Changes of mechanisms and product distributions in the hydrolysis of benzo[a]pyrene-7,8-diol 9,10-epoxide metabolites induced by changes in pH.
Changes of mechanisms and product distributions in the hydrolysis of benzo[a]pyrene-7,8-diol 9,10-epoxide metabolites induced by changes in pH.
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pH 变化引起苯并[a]芘-7,8-二醇 9,10-环氧化物代谢物水解机制和产物分布的变化。
DOI：
10.1021/ja00458a069
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发表时间：
1977
影响因子：
15
通讯作者：
D. Jerina
中科院分区：
文献类型：
--
作者：
D. Whalen;J. Montemarano;D. Thakker;H. Yagi;D. Jerina
普遍存在的环境致癌物苯并[a]芘的细胞毒性、致突变性和致癌作用。因此，了解这些代谢物的溶剂分解反应具有特殊的重要性。到目前为止，只有产品研究的定性率数据，23'46· 5和一个动力学研究6在一个非常有限的pH值范围内（约。5-6)在50%的二氧六环-水中出现。在后一项研究中，动力学数据表明1和2的水解仅存在酸催化机理，并且发现两种异构体具有相似的反应活性。7本研究报告了1和2在水和二氧六环-水混合物中水解的pH-速率曲线和产物分析。研究表明，1和2的水解机理从低pH的酸催化过程转变为在高水溶液中与溶剂在较高pH下的自发反应（图1），并伴随着产物分布的变化。而异构体2对酸催化水解的反应性约为异构体1的两倍，在自发水解条件下，1的反应性比2高30倍以上。1和2之间在生理pH范围内的反应性的巨大差异可能在1和2的相对致瘤特性中起重要作用。
I 2 the cytotoxic, mutagenic, 2 and carcinogenic3 action of the ubiquitous environmental carcinogen benzo [a] pyrene. Thus, a knowledge of the solvolytic reactions of these metabolites4 assumes a special importance. To date, only product studies with qualitative rate data, 23’46· 5 and one kinetic study6 over a very limited pH range (ca. 5-6) in 50% dioxane-water have appeared. In the latter study, kinetic data revealed only the existence of acid-catalyzed mechanisms for the hydrolysis of1 and 2, and both isomers were found to possess similar reac-tivities. 7 The present study reports the pH-rate profiles and product analysis for the hydrolysis of 1 and 2 in water and in dioxane-water mixtures. This study reveals that the mechanisms for hydrolysis of both 1 and 2 change from acid-cat a-lyzed processes at low pH to spontaneous reactionswith sol-vent at higher pH in highly aqueous solutions (Figure 1), accompanied by changes in product distributions. Whereas isomer 2 is about twice as reactive as isomer 1 toward acidcatalyzed hydrolysis, 1 is more than 30 times more reactive than 2 under conditions of spontaneous hydrolysis. The large difference in reactivity between 1 and 2 in the physiological pH range may play a significant role in the relative tumorgenic properties of 1 and 2.