from Pt to Pd enable us to devise a rational path to propose new compounds with expected good anticancer profiles, tuning alterations introduced by simultaneously changing both metal and ligands. Current results serve thus to enlarge the Cleare-Hoeschele guides for Pt(II) square-planar anticancer potential drugs to Pd(II) compounds, both using cis/trans scaffolds.