Understanding Reactive Sulfur Species Storage from Hybrid S/N Crosstalk Species: Perthionitrite (SSNO) and Thionitrite (SNO) Activation by a Mononuclear Nonheme Fe Complex.

S/N hybrid species, such as perthionitrite (SSNO) and thionitrite (SNO), play intricate roles in nitric oxide (NO) and hydrogen sulfide (HS) biological signaling and transport pathways. Despite this emerging significance, the fundamental reactivities of these species remain largely unexplored. In particular, a significant gap remains in understanding how these S/N hybrid species react with redox active metal centers.

Investigating Molybdenum and Tungsten Carbonyls as a Bridge between Elemental Chalcogens and CO: Formation of Carbonyl Sulfide and Selenium Complexes.

Carbonyl sulfide (COS) is hypothesized to play potential roles as a peptide coupling agent in prebiotic chemistry, and recent work harnessing the carbonic anhydrase-mediated COS hydrolysis for HS release has led to a resurgence of interest in COS-related chemistry. Building from the importance of metal chalcogenides in bioinorganic systems and the potential of forming metal carbonyls under reducing environments, we investigated whether simple metal carbonyl compounds could be a source of COS or COSe when treated with elemental S or Se, respectively. Using the simple carbonyl compounds [TpMo(CO)] and [TpW(CO)], we measured and quantified COS generation en route to [TpMo(S)(S)] and [TpW(S)] product formation, respectively.

Expanding the toolbox for supramolecular chemistry: probing host-guest interactions and binding with FTIR spectroscopy.

Association constant ( ) measurements provide fundamental information on host-guest interactions in supramolecular chemistry and other areas of science. Here we report the use of FTIR spectroscopy to measure the values across three classes of host-guest complexes that involve hydrogen bonding and halogen bonding. This approach can be performed with minimal sample preparation, does not require deuterated solvents, can measure association based on changes in host or guest vibrations, and benefits from a much shorter timescale than NMR spectroscopy.

Probing the Reversible Binding of Anionic Reactive Sulfur and Nitrogen Species in Imidazolium Receptors with Directional C-H Hydrogen Bonds.

HS and NO are physiologically important signaling molecules with complex roles in biology and intermolecular crosstalk. Although these species are often referred to as neutral on paper, they are primarily found in anionic and/or oxidized forms in aerobic solutions as HS or NO/NO, respectively. Despite the prominence of these anions in biology, particularly HS and NO, few investigations have focused on the molecular recognition and reversible binding of these important species.

Experimental Insights into the Formation, Reactivity, and Crosstalk of Thionitrite (SNO) and Perthionitrite (SSNO).

Hydrogen sulfide (HS) and nitric oxide (NO) are important gaseous biological signaling molecules that are involved in complex cellular pathways. A number of physiological processes require both HS and NO, which has led to the proposal that different HS/NO⋅ crosstalk species, including thionitrite (SNO) and perthionitrite (SSNO), are responsible for this observed codependence. Despite the importance of these S/N hybrid species, the reported properties and characterization, as well as the fundamental pathways of formation and subsequent reactivity, remain poorly understood.

Structural Deformations in Cucurbit[n]urils: Analysis, Host-Guest Dependence, and Automated Ellipticity Measurements Using ElliptiCB[n].

Cucurbit[n]urils (CB[n]s) are cyclic macrocycles with rich host-guest chemistry. In many cases, guest binding in CB[n]s results in host structural deformations. Unfortunately, measuring such deformations remains a major challenge, with only a handful of manual estimations reported in the literature.

Synthesis, Characterization, and Reactivity of a Synthetic End-On Cobalt(II) Alkyl Persulfide Complex as a Model Platform for Thiolate Persulfidation.

Persulfides (RSS) are ubiquitous source of sulfides (S) in biology, and interactions between RSS and bioinorganic metal centers play critical roles in biological hydrogen sulfide (HS) biogenesis, signaling, and catabolism. Here, we report the use of contact-ion stabilized [Na(15-crown-5)][BuSS] () as a simple synthon to access rare metal alkyl persulfide complexes and to investigate the reactivity of RSS with transition metal centers to provide insights into metal thiolate persulfidation, including the fundamental difference between alkyl persulfides and alkyl thiolates. Reaction of with [Co(TPA)(OTf)] afforded the η-alkyl persulfide complex [Co(TPA)(SSBu)] (), which was characterized by X-ray crystallography, UV-vis spectroscopy, and Raman spectroscopy.

