title: Density functional theory characterization and descriptive analysis of cisplatin and related compounds.
abstract: 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.
authors.affiliation: Laboratorio de Química Teórica y Computacional (LQTC), Instituto de Química Biológica, Facultad de Ciencias, Universidad de la Republica (UdelaR), 11400 Montevideo, Uruguay.
authors.forename: Pablo D
authors.initials: PD
authors.lastname: Dans
authors.forename: E Laura
authors.initials: EL
authors.lastname: Coitiño
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002945:Cisplatin / Q000737:chemistry*; D016000:Cluster Analysis; D055808:Drug Discovery; D008958:Models, Molecular; D008968:Molecular Conformation; D025341:Principal Component Analysis; D011789:Quantum Theory
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin