Intermolecular charge-transfer complexes between chlorothiazide antihypertensive drug against iodine sigma and picric acid pi acceptors: DFT and molecular docking interaction study with Covid-19 protease

doi:10.1016/j.jics.2022.100605

Journal of the Indian Chemical Society

Volume 99, Issue 8, August 2022, 100605

https://doi.org/10.1016/j.jics.2022.100605 Get rights and content

Highlights

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Two charge-transfer complexes between chlorothiazide (CH) as donor and picric acid (PA) and iodine (I₂) as p- and σ-acceptors, respectively, were synthesized and characterized.
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Physical parameters were determined using Benesi-Hildebrand and its modification methods, and 1:1 stoichiometry of CT complexes was obtained.
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The DFT calculations validate the experimental data; provide other physical parameters and intermolecular interactions.
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Molecular docking calculations between CT complexes and Covid-19 protease (6LU7) reveal the interaction between them and their inhibitory effect.

Abstract

The interaction of chlorothiazide (CH) as donor (D) with picric acid (PA) and iodine (I₂) as π- and σ-acceptors (A), respectively, gives charge-transfer (CT) complexes as a final products. The reaction of donor and acceptors were studied spectrophotometrically. The complexes are generally of the n-π* and n-σ* types, with the ground state wave function primarily characterized by the non-bonding structure. For the micro determination of chlorothiazide using picric acid and iodine as acceptors, the ideal conditions encouraging the formation of complexes are thoroughly explored. It was discovered that the stoichiometry of the molecular structure is 1:1 (D:A). The equilibrium constant and the molar extinction coefficient were calculated using Benesi-Hildebrand and its modifications. DFT/TD-DFT calculations with B3LYP/LanL2DZ and 6-311G++ level of theory were used to provide comparable theoretical data along with electronic energy gap of HOMO→LUMO. Molecular docking calculations have been performed between CT complexes and Covid-19 protease (6LU7) to study the interaction between them and their inhibitory effect.

Graphical abstract

Introduction

Chlorothiazide (Scheme 1) is a new form of highly effective diuretic agent, other compounds with similar properties will surely be developed. Because of this, it is necessary that we comprehend its mechanism of operation and limitations. The research of chlorothiazide pharmacology has already revealed fresh insights into certain fundamental issues with systemic arterial hypertension and kidney function [1]. The molar absorptivity of thiazide is sufficient to permit its direct determination by UV spectroscopy [2,3]. The determination of chlorothiazide by thin layer chromatography has been investigated [4]. Chlorothiazide has been found to be electrochemically active, with its reduction being observable in two waves [5]. Chlorothiazide, hydrochlorothiazide, and trichloromethiazide are popular diuretics that degrade in ethanolic solutions when exposed to UV light [6]. The coordination chemistry of chlorothiazide was studied, and it was discovered that when delivered in the form of metal complexes, it had a higher biological activity [7]. The interaction of donors with iodine and nitrophenols as acceptors were studied using the spectrophotometric method [8,9].

Interaction of the derivative of benzimidazole and benzothiazole with π-electron acceptors was found to give a 1:1 molecular species [10]. Using certain nitrophenols as a complexing agent, spectrophotometric measurement of flucloxacillin in pharmaceutical formulations [11], charge-transfer complexes of phenylephrine with nitrobenzene derivatives [12], the reactions of iodine with benzanthrone derivatives donor were studied photometrically in chloroform at room temperature [13]. Charge-transfer complexes formed between piperidine as donor with chloranilic acid and picric acid as acceptors have been studied spectrophotometrically [14]. Charge-transfer complexes of chlorothiazide as an n-donor have been recently studied, and their complexation and molecular composition were explored [15].

The present work represents the spectrophotometric method for the study of the reaction between chlorothiazide drug with picric acid and iodine in acetonitrile. The values of the equilibrium constant (K) and extinction coefficient (ε) were determined for the complexes. The solid complexes were synthesized and studied by elemental analysis, infrared and ¹H-HMR spectra, as well as molar ratio determination of the molecular complexes of CH-PA and CH–I₂. Optimized structures of CH/PA and CH/I₂ CT complexes with minimal energy were obtained, and experimental data were justified by DFT with B-3LYP/LanL2DZ and 6-311G++ level of theory. Various important structural, vibrational, chemical, spectroscopic, and thermodynamic properties of the CT complexes were calculated. Autodock Vina was used for molecular docking and to study the interactions between COVID-19 protease (6LU7) with the CT complexes. Binding energy along with hydrophobic and hydrogen bond surface were also obtained.

