Biochemistry of mobile zinc and nitric oxide revealed by fluorescent sensors

Abstract

Biological mobile zinc and nitric oxide (NO) are two prominent examples of inorganic compounds involved in numerous signaling pathways in living systems. In the past decade, a synergy of regulation, signaling, and translocation of these two species has emerged in several areas of human physiology, providing additional incentive for developing adequate detection systems for Zn(II) ions and NO in biological specimens. Fluorescent probes for both of these bioinorganic analytes provide excellent tools for their detection, with high spatial and temporal resolution. We review the most widely used fluorescent sensors for biological zinc and nitric oxide, together with promising new developments and unmet needs of contemporary Zn(II) and NO biological imaging. The interplay between zinc and nitric oxide in the nervous, cardiovascular, and immune systems is highlighted to illustrate the contributions of selective fluorescent probes to the study of these two important bioinorganic analytes.

Figure 1

Selection of fluorescent turn-on sensors for biological zinc. FluoZin-3, RhodZin-3, TSQ, 6-methoxy-8-p-toluenesulfonamidequinoline; Zinquin-A, carboxylic acid form of Zinquin; Zinquin-E, ethyl ester form of Zinquin; ZP1, ZPP1, ZnAF-2, Newport Green DCF.

Figure 2

Selected ratiometric fluorescent probes for biological zinc. Et₂N, ⁿBu, NEt₂, ZnIC, ZTRS, 1, fluorescein-rhodamine construct 1.

Figure 3

(a) Treatment of o-phenylenediamine with NO under aerobic conditions results in triazole formation. (b) Fluorescent probes for NO based on o-phenylenediamine functionality. DAC-P, DAN, 2,3-diaminonaphthalene; DAF-2, DAF-2 DA, DAF-FM, DAF-FM DA, DAQ, 1,2-diaminoanthraquinone; DAR-4, DAR-4M, DAR-4M AM, DAMBO-P^H, DAMBOO, nPr.

Figure 4

(a) Ligands with secondary amines able to bind Cu(II) are nitrosated upon treatment of NO. (b) Fluorescent probes for NO based on Cu(II)-mediated amine nitrosation. FL1, FL2, FL2E, FL2A, MNIP.