Extracellular Cu2+ pools and their detection: From current knowledge to next-generation probes

Copper (Cu) is an essential micronutrient for most organisms and serves mainly as a redox-active catalytic centre in enzymes cycling between Cu+ Cu2+. Membrane transporters shuttles are involved to bring insert Cu into these control tightly the copper metabolism, whose failure can lead severe diseases. The main oxidation state intracellularly Cu+, whereas Cu2+ found extracellular fluids. A basic approach investigate metabolism vivo cellulo contemplates use of luminescent (mostly fluorescent) or magnetic resonance imaging (MRI)-active probes. Here, we focus on sensors state. First, speciation revised, focusing fluids (blood plasma, urine, cerebrospinal fluid, synaptic cleft, milk, saliva, sweat) cell culture media, highlighting notion exchangeable pool. Indeed, contrast bulk measurements, only detect that labile thermodynamically accessible. Thus, kinetics thermodynamics pools determine quantity be measured influence design sensor. study best-known pool blood i.e. serum albumin, shows sensor might need sub-femtomolar affinity compete with endogenous ligands. selectivity probe also discussed, particular against Zn2+, which much more available than (e.g. at least 106 times blood). Finally, analysis literature MRI-active applied media show indeed how challenging such measurement is, none reported convincingly specifically detects biological system. when considering all sought parameters, Cu2+-sensor, specificity towards Cu2+, reversibility, sensitivity MRI response hence required concentration, it becomes clear this huge challenge stand just dawn field.