Spectroscopic and quantum chemical investigations to explore the effect of intermolecular interactions in a diuretic drug: Hydrochlorothiazide

Arti Yadav; Rajni Chaudhary; Ashok Singh Bahota; Preeti Prajapati; Jaya Pandey; Aditya Narayan; Poonam Tandon; Venu R Vangala

doi:10.1016/j.saa.2022.121931

Spectroscopic and quantum chemical investigations to explore the effect of intermolecular interactions in a diuretic drug: Hydrochlorothiazide

Spectrochim Acta A Mol Biomol Spectrosc. 2023 Jan 15:285:121931. doi: 10.1016/j.saa.2022.121931. Epub 2022 Sep 27.

Authors

Arti Yadav¹, Rajni Chaudhary¹, Ashok Singh Bahota¹, Preeti Prajapati¹, Jaya Pandey¹, Aditya Narayan², Poonam Tandon³, Venu R Vangala²

Affiliations

¹ Department of Physics, University of Lucknow, Lucknow 226 007, India.
² Centre for Pharmaceutical Engineering Science, School of Pharmacy and Medical Sciences, University of Bradford, Richmond Road, Bradford BD7 1DP, United Kingdom.
³ Department of Physics, University of Lucknow, Lucknow 226 007, India. Electronic address: tandon_poonam@lkouniv.ac.in.

PMID: 36198240
DOI: 10.1016/j.saa.2022.121931

Abstract

Hydrochlorothiazide (HCTZ) being a diuretic drug widely used in anti-hypertensive therapy as it lowers the blood pressure by reducing the reabsorption of electrolytes in kidney resulting an increment of urine output and lowering the blood pressure. The purpose of the present work is to study the structural, vibrational and chemical properties of HCTZ based on its monomeric, dimeric and trimeric models by utilizing computational methods and experimental techniques. Density functional theory (DFT) with functional B3LYP and 6-311++G (d, p) basis set was used for a detailed computational study. Monomeric, dimeric and trimeric models of HCTZ have been studied for a better understanding of inter- and intramolecular hydrogen bonding. FT-IR (400-3800 cm^-1) and FT-Raman (100-3600 cm^-1) spectroscopy have been utilized for the characterization of HCTZ. The shifting in wavenumber of NH₂ and OSO group were observed in dimer and trimer due to the formation of intermolecular hydrogen bonding. Quantum theory of atoms in molecules (QTAIM) along with natural bond orbital (NBO) analysis were performed to examine the nature and strength of hydrogen bonding which showed that all the interactions were medium and partially covalent in nature; transition from LP(3)O15 → σ*(H46 → N32) and LP(3)O39 → σ*(H74 → N51) were responsible for the formation of O15•••H46 and O39•••H74 H-bonds, respectively. HOMO-LUMO energies predicted the chemical reactivity and stability of the molecule and the energy gap for dimer (4.6240 eV) and trimer (4.0493 eV) was found to be lesser than the monomer (5.0888 eV) which showed that the dimer and trimer have predicted more chemical reactivity in comparison to monomer. The most electronegative electrostatic potential was observed around the OSO group and the most electropositive potential around the amide group from MEPS analysis. Global as well as local reactivity descriptors have predicted the reactivity and hence, stability of the title molecule.

Keywords: Density Functional Theory; Hydrochlorothiazide; Hydrogen bonding; Vibrational spectroscopy.

MeSH terms

Diuretics*
Hydrochlorothiazide*
Models, Molecular
Quantum Theory
Spectroscopy, Fourier Transform Infrared
Spectrum Analysis, Raman

Substances

Hydrochlorothiazide
Diuretics