AUTHOR=Aiello Donatella , Carnamucio Federica , Cordaro Massimiliano , Foti Claudia , Napoli Anna , Giuffrè Ottavia 

TITLE=Ca2+ Complexation With Relevant Bioligands in Aqueous Solution: A Speciation Study With Implications for Biological Fluids

JOURNAL=Frontiers in Chemistry

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.640219

DOI=10.3389/fchem.2021.640219

ISSN=2296-2646

ABSTRACT=<p>A speciation study on the interaction between Ca<sup>2+</sup> and ligands of biological interest in aqueous solution is reported. The ligands under study are <sc>l</sc>-cysteine (<italic>Cys</italic>), <sc>d</sc>-penicillamine (<italic>PSH</italic>), reduced glutathione (<italic>GSH</italic>), and oxidized glutathione (<italic>GSSG</italic>). From the elaboration of the potentiometric experimental data the most likely speciation patterns obtained are characterized by only protonated species with a 1:1 metal to ligand ratio. In detail, two species, CaLH<sub>2</sub> and CaLH, for systems containing <italic>Cys</italic>, <italic>PSH</italic>, and <italic>GSH</italic>, and five species, CaLH<sub>5</sub>, CaLH<sub>4</sub>, CaLH<sub>3</sub>, CaLH<sub>2</sub>, and CaLH, for system containing <italic>GSSG</italic>, were observed. The potentiometric titrations were performed at different temperatures (15 ≤ <italic>t</italic>/°C ≤ 37, at <italic>I</italic> = 0.15 mol L<sup>−1</sup>). The enthalpy and entropy change values were calculated for all systems, and the dependence of the formation constants of the complex species on the temperature was evaluated. <sup>1</sup>H NMR spectroscopy, MALDI mass spectrometry, and tandem mass spectrometry (MS/MS) investigations on Ca<sup>2+</sup>-ligand solutions were also employed, confirming the interactions and underlining characteristic complexing behaviors of <italic>Cys</italic>, <italic>PSH</italic>, <italic>GSH</italic>, and <italic>GSSG</italic> toward Ca<sup>2+</sup>. The results of the analysis of <sup>1</sup>H NMR experimental data are in full agreement with potentiometric ones in terms of speciation models and stability constants of the species. MALDI mass spectrometry and tandem mass spectrometry (MS/MS) analyses confirm the formation of Ca<sup>2+</sup>-L complex species and elucidate the mechanism of interaction. On the basis of speciation models, simulations of species formation under conditions of some biological fluids were reported. The sequestering ability of <italic>Cys</italic>, <italic>PSH</italic>, <italic>GSH</italic>, and <italic>GSSG</italic> toward Ca<sup>2+</sup> was evaluated under different conditions of pH and temperature and under physiological condition.</p>