Investigations of the Molecular Nature of Low-Molecular-Mass Copper(II) Ion Complexes in Human Saliva: Physiological and Toxicological Significance

Copper is an essential trace element that plays critical roles in enzymatic processes and cellular metabolism. However, excessive exposure to its ions can lead to toxicity through oxidative stress mechanisms. Therefore, the chemical ‘speciation’ of copper(II) ions (Cu(II)) in biological fluids such as saliva is of critical importance. However, currently this phenomenon remains poorly understood, despite its importance for our understanding of bioavailability, toxicity, and sensory perception. Therefore, this study employed 1H nuclear magnetic resonance (NMR) spectroscopy, Fourier-transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy, and scanning electron microscopy (SEM) to investigate the molecular nature and complexation characteristics of low-molecular-mass Cu(II) complexes formed in human whole mouth salivary supernatant (WMSS) samples. Findings obtained revealed that Cu(II) ions form distinct complexes with salivary biomolecules, particularly amino acids such as histidine and glutamine, aromatic metabolites, proteins, and further small organic biomolecules, e.g., carboxylic acid anions. These results provide new insights into copper speciation in the oral cavity, with implications for dietary Cu(II) ion availability, metallic taste perception, and potential toxicological risks associated with elevated oral exposure levels.