Synthesis, structural determination, in vitro antioxidant and antibacterial efficacy of dispirooxindolopyrrolidine embedded indole heterocycle

• Published in: Journal of molecular structure 2024-01, Vol.1295, p.136680, Article 136680
• Main Authors: Arumugam, Natarajan, Almansour, Abdulrahman I., Alkaltham, Manal Fahad, Soliman, Saied M., Viswanathan, Vijayan, Priya, R. Vishnu, Karuppaiah, Ponmurugan, Alaqeel, Shatha Ibrahim, Dege, Necmi, Perumal, Karthikeyan
• Format: Article
• Language: English
• Subjects: Antibacterial and antioxidant activities; Cycloaddition reaction; DFT studies; Hirshfeld topology analysis; Spirooxindolopyrrolidine
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.136680

•Synthesis of new class of dispiropyrrolidine grafted indole heterocycle.•Compound was achieved in excellent yield employing cycloaddition strategy.•Compound unambiguously assigned by spectroscopic and XRD analysis.•Structural determination of the compound was explored by theoretical study.•Compound displayed potent antibacterial and antioxidant activities. Synthesis of dispirooxindolopyrrolidine embedded indole hybrid heterocycle was achieved in excellent yield employing intermolecular 1,3-dipolar cycloaddition cascade reaction sequence. The non-stabilized 1,3-dipole component was derived from isatin and l-tryptophan under decarboxylative condensation methodology, was reacts with 3-(4-fluorobenzylidene)indolin-2-one to form 5-benzyl-spiro[2.3′]oxindolo-spiro[3.3′′]-oxindolo-4-[4-fluorophenyl-pyrrolidinewith four stereogenic center via two CC and one CN bonds in single synthetic operation. The structure of compound was undoubtably determined by 1D and 2D NMR spectroscopic analysis. The stereo and regiochemistry of cycloadduct was confirmed through single crystal X-ray diffraction studies. The packing aspects of compound 4 were analyzed using Hirshfeld calculations. It is found that the O…H, N…H, C…H and H…H interactions have major role in the crystal stability. Their percentages are estimated to be 10.1, 3.4, 25.0 and 51.0%, respectively indicating that the H…H contacts are the most dominant. Different electronic parameters such as charge population, dipole moment, molecular electrostatic potential map and frontier molecular orbitals as well as their derived reactivity descriptors were presented. Compound 4 showed potent antibacterial efficacy against E. coli with MIC value of >7.8 µg/mL, besides, compound 4 displayed significant antioxidant activity (84.05%) at the concentration of 500 µg/mL.