An Expanded Palette of Fluorescent COS/HS-Releasing Donors for HS Delivery, Detection, and In Vivo Application.

Hydrogen sulfide (HS) is an important reactive sulfur species that is involved in many biological functions, and HS imbalances have been indicated as a potential biomarker for various diseases. Different HS donors have been developed to deliver HS directly to biological systems, but few reports include donors with optical responses that allow for tracking of HS release. Moreover, donor systems that use the same chemistry to deliver HS across a palette of fluorescent responses remain lacking.

Activity-Based Fluorescent Probes for Hydrogen Sulfide and Related Reactive Sulfur Species.

Hydrogen sulfide (HS) is not only a well-established toxic gas but also an important small molecule bioregulator in all kingdoms of life. In contemporary biology, HS is often classified as a "gasotransmitter," meaning that it is an endogenously produced membrane permeable gas that carries out essential cellular processes. Fluorescent probes for HS and related reactive sulfur species (RSS) detection provide an important cornerstone for investigating the multifaceted roles of these important small molecules in complex biological systems.

Reversible Hydrosulfide (HS) Binding Using Exclusively C-H Hydrogen-Bonding Interactions in Imidazolium Hosts.

HS is a physiologically important signaling molecule with complex roles in biology and exists primarily as HS at physiological pH. Despite this anionic character, few investigations have focused on the molecular recognition and reversible binding of this important biological anion. Using a series of imidazole and imidazolium host molecules, we investigate the role of preorganization and charge on HS binding.

Advances and Opportunities in HS Measurement in Chemical Biology.

Hydrogen sulfide (HS) is an important biological mediator across all kingdoms of life and plays intertwined roles in various disciplines, ranging from geochemical cycles to industrial processes. A common need across these broad disciplines is the ability to detect and measure HS in complex sample environments. This Perspective focuses on key advances and opportunities for HS detection and quantification that are relevant to chemical biology.

2-λ-Phosphaquinolin-2-ones as Non-cytotoxic, Targetable, and pH-Stable Fluorophores.

Several phosphaquinolinone derivatives have been synthesized and characterized to explore their usefulness in the realm of cell imaging. Solution-state photophysical properties in both aqueous and organic solutions were collected for these derivatives. Additionally, CCK-8 cell viability assays and fluorescent imaging in HeLa cells incubated with the new heterocyclic derivatives show evidence of favorable cell permeability, cell viability, and moderate intracellular localization when appended with the well-known morpholine targeting motif.

Benchmarking the placement of hydrosulfide in the Hofmeister series using a bambus[6]uril-based ChemFET sensor.

Hydrosulfide (HS) is the conjugate base of gasotransmitter hydrogen sulfide (HS) and is a physiologically-relevant small molecule of great interest in the anion sensing community. However, selective sensing and molecular recognition of HS in water remains difficult because, in addition to the diffuse charge and high solvation energy of anions, HS is highly nucleophilic and readily oxidizes into other reactive sulfur species. Moreover, the direct placement of HS in the Hofmeister series remains unclear.

Understanding Reactive Sulfur Species through P/S Synergy.

We investigated the differential oxidative and nucleophilic chemistry of reactive sulfur and oxygen anions (SSNO, SNO, NO, S, and HS) using the simple reducing electrophile PPhCl. In the case of SSNO reacting with PPhCl, a complex mixture of mono and diphosphorus products is formed exclusively in the P(V) oxidation state. We found that the phosphine stoichiometry dictates selectivity for oxidation to P=S/P=O products or transformation to P species.

Direct hydrogen selenide (HSe) release from activatable selenocarbamates.

Hydrogen selenide (HSe) is a possible bioregulator, potential gasotransmitter, and important precursor in biological organoselenium compound synthesis. Early tools for HSe research have benefitted from available mechanistic understanding of analogous small molecules developed for detecting or delivering HS. A now common approach for HS delivery is the use of small molecule thiocarbamates that can be engineered to release COS, which is quickly converted to HS by carbonic anhydrase.

Taming the Dichalcogenides: Isolation, Characterization, and Reactivity of Elusive Perselenide, Persulfide, Thioselenide, and Selenosulfide Anions.

