A combined computational and experimental study of the hydrogen-bonded dimers of xanthine and hypoxanthine.
In addition to uracil, the noncanonical nucleobases xanthine and hypoxanthine are important lesions that are formed from the canonical bases when a cell is under oxidative stress. It is known that they lead to point mutations; however, more detailed information about their ability to form hydrogen-bonded complexes is not available. In the present paper such information is obtained by a combined experimental and theoretical approach. Accurate association constants of xanthosine and inosine dimers are determined by concentration dependent 1H NMR experiments, and a structural characterization of individual complexes formed in solution is performed through measurements under slow exchange conditions at very low temperatures. An interpretation of the experimental data concerning complex geometries becomes possible through a comparison of measured and computed NMR chemical shifts. Further qualitative insights into the hydrogen bonding abilities of xanthine and hypoxanthine are obtained by a theoretical characterization of all possible pairing modes of xanthine and hypoxanthine dimers and by a comparison with simplified model systems. The influence of a polar medium on the bonding properties is also estimated and the importance of the various effects is discussed. Our analysis shows to what extent secondary electronic and electrostatic effects influence the hydrogen bonding properties of xanthine and hypoxanthine in the gas phase and in polar solvents.
Hupp
Thomas
T
Institut für Organische Chemie, Universität Würzburg, Am Hubland, D-97070 Würzburg.
Sturm
Christian
C
Basílio Janke
Eline M
EM
Cabre
Montserrat Pérez
MP
Weisz
Klaus
K
Engels
Bernd
B