Computational and experimental evidence for the structural preference of phenolic C-8 purine adducts.
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...N3 hydrogen bond, where the anti minima are 20-30 kJ mol-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...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...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.
Millen
Andrea L
AL
Department of Chemistry, University of Lethbridge, 4401 University Drive, Lethbridge, Alberta, Canada.
McLaughlin
Christopher K
CK
Sun
Kewen M
KM
Manderville
Richard A
RA
Wetmore
Stacey D
SD
D003198:Computer Simulation; D062385:Hydroxybenzoates / Q000737:chemistry*; D008956:Models, Chemical; D011687:Purines / Q000737:chemistry*
D062385:Hydroxybenzoates; D011687:Purines; C017616:phenolic acid; C030985:purine