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

Area of Science:

• Biochemistry
• Analytical Chemistry
• Coordination Chemistry

Background:

• Calcium ions (Ca²⁺) are crucial in biological systems.
• Understanding Ca²⁺ interactions with biomolecules is vital for physiology.
• Ligands such as l-cysteine (Cys), d-penicillamine (PSH), reduced glutathione (GSH), and oxidized glutathione (GSSG) play significant roles in biological processes.

Purpose of the Study:

• To investigate the speciation of Ca²⁺ with biologically relevant ligands in aqueous solution.
• To determine the stoichiometry and stability of Ca²⁺-ligand complexes.
• To evaluate the sequestering ability of these ligands for Ca²⁺ under various conditions.

Main Methods:

• Potentiometric titrations were performed at different temperatures (15–37 °C) and ionic strength (0.15 mol L^-1).
• ¹H NMR spectroscopy, MALDI mass spectrometry, and tandem mass spectrometry (MS/MS) were used to confirm interactions and elucidate mechanisms.
• Enthalpy and entropy changes were calculated, and temperature dependence of formation constants was evaluated.

Main Results:

• Speciation patterns revealed protonated species with a 1:1 metal-to-ligand ratio for Cys, PSH, and GSH.
• Five species (CaLH₅ to CaLH) were identified for the Ca²⁺-GSSG system.
• NMR, MS, and MS/MS results corroborated potentiometric findings, confirming complex formation and interaction mechanisms.
• Simulations predicted species formation in biological fluids, and sequestering abilities were quantified.

Conclusions:

• The study elucidates the complex speciation of Ca²⁺ with Cys, PSH, GSH, and GSSG.
• Thermodynamic data provide insights into the stability and interaction mechanisms.
• The findings are relevant for understanding calcium homeostasis and the role of these ligands in biological systems.