Regiochemistry of nucleophilic attack by the guanine 2-amino group at the ring positions of nitrenium ions derived from carcinogenic polycyclic arylamines and nitroarenes: molecular orbital calculations and simple models.
Semiempirical AM1 molecular orbital calculations are used to compute the energetics of addition of the guanine 2-amino group to alternative ring positions of aryl nitrenium ions with the general structure ArNH+, where Ar is the phenyl and various positional isomers of the naphthyl, pyrenyl, and benzo[a]pyrenyl groups. The syn or anti orientation of the NH+ group, and factors akin to classical localization energies, are identified as key components of the differential energetics of addition to alternative ring sites. The regiochemistry predicted by the AM1 method can be qualitatively reproduced using simple HMO calculations that require trivial computational effort and, almost as well, using PMO theory that does not require the use of a computer at all. In the latter approach, the most reactive ring positions are predicted to be those where the nonbonding orbital coefficients, a0r, in the analogous odd alternant hydrocarbons are largest. These results are discussed in relation to the available experimental data for the formation of deoxyguanosin-2-yl adducts when DNA is exposed to presumed nitrenium ion precursors.
Ford
G P
GP
Department of Chemistry, Southern Methodist University, Dallas, Texas 75275-0314, USA. gford@smu.edu
Thompson
J W
JW
D000478:Alkylation; D002273:Carcinogens / Q000737:chemistry*; D002412:Cations; D004247:DNA / Q000737:chemistry; D006147:Guanine / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry*; D011789:Quantum Theory; D013237:Stereoisomerism; D013816:Thermodynamics
D002273:Carcinogens; D002412:Cations; D011084:Polycyclic Aromatic Hydrocarbons; D006147:Guanine; D004247:DNA