Platinum (II) Compounds With Antitumor Activity Studied by Molecular Mechanics

Abstract

A series of Pt(ll) complexes with antitumor properties: [1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]PtL₂ (meso-1-PtL₂) and [erythro-1-(2,6-dichloro-4-hydroxyphenyl)-2-(2-halo-4-hydroxyphenyl)ethylenediamine]PtL₂, [2L=2Cl−,2I−,SO₄²−; halo = F (erythro-8-PtL₂),halo = Cl (erythro-9-PtL₂)] has been modelled by molecular mechanics (MM). The MM calculations were carried out for different isomers and ligand conformations meso-δ, meso-λ, d,l-δ, d,I-λ. The compounds with the lowest MM energies have the same geometries as those obtained by X-ray analysis. The calculated MMX energy orders: meso-1-PtL₂ < erythro-9-PtL₂ < erythro-8-PtL₂ for L=I−, Cl− and SO₄²⁻ are reverse to the known antitumor activity order - the lowest energy complex (the most stable one)is the one with the highest estrogen activity (meso-1-PtL₂). The type of the leaving group (L) does not alter the energy order, which is in agreement with the biological experiments that show a slight dependence of the estrogen properties on the leaving group type.

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