| A cooperative reaction is defined as one in which solvent molecules participate actively in the mechanism in order to circumvent the formation of charged intermediates. This Thesis presents evidence that cooperativity exists in water solvent in the neutral and acetic acid catalyzed hydration of acetone, and in the neutral hydrolysis of methyl acetate. These findings support the contention that penicillin-binding proteins (PBP's) and beta-lactamases, which catalyze one or more acyl transfer reactions, also function by cooperative mechanisms, which are enabled in the mainly hydrophobic active sites of these enzymes by the hydroxyl groups of serine, threonine or tyrosine.;The theoretical proton inventories of the acetic acid and 2-hydroxypyridine-catalyzed reactions have been determined, and are in agreement with experiment.;The kinetics of the neutral hydrolysis of methyl acetate have been determined experimentally at 90°, 100° and 110°C, and extrapolated to 298 K for comparison with the results of theoretical 3-21G/SCRF calculations. These have been performed for both one-step and two-step mechanisms, with cooperative assistance from one to three additional water molecules. The mechanisms are distinguished by the ratio of khyd, the hydrolysis rate constant, to kex, the rate constant for 18O-exchange in the ester. The experimental kex/khyd agrees with that calculated for the one-step mechanism.;Topochemistry is a special form of cooperativity in which adjacent molecules in a crystal cooperate to bring about a reaction that would normally be difficult to achieve. In the solid state 2-benzyloxypyridine-1-oxide has been found to rearrange to 1-benzyloxy-2-pyridone with complete inversion of configuration in the benzyl group.;Using 2-13C-labelled acetone and H2 18O, and taking advantage of the 18O-isotope shift in the 13C-nmr spectrum of acetone, the hydration kinetics have been determined at 298 K in the presence and absence of acetic acid. 2-hydroxypyridine and 3-hydroxypyridine. All of the results are reproduced by extension of a previously described 3-21G/SCRF computational strategy: three additional water molecules participate in a cyclic mechanism in the neutral reaction; two water molecules participate, with acetic acid, in the catalyzed mechanism; and the bifunctional catalysis by 2-hydroxypyridine has been found to reside in an exceptionally stable complex between acetone, the tautomeric 2-pyridone and two water molecules, and not in a transition structure having two active hydrons. |
