Investigation into the Reaction Kinetics of the Hydrolysis of Molnupiraivir to 4N-hydroxycytidine

Abstract

Throughout the COVID-19 outbreak many new pharmaceuticals have been developed to help stop the spread and treat patients suffering from the virus. One of these potential drug candidates is molnupiravir. Molnupiravir is a compound that is hydrolyzed in the body to its product 4N-hydroxycytidine which prevents replication of COVID-19 in cells by inhibiting RNA virus replication. Because molnupiravir was only recently discovered there is little information regarding the degradation of the compound. In this study, various hydrolysis reactions of molnupiravir were conducted under varying pHs and temperatures to determine different values including the rate constant, half-life, and activation energy of MOL. To obtain these values, samples were extracted from the hydrolysis reaction. The samples were then analyzed by liquid chromatography-mass spectrometry to acquire the concentrations of molnupiravir and 4N-hydroxyciditine in the reaction. This allowed for the calculation of the reaction rate constants through a nonlinear regression program and therefore find the half-life and activation energy. The pKa values from the protonated form to neutral from of 2.0 and neutral form to deprotonated form of 10.5 were also found by measuring the UV/VIS spectra of molnupiravir at varying pH values and analyzing the data with the same nonlinear regression program. It was found that as the pH increases, the rate constant of the hydrolysis reaction also increases. Important equations were also determined that made it possible to calculate the activation energy of 90 kJ/mol and the rate constants and lifetime of molnupiravir at specific pHs and temperatures. These values are of interest to understand the properties of molnupiravir to make more information available to scientists who study molnupiravir or similar compounds in the future.