Force field conformational analysis of aminofluorene and acetylaminofluorene substituted deoxyguanosine

The hepatocarcinogen N-hydroxy-2-acetylaminofluorene forms two C8-substituted deoxyguanosine adducts in vivo. The conformation of these adducts, as well as 2'-deoxyguanosine and 8-amino-2'-deoxyguanosine has been studied with Allinger's force field. Using the glycoside rotation as a reaction coordinate, multidimensional potential energy surface were determined by relaxing all internal degrees of freedom. The calculations indicate the 2'-deoxyguanosine should exist as a mixture of syn and anti forms, that the syn form is slightly favored for 8-amino-2'-deoxyguanosine, that N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-C8-AAF) will only be found in the syn conformation and that, although the syn form is also more stable for N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF), it will have a substantially greater proportion of the anti-conformer than is found with dG-C8-AAF. The results of the force field calculations are discussed in relation to the effects these adducts may have on DNA structure.