Lanthanide (Ln3+) complexes of bifunctional chelate: Synthesis, physicochemical study and interaction with human serum albumin (HSA)

Abstract

Bifunctional chelate EDTA-bis amide (N,N'-bis (tyramide)ethylenediamine-N,N'-diacetic acid) that has ability to mimic natural amino acids was synthesized and analyzed by various spectroscopic techniques. The physicochemical studies were performed to calculate the various thermodynamic and kinetic parameters for the synthesized poly-amino carboxylate ligand. The two protonation constant (pka's = 3.460 and 6.722) of the prepared ligand and stability constants (log K_ML's = 15.8, 18.1, 16.2, 18.4, 17.5, 18.9, 13.6 and 12.8) of the complexes formed with Ce³⁺, Sm³⁺, Eu³⁺, Gd³⁺, Tb³⁺, Lu³⁺, Zn²⁺ and Cu²⁺ were determined by potentiometric titration using 0.1 M Me₄NOH as non-aqueous base. The formation kinetics of [EuEDTA-TA₂]⁺ and [CeEDTA-TA₂]⁺ was studied and the rate constants were found to be 2.95 × 10-5 s^-1 and 4.414 × 10-5 s^-1respectively including the exchange reaction of [EuEDTA-TA₂]⁺ with Zn²⁺ and Cu²⁺ spectrophotometrically. The Eu(III) complex of EDTA(TA)₂ gives three emission bands at 480 nm, 540 nm and 610 nm (λ_max = 270 nm, excitation) which shows efficacy of the ligand as an optical imaging agent. Molecular docking studies with Human Serum Albumin (HSA: PDB 1E78) showed binding pattern with the residues Arg218, Arg222, Lys195 and Lys444 in sub domain II A of site I via hydrogen bond and identifies the ligand-HSA interaction and specific insight for transportation to the target sites. Subsequently, fluorescence spectroscopy was performed at λ_ex = 350 nm binding constant for HSA was 5.847 × 10⁴ M^-1 which showed effective quenching effect.

Keywords: EDTA; HSA; Metal kinetics; PDB and log K(ML).