As vital important bioactive species, human serum albumin (HSA) and sulfur dioxide (SO2) are essential molecules in the organisms and act a pivotal part in many biological events. Although studies ...have shown that SO2-induced HSA radicals can cause oxidative damage, the underlying mechanism of the synergistic effect of HSA and SO2 in various diseases is obscure, mainly because of the lack of powerful tools that can simultaneously detect HSA and SO2 in living systems. In this work, we report a novel single-site, double-sensing fluorescent probe 1 for the simultaneous detection of HSA and SO2. The probe is based on our finding that HSA can catalyze a Michael addition reaction between the probe and SO2, which induces a change in fluorescence. Probe 1 can effectively entered the endoplasmic reticulum and can be used to image exogenously introduced and de novo synthesis of HSA in endoplasmic reticulum. Furthermore, the simultaneous detection of HSA and SO2 was realized for the first time with probe 1. More important, we observed that HSA still retains its activity to catalyze the Michael addition reaction of 1 and SO2 in living cells, which may provide a significant boost in the study of the role of HSA in medicine and pharmacy.
A new mitochondria-targeted fluorescent probe HCy-D, constructed by dansyl and hemicyanine fluorophores, for SO2 derivatives (HSO3(-)/SO3(2-)) was presented. This probe was designed based on a new ...FRET platform. HCy-D showed a ratiometric, sensitive and rapid response to HSO3(-)/SO3(2-). Importantly, HCy-D was successfully used for fluorescence imaging of endogenous bisulfite in HepG2 cells, which may benefit cancer diagnosis by discriminating liver cancer cells from normal liver cells.
Abstract Sulfur dioxide (SO2 ) can be endogenously produced by enzymes in mitochondria during oxidation of H2 S or sulphur-containing amino acids, and plays important roles in several physiological ...processes. However, the design and synthesis of fluorescent probes which can detect mitochondrial SO2 and its derivatives in living cells still remain unresolved. Herein, we report the preparation of a lipophilic cationic dye 1 ( Mito-Ratio-SO 2 ), which targets the mitochondria in living cells and is sensitive to the presence of SO2 derivatives. The ratiometric probe Mito-Ratio-SO 2 displays a 170 nm blue-shift in emission with two well-resolved emission bands upon addition of sulfite. Mechanistic studies indicate that three probe-SO2 adducts coexist after reaction, as supported by liquid chromatography and density function theory investigations. Importantly, the ratiometric probe is highly selective for sulfite over other bio-species including H2 S. Fluorescence co-localization studies indicate that the probe localizes solely in the mitochondria of HeLa cells. Last but not least, fluorescent imaging of HeLa cells successfully demonstrates the detection of intrinsically generated intracellular SO2 derivatives in living cells.
A three-component reaction of alkenyl-tethered oxime ethers, sodium metabisulfite, and aryldiazonium tetrafluoroborates under mild conditions is developed. This reaction proceeds at room temperature ...without any oxidants or additives, affording β-amino sulfones with good functional group tolerance through aminosulfonylation of unactivated alkene. Mechanistic studies show that this transformation undergoes a radical process, including radical trapping with sulfur dioxide and radical 1,4-amino migration.
Sulfur dioxide (SO
), long considered to be a harmful atmospheric pollutant, has recently been posited as the fourth gasotransmitter, as it is produced endogenously in mammals and has important ...pathophysiological effects. The field of tumor therapy has witnessed a paradigm shift with the emergence of SO
-based gas therapy. This has been possible because SO
is a potent glutathione consumer that can promote the production of reactive oxygen species, eventually leading to oxidative-stress-induced cancer cell death. Nevertheless, this therapeutic gas cannot be directly administrated in gaseous form. Thus, various nano formulations incorporating SO
donors or prodrugs capable of storing and releasing SO
have been developed in an attempt to achieve active/passive intratumoral accumulation and SO
release in the tumor microenvironment. In this review article, the advances over the past decade in nanoplatforms incorporating sulfur SO
prodrugs to provide controlled release of SO
for cancer therapy are summarized. We first describe the synthesis of polypeptide SO
prodrugs to overcome multiple drug resistance that was pioneered by our group, followed by other macromolecular SO
prodrug structures that self-assemble into nanoparticles for tumor therapy. Second, we describe nanoplatforms composed of various small-molecule SO
donors with endogenous or exogenous stimuli responsiveness, including thiol activated, acid-sensitive, and ultraviolet or near-infrared light-responsive SO
donors, which have been used for tumor inhibition. Combinations of SO
gas therapy with photodynamic therapy, chemotherapy, photothermal therapy, sonodynamic therapy, and nanocatalytic tumor therapy are also presented. Finally, we discuss the current limitations and challenges and the future outlook for SO
-based gas therapy. STATEMENT OF SIGNIFICANCE: Gas therapy is attracting increasing attention in the scientific community because it is a highly promising strategy against cancer owing to its inherent biosafety and avoidance of drug resistance. Sulfur dioxide (SO
) is recently found to be produced endogenously in mammals with important pathophysiological effects. This review summarizes recent advances in SO
releasing nanosystems for cancer therapy, including polymeric prodrugs, endogenous or exogenous stimulus-activated SO
donors delivered by nanoplatform and combination therapy strategies.
Sulfur dioxide (SO2) is a common air pollutant and is detrimental to many organs. Its toxic effects including oxidative damage, deoxyribonucleic acid (DNA) damage and inflammation have been ...extensively studied. However, recent studies showed that SO2 can be generated endogenously in mammals. In contrast to the toxic effects of SO2, protective effects have also been found in mammals. Endogenous SO2 has antioxidant, anti-inflammatory, anti-hypertension, and anti-atherogenic effects and regulates vascular tone and cardiac function in mammals. SO2 may have a dual role in regulating physiological and pathophysiological effects in mammals. The biological effects of SO2 in mammals are reviewed in this study.
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Fluorescent probes, as noninvasive tools for visualizing the metabolism of biomolecules, hold great potential to explore their physiological and pathological processes. For cysteine (Cys), however, ...none of the reported fluorescent probes could image the metabolic processes in living cells. To achieve this goal, we developed a coumarin derivative based on rational design of the dual recognition sites for Cys and its metabolite, SO2. The probe displayed distinct two channels with turn-on fluorescent emission toward Cys and SO2, which were successfully applied for imaging both A549 cells and zebrafish. Further, with reversible fluorescent responses toward Cys, the probe could image the enzymatic conversion of Cys to SO2 in living A549 cells in a ratiometric manner. The present work reports the first probe to image the endogenous generated SO2 without incubation of the SO2 donors.
Although sulfur dioxide (SO
2
) has been used as a reagent for organic chemistry for more than one hundred years, being endowed with quite a distinct and varied reactivity profile, which allows the ...synthesis of a large range of compounds, its notorious toxicity as well as its gaseous state have impeded its frequent utilization by chemists. We summarize recent studies in this emerging area aimed at stimulating its utilization in organic (including organometallic) chemistry thanks to the development of innocuous, bench-stable reliable SO
2
donors. Proof-of-concept experiments have also been recently performed in biology with the design of organic SO
2
donors having controlled release profiles under physiological conditions, either active against mycobacteria or used for clarifying the role of endogenously produced SO
2
in living cells.
The development of bench-stable and reliable SO
2
donors is gaining prominence in synthetic organic chemistry as well as in life sciences.
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