Title

Guanine nucleobase adducts formed by a monofunctional complex: [Pt(N-(6-methyl-2-picolyl)-N-(2-picolyl)amine)Cl]Cl

Document Type

Article

Publication Date

12-1-2015

Abstract

© 2015 Elsevier Inc. Monofunctional Pt(II) complexes bind to G residues in DNA and, if the carrier ligands are bulky, cause DNA structural distortions that lead to anticancer activity. We assessed the steric effects of the tridentate carrier ligand, N(H)6-Medpa (N-(6-methyl-2-picolyl)-N-(2-picolyl)amine), bearing a 6-methyl group and a 6′-proton projecting toward the nucleobase in Pt(N(H)6-Medpa)G adducts (G = 9-ethylguanine, 3′-GMP, 5′-GMP, 5′-GTP). Pt(N(H)6-Medpa)G adducts form syn and anti rotamers with the guanine O6 and the central N-H of N(H)6-Medpa on the same or opposite side of the coordination plane, respectively. Pt(N(H)6-Medpa)G adducts have some properties (ease of rotamer interchange and extent of conversion to bis adducts, Pt(N(H)6-Medpa)G2) intermediate to properties reported for analogs having a tridentate ligand with zero or two methyl groups. However, in comparison, the syn rotamer of Pt(N(H)6-Medpa)G adducts has an unexpectedly high abundance. This result is attributable to guanine base canting, such that the 6-membered guanine ring is positioned away from the bulky 6-Me group. This canting both relieves electrostatic repulsion between the partially positive H6′ and the guanine H8 protons and creates a favorable electrostatic attraction between the H6′ proton and the partially negative guanine O6. This combined information provides insight useful for designing monofunctional anticancer agents.

Publication Source (Journal or Book title)

Journal of Inorganic Biochemistry

First Page

219

Last Page

230

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