Platinum complexes with NH groups on the carrier ligand and with only one guanine or hypoxanthine derivative. Informative models for assessing relative nucleobase and nucleotide hydrogen-bond interactions with amine ligands in solution.
Complexes of the type syn-(R,S)-Me(3)dienPtL (Me(3)dien = N,N',N' '-trimethyldiethylenetriamine; L = guanine or hypoxanthine derivative) have two rotamers, a feature useful for assessing hydrogen-bond interactions between a Me(3)dien NH group and either the O6 or the phosphate group of the coordinated L. The two rotamers are defined as endo and exo for the rotamer with the six-membered ring of the purine on the same side and on the opposite side, respectively, of the coordination plane as the N-Me's. For L = 5'-GMP and 5'-IMP the endo rotamer is the exclusive form (at neutral and basic pH) or is present at 90% and more (low pH where 5'-phosphate group is protonated). A 5'-phosphate group can be positioned to form a direct H-bond with a Me(3)dien NH group only in the endo form; such an H-bond explains this high endo preference. Such a direct phosphate-NH H-bond is not possible for other complexes used in this study because either L has no phosphate group (9-EtG, Guo) or the phosphate is at the 3'-position (3'-GMP and 3'-IMP), too far for H-bonding. Nevertheless, a preference for the endo rotamer was observed for these L also. This result is opposite to that expected both from potential steric repulsion of the L O6 with the N-Me groups and also from the lack of a potential favorable H-bond interaction between L O6 and a Me(3)dien NH. For the 9-EtG adduct, the temperature dependence of the endo/exo equilibrium and the activation parameters for endo/exo interconversion suggest that the preference for the endo rotamer arises from the hydration of the Me(3)dien NH groups; such hydration is favorable in the endo rotamer. At basic pH, N1H deprotonation increases the H-bond capacity of O6, and the exo rotamer increases in stability, becoming the dominant rotamer for the 9-EtG and Guo adducts. For L = 3'-GMP and 3'-IMP, stabilization of the endo form upon phosphate deprotonation at neutral pH was observed. This result is attributed to an H-bonding network involving water, the 3'-phosphate, and the Me(3)dien NH groups.
Carlone
Maria
M
Dipartimento Farmaco-Chimico, Università degli Studi di Bari, Via E. Orabona 4, 70125 Bari, Italy.
Marzilli
Luigi G
LG
Natile
Giovanni
G
D000588:Amines / Q000737:chemistry*; D002945:Cisplatin / Q000737:chemistry; D006147:Guanine / Q000737:chemistry*; D006151:Guanosine / Q000737:chemistry; D006157:Guanosine Monophosphate / Q000737:chemistry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007042:Hypoxanthines / Q000737:chemistry*; D007291:Inosine Monophosphate / Q000737:chemistry; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D009711:Nucleotides / Q000737:chemistry*; D009944:Organoplatinum Compounds / Q000737:chemistry*
D000588:Amines; D007042:Hypoxanthines; D008024:Ligands; D009711:Nucleotides; D009944:Organoplatinum Compounds; D006151:Guanosine; D007291:Inosine Monophosphate; D006147:Guanine; D006157:Guanosine Monophosphate; D002945:Cisplatin