Méndez R, Alemany T, Martín-Villacorta J
Departamento de Bioquímica y Biología Molecular, Facultades de Biología y Veterinaria, Universidad de León, Spain.
Chem Pharm Bull (Tokyo). 1992 Dec;40(12):3228-33. doi: 10.1248/cpb.40.3228.
The Zn(2+)-tris (hydroxymethyl)aminomethane (Tris) system has a great catalytic effect on the hydrolysis and aminolysis of some beta-lactam antibiotics. In order to ascertain the mechanism of this catalysis we have analysed the effects of the beta-lactam antibiotic structure. First we studied the kinetics of the decomposition of imipenem, SCH 29482, aztreonam and nocardicin A in aqueous solution of Tris at 35.0 degrees C, 0.5 mol.dm-3 ionic strength and in the presence of metal ions (Zn2+, Cd2+, Co2+, Cu2+, Ni2+ and Mn2+). From these studies, we conclude that Tris and metal ions (in separate solutions) exert a great catalytic effect on the hydrolysis of imipenem and SCH 29482. We suggest that in metal ion solutions a 1:1 complex is formed between the metal ion and beta-lactam antibiotic, which is attacked by hydroxide ions. Studies of the degradation of the antibiotics studied in solutions of Tris and metal ions together indicate that the systems Cd(2+)-Tris and Zn(2+)-Tris have a great catalytic effect on the hydrolysis and aminolysis of imipenem and SCH 29482. We suggest that this catalysis takes place via a ternary complex in which the metal ion plays a double role by (a) placing the antibiotic and the Tris in the right position for the reaction and (b) lowering the pKa of the hydroxide group of Tris, which is coordinated with the metal ion, generating a strong nucleophile.
锌（2+）-三（羟甲基）氨基甲烷（Tris）体系对某些β-内酰胺类抗生素的水解和氨解具有显著的催化作用。为了确定这种催化作用的机制，我们分析了β-内酰胺类抗生素结构的影响。首先，我们研究了亚胺培南、SCH 29482、氨曲南和诺卡菌素A在35.0℃、0.5 mol·dm⁻³离子强度且存在金属离子（锌2+、镉2+、钴2+、铜2+、镍2+和锰2+）的Tris水溶液中的分解动力学。通过这些研究，我们得出结论，Tris和金属离子（在单独溶液中）对亚胺培南和SCH 29482的水解具有显著的催化作用。我们认为在金属离子溶液中，金属离子与β-内酰胺类抗生素形成1:1络合物，该络合物会受到氢氧根离子的攻击。对在Tris和金属离子混合溶液中所研究抗生素降解的研究表明，镉（2+）-Tris和锌（2+）-Tris体系对亚胺培南和SCH 29482的水解和氨解具有显著的催化作用。我们认为这种催化作用是通过三元络合物发生的，其中金属离子通过以下方式发挥双重作用：（a）将抗生素和Tris置于反应的合适位置；（b）降低与金属离子配位的Tris羟基的pKa，生成强亲核试剂。
