Kinetic and thermodynamic characterization of camptothecin hydrolysis at physiological pH in the absence and presence of human serum albumin

✍ Scribed by Rishi Thakur; Sasank Kunadharaju; Michalakis Savva

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 183 KB
• Volume: 41
• Category: Article
• ISSN: 0538-8066
• DOI: 10.1002/kin.20449

✦ Synopsis

Abstract

To accurately derive the kinetic and thermodynamic parameters governing the hydrolysis of the lactone ring at physiological pH, a derivative spectrophotometric technique was used for the simultaneous estimation of lactone and carboxylate forms of camptothecin (CPT). The hydrolysis of the CPT‐lactone and the lactonization of CPT‐carboxylate at 310.15 K followed a first‐order decay with apparent rate constants equal to 0.0279 ± 0.0016 min^−1^ and 0.0282 ± 0.0024 min^−1^, respectively. The activation energy associated with the hydrolysis of the CPT‐lactone and the lactonization of the CPT‐carboxylate as calculated from the Arrhenius equation was 89.18 ± 0.84 and 86.49 ± 2.7 kJ mol^−1^, respectively. The enthalpy and entropy of the thermodynamically favored hydrolysis reaction were on average 10.49 kJ mol^−1^ and 48.00 J K^−1^ mol^−1^, respectively. The positive enthalpy and entropy values of the CPT‐lactone hydrolysis indicate that the reaction is endothermic and entropically driven. The stability of CPT‐lactone in the presence of human serum albumin (HSA) was also analyzed. Notwithstanding the much faster hydrolysis of the CPT‐lactone in the presence of HSA at various temperatures, the energy of activation was determined to be similar to the one estimated in the absence of HSA, suggesting that HSA does not catalyze the hydrolysis reaction, but it merely binds, sequesters, and stabilizes the CPT‐carboxylate species. © 2009 Wiley Periodicals, Inc. Int J Chem Kinet 41: 704–715, 2009