A solution of six-coordinate [Mn(PS2)2] (1) is inert towards nitric oxide (NO) at room temperature. In the presence of a proton source such as p-toluenesulfonic acid or perchloric acid, however, the treatment of 1 with NO in the dark leads to the formation of {MnNO}6 [Mn(NO)(SPS-SPS)] (2) with a metal-diaryldisulphide ligand, as confirmed by several spectroscopy investigations, including single-crystal X-ray diffraction. A possible pathway for the formation of 2 was determined through theoretical studies and involves the following: (i) the thiolato sulphur in 1 interacts with H+ to generate an intermediate [Mn(PS2)(PS2H)]+ (A) with an S⋯H interaction; (ii) the reaction of A with NO yields HNO and an Mn(IV)-bound-thiyl radical species (B); and (iii) the nucleophilicity of the thiyl radical B to an adjacent thiolato sulphur produces a five-coordinate Mn(III)-diaryldisulphide species (C), which reacts with the generated HNO to yield 2. Complex 2 is sensitive to visible light. When photolysis of 2 in solution is performed, complex 1 is regenerated and NO is released, which is related to metal-disulphide/metal-thiolate interconversion.

Nitroxyl (HNO) plays an important role in various physiological activities. It has the potential to be used as a treatment for certain diseases such as alcohol poisoning, acute hypertension, and atherosclerosis. However, traditional methods for detecting HNO are challenging due to its rapid polymerization and elimination into N2O. Therefore, it is crucial to establish direct and effective HNO detection methods to comprehend these physiological processes better. In this study, a new near-infrared fluorescent probe called HXM-P based on the intramolecular charge transfer (ICT) mechanism was designed and synthesized. This probe employs 2-((6-hydroxy-2,3dihydro-1 H-xanthen-4-yl)methylene)malononitrile as a fluorophore and 2-(diphenylphosphine) benzoate as a recognition group. The results showed that probe HXM-P can detect HNO with high sensitivity (1.07 × 10- 8 M). A good linear correlation was observed between the fluorescence intensities at 640 nm and the concentrations of HNO in the range of 0-80 µM (R2 = 0.997). Moreover, probe HXM-P exhibited a rapid response rate (within 15 s) toward HNO, and the fluorescent intensity reached a plateau within 5 min, making it easier to track the highly reactive and short-lived HNO in living systems. Additionally, HXM-P was successfully employed for imaging HNO in HepG2 cells.

Nitroxyl (HNO) is an important reactive nitrogen that is associated with various states in physiology and pathology and plays a unique function in living systems. So, it is important to exploit fluorescent probes with high sensitivity and selectivity for sensing HNO. In this paper, a novel ratiometric fluorescent probe for HNO was developed utilizing intramolecular charge transfer (ICT) and fluorescence resonance energy transfer (FRET) mechanisms. The probe selected coumarin as energy donor, naphthalimide as energy receptor and 2-(diphenylphosphino)benzoate as the sensing site for detecting HNO. When HNO was not present, the 2-(diphenylphosphino)benzoate unit of the probe restricted electron transfer and the ICT process could not occur, leading to the inhibition of FRET process as well. Thus, in the absence of HNO the probe displayed the intrinsic blue fluorescence of coumarin. When HNO was added, the HNO reacted with the 2-(diphenylphosphino)benzoate unit of the probe to yield a hydroxyl group which resulting in the opening of ICT process and the occurring of FRET process. Thus, after providing HNO the probe displayed yellow fluorescence. In addition, the probe showed good linearity in the ratio of fluorescence intensity at 545 nm and 472 nm (I545 nm/I472 nm) with a concentration of HNO (0.1-20 μM). The probe processed a detection limit of 0.014 μM and a response time of 4 min. The probe also specifically identified HNO over a wide pH scope (pH = 4.00-10.00), including physiological conditions. Cellular experiments had shown that this fluorescent probe was virtually non-cytotoxic and could be applied for ratiometric sensing of HNO in A549 cells.

As an important reactive nitrogen species (RNS), HNO has been identified as an essential signaling molecule in many physiological processes. Ferroptosis produces a large amount of reactive oxygen species and reactive nitrogen species. However, the detailed mechanism of HNO during process of ferroptosis is rarely reported, especially in the near-infrared range. So, we designed a new near-infrared (NIR) HNO fluorescent probe X-1 based on a tricyanofuran (TCF) derivative and then applied it in ferroptosis imaging. The TCF derivative was chosen as the NIR fluorophore and 2-(diphenylphosphino)benzoate was used as the recognition group.

In this paper, a novel NIR HNO fluorescent probe X-1 based on tricyanofuran (TCF) derivatives was synthesized using the Staudinger linkage reaction. X-1 exhibited high selectivity for HNO in the near-infrared region (λem = 660 nm). When the recognition group undergoes the Staudinger linkage reaction with HNO, the NIR fluorescence emission increased significantly with the enhancement of the ICT effect. The response mechanism of X-1 to HNO was verified by high-resolution mass spectrometry (HRMS). Probe X-1 has the advantages of fast response (5 min), low detection limit, a large Stokes shift (120 nm) and strong anti-interference ability for HNO recognition. CCK-8 staining result indicates that the probe X-1 has good biocompatibility and little toxic effect on the cells. The probe was successfully applied to imaging the exogenous and endogenous HNO in living cells.

In the near-infrared range, HNO was discovered as a mediator of cellular signaling molecules, increasing in concentration during the process of ferroptosis. Furthermore, using this probe, it was further verified that sorafenib, a commonly used drug for cancer treatment, exerts its therapeutic effect by inducing ferroptosis in cancer cells, leading to cell death.

