O→S Relay Deprotection: A General Approach to Controllable Donors of Reactive Sulfur Species

Reactive sulfur species (RSS) are biologically important molecules. Among them, H₂S, hydrogen polysulfides (H₂S_n, n>1), persulfides (RSSH), and HSNO are believed to play regulatory roles in sulfur‐related redox biology. However, these molecules are unstable and difficult to handle. Having access to their reliable and controllable precursors (or donors) is the prerequisite for the study of these sulfur species. Reported in this work is the preparation and evaluation of a series of O‐silyl‐mercaptan‐based sulfur‐containing molecules which undergo pH‐ or F^?‐mediated desilylation to release the corresponding H₂S, H₂S_n, RSSH, and HSNO in a controlled fashion. This O→S relay deprotection serves as a general strategy for the design of pH‐ or F^?‐triggered RSS donors. Moreover, we have demonstrated that the O‐silyl groups in the donors could be changed into other protecting groups like esters. This work should allow the development of RSS donors with other activation mechanisms (such as esterase‐activated donors).     

A Dual‐Response Fluorescent Probe Reveals the H2O2‐Induced H2S Biogenesis through a Cystathionine β‐Synthase Pathway

The two signaling molecules H₂S and H₂O₂ play key roles in maintaining intracellular redox homeostasis. The biological relationship between H₂O₂ and H₂S remains largely unknown in redox biology. In this study, we rationally designed and synthesized single‐ and dual‐response fluorescent probes for detecting both H₂O₂ and H₂S in living cells. The dual‐response probe was shown to be capable of mono‐ and dual‐detection of H₂O₂ and H₂S selectively and sensitively. Detailed bioimaging studies based on the probes revealed that both exogenous and endogenous H₂O₂ could induce H₂S biogenesis in living cells. By using gene‐knockdown techniques with bioimaging, the H₂S biogenesis was found to be majorly cystathionine β‐synthase (CBS)‐dependent. Our finding shows the first direct evidence on the biological communication between H₂O₂ (ROS) and H₂S (RSS) in vivo.     

Tumor Microenvironment‐Activated NIR‐II Nanotheranostic System for Precise Diagnosis and Treatment of Peritoneal Metastasis

Activatable theranostic systems show potential for improved tumor diagnosis and therapy owing to high detection specificities, effective ablation, and minimal side‐effects. Herein, a tumor microenvironment (TME)‐activated NIR‐II nanotheranostic system (FEAD1) for precise diagnosis and treatment of peritoneal metastases is presented. FEAD1 was fabricated by self‐assembling the peptide Fmoc‐His, mercaptopropionic‐functionalized Ag₂S quantum dots (MPA‐Ag₂S QDs), the chemodrug doxorubicin (DOX), and NIR absorber A1094 into nanoparticles. We show that in healthy tissue, FEAD1 exists in an NIR‐II fluorescence “off” state, because of Ag₂S QDs‐A1094 interactions, while DOX remains in stealth mode. Upon delivery of FEAD1 to the tumor, the acidic TME triggers its disassembly through breakage of the Fmoc‐His metal coordination and DOX hydrophobic interactions. Release of A1094 switches on Ag₂S fluorescence, illuminating the tumor, accompanied by burst release of DOX within the tumor tissue, thereby achieving precise tumor theranostics. This TME‐activated theranostic strategy holds great promise for future clinical applications.     

Solvo‐thermal Preparation of One Novel Cadmium(II) Coordination Polymer with 1‐(4‐Aminobenzyl)‐1,2,4‐Triazole and Bi‐functional Photo‐Luminescent Sensing for Acetone and Dichromate

In this work a 1,2,4‐triazole derivative 1‐(4‐aminobenzyl)‐1,2,4‐triazole (abtz) was utilized, one new cadmium(II) coordination polymer, namely [Cd(abtz)I₂]_n ( 1 ) was prepared through the powerful solvo‐thermal synthetic strategy. In compound 1 , the abtz building blocks are interlinked through the central Cd^II ions forming the two‐dimensional (2D) layer coordination framework. Powder X‐ray diffraction (PXRD) characterization also reveals that we have prepared the pure phases of coordination polymer 1 . Optical properties have been determined, which can behave the excellent photo‐luminescent emission of coordination polymer 1 . Photo‐luminescent experiment also reveals that coordination polymer 1 can behave the highly sensitive detection for acetone molecules with high K_sv value (K_sv = 4.12 ×10⁴ L · mol^–1) in the recyclable detection fashion. Additionally, coordination polymer 1 also can behave the highly sensitive detection for pollutant dichromate with excellent quenching efficiency K_sv (K_sv = 2.12 × 10⁴ L · mol^–1) and low detection limit [38 × 10^–3 mM (S/N = 3)]. UV/Vis, photo‐luminescent lifetime, and PXRD patterns also have been determined to analyze the detection mechanism.     

