Effects of N7-methylation, N7-platination, and C8-hydroxylation of guanine on H-bond formation with cytosine: platinum coordination strengthens the Watson-Crick pair.
The hydrogen bonding properties of 1-methylcytosine (1-MeC) with the following guanine base derivatives have been studied in DMSO-d6, applying concentration-dependent 1H NMR spectroscopy: 9-ethylguanine, 7,9-dimethylguanine (7,9-DimeGH+), and 7,8-dihydro-8-oxo-9-methylguanine (8-O-9-MeGH), as well as three 9-ethylguanine complexes carrying different Pt(II) moieties at the N7 position. The association constants K for the Watson-Crick pairing schemes are by a factor 2-3 higher in the cases of platinated guanine complexes compared to the Watson-Crick pair between 9-ethylguanine and 1-methylcytosine (K = 6.9 +/- 1.3 M(-1)). Similar enhanced stabilities are observed for the pairs formed between 1-MeC and 7,9-DimeGH+ or 8-O-9-MeGH. The increase in N1H acidity of the guanine derivative upon modification at the N7 or C8 positions can be correlated with the association constants K; the result is a bell-shaped curve meaning that acidification initially stabilizes hydrogen bond formation up to a certain maximum; further acidification then leads to a destabilization. For two of the examples studied in solution, hydrogen bonding according to Watson-Crick between N7-platinated 9-ethylguanine and 1-methylcytosine has also been established by X-ray crystallography.
Sigel
R K
RK
Department of Chemistry, University of Dortmund, Germany.
Freisinger
E
E
Lippert
B
B
D018360:Crystallography, X-Ray; D003596:Cytosine / Q000737:chemistry*; D019175:DNA Methylation; D006147:Guanine / Q000737:chemistry*; D006860:Hydrogen Bonding; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D017671:Platinum Compounds / Q000737:chemistry*; D013055:Spectrophotometry, Infrared
D017671:Platinum Compounds; D006147:Guanine; D003596:Cytosine