A New Proton Transfer Complex Between 3,4-Diaminopyridine Drug and 2,6-Dichloro-4-nitrophenol: Synthesis, Spectroscopic Characterization, DFT Studies, DNA Binding Analysis, and Antitumor Activity

The proton transfer (PT) complexation reaction between 3,4-diaminopyridine (3,4-DAP), an important drug, and 2,6-dichloro-4-nitrphenole (DCNP) was investigated experimentally and theoretically. The experimental results indicated a chemical reaction occurred because of a hydrogen bonding, followed by...

Full description

Saved in:
Bibliographic Details
Main Authors: Reem M. Alghanmi, Maram T. Basha, Ahlam I. Al-Sulami, Saied M. Soliman, Laila H. Abdel-Rahman
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/29/21/5120
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The proton transfer (PT) complexation reaction between 3,4-diaminopyridine (3,4-DAP), an important drug, and 2,6-dichloro-4-nitrphenole (DCNP) was investigated experimentally and theoretically. The experimental results indicated a chemical reaction occurred because of a hydrogen bonding, followed by proton transfer from the DCNP to the 3,4-DAP in different polar media. The Benesi–Hildebrand equation was used to estimate the formation constant (<i>K</i><sub>f</sub>), molar absorptivity (ε<sub>PT</sub>), and other physical parameters. The formed PT complex was characterized using FTIR, <sup>1</sup>H, and <sup>13</sup>C NMR spectra. In addition, the nanocrystalline structure, particle sizes, and surface morphology of the complex were investigated by XRD and SEM-EDX. The structure of the 1:1 PT complex was calculated theoretically in the gas phase and the presence of solvent effects. Using TD-DFT calculations, the band observed at 406 nm (Calc. 379.5 nm) and 275 nm (Calc. 272.3 nm) could be assigned to the HOMO→LUMO transition (99%), and HOMO→L+3 transition (87%), respectively. The DNA binding ability of the PT complex was investigated, revealing an intercalative binding mechanism with a binding constant K<sub>b</sub> of 4.6 × 10<sup>4</sup> M<sup>−1</sup>. Based on the results of the Ct-DNA binding study, the binding free energy of the PT complex with the receptor of human DNA (PDB ID:1BNA) is found to be −7.2 kcal/mol. The cytotoxic effects of the PT complex were evaluated on selected cancer cell lines, demonstrating significant antitumor activity against A-549 and MCF-7 cancer cell lines.
ISSN:1420-3049