Humphry Tim, Forconi Marcello, Williams Nicholas H, Hengge Alvan C
Department of Chemistry and Biochemistry, Utah State University, Logan, UT 84322-0300, USA.
J Am Chem Soc. 2002 Dec 18;124(50):14860-1. doi: 10.1021/ja027671c.
Isotope effects in the nucleophile and in the leaving group were measured to gain information about the mechanism and transition state of the hydrolysis of methyl p-nitrophenyl phosphate complexed to a dinuclear cobalt complex. The complexed diester undergoes hydrolysis about 1011 times faster than the corresponding uncomplexed diester. The kinetic isotope effects indicate that this rate acceleration is accompanied by a change in mechanism. A large inverse 18O isotope effect in the bridging hydroxide nucleophile (0.937 +/- 0.002) suggests that nucleophilic attack occurs before the rate-determining step. Large isotope effects in the nitrophenyl leaving group (18Olg = 1.029 +/- 0.002, 15N = 1.0026 +/- 0.0002) indicate significant fission of the P-O ester bond in the transition state of the rate-determining step. The data indicate that in contrast to uncomplexed diesters, which undergo hydrolysis by a concerted mechanism, the reaction of the complexed diester likely proceeds via an addition-elimination mechanism. The rate-limiting step is expulsion of the p-nitrophenyl leaving group from the intermediate, which proceeds by a late transition state with extensive bond fission to the leaving group. This represents a substantial change in mechanism from the hydrolysis of uncomplexed aryl phosphate diesters.
对亲核试剂和离去基团中的同位素效应进行了测量，以获取有关与双核钴配合物络合的对硝基苯磷酸甲酯水解的机理和过渡态的信息。与相应的未络合二酯相比，络合二酯的水解速度快约1011倍。动力学同位素效应表明，这种速率加速伴随着机理的变化。桥连氢氧根亲核试剂中较大的反向18O同位素效应（0.937±0.002）表明亲核攻击发生在速率决定步骤之前。对硝基苯离去基团中较大的同位素效应（18Olg = 1.029±0.002，15N = 1.0026±0.0002）表明在速率决定步骤的过渡态中P-O酯键发生了显著断裂。数据表明，与通过协同机理进行水解的未络合二酯不同，络合二酯的反应可能通过加成-消除机理进行。限速步骤是从中间体中排出对硝基苯离去基团，这通过与离去基团发生广泛键断裂的晚期过渡态进行。这代表了与未络合芳基磷酸二酯水解机理的重大变化。