Multifluorinated Aryl Azides for the Development of Improved H2S Probes,and Fast Strain‐promoted Azide‐Alkyne Cycloaddition and Staudinger Reactions

The development of advanced bioorthogonal reactions for detection and labeling of biomolecules is significant in chemical biology. Recently, researchers have found that multifluorinated aryl azides hold great potential for the development of improved bioorthogonal reactions. The fluorine atom can be a perfect substituent group because of its properties of excellent electronegativity and small steric hindrance. In this Minireview, we discuss recent developments of improved hydrogen sulfide (H₂S) fluorescence probes, fast strain‐promoted azide‐alkyne cycloaddition (SPAAC) and nonhydrolysis Staudinger reactions based on the use of multifluorinated aryl azides. Additionally, kinetic studies and biological applications of these reactions are also presented.     

A Native‐Chemical‐Ligation‐Mechanism‐Based Ratiometric Fluorescent Probe for Aminothiols

Thiol‐containing amino acids (aminothiols) such as cysteine (Cys) and homocysteine (Hcy) play a key role in various biological processes including maintaining the homeostasis of biological thiols. However, abnormal levels of aminothiols are associated with a variety of diseases. The native chemical ligation (NCL) reaction has attracted great attention in the fields of chemistry and biology. NCL of peptide segments involves cascade reactions between a peptide‐α‐thioester and an N‐terminal cysteine peptide. In this work, we employed the NCL reaction mechanism to formulate a Förster resonance energy transfer (FRET) strategy for the design of ratiometric fluorescent probes that were selective toward aminothiols. On the basis of this new strategy, the ratiometric fluorescent probe 1 for aminothiols was judiciously designed. The new probe is highly selective toward aminothiols over other thiols and exhibits a very large variation (up to 160‐fold) in its fluorescence ratio (I₄₅₈/I₆₀₃). The new fluorescent probe is capable of ratiometric detection of aminothiols in newborn calf and human serum samples and is also suitable for ratiometric fluorescent imaging of aminothiols in living cells.     

Hydrogen‐bonded chains of rings in 1‐(4‐chloroanilinomethyl)‐5‐(4‐chlorophenyl)‐1,3,5‐triazinane‐2‐thione and hydrogen‐bonded sheets in 1‐anilinomethyl‐5‐phenyl‐1,3,5‐triazinane‐2‐thione

In 1‐(4‐chloroanilinomethyl)‐5‐(4‐chlorophenyl)‐1,3,5‐triazinane‐2‐thione, C₁₆H₁₆Cl₂N₄S, there are two independent molecules in the asymmetric unit which form inversion dimers via two weak N—H...S hydrogen bonds. The dimers are then linked into C(9)C(14) chains by a C—H...S hydrogen bond and a C—H...Cl contact. In 1‐(anilinomethyl)‐5‐phenyl‐1,3,5‐triazinane‐2‐thione, C₁₆H₁₈N₄S, molecules are linked into complex sheets via a combination of N—H...S and C—H...π hydrogen bonds.     

A Nitro‐Functionalized Metal–Organic Framework as a Reaction‐Based Fluorescence Turn‐On Probe for Rapid and Selective H2S Detection

The toxic gas H₂S has recently emerged as one of the important signaling molecules in biological systems. Thus understanding the production, distribution, and mode of action of H₂S in biological system is important, but the fleeting and reactive nature of H₂S makes it a daunting task. Herein we report a biocompatible, nitro‐functionalized metal–organic framework as reaction‐based fluorescence turn‐on probe for fast and selective H₂S detection. The selective turn‐on performance of MOF remains unaffected even in presence of competing biomolecules.     