Section snippets

Reagents

The chlorothiazide (CH) emperical formula C₇H₆CLN₃O₄S₂, M.W = 295.725 g/mol, and melting point = 330 °C were purchased from Aldrich. All the solvents used were of analytical reagent grade.

Instruments

A Unicam-Mattson 1000 FT-IR spectrometer was used to make IR measurements (KBr discs). A Spectrospin-Bruker Ac 200 MHz Spectrometer was used to perform ¹H-NMR measurements. TMS was used as an internal reference while the samples were dissolved in DMSO. On a Unicam UV2-300 UV-VIS spectrophotometer, electronic

Absorption spectra

In the wavelength range 200–500 nm, the electronic absorption spectra of the formed CT complexes which resulted from reacting picric acid (PA) to chlorothiazide (CH) in acetonitrile, were scanned (Fig. 1a). The absorption bands in the spectrum of picric acid appeared at 315, 340, and 400 nm, and chlorothiazide at 200 nm. The new absorption bands of the resulting CH/PA CT complex appeared at 295, 345, and 430(sh) nm. Fig. 1b shows UV–vis spectra of acetonitrile solutions of chlorothiazide (CH)

Conclusion

Successfully synthesized two charge-transfer (CT) complexes between chlorothiazide (CH) as a donor and picric acid (PA) and iodine (I₂) as π- and σ-acceptors, respectively. The synthesized complexes were characterized by FTIR, ¹H-NMR, and UV–vis spectroscopy. The stoichiometry of the CT complexes was found to be 1:1 (D:A). The equilibrium constant and molar extinction coefficient was determined using Benesi-Hildebrand and its modification methods. The theoretical data obtained by DFT

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgement

Taif University Researchers Supporting Project number (TURSP-2020/01), Taif University, Taif, Saudi Arabia.

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View full text

Intermolecular charge-transfer complexes between chlorothiazide antihypertensive drug against iodine sigma and picric acid pi acceptors: DFT and molecular docking interaction study with Covid-19 protease

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Reagents

Instruments

Absorption spectra

Conclusion

Declaration of competing interest

Acknowledgement

Clinical evaluation of chlorothiazide

Circulation

J. Pharm. Pharmacol.

Pharmazie

Interactions of intrinsically disordered proteins with the unconventional chaperone human serum albumin: from mechanisms of amyloid inhibition to therapeutic opportunities

Biophys. Chem.

Polarographic reduction of 1, 2, 4-benzothiadiazine-1, 1-dioxides and related compounds

Anal. Chem.

Spectrophotometric studies on the photostability of some thiazide diuretics in ethanolic solution

J. Pharmaceut. Biomed. Anal.

Rev.Roum.Chim.

Charge transfer complexes of pyrazolones with iodine

Microchem. J.

Charge transfer complexes of benzimidazoles with pi-acceptors, Egypt

J. Chem.

Spectroscopic and X-ray crystal structure of 2-aminobenzimidazole-trinitrobenzene charge transfer and 2-aminobenzimidazole-picric acid ion-pair derivatives

J. Mol. Struct.

Spectroscopic and X-ray crystal structure studies of 2-aminothiazole-3, 5-dinitrobenzoic acid and 3, 5-dinitrosalicylic acid derivatives

J. Indian Chem. Soc.

Spectrophotometric determination of flucloxacillin in pharmaceutical preparations using some nitrophenols as a complexing agent

Spectrochim. Acta Mol. Biomol. Spectrosc.

Charge-transfer complexes of phenylephrine with nitrobenzene derivatives

Spectrochim. Acta Mol. Biomol. Spectrosc.

Spectroscopic and physicochemical studies of charge-transfer complexes of some benzanthrone derivatives" luminophore dyes" with iodine as s--acceptor

Can. J. Anal. Sci. Spectrosc.

Can. J. Anal. Sci. Spectrosc.

Study of Charge transfer complexes of chlorothiazide

Aswan Univ. J. Environ. stud.

The effect of d-functions on molecular orbital energies for hydrocarbons

Chem. Phys. Lett.

Chemcraft-Graphical Program for Visualization of Quantum Chemistry Computations, Trial Version. Ivanovo, Russia, Academic Version, 1

Open Babel: an open chemical toolbox

J. Cheminf.