Synthesis, and spectroscopic, nanostructure, surface morphology, and density functional theory studies of new charge-transfer complexes of amifampridine with π-acceptors

Abstract

The charge transfer (CT) complexes formed between the potassium-channel-blocking drug amifampridine (AMFP) and the π-acceptors; chloranilic acid (CLA) and 2,5-dihydroxy-p-benzoquinone (DHBQ) in both MeOH solutions, and the solid-state were synthesized and fully characterized. The stoichiometry of the complexes formed in MeOH is 1:1, while those of the solid complexes are 2:1 and 1:1 (donor: acceptor) for CLA and DHBQ, respectively. The CT complexes were studied in terms of their formation constants (KCT), molar extinction coefficients (εCT), and spectrophysical and thermodynamic properties, and the results demonstrated the high stability of the complexes in MeOH. The limits of detection and quantification for the complexes by UV–Vis spectrophotometry were also determined. The surface morphologies, particle sizes, and elemental compositions of the complexes were determined, utilizing X-ray powder diffraction, scanning electron microscope, and energy-dispersive X-ray techniques. The molecular structures, and the electronic properties of the complexes were investigated using B3LYP and WB97XD DFT calculations employing 6–31++G(d,p) basis sets, revealing that the magnitude of the CT is 0.357 e in AMFP-CLA and 0.317 e in AMFP-DHBQ, indicating that CLA is a better electron acceptor than DHBQ. The UV–Vis spectral bands observed for AMFP-CLA and AMFP-DHBQ experimentally in MeOH at 488 and 535 nm, respectively, while these bands were calculated at 493.0 at 535.6 nm, respectively, in the same solvent (MeOH). Both bands were found to be due to HOMO→LUMO excitation, where that in the AMFP-CLA complex is an internal electronic transition and that in AMFP-DHBQ complex is a charge transfer based transition from AMFP to DHBQ. Natural bond orbital calculations indicated that the CT processes LP(2)O11→LP*(1)H12 (127.62 kcal mol−1) and LP(1)N20→LP*(1)H12 (317.46 kcal mol−1) in AMFP-DHBQ, and LP(2)O9→LP*(1)H10 (94.84 kcal mol−1) and LP(1)N23→ LP*(1)H10 (363.42 kcal mol−1) in AMFP-CLA provide extra stability to the complexes.