H2S Sensors: Fumarate‐Based fcu‐MOF Thin Film Grown on a Capacitive Interdigitated Electrode

Herein we report the fabrication of an advanced sensor for the detection of hydrogen sulfide (H₂S) at room temperature, using thin films of rare‐earth metal (RE)‐based metal–organic framework (MOF) with underlying fcu topology. This unique MOF‐based sensor is made via the in situ growth of fumarate‐based fcu ‐MOF (fum‐ fcu ‐MOF) thin film on a capacitive interdigitated electrode. The sensor showed a remarkable detection sensitivity for H₂S at concentrations down to 100 ppb, with the lower detection limit around 5 ppb. The fum‐ fcu ‐MOF sensor exhibits a highly desirable detection selectivity towards H₂S vs. CH₄, NO₂, H₂, and C₇H₈ as well as an outstanding H₂S sensing stability as compared to other reported MOFs.     

NIR‐II Fluorescent Self‐Assembled Peptide Nanochain for Ultrasensitive Detection of Peritoneal Metastasis

Fluorescence‐guided cytoreductive surgery is one of the most promising approaches for facile elimination of tumors in situ, thereby improving prognosis. Reported herein is a simple strategy to construct a novel chainlike NIR‐II nanoprobe (APP‐Ag₂S‐RGD) by self‐assembly of an amphiphilic peptide (APP) into a nanochain with subsequent chemical crosslinking of NIR‐II Ag₂S QDs and the tumor‐targeting RGD peptide. This probe exhibits higher capability for cancer cell detection compared with that of RGD‐functionalized Ag₂S QDs (Ag₂S‐RGD) at the same concentration. Upon intraperitoneal injection, superior tumor‐to‐normal tissue signal ratio is achieved and non‐vascularized tiny tumor metastatic foci as small as about 0.2 mm in diameter could be facilely eliminated under NIR‐II fluorescent imaging guidance. These results clearly indicate the potential of this probe for fluorescence‐guided tumor staging, preoperative diagnosis, and intraoperative navigation.     

o‐Fluorination of Aromatic Azides Yields Improved Azido‐Based Fluorescent Probes for Hydrogen Sulfide: Synthesis,Spectra, and Bioimaging

Hydrogen sulfide (H₂S) is an endogenously produced gaseous signaling molecule with multiple biological functions. To visualize the endogenous in situ production of H₂S in real time, new coumarin‐ and boron‐dipyrromethene‐based fluorescent turn‐on probes were developed for fast sensing of H₂S in aqueous buffer and in living cells. Introduction of a fluoro group in the ortho position of the aromatic azide can lead to a greater than twofold increase in the rate of reaction with H₂S. On the basis of o‐fluorinated aromatic azides, fluorescent probes with high sensitivity and selectivity toward H₂S over other biologically relevant species were designed and synthesized. The probes can be used to in situ to visualize exogenous H₂S and D ‐cysteine‐dependent endogenously produced H₂S in living cells, which makes them promising tools for potential applications in H₂S biology.     

Dual‐Reactable Fluorescent Probes for Highly Selective and Sensitive Detection of Biological H2S

Hydrogen sulfide (H₂S) is an important endogenous signaling molecule with a variety of biological functions. Development of fluorescent probes for highly selective and sensitive detection of H₂S is necessary. We show here that dual‐reactable fluorescent H₂S probes could react with higher selectivity than single‐reactable probes. One of the dual‐reactable probes gives more than 4000‐fold turn‐on response when reacting with H₂S, the largest response among fluorescent H₂S probes reported thus far. In addition, the probe could be used for high‐throughput enzymatic assays and for the detection of Cys‐induced H₂S in cells and in zebrafish. These dual‐reactable probes hold potential for highly selective and sensitive detection of H₂S in biological systems.     

Comparsion of an immunochromatographic strip with ELISA for simultaneous detection of thiamphenicol,florfenicol and chloramphenicol in food samples

Rapid and sensitive indirect competitive enzyme‐linked immunosorbent assays (ic‐ELISA) and gold nanoparticle immunochromatographic strip tests were developed to detect thiamphenicol (TAP), florfenicol (FF) and chloramphenicol (CAP) in milk and honey samples. The generic monoclonal antibody for TAP, FF and CAP was prepared based on a hapten [D ‐threo‐1‐(4‐aminophenyl)‐2‐ dichloroacetylamino‐1,3‐propanediol], and the haptenwas linked to a carrier protein using the diazotization method. After the optimization of several parameters (coating, pH, sodium chloride content and methanol content), the ic‐ELISA was established. The quantitative working range for TAP was 0.11–1.36 ng/mL, with an IC₅₀ of 0.39 ng/mL. The optimized ELISA showed cross‐reactivity to CAP (300%) and FF (15.6%), with IC₅₀ values of 0.13 and 2.5 ng/mL, respectively. The analytical recovery of TAP, FF and CAP in milk and honey samples in the ic‐ELISA ranged from 81.2 to 112.9%. Based on this monoclonal antibody, a rapid and sensitive immunochromatographic test strip was also developed. This strip had a detection limit of 1 ng/mL for TAP, FF and CAP in milk and honey samples. Moreover, the test was completed within 10 min. Our results showed that the proposed ic‐ELISA and immunochromatographic test strip method are highly useful screening tools for TAP, FF and CAP detection in milk and honey samples. Copyright © 2015 John Wiley & Sons, Ltd.     

