The mechanism of tirapazamine enzymatic catalysis to release hydroxyl radical has been studied by density functional theory (DFT) at the B3LYP3/6-31G(d) and B3LY-P/6-311+G(d) levels. The results indicated that there were two parallel reaction channels in the microcosmic processes of the enzymatic catalysis to release hydroxyl radical. The calculated B3LY-P activation barriers including solvent effects were very close to the experimental values. (c) 2005 Elsevier B.V. All rights reserved.