Spectroscopic and molecular structure (monomeric and dimeric model) investigation of Febuxostat: A combined experimental and theoretical study Jaya Pandey a , Preeti Prajapati a , Anubha Srivastava a , Poonam Tandon a, ⁎, Kirti Sinha a , Alejandro P. Ayala b , Arvind K. Bansal c a Department of Physics, University of Lucknow, Lucknow 226007, India b Departamento de Fisica, Universidade Federal do Ceará, C.P. 6030, 60.455-900 Fortaleza, CE, Brazil c Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062, India abstract article info Article history: Received 10 April 2018 Accepted 20 May 2018 Available online 22 May 2018 Febuxostat (FXT) is a urate-lowering drug and xanthine oxidase inhibitor which is used for the treatment of hy- peruricemia and gout caused by increased levels of uric acid in the blood (hyperuricemia). The present study aims to provide deeper knowledge of the structural, vibrational spectroscopic and physiochemical properties of FXT based on monomeric and dimeric model with the aid of combination of experimental and computational methods. The conformational analysis of form Q has been done to predict the possible structure of unknown form A. Vibrational spectra of form A and Q has been compared to get an idea of hydrogen bonding interactions of form A. A computational study of FXT has been executed at different level (B3LYP, M06-2X, WB97XD) of theory and 6–31 G (d, p) basis set for dimeric model to elucidate the nature of intermolecular hydrogen bond. The red shift observed in the stretching modes of OH, C_O groups and blue shift in stretching mode of C`N group in ex- perimental as well as in theoretical spectra explains the involvement of these groups in intermolecular hydrogen bonding. NBO analysis shows that change in electron density (ED) in the lone pair orbital to σ* antibonding or- bital (LP1 (N39) → σ* (O3-H38)) with maximum value of E(2) energy confirms the presence of hydrogen bond (N39⋯H38-O3) leading to dimer formation. Study of topological parameters was executed for dimer using Bader's atoms in molecules (AIM) theory predicting the partially covalent nature of hydrogen bonds present in the molecule. The study of molecular electrostatic potential surface (MEPS) map ascertains that the C_O, C`N group are prone to electrophilic attack and OH group is active towards nucleophilic attack. The lower en- ergy band gap and higher value of softness of dimeric model of FXT indicates its more reactivity, polarisability than monomeric model. The local reactivity descriptors predict the order of reactive sites towards electrophilic, nucleophilic and radical attack. An investigation made to determine the ligand protein interaction of FXT through docking with different molecular targets reveals the inhibitive as well as antibacterial nature of FXT. © 2017 Elsevier B.V. All rights reserved. Keywords: Febuxostat Polymorphism FT-IR FT-Raman DFT Chemical reactivity Molecular docking 1. Introduction Febuxostat (FXT, 2-[3-cyano-4-(2-methylpropoxy) phenyl]-4- methylthiazole-5-carboxylic acid) is a urate-lowering drug (a xanthine oxidase inhibitor) and used for the treatment of hyperuricemia and gout [1–3] which is caused by increased levels of uric acid in the blood (hy- peruricemia) [4]. At present, the commercially available drug allopuri- nol is a xanthine oxidase inhibitor. Since it is a xanthine oxidase inhibitor thus it lowers the oxidation of hypoxanthine to xanthine and xanthine to uric acid thereby resulting in reduction of serum uric acid and uric acid excretion and thus increases the concentration of the hypoxanthine and xanthine in the blood and urine. Hence, allopurinol is effective when the hyperuricaemia is due to overproduction or underexcretion of uric acid. Therefore, FXT can be used as an alternative to allopurinol [5,6]. The structure of FXT is shown in Fig. 1. The spectro- scopic techniques are the best tools to obtain information about the structure, conformation, inter and intramolecular interactions of mole- cules [7]. Theoretical simulations give a deeper understanding of the vi- brational spectra of complicated molecules [8]. Density functional theory (DFT), a powerful computational method widely used to study molecular structure, electronic properties, hydrogen bonding, chemical reactivity and biological activity of pharmaceutical compounds [9,10]. In continuation to our previous work on the study of hydrogen bonding, conformation, chemical and biological activity of active phar- maceutical ingredients (API) [11–13], FXT has been studied using Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 203 (2018) 1–12 ⁎ Corresponding author. E-mail address: tandon_poonam@lkouniv.ac.in (P. Tandon). https://doi.org/10.1016/j.saa.2018.05.074 1386-1425/© 2017 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy journal homepage: www.elsevier.com/locate/saa