Design and synthesis of zinc-selective chelators for extracellular applications

Zinc (Zn2+) is found in every cell in human bodies. A few millimolar of free Zn2+ exists in the vesicles of presynaptic neurons in the mammalian brain and is released by synaptic activity or depolarization, modulating the function of certain ion channels and receptors. Although various chemical tools for measuring Zn2+ in biological samples, such as fluorescent probes for Zn2+, have been developed, Zn2+-selective chelators have room to be improved. Research on Zn2+ signals in the brain has traditionally employed several chelators, which have several shortcomings for biological applications. Here we report the design, synthesis, and properties of new membrane-impermeable chelators selective for Zn2+ and describe biological applications in hippocampal slices. As a result, our newly designed chelator revealed the first biological implication that presynaptic Zn2+ can be released in the CA1 region. This confirms the utility of these new chelatotrs as extracellular Zn2+ chelators for biological applications.