title: Unusual Example of Chelate Ring Opening upon Coordination of the 9-Ethylguanine Nucleobase to [Pt(di-(6-methyl-2-picolyl)amine)Cl]Cl.
abstract: 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.
authors.affiliation: Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
authors.forename: Chase
authors.initials: C
authors.lastname: Andrepont
authors.affiliation: Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Pakhomova
authors.affiliation: Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Marzilli
authors.affiliation: Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, United States.
authors.forename: Luigi G
authors.initials: LG
authors.lastname: Marzilli
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D001665:Binding Sites; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D010847:Picolines / Q000737:chemistry*; D012996:Solutions; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009944:Organoplatinum Compounds; D010847:Picolines; D012996:Solutions; D006147:Guanine; C014542:9-ethylguanine; D004247:DNA