Highly Selective and Sensitive Near‐Infrared‐Fluorescent Probes for the Detection of Cellular Hydrogen Sulfide and the Imaging of H2S in Mice

Herein, we report the development of two fluorescent probes for the highly selective and sensitive detection of H₂S. The probes take advantage of a Cu^II? cyclen complex, which acts as a reaction center for H₂S and as a quencher of BODIPY (boron‐dipyrromethene)‐based fluorophores with emissions at 765 and 680 nm, respectively. These non‐fluorescent probes could only be turned on by the addition of H₂S, and not by other potentially interfering biomolecules, including reactive oxygen species, cysteine, and glutathione. In a chemical system, both probes detected H₂S with a detection limit of 80 nM . The probes were successfully used for the endogenous detection of H₂S in HEK 293 cells, for measuring the H₂S‐release activity of dietary organosulfides in MCF‐7 cells, and for the in vivo imaging of H₂S in mice.     

4,5‐Propyl­enedi­thio‐1,3‐di­thiole‐2‐thione and 4,5‐propyl­enedi­thio‐1,3‐di­thiol‐2‐one

4,5‐Propyl­ene­di­thio‐1,3‐di­thiole‐2‐thione, C₆H₆S₅, (I), crystallizes in the centrosymmetric space group P2₁/c. The molecular packing is characterized by pairs of S⋯S intermolecular contacts between neighbouring mol­ecules, which may account for the rather high thermal stablity of the crystal. 4,5‐Propyl­ene­di­thio‐1,3‐di­thiol‐2‐one, C₆H₆OS₄, (II), in which an O atom replaces the terminal S atom of (I), crystallizes in the non‐centrosymmetric polar space group Cc. The packing pattern of (II) indicates that the macropolarization direction is along [101]. Although the packing patterns are qualitatively significantly different, the molecular structures of (I) and (II) are similar, each exhibiting a chair conformation.     

Epitaxial Seeded Growth of Rare‐Earth Nanocrystals with Efficient 800 nm Near‐Infrared to 1525 nm Short‐Wavelength Infrared Downconversion Photoluminescence for In Vivo Bioimaging

Novel β‐NaGdF₄/Na(Gd,Yb)F₄:Er/NaYF₄:Yb/NaNdF₄:Yb core/shell 1/shell 2/shell 3 (C/S1/S2/S3) multi‐shell nanocrystals (NCs) have been synthesized and used as probes for in vivo imaging. They can be excited by near‐infrared (800 nm) radiation and emit short‐wavelength infrared (SWIR, 1525 nm) radiation. Excitation at 800 nm falls into the “biological transparency window”, which features low absorption by water and low heat generation and is considered to be the ideal excitation wavelength with the least impact on biological tissues. After coating with phospholipids, the water‐soluble NCs showed good biocompatibility and low toxicity. With efficient SWIR emission at 1525 nm, the probe is detectable in tissues at depths of up to 18 mm with a low detection threshold concentration (5 nM for the stomach of nude mice and 100 nM for the stomach of SD rats). These results highlight the potential of the probe for the in vivo monitoring of areas that are otherwise difficult to analyze.     

5‐Methyl‐2‐thiouracil

The molecular structure of the title compound, also known as 2‐thio­thymine [systematic name: 2,3‐di­hydro‐5‐methyl‐2‐thioxopyrimidin‐4(1H)‐one], C₅H₆N₂OS, is similar to that of thymine, with only small changes in the ring structure, apart from a significant difference at the substitution site [S=C = 1.674 (1) Å]. The mol­ecules are connected by hydrogen bonds, with N—H?O = 2.755 (2) Å and N—H?S = 3.352 (1) Å. The hydrogen‐bond network is different from that in thymine, since it involves all the donor and acceptor atoms.     

