Journal of Molecular Structure 1224 (2021) 129267 Contents lists available at ScienceDirect Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstr Synthesis, crystal structure, anti-cancer, anti-inflammatory anti-oxidant and quantum chemical studies of 4-(pyrrolidine-2,5–dione–1-yl)phenol Saba Zulfiqar a , Muhammad Haroon a , Mirza Wasif Baig b , Muhammad Tariq c , Zahoor Ahmad a , Muhammad Nawaz Tahir d , Tashfeen Akhtar a,∗ a Department of Chemistry, Mirpur University of Science and Technology (MUST), 10250 Mirpur, AJK, Pakistan b J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, Czech Republic c Department of Biotechnology, Mirpur University of Science and Technology (MUST), 10250 Mirpur, AJK, Pakistan d Department of Physics, University of Sargodha, Sargodha Punjab, Pakistan a r t i c l e i n f o Article history: Received 27 May 2020 Revised 4 September 2020 Accepted 13 September 2020 Available online 18 September 2020 Keywords: Pyrrolidinedione Anti-inflammatory Antioxidant Anticancer Quantum chemical DFT DLPNO-STEOM-CCSD a b s t r a c t 4-(Pyrrolidine-2,5–dione–1-yl)phenol (PDP) prepared by establishing a new protocol from 4-aminophenol and succinic anhydride using glacial acetic acid as a solvent. The structure of PDP was initially verified by FT-IR, 1 H and 13 C NMR spectroscopy and further confirmed by single crystal XRD and mass spec- trometry techniques. These properties of PDP were also evaluated by DFT, TD-DFT and quantum chemical methods. The molecular structure of PDP was computationally examined by density functional theory (DFT/B3LYP/cc-pVTZ and DFT/PBE0/cc-pVTZ methods). The MEP map shows that phenyl ring with neg- ative electrostatic potential while pyrrolidine ring has slight positive electrostatic potential. Vibrational assignments, chemical shifts and geometrical parameters (bond lengths, bond angles, torsion angles) of PDP were calculated and found in good agreement with experimental results. The computed mass spec- trum also exhibited important peaks including the base peak. PDP has higher anti-inflammatory activity 64.9 ± 2.2% at 50 mg/kg as compared to standard COX-1 inhibitor Ibuprofen 47±1.9%. The anticancer activity also exhibited significant inhibition of cancer for HT-29 cell line. The results imply the possible anti-inflammatory application of the compound beside some structural modifications may lead to estab- lishing a new anticancer drug. © 2020 Published by Elsevier B.V. 1. Introduction Cyclic imides attain a prestigious position in chemistry and pharmaceutical industry [1]. They possess many pharmacological and chemotherapeutical applications. A large number of hetero- cyclic compounds have been synthesized, using imides as sub- strate, reagent or catalyst, specifically containing phthalimide, NBS or succinimide [2]. Succinimide being part of many therapeutical agents possessing many biological applications like analgesic [3], CNS depressant [4], anti-tumor [5], anorectic [6], cytostatic [7], anti-spasmodic [8], nerve conduction blocking [9], muscle relaxant [10], bacteriostatic [11], anti-fungal [12], anti-bacterial [13], anti- convulsant [14], hypotensive [15] and anti-tubercular [16]. In agri- culture, some imides are used to stimulate the growth of plants e.g.,2,4-dichlorophenyl succinimide for the growth of wheat [17]. A ∗ Corresponding author. E-mail address: tashfeenchem@must.edu.pk (T. Akhtar). large number of aromatic imides are used as drugs and brightening agents in industry [18]. The major focus in the synthesis of imides remain in the area of biological applications. The compound, 4- (pyrrolidine-2,5-–dione–1-yl)phenol [19], was synthesized as part of a project on the synthesis of modified phenol formaldehyde resins. The compound was found interesting as similar derivatives of malei and succinic anhydride were reported by Ferera et al. [19]. exhibiting inhibition of acetylcholinesterase. The present study is focused on the comparison of the structural features of the ti- tle compounds, using DFT and experimentally observed results. The purpose of this study is to compare the 3D structure, ob- tained by XRD and DFT. The quantum chemical calculation will assist the researcher in the field of biological studies, who want to perform docking studies and establish SAR. It would assist in explaining the possible interaction sights of such molecules with enzymes. Besides the structural investigations the biological activi- ties of the compound especially anti-cancer, anti-inflammatory and anti-oxidant are also studied. https://doi.org/10.1016/j.molstruc.2020.129267 0022-2860/© 2020 Published by Elsevier B.V.