Synthesis, antioxidant, DNA interaction, electrochemical, and spectroscopic properties of chromene-based Schiff bases: Experimental and theoretical approach

Abstract

Two chromene-based Schiff base ligands were synthesized by the condensation of 5-hydroxy-2,2-dimethyl-2H-chromene-6-carbaldehyde with 2-aminodiphenylamine and 1,8-diaminonaphthalene: (E)-2,2-dimethyl-6-(((2-(phenylamino)phenyl)imino)methyl)-2H-chromen-5-ol (2) and (E)-6-(((8-aminonaphthalen-1-yl)imino)methyl)-2,2-dimethyl-2H-chromen-5-ol (3). The compounds were characterized by Fourier transform infrared (FT-IR), absorption (UV-Vis) and nuclear magnetic resonance (NMR) spectroscopies, in addition to mass spectrometry (MS) analyses; the results of which were rationalized using density functional theoretical (DFT) calculations. Antioxidant activity of the Schiff bases was determined using the DPPH free radical scavenging and CUPric Ion Reducing Antioxidant Capacity (CUPRAC) assays. Compound 3 (IC50 = 14 μM) showed greater free radical scavenging ability than compound 2 (35 μM), and was also more effective than ascorbic acid and Trolox. DFT studies indicate that the HAT mechanism is favored over SET for DPPH scavenging. Both compounds exhibited stronger Cu(II) ion reducing capacity than Trolox and ascorbic acid with Trolox equivalent activity coefficient (TEAC) values of 2.0 and 1.6 for compounds 2 and 3, respectively. Furthermore, DNA cleavage and binding properties were determined using gel electrophoresis, UV-Vis spectroscopy, and cyclic voltammetry. The compounds showed copper-mediated cleavage of plasmid DNA and strong binding to DNA, with binding constants on the order of 104 M−1. The strength of DNA binding was verified by molecular docking analysis using two DNA models: a B-DNA dodecamer (-8.4 to -9.3 kcal/mol) and a hexamer (-7.8 to -7.9 kcal/mol). Overall, the chromene Schiff bases show promise as antioxidant and DNA binding agents.