Volume 4 | Issue 3 | 1 of 9 Chem Pharm Res, 2022 Structure, Quantum Chemical and In Silico Molecular Docking Analysis of some Di-Ortho-Substituted Halogenated Biphenyls 1 Chemical Crystallography Laboratory, Department of Physics, University of Jammu, Jammu Tawi–180006, Jammu & Kashmir (UT), India. 2 Department of Physics, Thanthai Periyar Government Institute of Technology, Vellore- 632002, Tamil Nadu, India. 3 Department of Physics, Agni College of Technology, Old Mahabalipuram Road, Thalambur, Chennai-600130, Tamil Nadu, India. Neha Kumari 1 , Ruchika Sharma 1 , Mulveer Singh 1 , Jayakumar Mohan Raj 2 , Saminathan Murugavel 2 , Sonachalam Sundramoorthy 3 , and Rajni Kant 1* Chemical & Pharmaceutical Research ISSN 2689-1050 Review Article Citation: Kumari N, Sharma R, Singh M, et al. Structure, Quantum Chemical and In Silico Molecular Docking Analysis of some Di- Ortho-Substituted Halogenated Biphenyls. Chem Pharm Res. 2022; 4(3): 1-9. * Correspondence: Rajni Kant, Chemical Crystallography Laboratory, Department of Physics, University of Jammu, Jammu Tawi-180006, India, Tel/Fax [O]: +91 191 243 2051. Received: 24 Jul 2022; Accepted: 10 Sep 2022; Published: 16 Sep 2022 ABSTRACT The structures of three di-ortho-substituted halogenated biphenyls have been revisited for their optimized geometry and other quantum chemical investigations. The X-ray data, in conjunction with quantum chemical investigations, reveals some interesting results. The Hirshfeld surface analysis helps visualize various intermolecular interactions and the energy frameworks dwell further on the dominant interaction energy component for each structure. To study the inhibitory behaviour of each biphenyl against Cytochrome-P450-14alpha-sterol demethylase fungal enzyme (PDB code: 1EA1), the results of molecular docking studies suggest that the di-ortho-substituted halogenated biphenyls may be regarded as efective and efcient antifungal drugs. Keywords Density functional theory, Hirshfeld surface analysis, Interaction energy, Mulliken charges, Molecular docking. Introduction Biphenyls are an important intermediate in organic chemistry that serves as the structural moiety in a wide range of compounds with signifcant biological activities [1]. Being a neutral molecule, it is least reactive and required to be functionalized by the introduction of some active groups [2]. Substituted biphenyls have been reported as important pharmacologically important molecules exhibiting sufcient antifungal activity [3]. These molecules have caught the interest of researchers, particularly for their molecular geometry, crystallization behaviour, crystal packing, thermal motion analysis, the torsion around the biaryl bond (that is considered to have a signifcant impact on bioactivities of biphenyls) [4,5] and their coplanar conformation in the crystalline state at room temperature (indicating a dihedral twist of ~ 44º in the gas phase) [6]. Halogenated-substituted biphenyls have been extensively used as an industrial intermediate in the production of heat transfer fuids, in the synthesis of chemical compounds, formulations for dye carriers in textile dyeing and pesticides in the form of PCB (Polychlorinated biphenyl). These are reportedly being used in medical chemistry for antimicrobial, antifungal, antidiabetic, analgesic, anti-infammatory activities, etc [7-10]. In view of some wide-ranging applications of ortho-substituted halogenated biphenyls, the theoretical studies (DFT, Hirshfeld surface, energy frameworks, and molecular docking) on three CSD- mined crystal structures of biphenyls, (M-1) 2,2’difuorobiphenyl (CSD code: PUGPIQ), (M-2) 2,2’dichlorobiphenyl (DCLBIP) and (M-3) 2,2’bromobiphenyl (HIQQON), have been reported. The X-ray crystallographic structures of these three chemically- similar-looking structures [11-13] have been identifed from the CSD database (version: 2022) and their chemical structures are presented in Figure 1.