Integrated Experimental and Computational Investigation of a Dual-Functional Colorimetric Probe for Selective Arginine Sensing with Anticancer Activity: Insights from DFT, Molecular Docking, and Molecular Dynamics Simulations

Abstract

A novel anthracene-based Schiff base probe (P1) was synthesized through a facile condensation reaction between an aldehyde and hydrazine hydrate. The resulting compound exhibited exceptional sensitivity and selectivity as a colorimetric chemosensor for arginine detection, with a detection limit of 1.24 nM. Binding stoichiometry and interaction mechanisms were elucidated via UV-Vis spectroscopy, while 1 H NMR titration experiments supported the proposed binding model. Density functional theory studies, including potential energy surface, electrostatic potential, and non-covalent interaction analyses, further corroborated the interaction. These investigations revealed that the optical response of P1 arises from an intramolecular charge transfer mechanism, as confirmed by frontier molecular orbital analysis.Importantly, P1 exhibited promising real-world applicability by successfully detecting arginine in commercial dietary supplements. In addition to its sensing capabilities, P1 demonstrated notable anticancer activity with an IC₅₀ value of 20 µM, indicating its potential therapeutic utility. Molecular docking studies further revealed a significant binding affinity of P1 towards the anti-apoptotic protein Myeloid Cell Leukemia 1 (Mcl-1). This stability was further confirmed via molecular dynamics simulation studies of the 5FC4_P1 complex. Moreover, the haemolysis assay results confirmed that P1 exhibits excellent biocompatibility, further supporting its safety and applicability in therapeutic contexts. These findings suggest that P1 may serve as a dual-function agent with both diagnostic and therapeutic potential in biomedical applications.