Journal of Molecular Structure 1225 (2021) 129146 Contents lists available at ScienceDirect Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstr Spectroscopic, quantum chemical, hydrogen bonding, reduced density gradient analysis and anti-inflammatory activity study on piper amide alkaloid piperine and wisanine J. Priscilla a,b , D. Arul Dhas b,∗ , I. Hubert Joe c , S. Balachandran d a Research Scholar, Register number: 12097, Manonmaniam Sundaranar University, Abishekapatti, Tirunelveli - 627 012, Tamil Nadu, India b Department of Physics, Physics Research Centre, Nesamony Memorial Christian College, Marthandam - 629 165, Kanyakumari District, Tamilnadu, India c Centre for Molecular and Biophysics Research, Department of Physics, Mar Ivans College, Thiruvananthapuram 695015, Kerala, India d NSS College Ottapalam, Palakad - 679103, Kerala, India a r t i c l e i n f o Article history: Received 18 January 2020 Revised 14 August 2020 Accepted 24 August 2020 Available online 25 August 2020 Keywords: Alkaloid NCA RDG Fukui function Hirshfeld Anti-inflammatory activity a b s t r a c t A combined experimental and theoretical quantum chemical calculations have been carried out to study the geometry, vibrational wavenumbers, electronic transition and anti-inflammatory activity of piper amide alkaloid compound piperine (PP). Computational study is done on other piper amide alkaloid wisa- nine (WS) using B3LYP/6–311G(d,p) basis set. The conformational analysis is carried out to find the most stable geometry of PP and WS. Normal coordinate analysis (NCA) is performed to analyse the vibrational wavenumber and potential energy distribution (PED) assignments. The interaction of PP and WS with water molecule is also performed to know the effect of hydrogen bond on its geometry and vibrational spectra. Natural bond orbital (NBO) analysis was performed to study the charge delocalization, hyper- conjugative interaction, inter and intramolecular hydrogen bonding interaction in the molecule to know about anti-inflammatory active site. Non-covalent interactions are analyzed using reduced density gradi- ent (RDG) analysis. The UV–visible spectrum of PP in ethanol and water solvent is recorded and com- pared with calculated data. The 1 H and 13 C NMR spectra of PP are recorded and analyzed. The chemical stability and anti-inflammatory activity of title compound are evaluated by HOMO-LUMO analysis. The chemical reactivity descriptors are calculated to predict the reactivity and stability of the molecule. The intermolecular interactions and crystal packing of title compound are studied by Hirshfeld surface anal- ysis techniques. PP is screened for its anti-inflammatory activity. Molecular docking study predicts the binding site of PP and WS into its target protein. © 2020 Elsevier B.V. All rights reserved. 1. Introduction Alkaloids are secondary plant substances, specific to partic- ular plants and plant parts [1]. Alkaloids are of great inter- est to researcher, due to their substantial applications in phar- macological industry. Piperine (PP) [(2E,4E)−5-(1,3-benzodioxol-5- yl)−1-piperidin-1-ylpenta-2,4–dien–1-one] is the naturally occur- ring piper amide alkaloid isolated from plant spices of Piper ni- grum and Piper guineense [2]. The molecular formula of PP is C 17 H 19 O 3 N. Piperine was first synthesized in 1876. Its molecule consists of a benzodioxole ring and a piperidine ring, linked through a carbonyl amide moiety and side chain with an alkene bridge. PP finds application in a variety of areas such as insecticide, anti-inflammatory, antimalarial, antioxidant, an- ∗ Corresponding author. E-mail address: aruldhas2k4@gmail.com (D. Arul Dhas). timutagenic, antitumor, analgesic, anticonvulsant, antibacterial, an- tidepressant and anti-proliferative agent [3,4]. Bioactive amide [2] piperine inhibits cancer by targeting human G-quadruplex DNA like telomeric DNA [5]. For piper amide compounds Ped- ersen et al. suggest that the active site of piperine is lipophilic chain, that contains four carbon atoms which are alternatively at- tached as single and double conjugated bonds adjacent to the amide carbonyl moiety responsible for binding with target pro- tein [6]. Wisanine (WS) [(2E,4E)−5-(6–methoxy-1,3-benzodioxol-5- yl)−1-(1-piperidinyl)−2,4-pentadien-1-one] is extracted from the root of P.gunieense [7] and chemical formula C 18 H 21 O 4 N, which also belongs to the alkaloid family. Wisanine is the 2–methoxy derivative of piperine. WS has attracted increasing attention due to numerous pharmacological applications as sedative, transquilliz- ing, insecticide, anti-inflammatory and some anticonvulsant prop- erties [8]. The study of the compounds with their interaction with water is very important because it plays an important role in https://doi.org/10.1016/j.molstruc.2020.129146 0022-2860/© 2020 Elsevier B.V. All rights reserved.