Nitroxyl (HNO) plays a vital role in various biological functions and pharmacological activities, so the development of an excellent near-infrared fluorescent (NIRF) and photoacoustic (PA) dual-modality probe is crucial for understanding HNO-related physiological and pathological progression. Herein, we proposed and synthesized a novel NIRF/PA dual probe (QL-HNO) by substituting an indole with quinolinium in hemicyanine for the sensitive detection of exogenous and endogenous HNO in vivo. The designed probe showed the highest sensitivity in NIRF mode and a desirable PA signal-to-noise ratio for HNO detection in vitro and was further applied for NIRF/PA dual-modal imaging of HNO with high contrast in living cells and tumor-bearing animals. Based on the excellent performance of QL-HNO, we believe that this study provides a promising molecular tool for further understanding of HNO-related physiological and pathological progression.

The precise release and characterization of nitroxyl (HNO) gas signaling molecule remain a challenge due to its short lifetime to date. To solve this issue, an azobenzene-based HNO donor (Azo-D1) was proposed as a colorimetric and fluorometric chemosensor for HNO releasing, to release both HNO and an azobenzene fluorescent reporter together. Specifically, the Azo-D1 has an HNO release half-life of ∼68 min under physiological conditions. The characteristic color change from the original orange to the yellow color indicated the decomposition of the donor molecule. In addition, the stoichiometry release of HNO was qualitatively and quantitatively verified through the classical phosphine compound trap. As compared with the donor molecule by itself, the decomposed product demonstrates a maximum fluorescence emission at 424 nm, where the increase of fluorescence intensity by 6.8 times can be applied to infer the real-time concentration of HNO. Moreover, cellular imaging can also be achieved using this Azo-D1 HNO donor through photoexcitation at 405 and 488 nm, where the real-time monitoring of HNO release was achieved without consuming the HNO source. Finally, the Azo-D1 HNO donor would open a new platform in the exploration of the biochemistry and the biology of HNO.

Nitroxyl (HNO) exhibits unique favorable properties in regulating biological and pharmacological activities. However, currently, there is only one Cu-based HNO sensor that can be recycled for reusable detection, which is a Cu cyclam derivative with a mixed thia/aza ligand. To elucidate the missing mechanistic origin of its high HNO reactivity and subsequent favorable conformation change toward a stable CuI product that is critical to be oxidized back by the physiological O2 level for HNO detection again, a density functional theory (DFT) computational study was performed. It not only reproduced experimental structural and reaction properties but also, more importantly, revealed an unknown role of the coordination atom in high reactivity. Its conformation change mechanism was found to not follow the previously proposed one but involve a novel favorable rotation pathway. Several newly designed complexes incorporating beneficial effects of coordination atoms and substituents to further enhance HNO reactivity while maintaining or even improving favorable conformation changes for reusable HNO detection were computationally validated. These novel results will facilitate the future development of reusable HNO sensors for true spatiotemporal resolution and repeated detection.

Nitroxyl (HNO) and endoplasmic reticulum (ER) stress are considered to play important effects in the administration of many pathological processes of Parkinson's disease (PD). However, the intricate relationship between the neurotoxicity of HNO and ER stress in the processes of PD is still unknown. To completely comprehend the pathogenic activity of HNO during ER stress and achieve early diagnosis of PD, developing sensitive tools for HNO sensing in vivo is essential. In this work, a two-photon fluorescent probe (KD-HNO) was developed with highly selective and sensitive (7.93 nM) response for HNO in vitro. Then, utilizing KD-HNO, we found that HNO levels were distinctly increased in tunicamycin-stimulated PC12 cells, which are characterized by ER stress and PD features. Most importantly, we detected a considerable increase in HNO levels in the brains of PD-model mice, indicating a positive correlation between PD and HNO levels for the first time. Collectively, these findings revealed that KD-HNO is an excellent tool not only for understanding the biological effects of HNO in pathological processes of PD but also for early PD diagnosis.

In the past decade, gasotransmitters NO^• and H₂S have been thoroughly studied in biological contexts, as their biosynthesis and physiological effects became known. Moreover, an additional intricate crosstalk reaction scheme between these compounds and related species is thought to exist as part of the cascade signaling processes in physiological conditions. In this context, heme enzymes, as modeled by iron porphyrins, play a central role in catalyzing the key interconversions involved. In this work, iron porphyrin interactions with sulfide and nitric-oxide-related species are described. The stability and reactivity of mixed ternary systems are also described, and future perspectives are discussed.

Luminescent molecular probes and nanoscale materials have become important tools in biosensing and bioimaging applications because of their high sensitivity, fast response, specificity, and methodological simplicity. In recent years, there has been a notable advancement in fluorescent probes that respond to the subtle changes in subcellular microenvironments (e.g., polarity, pH, and viscosity) or distribution of certain crucial biomarkers (e.g., reactive oxygen species, ions, amino acids, and enzymes). The dynamic fluctuations of these bio-molecules in subcellular microenvironments control cellular homeostasis, immunity, signal conduction, and metabolism. Their abnormal expressions are linked to various biological disorders and disease states. Thus, the real-time monitoring of such bioactive species is intimately linked to clinical diagnostics. Appropriately designed luminescent probes are ideally suited for desired organelle specificity, as well as for reporting intracellular changes in biochemicals/microenvironmental factors with the luminescence ON response. In this perspective, we review our recent work on the development of fluorescent probes for sensing and imaging within sub-cellular organelles. We have also discussed the design aspects for developing a prodrug with a fluorescent probe as an integral part of possible theranostic applications. An overview of the design principles, photophysical properties, detection mechanisms, current challenges, and potential future directions of fluorescent probes is presented in this feature article. We have also discussed the limitations and challenges of developing the solution platform for sensing technologies in clinical diagnostics.