Rohit Bose - University of Saskatchewan

Placement: University of Toronto
Supervisor: Dr. Bob McClelland

Characterization of the Intermediates from Photolysis of 4-Azidostilbene

Nitrenium ions are nitrogen analogs of carbenium ions (carbocations). They can form covalent adducts with DNA, resulting in the onset of cancer. The title compound, 4-aminostilbene, is converted to a nitrenium ion intermediate via metabolic activation. This particular intermediate was studied using laser flash photolysis. Irradiation of 4-azidostilbene resulted in the formation of the desired nitrenium ion intermediate (l_max = 520nm, t = 160ns). There were three pieces of evidence for nitrenium ion formation. Firstly, the reaction had azide quenching properties characteristic of a nitrenium ion intermediate. Secondly, if the reaction proceeded through the nitrenium ion intermediate, then the major product was predicted to be a diol. The predicted diol was synthetically constructed and shown to elute at an identical time to the major reaction product using HPLC. Thirdly, in the predicted mechanism, the chemistry of the nitrenium ion intermediate is dictated by its iminocyclohexadienyl cation resonance contributor. Indeed, the reaction exhibited substituent effects expected of iminocyclohexadienyl cation formation. A second intermediate was observed at 370nm whose rate of formation was identical to the rate of decay of the nitrenium ion. For this intermediate, a quinone imine methide, t was 1.6ms. In the predicted reaction mechanism, the quinone imine methide must be protonated in order for the diol product to be formed. The nature of the reaction rate dependence on pH fit the predicted mechanism, and the pKa of the protonated quinone imine methide was found to be 8.4. Thus, photolysis of 4-azidostilbene resulted in the formation of a nitrenium ion intermediate (t = 160 ns) which was converted to the quinone imine methide intermediate (t = 1.6 ms) which was converted to the diol product.