Structure of the planar complex of N4-methoxycytosine with adenine, and its relevance to the mechanism of hydroxylamine mutagenesis.
Infrared, and 1H- and 13C-NMR spectroscopy has been applied to a study of the planar interaction in apolar media between 1-substituted N4-methoxycytosine (and the corresponding 5-methyl analogue) and 9-substituted adenines. In both chloroform and carbon tetrachloride solutions, the exocyclic N4-methoxy group of N4-methoxycytosine, and of 5-methyl N4-methoxycytosine (which is in the oxime form under these conditions), is so oriented that it is predominantly syn to the ring N(3), and neither compound forms planar auto-associates. In chloroform solution, both the N(3)-H and the C(2) = O interact weakly with the solvent, the interaction being of the nature of non-typical hydrogen bonding. The 13C-NMR chemical shift of the C(2) of N4-methoxycytosine is modified during formation of hetero-associates with 9-substituted adenine, in accordance with the C(2) = O of the former being the acceptor of an adenine amino proton. The resulting planar hetero-associate is a non-Watson-Crick type of base-pair. This was further substantiated by infrared absorption studies of the carbonyl frequency during complex formation. The results are examined in the light of the mechanism of hydroxylamine (and methoxyamine) mutagenesis.
D000225:Adenine; D003596:Cytosine / Q000031:analogs & derivatives*; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000633:toxicity*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009153:Mutagens; D009154:Mutation; D009690:Nucleic Acid Conformation; D013055:Spectrophotometry, Infrared
D006898:Hydroxylamines; D009153:Mutagens; C036689:N(4)-methoxycytosine; D019811:Hydroxylamine; D003596:Cytosine; D000225:Adenine