Synthesis, spectroscopic and computational studies on hydrogen bonded charge transfer complex of duvelisib with chloranilic acid: Application to development of novel 96-microwell spectrophotometric assay

Ibrahim A Darwish; Abdulrahman A Almehizia; Ahmed Y Sayed; Nasr Y Khalil; Nourah Z Alzoman; Hany W Darwish

doi:10.1016/j.saa.2021.120287

Synthesis, spectroscopic and computational studies on hydrogen bonded charge transfer complex of duvelisib with chloranilic acid: Application to development of novel 96-microwell spectrophotometric assay

Spectrochim Acta A Mol Biomol Spectrosc. 2022 Jan 5:264:120287. doi: 10.1016/j.saa.2021.120287. Epub 2021 Aug 21.

Authors

Ibrahim A Darwish¹, Abdulrahman A Almehizia², Ahmed Y Sayed², Nasr Y Khalil², Nourah Z Alzoman², Hany W Darwish³

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: idarwish@ksu.edu.sa.
² Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
³ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Analytical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt. Electronic address: hdarwish@ksu.edu.sa.

PMID: 34455386
DOI: 10.1016/j.saa.2021.120287

Abstract

Duvelisib (DUV) is a is a small-molecule with inhibitory action for phosphoinositide 3-kinase (PI3K). It has been recently approved for the effective treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Novel charge transfer complex (CTC) between DUV, as electron donor, with chloranilic acid (CLA), as π electron acceptor has been synthesized and characterized using different spectroscopic and thermogravimetric techniques. UV-visible spectroscopy ascertained the formation of the CTC in different solvents of varying polarity indexes and dielectric constants via formation of new broad absorption band with maximum absorption peak (λ_max) in the range of 488-532 nm. The molar absorptivity of the CTC was dependent on the polarity index and dielectric constant of the solvent; the correlation coefficients were 0.9955 and 0.9749, respectively. The stoichiometric ratio of DUV:CLA was 1:1. Electronic spectral analysis was conducted for characterization of the complex in terms of its electronic constants. Computational calculation for atomic charges of energy minimized DUV was conducted and the site of interaction on DUV molecule was assigned. The solid-state CTC of DUV:CLA (1:1) was synthesized, and its structure was characterized by UV-visible, mass, FT-IR, and ¹H NMR spectroscopic techniques. Both FT-IR and ¹H NMR confirmed that both CT and hydrogen bonding contributed to the molecular composition of the complex. The reaction was adopted as a basis for developing a novel 96-microwell spectrophotometric assay (MW-SPA) for DUV. The assay limits of detection and quantitation were 0.57 and 1.72 µg/well, respectively. The assay was validated and all validation parameters were acceptable. The method was implemented successfully with great precision and accuracy to the analysis of the DUV in its bulk and capsules.

Keywords: Charge transfer complex; Chloranilic acid; Duvelisib; High throughput analysis; Lymphocytic leukemia; Microwell assay; Spectroscopy.

MeSH terms

Benzoquinones
Hydrogen*
Isoquinolines
Phosphatidylinositol 3-Kinases*
Purines
Spectroscopy, Fourier Transform Infrared

Substances

Benzoquinones
Isoquinolines
Purines
duvelisib
Hydrogen
chloranilic acid