Charge-transfer chemistry of azithromycin, the antibiotic used worldwide to treat the coronavirus disease (COVID-19). Part I: Complexation with iodine in different solvents

Abdel Majid A Adam; Hosam A Saad; Amnah M Alsuhaibani; Moamen S Refat; Mohamed S Hegab

doi:10.1016/j.molliq.2020.115187

Charge-transfer chemistry of azithromycin, the antibiotic used worldwide to treat the coronavirus disease (COVID-19). Part I: Complexation with iodine in different solvents

J Mol Liq. 2021 Mar 1:325:115187. doi: 10.1016/j.molliq.2020.115187. Epub 2020 Dec 26.

Authors

Abdel Majid A Adam¹, Hosam A Saad¹, Amnah M Alsuhaibani², Moamen S Refat¹, Mohamed S Hegab³

Affiliations

¹ Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
² Department of Physical Sport Science, Princess Nourah bint Abdulrahman University, 4545 - King Khalid Airport Unit No. 1, Riyadh 13415-7132, Saudi Arabia.
³ Deanship of Supportive Studies (D.S.S.), Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.

Abstract

Around the world, the antibiotic azithromycin (AZM) is currently being used to treat the coronavirus disease (COVID-19) in conjunction with hydroxychloroquine or chloroquine. Investigating the chemical and physical properties of compounds used alone or in combination to combat the COVID-19 pandemic is of vital and pressing importance. The purpose of this study was to characterize the charge transfer (CT) complexation of AZM with iodine in four different solvents: CH₂Cl₂, CHCl₃, CCl₄, and C₆H₅Cl. AZM reacted with iodine at a 1:1 M ratio (AZM to I₂) in the CHCl₃ solvent and a 1:2 M ratio in the other three solvents, as evidenced by data obtained from an elemental analysis of the solid CT products and spectrophotometric titration and Job's continuous variation method for the soluble CT products. Data obtained from UV-visible and Raman spectroscopies indicated that AZM strongly interacted with iodine in the CH₂Cl₂, CCl₄, and C₆H₅Cl solvents by a physically potent n→σ* interaction to produce a tri-iodide complex formulated as [AZM·I⁺]I₃ ^-. XRD and TEM analyses revealed that, in all solvents, the AZM-I₂ complex possessed an amorphous structure composed of spherical particles ranging from 80 to 110 nm that tended to aggregate into clusters. The findings described in the present study will hopefully contribute to optimizing the treatment protocols for COVID-19.

Keywords: Azithromycin; Charge–transfer; Iodine; Solvent effect; Tri–iodide ion.