A SEMIEMPIRICAL TRANSITION-STATE STRUCTURE FOR THE FIRST STEP IN THE ALKALINE-HYDROLYSIS OF COCAINE - COMPARISON BETWEEN THE TRANSITION-STATE STRUCTURE, THE PHOSPHONATE MONOESTER TRANSITION-STATE ANALOG, AND ANEWLY DESIGNED THIOPHOSPHONATE TRANSITION-STATE ANALOG

Semiempirical molecular orbital calculations have been performed for t he first step in the alkaline hydrolysis of the neutral benzoylester o f cocaine. Successes, failures, and limitations of these calculations are reviewed. A PM3 calculated transition state structure is compared with the PM3 calculated structure for the hapten used to induce cataly tic antibodies for the hydrolysis of cocaine. Implications of these ca lculations for the computer-aided design of transition state analogs f or the induction of catalytic antibodies are discussed.