Small-molecular Fluorescent Probes for the Detection of Hydrogen Polysulfides and Nitroxyl

It is generally established that the intracellular reactive nitrogen species (RNS) which contain nitrogen atoms are one class of highly chemical active species. These species have attracted increasing attention and become an active research field based on their key roles in special functions during a series of physiological and pathological processes. In order to elucidate these roles of RNS, the design and development technology for selective and sensitive detection to RNS in vivo are crucial. Advanced with high sensitivity, good selectivity, noninvasive detection and real-time visualization in situ, fluorescent probes provide facilitative and effective chemical approaches in modern biochemistry analysis. Progress in the field of fluorescent probes for RNS promises to advance our knowledge of essential cellular signal transduction during the varieties of physiological and pathological processes, which is indicated in human health and disease. According to the current situation, we review the past four years' latest five types of RNS probes for nitric oxide (NO), peroxynitrite (ONOO-), nitroxyl (HNO), nitrite (NO2-) and nitrogen dioxide (NO2). In this article, the design strategies, fluorescent response mechanisms and biological applications of the probes are discussed. Finally, the prospect to design and applications of probes is given.

Using single crystal X-ray diffraction the structure of polynuclear [Ni6(OH)4(Piv)7(HOC4H8O)(HPiv)4], {K4[Ni12(CO3)2(Piv)16(OH)8(HOC4H8OH)2]}HPiv, {[Ni6(OH)4(Piv)6(HOC4H8O)(Me2CO)(HOC4H8OH)2]4×(Piv)4}, and {K[Ni2L2(Piv)3]}∞ complexes, where HOC4H8OH is 1,4-butanediol, HPiv is pivalic acid, and L is the anion of nitroxyl radical 2,2,5,5-tetramethyl-4-(3′,3′,3′-trifluoro-2′-oxy-1′-propenyl)-3-imidazolin-1-oxyl is determined.

Coordinated nitroxyl anion is produced and released as nitrous oxide by the decomposition of iridium-coordinated nitrosothiols

NO potently up-regulates vascular haem oxygenase-1 (HO-1), an inducible defensive protein that degrades haem to CO, iron and the antioxidant bilirubin. Since several pathological states are characterized by increased NO production and liberation of haem from haem-containing proteins, we examined how NO influences HO-1 induction mediated by haemin. Aortic endothelial cells treated with S-nitroso-N-acetylpenicillamine (SNAP), sodium nitroprusside (SNP) or diethylenetriamine-NONOate (DETA/NO) and haemin exhibited higher levels of haem oxygenase activity compared with cells exposed to NO donors or haemin alone. This was accompanied by a marked increase in bilirubin production and, notably, by a strong magnification of cellular haem uptake. A role for haem metabolites in modulating HO-1 expression by NO was assessed by exposing cells to SNAP, SNP or DETA/NO in medium derived from cells treated with haemin, which contained increased bilirubin levels. This treatment considerably potentiated HO-1 expression and haem oxygenase activity mediated by NO and the use of a haem oxygenase inhibitor abolished this effect. Both iron liberated during haem breakdown and the formation of nitroxyl anion from NO appeared to partially contribute to the amplifying phenomenon; in addition, medium from haemin-treated cells significantly augmented the release of NO by NO donors. Thus we have identified novel mechanisms related to the induction of HO-1 by NO indicating that the signalling actions of NO vary significantly in the presence of haem and haem metabolites, ultimately increasing the defensive abilities of the endothelium to counteract oxidative and nitrosative stress.

The magnetic coupling between the unpaired spin of nitroxyl group (N--O) and its neighbor sp~2 carbon atom has been studied in detail by UHF/6--31G and MP4/6-31G methods. and a number of conjugate nitroxyl diradicals have also been studied by ab initio UHF method. A simple topological rule about the ferromagnetic coupling between two nitroxyl groups has been revealed by our calculation. Based on this rule as well as ab initio cal- culation, some nitroxyl radical models of organic ferromagnets (OFM) have been proposed, and the possible way of synthesis has also been suggested. Moreover, the ab initio UHF- crystal orbital (UHF--CO) method has been used to characterize the electronic band struc- ture of one of the models. The ab initio UHF--CO results show that this model is a very promising candidate of OFM,