Synthesis, structure, Hirshfeld surface, DFT and in silico studies of 4- [(E)-(2, 5-dimethoxybenzylidene)amino]-1,5-dimethyl-2-phenyl-1,2- dihydro-3H-pyrazol-3-one (DMAP) and its metal complexes Lilian C. Ekowo a , Samson I. Eze a, * , Julius C. Ezeorah a , Tania Groutso b , Simeon Atiga c , Joseph R. Lane c , Sunday Okafor d , Kovo G. Akpomie a, e , Obinna C. Okparaeke a, c a Department of Pure and Industrial Chemistry, University of Nigeria, Nsukka, 410001, Nigeria b School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland,1142, New Zealand c School of Science, University of Waikato, Private Bag 3105, Hamilton, 3240, New Zealand d Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, 410011, Nsukka, Enugu State, Nigeria e Department of Chemistry, University of the Free State, Bloemfontein, South Africa article info Article history: Received 7 January 2020 Received in revised form 25 February 2020 Accepted 29 February 2020 Available online 3 March 2020 Keywords: Schiff base XRD DFT Complexes abstract The synthesis of the Schiff base ligand 4-[(E)-(2,5-dimethoxybenzylidene)amino]-1,5-dimethyl-2- phenyl-1,2-dihydro-3H-pyrazol-3-one (DMAP) and its Co(II) and Ni(II) complexes is reported. The ligand and complexes were characterized by NMR, ESI-MS and IR techniques. The XRD data showed that the compound crystallized in the orthorhombic crystal system with the P2 1 2 1 2 1 space group. The mo- lecular structure of the ligand shows the phenyl-pyrazole and di-methoxyphenyl group on alternate sides of the azomethine functionality. The Cu(II) and Co(II) complexes of the ligand were obtained by the reaction of a 2:1 mol ratio of the ligand and the metal salts respectively. Evidence from U$Vevis, IR and ESI-mass spectral analysis of the complexes suggest the formation of bidentate tetrahedral complexes. Drug activity relationship of the synthesized ligand and complexes were evaluated and DMAP showed significant binding affinity upon interaction with 4KW5 (antitubercular drug target) and 1REV (antiviral drug target). DMAPCo and DMAPCu showed positive interactions with the bacterial agents that were used. Hirshfeld surface analysis was employed to estimate the strength of the intermolecular non- covalent interactions in the ligand. © 2020 Elsevier B.V. All rights reserved. 1. Introduction Schiff bases are an interesting class of organic compounds because of their medicinal properties and participation in vital chemical processes [1 ,2]. The azomethine functional group (C]N) has exceptional donor properties and is vital in-terms of coordi- nation chemistry. A good number of the transition metal complexes containing Schiff base ligands have been reported in the literature, and their applications in clinical, analytical and industrial catalysis are also well documented [1e3]. Multidentate Schiff bases have been widely used in coordination chemistry and their metal com- plexes are widely used as catalysts as well as-antifungal, antitumor and anti-HIV agents [4e6]. The synthesis of Schiff base ligands ranges from tedious refluxing to simple condensation reactions [1 ,4,7 ,8]. Recently Ezeorah et al. reported a one-pot condensation of amino alcohol and dihydroxy benzaldehyde using water as the solvent [1]. Other synthetic methods for a variety of Schiff base li- gands exist in the literature [410] 4-Aminoantipyrine is commonly applied with benzocaine as an analgesic to treat ear pain and discomfort. Studies have shown that 4-aminoantipyrine exhibits minimum protein binding and is fully absorbed in the gastrointestinal tract, before being extensively metabolized by cytochrome P450 [10]. It has also been identified as an intermediate in the biochemical production of peroxides or phenols and colorimetric determinations of phenols [10]. More- over, free amino groups in the pyrazole ring of 4-aminoantipyrine allows them to form Schiff bases with aldehydes and ketones [10, 11]. Furthermore, heterocycles, based on 4-aminoantipyrine are of * Corresponding author. Department of Pure and Industrial Chemistry, University of Nigeria, Nsukka, 410001, Nigeria. E-mail addresses: eze.samson@unn.edu.ng (S.I. Eze), obinna.okpareke@unn.edu. ng (O.C. Okparaeke). Contents lists available at ScienceDirect Journal of Molecular Structure journal homepage: http://www.elsevier.com/locate/molstruc https://doi.org/10.1016/j.molstruc.2020.127994 0022-2860/© 2020 Elsevier B.V. All rights reserved. Journal of Molecular Structure 1210 (2020) 127994