Abstract
Oxidation is a vital step of drug metabolism and hence a pharmaceutically relevant process. This study explores the potential of Donepezil, a widely used drug against mild to moderately severe Alzheimer's disease, to undergo oxidation using a mild, versatile oxidant Chloramine-T in acidic medium. A first-order dependency of rate on Donepezil and oxidant, fractional-order dependency on acid medium, independency of the rate on ionic concentration and an elevation of rate with increasing dielectric constant are revealed by the kinetic studies. The stoichiometry, thermodynamic properties, rate equation, mechanistic details are outlined, and identification of reaction products is supported by consistent oxidative degradation related UV, IR, 1H NMR and mass spectroscopic data. The spectroscopic results are in good agreement with theoretical predictions, providing an insight and deepen the understanding of oxidative metabolic pathway of Donepezil.
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The authors thank the management of BMS College of Engineering, Bangalore, for the encouragement and support extended.
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This work resulted from the collaboration between all authors. Author Malini.S performed the literature search, laboratory experiments, data analysis, designed and managed the study, wrote the first draft of the manuscript and communicated it to the journal. Author Kalyan Raj provided the instrumental facilities and valuable discussion. Author Suresha.N formulated the quantification of the data. Author K.S. Anantharaju edited and approved the final manuscript.
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Malini, S., Raj, K., Suresha, N. et al. Donepezil oxidation: complementary chemical and spectroscopic exploration of products, mechanism and kinetics. Chem. Pap. 76, 1457–1470 (2022). https://doi.org/10.1007/s11696-021-01934-y
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DOI: https://doi.org/10.1007/s11696-021-01934-y