title: Physicochemical aspects of the enzymatic hydrolysis of carboxylic esters.
abstract: 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.
authors.affiliation: IVAX Research, Inc., Miami, Florida, USA. Peter_Buchwald@ivax.com
authors.forename: P
authors.initials: P
authors.lastname: Buchwald
authors.forename: N
authors.initials: N
authors.lastname: Bodor
mesh_terms: 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
chemical_list: D002264:Carboxylic Acids; D004952:Esters; D004364:Pharmaceutical Preparations; D004950:Esterases