Synthesis, X-ray crystallography, COSMO-RS, and molecular electronic property investigation of a novel N-alkyl-substituted 5-chloroisatin derivative

Abstract

A novel isatin derivative namely, 5‑chloro-1-pentylindoline-2,3‑dione was synthesized and thoroughly examined through a multi-technique approach encompassing single-crystal X-ray diffraction (XRD), density functional theory (DFT) computations, wavefunction-based topological analyses, and COSMO-RS solvation modeling. The XRD experiments confirmed the core indoline-2,3‑dione geometry, revealing a pentyl substituent in an all-trans conformation. DFT (B3LYP/6–311+G(d,p)) calculations closely reproduced these structural parameters, enabling deeper exploration of frontier molecular orbitals (FMOs), global reactivity descriptors, and molecular electrostatic potential (MESP). A Natural Bond Orbital (NBO) analysis revealed pronounced hyperconjugation and electron delocalization around the ring system and carbonyl moieties, while the Fukui functions indicated nucleophilic sites near the ring nitrogen and carbonyl oxygens, with electrophilic susceptibility at various ring carbons. The compound’s moderate first hyperpolarizability (β_tot​) suggested potential for second-order nonlinear optical responses. In addition, COSMO-RS (Conductor-like Screening Model for Real Solvents) simulations in water, ethanol, and DMSO highlighted stable solvation energies and a significant hydrogen-bond acceptor capacity at the carbonyl sites. Overall, this integrated study underscores how alkylation modulates the structural, electronic, and solvation characteristics of isatin-based scaffolds, paving the way for further functional or therapeutic applications.