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© 2015 American Chemical Society. Anticancer-active monofunctional Pt(II) complexes have bulky carrier ligands and bind to G residues in DNA, causing structural distortions. To gain fundamental chemical information on such monofunctional adducts, we assessed the 9-ethylguanine (9-EtG) adducts formed by [Pt(N(H)6,6′-Me2dpa)Cl]Cl (N(H)6,6′-Me2dpa = di-(6-methyl-2-picolyl)amine). 9-EtG added to [Pt(N(H)6,6′-Me2dpa)Cl]Cl to form not only the expected [Pt(N(H)6,6′-Me2dpa)(9-EtG)]2+ monoadduct having syn and anti conformers but also a [Pt(N(H)6,6′-Me2dpa)(9-EtG)2]2+ bisadduct consisting of ΛHT and ΔHT conformers (HT = head-to-tail). For both adducts, the two conformers exist as a dynamic equilibrium mixture. Concomitant with formation of the bisadduct, the binding mode of the N(H)6,6′-Me2dpa ligand converts from tridentate to bidentate. A Pt(II)-bound 6-methyl-2-picolyl chain and the secondary amine constitute the bidentate chelate ring. The other 6-methyl-2-picolyl chain is dangling. The secondary nitrogen is an asymmetric center, and each conformer exists as a racemic mixture of two enantiomers. For a given configuration at the secondary amine of the [Pt(N(H)6,6′-Me2dpa)(9-EtG)2]2+ adduct, the more abundant HT conformer can form a hydrogen bond between the NH of the bidentate ligand and the cis 9-EtG O6. [Pt(N(H)6,6′-Me2dpa)Cl]Cl forms the monoadduct in ∼1/20 the time for its parent, [Pt(N(H)dpa)Cl]Cl (N(H)dpa = di(2-picolyl)amine), which exhibited typical behavior in forming only a monoadduct. We attribute the unusual new findings for [Pt(N(H)6,6′-Me2dpa)Cl]Cl to Pt-N bond weakening induced by the steric bulk of 6/6′-Me groups. We hypothesize that undetectable intermediates with a dangling 6-methyl-2-picolyl chain facilitate both rapid monoadduct formation and also bisadduct formation. Consistent with the intermediacy of such species with a dangling chain, addition of HCl to a [Pt(N(H)6,6′-Me2dpa)Cl]Cl solution readily produced a dichloro complex with the N(H)6,6′-Me2dpa chelate ligand in the bidentate mode, whereas HCl addition had no effect on [Pt(N(H)dpa)Cl]Cl. (Chemical Equation Presented).

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Inorganic Chemistry

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