Reactive sulfur species (RSS) and reactive selenium species (RSeS) play integral roles in hydrogen sulfide (HS) and hydrogen selenide (HSe) biological signaling pathways, and dichalcogenide anions are proposed transient intermediates that facilitate a variety of biochemical transformations. Herein we report the selective synthesis, isolation, spectroscopic and structural characterization, and fundamental reactivity of persulfide (RSS), perselenide (RSeSe), thioselenide (RSSe), and selenosulfide (RSeS) anions. The isolated chalcogenides do not rely on steric protection for stability and have steric profiles analogous to cysteine (Cys).

Solubilization of elemental sulfur by surfactants promotes reduction to HS by thiols.

Elemental sulfur (S) may contribute to sulfane sulfur (S) storage in biological systems. We demonstrate that surfactants can solubilize S in water and promote S reduction to HS by thiols. Moreover, anionic and cationic surfactants interact differently with intermediate S carriers, highlighting how specific hydrophobic microenvironments impact reactive sulfur species.

Subcellular Delivery of Hydrogen Sulfide Using Small Molecule Donors Impacts Organelle Stress.

Hydrogen sulfide (HS) is an endogenously produced gaseous signaling molecule with important roles in regulating organelle function and stress. Because of its high reactivity, targeted delivery of HS using small molecule HS donors has garnered significant interest to minimize off-target effects. Although mitochondrially targeted HS donors, such as AP39, have been reported previously and exhibit significantly higher potency than nontargeted donors, the expansion of targeted HS delivery to other subcellular organelles remains largely absent.

Synthesis and reactivity of a tris(carbene) zinc chloride complex.

The [B(BuIm)] ligand has gained increased attention since it was first reported in 2006 due to its ability to stabilize highly reactive first row transition metal complexes. In this work, we investigate the coordination chemistry of this ligand with redox-inert zinc to understand how a zinc metal center behaves in such a strong coordinating environment. The B(BuIm)ZnCl (1) complex can be formed deprotonation of [B(BuIm)][OTf] followed by the addition of ZnCl.

Thiol-Activated 1,2,4-Thiadiazolidin-3,5-diones Release Hydrogen Sulfide through a Carbonyl-Sulfide-Dependent Pathway.

Recent efforts have expanded the development of small molecule donors that release the important biological signaling molecule hydrogen sulfide (HS). Previous work on 1,2,4-thiadiazolidin-3,5-diones (TDZNs) reported that these compounds release HS directly, albeit inefficiently. However, TDZNs showed promising efficacy in HS-mediated relaxation in ex vivo aortic ring relaxation models.

Reactive sulfur and selenium species in the regulation of bone homeostasis.

Reactive oxygen species (ROS) are important modulators of physiological signaling and play important roles in bone tissue regulation. Both reactive sulfur species (RSS) and reactive selenium species (RSeS) are involved in ROS signaling, and recent work suggests RSS and RSeS involvement in the regulation of bone homeostasis. For example, RSS can promote osteogenic differentiation and decrease osteoclast activity and differentiation, and the antioxidant activity of RSeS play crucial roles in balancing bone remodeling.

Supramolecular Activation of S by Cucurbiturils in Water and Mechanism of Reduction to HS by Thiols: Insights into Biological Sulfane Sulfur Trafficking.

Reactive sulfur species (RSS) play critical roles in diverse chemical environments. Molecules containing sulfane sulfur (S) have emerged as key species involved in cellular redox buffering as well as RSS generation, translocation, and action. Using cucurbit[7]uril (CB[7]) as a model hydrophobic host, we demonstrate here that S can be encapsulated to form a 1:1 host guest complex, which was confirmed by solution state experiments, mass spectrometry, and X-ray crystallography.

A Cell Trappable Methyl Rhodol-Based Fluorescent Probe for Hydrogen Sulfide Detection.

Hydrogen sulfide is a biologically important molecule and developing chemical tools that enable further investigations into the functions of H S is essential. Fluorescent turn-on H S probes have been developed for use in cellulo and in vivo, but the membrane permeability of these probes can lead to probe leakage and signal attenuation over time. Here we report a cell trappable fluorescent probe for H S, CT-MeRhoAz, which is based on a methylrhodolazide scaffold derivatized with an acetoxymethyl ester group.