Competitive coordination of Cu²⁺ between cysteine and pyrophosphate ion: Toward sensitive and selective sensing of pyrophosphate ion in synovial fluid of arthritis patients

Direct selective and sensitive sensing of pyrophosphate ion (PPi) in synovial fluid of arthritis patients is of great importance because of its crucial roles in the diagnosis and therapy of arthritic diseases. In this study, we demonstrate a sensitive and selective method for PPi sensing in synovial fluid of arthritis patients with gold nanoparticles (Au-NPs) as the signal readout based on the competitive coordination chemistry of Cu²⁺ between cysteine and PPi. Initially, Au-NPs stabilized with cysteine are red in color and exhibit absorption at 519 nm in the UV-vis spectrum. The addition of an aqueous solution of Cu²⁺ to the Au-NPs dispersion containing cysteine causes the aggregation of Au-NPs, resulting in the wine red-to-blue color change and the appearance of a new absorption at 650 nm in the UV-vis spectrum of the Au-NPs dispersion. The subsequent addition of PPi to the Au-NPs aggregation well solubilizes the aggregated Au-NPs with the changes in both the color and the UV-vis spectrum of the Au-NPs dispersion. These changes are ascribed to the higher coordination reactivity between Cu²⁺ and PPi than that between Cu²⁺ and cysteine. On the basis of this, the concentration of PPi can be visualized with the naked eyes through the blue-to-wine red color change of the Au-NPs dispersion and quantitatively determined by UV-vis spectroscopy. Under the optimized conditions, the ratio of the absorbance at 650 nm (A₆₅₀) to that at 519 nm (A₅₁₉) shows a linear relationship with PPi concentration within a concentration range from 130 nM to 1.3 mM. The method demonstrated here is highly sensitive, free from the interference from other species in the synovial fluid, and is thus particularly useful for fast and simple clinic diagnosis of arthritic diseases.