Physicochemical aspects of the enzymatic hydrolysis of carboxylic esters.
Considering the important role played by enzymatic hydrolysis in the metabolism of therapeutic agents designed by retrometabolic approaches (soft drugs and chemical delivery systems), the present article offers a review of a number of issues related to the enzymatic hydrolysis of carboxylic esters. Current knowledge regarding interorgan- and interspecies variability, stereospecificity, activation energy, proposed mechanism, and quantitative structure-metabolism relationship is summarized. The effects of chain-length and branching in the alcohol or acyl substituent on the rate of hydrolysis in congener series are also summarized. Available in vitro human blood data suggest that shortest half-lives are achieved with sterically non-hindered chains that are neither too short nor too long and are of around four carbon-atom long.
Buchwald
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IVAX Research, Inc., Miami, Florida, USA. Peter_Buchwald@ivax.com
Bodor
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N
D000818:Animals; D002264:Carboxylic Acids / Q000737:chemistry* / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004950:Esterases / Q000378:metabolism*; D004952:Esters / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D013045:Species Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002264:Carboxylic Acids; D004952:Esters; D004364:Pharmaceutical Preparations; D004950:Esterases