Mechanistic insights into the reaction of an estrogen o-quinone with deoxyguanosine has been further investigated using high level density redken shades eq 07m driftwood functional calculations in addition to the use of 4-hyroxycatecholestrone (4-OHE1) regioselectivity labeled with deuterium at the C1-position.Calculations using the M06-2X functional with large basis sets indicate the tautomeric form of an estrogen-DNA adduct present when glycosidic bonds cleavage occurs is comprised of an aromatic A ring structure.This tautomeric form was further verified by use of deuterium labelling of the catechol precursor use to form the estrogen o-quinone.Regioselective deuterium labelling at the C1-position of the estrogen A ring allows discrimination between two tautomeric forms of a reaction intermediate either of which could be present during glycosidic bond cleavage.HPLC-MS analysis indicates a reactive intermediate with a m/z of 552.
22 popularfilm.blog consistent with a tautomeric form containing no deuterium.This intermediate is consistent with a reaction mechanism that involves: (1) proton assisted Michael addition; (2) re-aromatization of the estrogen A ring; and (3) glycosidic bond cleavage to form the known estrogen-DNA adduct, 4-OHE1-1-N7Gua.