Hydrogen sulfide (H2S) is a critical gaseous signaling molecule emerging at the center of a rich field of chemical and biological research. As our understanding of the complexity of physiological H2S in signaling pathways evolves, advanced chemical and technological investigative tools are required to make sense of this interconnectivity. Toward this goal, we have developed an azide-functionalized O-methylrhodol fluorophore, MeRho-Az, which exhibits a rapid >1000-fold fluorescence response when treated with H2S, is selective for H2S over other biological analytes, and has a detection limit of 86 nM. Additionally, the MeRho-Az scaffold is less susceptible to photoactivation than other commonly used azide-based systems, increasing its potential application in imaging experiments. To demonstrate the efficacy of this probe for H2S detection, we demonstrate the ability of MeRho-Az to detect differences in H2S levels in C6 cells and those treated with AOAA, a common inhibitor of enzymatic H2S synthesis. Expanding the use of MeRho-Az to complex and heterogeneous biological settings, we used MeRho-Az in combination with light sheet fluorescence microscopy (LSFM) to visualize H2S in the intestinal tract of live zebrafish. This application provides the first demonstration of analyte-responsive 3D imaging with LSFM, highlighting the utility of combining new probes and live imaging methods for investigating chemical signaling in complex multicellular systems.

Metrics & MoreArticle Recommendations CONSPECTUS: Ring-opening metathesis polymerization (ROMP), which is derived from transition-metal-based olefin metathesis, has evolved into one of the most prevalent technologies for making functional polymeric materials in academia and in industry. The initial discovery of and advances in ROMP used ill-defined mixtures of metal salts to initiate polymerization.The initiators most commonly used today, developed with tremendous efforts, are well-defined metal−alkylidene complexes that have enabled a good mechanistic understanding of the polymerization as well as improvement of the initiators' activity, stability, and functional group tolerance.The evolution of ROMP has been decidedly metal-centric, with the path to accolades being paved primarily in ruthenium-, molybdenum-, and tungstenbased systems. Our departure from the ROMP trailhead was inspired in part by recent breakthroughs in radical-mediated polymerizations, whereby their mechanisms were leveraged to develop metal-free reaction conditions. Inventing a metal-free complement to traditional ROMP would essentially involve stepping away from decades of inorganic and organometallic developments, but with the promise of crossing new synthetic capabilities and curiosities.Driven by this motivation, as well as a community-inspired desire to develop "greener" controlled polymerizations, our team pioneered the search for, and discovery of, a wholly organic alternative to traditional metal-mediated ROMP. In this Account, we review our recent efforts to develop metal-free ring-opening metathesis polymerization (MF-ROMP), which is inspired by previous reports in electro-and photo-mediated organic transformations. This work began with an exploration of the direct oxidation of enol ethers and the propensity of the ensuing radical cations to initiate ROMP. To overcome limitations of the electrochemical conditions, a photoredox-mediated method was investigated next, using photoexcited pyrylium salts to oxidize the enol ethers. With this system, we demonstrated the ability to produce ROMP products and temporally control the polymerization. Further investigations into different aspects of the reaction included monomer scope, functional group tolerance, the impact of changing photocatalyst properties, and the ability to control molecular weight. The unique mechanism of MF-ROMP, along with the relative ease of synthesizing enol ether initiators, enabled the preparation of numerous polymeric materials that are hard to access through traditional metal-mediated pathways. At the end of this Account, we provide a perspective on future opportunities in this emerging area.

Benzo[1,dithiophenes were oxidized under mild conditions with m-CPBA to yield the corresponding bis-sulfones (or tetraoxides). These sulfones possess redshifted absorption and emission spectra relative to the parent molecules. Electrochemical analyses reveal that the benzodithiophene molecules are transformed from electron donors to electron acceptors.

A new method for the synthesis of heteroleptic alkylphosphine oxides (R 2 R 1 PO, where R ≠ R 1 ) from secondary phosphine oxides (or SPOs, R 2 HPO) is presented. These reactions were fast at room temperature, sterically selective, high yielding, and >95% pure after an aqueous wash. Deprotonation of an SPO generates a phosphinite anion ([R 2 P− O] − ) that was found to be highly selective for nucleophilic P−C bond formation (as opposed to O−C bond formation) with alkyl halides. Surprisingly, most strong organometallic bases failed to deprotonate SPOs to their respective phosphinite anions (pK a s for most SPOs are <27). Only sodium bis(trimethylsilyl)amide (NaHMDS) cleanly formed the phosphinite anion, which was stable in solution (0.1 M, 23 °C in THF) for over 24 h. The need for a very specific base to deprotonate suggests that both ion pairing and the conjugate acid play a role in stabilizing the phosphinite anion. Phosphinite anion reactivity followed the expected trend for an S N 2 mechanism on reaction with alkyl halides; elimination products were never observed. A wide variety of heteroleptic alkylphosphine oxides were isolated in near-quantitative yield with only an aqueous wash as purification. This methodology was then used to make new bis(phosphine oxide)alkanes and unsymmetrical α,ω-bis(phosphine oxide)alkanes (R 2 P(O)(CH 2 ) 3 P(O)R 12 ) on the benchtop with unprecedented ease.

Highly efficient biphasic ozonolysis of alkenes using a high-throughput film-shear flow reactor