title: Guanine nucleobase adducts formed by [Pt(di-(2-picolyl)amine)Cl]Cl: evidence that a tridentate ligand with only in-plane bulk can slow guanine base rotation.
abstract: Pt(II) complexes bind preferentially at N7 of G residues of DNA, causing DNA structural distortions associated with anticancer activity. Some distortions induced by difunctional cisplatin are also found for monofunctional Pt(II) complexes with carrier ligands having bulk projecting toward the guanine base. This ligand bulk can be correlated with impeded rotation about the Pt-N7(guanine) bond. Pt(N(H)dpa)(G) adducts (N(H)dpa = di-(2-picolyl)amine, G = 5'-GMP, 5'-GDP, 5'-GTP, guanosine, 9-EtG, and 5'-IMP) were used to assess whether a tridentate carrier ligand having bulk concentrated in the coordination plane can impede guanine nucleobase rotation. Because the Pt(N(H)dpa) moiety contains a mirror plane but is unsymmetrical with respect to the coordination plane, Pt(N(H)dpa)(G) adducts can form anti or syn rotamers with the guanine O6 and the central N-H of N(H)dpa on the opposite or the same side of the coordination plane, respectively. The observation of two sharp, comparably intense guanine H8 NMR signals provided evidence that these Pt(N(H)dpa)(G) adducts exist as mixtures of syn and anti rotamers, that rotational interchange is impeded by N(H)dpa, and that the key interactions involves steric repulsions between the pyridyl and guanine rings. The relative proximity of the guanine H8 to the anisotropic pyridyl rings allowed us to conclude that the syn rotamer was usually more abundant. However, the anti rotamer was more abundant for the Pt(N(H)dpa)(5'-GTP) adduct, in which a hydrogen bond between the 5'-GTP γ-phosphate group and the N(H)dpa central N-H is geometrically possible. In all previous examples of the influence of hydrogen bond formation on rotamer abundance in Pt(II) guanine adducts, these hydrogen bonding interactions occurred between ligand groups in cis positions. Thus, the role of a trans ligand group in influencing rotamer abundance, as found here, is unusual.
authors.affiliation: Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
authors.forename: Chase
authors.initials: C
authors.lastname: Andrepont
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Marzilli
authors.forename: Luigi G
authors.initials: LG
authors.lastname: Marzilli
mesh_terms: D000588:Amines / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D018736:DNA Adducts / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry*; D006157:Guanosine Monophosphate / Q000737:chemistry; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000494:pharmacology; D010848:Picolinic Acids / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C501847:2,2'-dipicolylamine; D000588:Amines; D000970:Antineoplastic Agents; D018736:DNA Adducts; D008024:Ligands; D009944:Organoplatinum Compounds; D010848:Picolinic Acids; D006147:Guanine; D006157:Guanosine Monophosphate