Computational and Experimental Evidence for the Structural Preference of Phenolic C-8 Purine Adducts

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Molecules, spectroscopy, kinetics, environment, & general theory, 2008-01, Vol.112 (16), p.3742-3753
• Main Authors: Millen, Andrea L, McLaughlin, Christopher K, Sun, Kewen M, Manderville, Richard A, Wetmore, Stacey D
• Format: Article
• Language: English
• ISSN: 1089-5639; 1520-5215
• DOI: 10.1021/jp712058aPII:S1089-5639(71)02058-9

The structural and spectral properties of (ortho and para) C8-aryl-purine adducts formed from carbon attachment by phenolic toxins were investigated through DFT calculations and UV-vis absorbance and emission studies. The global minima of both the deoxyadenosine (dA) and deoxyguanosine (dG) adducts adopted a syn conformation about the glycosidic bond due to the presence of an O5'-H super(.) super(.) super(.)N3 hydrogen bond, where the anti minima are 20-30 kJ mol super(- 1) higher in energy. While the nucleobase adducts are planar, the presence of the deoxyribose sugar induces a twist about the carbon-carbon bond connecting the phenol and nucleobase rings. ortho-Phenolic adducts are less twisted than the corresponding para adducts due to stabilization provided by an intramolecular O-H super(.) super(.) super(.)N7 bond. Solvation calculations, in combination with UV-vis studies, demonstrate that the structural preference is solvent dependent, where solvents with hydrogen-bonding abilities disrupt the intramolecular O-H super(.) super(.) super(.)N7 hydrogen bond such that a greater degree of twist is observed, and less polar solvents stabilize the planar structure. Indeed, the ratio of twisted to planar conformers is estimated to be as large as 50:50 in some aprotic solvents. Thus, the combined experimental and computational approach has provided a greater understanding of the structure of the ortho- and para-dA and dG C-bonded phenoxyl adducts as the first step to understanding the biological consequences of this form of DNA damage.