Structural studies of malonaldehyde–glyoxal and malonaldehyde–methylglyoxal etheno adducts of adenine nucleosides based on spectroscopic methods and DFT-GIAO calculations†

Etheno adducts are formed in the reactions of DNA bases with chloroacetaldehyde, with lipid peroxidation products, and also with metabolites of vinyl chloride and furan. The presence of such modifications in the genetic material may lead to errors in replication with consequences of mutations and even carcinogenesis. For an understanding of the biological significance of etheno adducts it is important to determine their structures. Structural identification is also essential for using these adducts as inflammatory or cancer biomarkers. This paper reports structural studies on two adducts formed in the reactions of malonaldehyde and glyoxal with adenosine (M1Gx-A), and malonaldehyde and methylglyoxal with 20-deoxyadenosine (M1MGx-dA). NMR spectroscopy and theoretical methods have been used. DFT-GIAO calculations were performed at M06/6-311++G(2df,2pd), B3LYP/6-311++G(2df,2pd) and M06/6-31++G(d,p) levels both in the gas phase and taking into account the effect of solvents (water, methanol and DMSO) using PCM approximation. It has been shown that when M06 or B3LYP functionals with the 6-311++G(2df,2pd) basis set are used, H NMR chemical shifts very close to experimental values are obtained and that the results of GIAO calculations at the M06/6-31++G(d,p) level have a better correlation with measured C NMR chemical shift values. PCM improves the correlation of results in both cases.