Polyisobutylene‐based polyurethanes. VIII. Polyurethanes with ‐O‐S‐PIB‐S‐O‐ soft segments

We describe the synthesis, characterization, and select properties of a novel polyurethane (PU) prepared using a new polyisobutylene diol, HO‐CH₂CH₂‐S‐PIB‐S‐CH₂CH₂‐OH, soft segment and conventional hard segments. The diol is synthesized by terminal functionalization of ally‐telechelic PIB followed by low‐cost thiol‐ene click chemistry. Properties of ‐S‐ containing PU (PIB_S‐PU) containing 72.5% PIB were investigated and compared to similar PUs made with HO‐PIB‐OH (PIB_O‐PU). Hydrolytic resistance was studied by contact with phosphate‐buffered saline, oxidative resistance by immersing in concentrated HNO₃, and metal ion oxidation resistance by exposure to CoCl₂/H₂O₂. Hydrolytic and oxidative resistances of PIB_S‐PU and PIB_O‐PU are similar and superior to a commercial PDMS‐based PU, Elast‐Eon? E2A. According to ¹H NMR spectroscopy the ‐S‐ in PIB_S‐PUs remained unchanged upon treatment with HNO₃, however, oxidized mainly to ‐SO₂‐ by CoCl₂/H₂O_2. Static mechanical properties of PIB_S‐PU and PIB_O‐PU are similar, except creep resistance of PIB_S‐PU is surprisingly superior. The thermal stability of PIB_S‐PUs is ～15 °C higher than that of PIB_O‐PU. FTIR spectroscopy indicates H bonded S atoms (N‐H…S) between soft and hard segments, which noticeably affect properties. DSC and XRD studies suggest random low‐periodicity crystals dispersed within a soft matrix. Energy dispersive X‐ray spectroscopy–scanning electron microscopy indicates homogeneous distribution of S atoms on PIB_S‐PU surfaces. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1119–1131     

The Structure of Bis[N‐6‐aminopyridyl‐N‐(1S)‐(+)‐10‐camphorsulfonylamino]palladium in the Solid State and in Solution

The complex, bis[N‐6‐aminopyridyl‐N‐(1S)‐(+)‐10‐camphorsulfonylamino]palladium, Pd[(S)‐APCS]₂, 1 , was prepared by reaction of 2‐[(1S)‐(+)‐10‐camphorsulfonamino]‐6‐aminopyridine with PdCl₂ in THF. Complex 1 has been characterized by spectroscopic methods and its structure has been determined by X‐ray crystallography. Crystal data: space group C2, a= 16.082 (2), b = 17.104 (2), c = 13.051 (2)Å, β = 99.95 (1)°, V = 3535.9 (8) ų, Z = 2 with final residuals R1 = 0.0491 and wR2 = 0.0944. Two independent molecules, (S,S)‐Pd[(S)‐APCS]2, 1a , and (R,R)‐Pd[(S)‐APCS]2, 1b , were found in each asymmetric unit, which exchange to each other via a series of nitrogen inversion and C‐C bond rotation. The inversion energy (ΔGc₁^≠) and the energy barrier (δGc₂^≠) were 11.5 ± 0.1 Kcal mol^?1 at 246 K and 9.8 ± 0.1 Kcal mol^?1 at 199 K, respectively, calculated by dynamic NMR data.     

trans‐Bis­[ethane‐1,2‐di­thiol­ato(2–)‐S,S′]­bis(2‐mer­cap­to­pyri­dine‐S)­tin(IV)

The title compound, [Sn(C₅H₅NS)₂(C₂H₄S₂)₂], was obtained from a 1:2 mixture of bis­(ethane‐1,2‐di­thiol­ato)­tin(IV) and 2‐mercapto­pyridine. The mol­ecules are discrete monomeric trans‐octahedral units, with the Sn^IV atom at the centre of symmetry, planar 2‐mercapto­pyridine zwitterions and SnS₂C₂ groups in twist–envelope conformations. The 2‐mercapto­pyridine ligands are monodentate and are bonded through the S atoms. The S—Sn distances between the S atom of edt (edt is ethane‐1,2‐di­thiol­ate) and the Sn atom are 2.473 (1) and 2.505 (1) Å, which are slightly longer than the S—Sn distance in Sn(edt)₂ of 2.390 (1) Å. The bond between the 2‐mercapto­pyridine S atom and the Sn atom are, remarkably, weaker than the S—Sn bond involving edt.