Mechanism and Kinetics of the Degradation of Nitazoxanide and Hydroxychloroquine Drugs by Hydroxyl Radicals: Theoretical Approach to Ecotoxicity

Abstract

The efforts of contrasting the effects caused by the COVID-19 (coronavirus disease 2019) pandemic increased the disposal of active pharmaceutical ingredients. This paper reports the mechanisms and kinetics of the degradation in aqueous environments induced by •OH of two drugs, among those most widely probed at the outbreak of coronavirus, nitazoxanide and hydroxychloroquine. The investigation exploits quantum chemistry techniques and a reaction rate theory combined with diffusion-controlled processes and quantum mechanical tunneling. The reaction rate constants are obtained in an environmentally relevant temperature range. The results show that (i) the deacetylation of nitazoxanide with formation of tizoxanide is kinetically the most favorable channel, in agreement with experimental work; (ii) for hydroxychloroquine, the present theoretical calculations show that the most favorable channel is the addition of •OH at the aromatic ring. The half-life time degradation products are for both cases in the range between 12 to 138 days. Both drugs presented toxicities between harmful and toxic as obtained by computational toxicology calculations. The toxicity is also calculated for the degradation products: (i) in the nitazoxanide degradation process, tizoxanide was characterized as more toxic, while (ii) in the case of hydroxychloroquine, the major degradation product showed a decrease in the toxicity.