Synthesis, spectroscopic and computational characterization of charge transfer complex of remdesivir with chloranilic acid: Application to development of novel 96-microwell spectrophotometric assay

Ibrahim A Darwish; Nasr Y Khalil; Hany W Darwish; Nourah Z Alzoman; Abdullah M Al-Hossaini

doi:10.1016/j.molstruc.2022.133104

Synthesis, spectroscopic and computational characterization of charge transfer complex of remdesivir with chloranilic acid: Application to development of novel 96-microwell spectrophotometric assay

J Mol Struct. 2022 Sep 5:1263:133104. doi: 10.1016/j.molstruc.2022.133104. Epub 2022 Apr 17.

Authors

Ibrahim A Darwish¹, Nasr Y Khalil¹, Hany W Darwish^{1

2}, Nourah Z Alzoman¹, Abdullah M Al-Hossaini¹

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
² Department of Analytical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt.

Abstract

Remdesivir (REM) is an adenosine triphosphate analog antiviral drug that has received authorization from European Commission and approval from the U.S. Food and Drug Administration for treatment of coronavirus disease 2019 (Covid-19). This study, describes, for the first time, the synthesis of a novel charge transfer complex (CTC) between REM, as electron donor, with chloranilic acid (CLA), as π electron acceptor. The CTC was characterized using different spectroscopic and thermogravimetric techniques. UV-visible spectroscopy ascertained the formation of the CTC in methanol via formation of a new broad absorption band with maximum absorption peak (λ_max) at 530 nm. The molar absorptivity (ε) of the complex was 3.33 × 10³ L mol^-1 cm^-1 and its band gap energy was 1.91 eV. The stoichiometric ratio of REM:CLA was found to be 1:1. The association constant of the complex was 1.11 × 10⁹ L mol^-1, and its standard free energy was 5.16 × 10⁴ J mole^-1. Computational calculation for atomic charges of energy minimized REM was conducted, the site of interaction on REM molecule was assigned and the mechanism of the reaction was postulated. The solid-state CTC was further characterized by FT-IR and ¹H NMR spectroscopic techniques. Both FT-IR and ¹H NMR confirmed the formation of the CTC and its structure. The reaction was adopted as a basis for developing a novel 96-microwell spectrophotometric method (MW-SPA) for REM. The assay limits of detection and quantitation were 3.57 and 10.83 µg/well, respectively. The assay was validated, and all validation parameters were acceptable. The assay was implemented successfully with great precision and accuracy to the determination of REM in its bulk form and pharmaceutical formulation (injection). This assay is simple, economic, and more importantly, has high throughput property. Therefore, the assay can be valuable for routine in quality control laboratories for analysis of REM's bulk form and pharmaceutical injection.

Keywords: 96-microwell assay; Charge transfer complex; Chloranilic acid; Remdesivir; Spectroscopy.