Glycyl Radical Enzymes and Sulfonate Metabolism in the Microbiome.

Sulfonates include diverse natural products and anthropogenic chemicals and are widespread in the environment. Many bacteria can degrade sulfonates and obtain sulfur, carbon, and energy for growth, playing important roles in the biogeochemical sulfur cycle. Cleavage of the inert sulfonate C-S bond involves a variety of enzymes, cofactors, and oxygen-dependent and oxygen-independent catalytic mechanisms. Sulfonate degradation by strictly anaerobic bacteria was recently found to involve C-S bond cleavage through O2-sensitive free radical chemistry, catalyzed by glycyl radical enzymes (GREs). The associated discoveries of new enzymes and metabolic pathways for sulfonate metabolism in diverse anaerobic bacteria have enriched our understanding of sulfonate chemistry in the anaerobic biosphere. An anaerobic environment of particular interest is the human gut microbiome, where sulfonate degradation by sulfate- and sulfite-reducing bacteria (SSRB) produces H2S, a process linked to certain chronic diseases and conditions.

Hydrazine Sulfonic Acid, NH3 NH(SO3 ), the Bigger Sibling of Sulfamic Acid.

The reaction of hydrazine hydrate, N2 H4 ⋅ H2 O, and SO3 leads to hydrazine sulfonic acid (Pca21 , a=849.59(4) pm, b=482.18(2) pm, c=832.17(4) pm). Structure elucidation reveals the zwitter-anionic nature of the compound according to NH3 NH(SO3 ). With the barium salt Ba[NH2 NH(SO3 )]2 (H2 O), a first salt of hydrazine sulfonic acid has been prepared (P 1 ‾ $\bar 1$ , a=489.75(5) pm, b=737.52(7) pm, c=1317.4(1) pm, α=88.238(4)°, ß=84.761(4)°, γ=79.701(4)°). The compounds were characterized by vibrational spectroscopy, DFT calculations and thermal analyses.

Triflate's bigger brother: The unprecedented tribrate anion, [Br3 CSO3 ].

The synthesis of the unprecedented [Br3 CSO3 ]- anion starts with the bromination of phenylmethanesulfonate, C6 H5 OSO2 CH3 , with KOBr leading to C6 H5 OSO2 CBr3 . The formation of the [CBr3 ] moiety has been proved, also by an X-ray structure determination of the compound (triclinic, P-1, a=685.9(2), b=698.1(2), c=1190.2(3) pm, α=93.99(1)°, ß=97.42(1)°, γ=94.45(1)°). The ester C6 H5 OSO2 CBr3 can be split under basic conditions. The resulting acid provides access to the yet unknown tribromomethanesulfates ("tribrates"). K[Br3 CSO3 ] ⋅ H2 O, the first tribrate known so far has been characterized comprehensively, including an X-ray structure determination (monoclinic, C2/c, a=2267.1(2), b=1282.25(8), c=2618.2(2) pm, ß=111.266(2)°), vibrational spectroscopy and theoretical calculations. Moreover, the thermal analysis shows that, after loss of the crystal water, the tribrate decomposes between 530 and 630 K.

Persistence of PFOA Pollution at a PTFE Production Site and Occurrence of Replacement PFASs in English Freshwaters Revealed by Sentinel Species, the Eurasian Otter (Lutra lutra).

Concentrations of 33 PFASs were determined in 20 Eurasian otters, sampled 2015-2019, along a transect away from a factory, which used PFOA in PTFE manufacture. Despite cessation of usage in 2012, PFOA concentrations remained high near the factory (>298 µg/kg ww <20 km from factory) and declined with increasing distance (<57 µg/kg ww >150 km away). Long-chain legacy PFASs dominated the Σ33PFAS profile, particularly PFOS, PFOA, PFDA, and PFNA. Replacement compounds, PFECHS, F-53B, PFBSA, PFBS, PFHpA, and 8:2 FTS, were detected in ≥19 otters, this being the first report of PFBSA and PFECHS in the species. Concentrations of replacement PFASs were generally lower than legacy compounds (max: 70.3 µg/kg ww and 4,640 µg/kg ww, respectively). Our study underscores the utility of otters as sentinels for evaluating mitigation success and highlights the value of continued monitoring to provide insights into the longevity of spatial associations with historic sources. Lower concentrations of replacement, than legacy, PFASs likely reflect their lower bioaccumulation potential, and more recent introduction. Continued PFAS use will inevitably lead to increased environmental and human exposure if not controlled. Further research is needed on fate, toxicity, and bioaccumulation of replacement compounds.

Penetration of Perfluorooctanesulfonate Isomers and Their Alternatives from Maternal Blood to Milk and Its Associations with Chemical Properties and Milk Primary Components.

Perfluorooctanesulfonate (PFOS) and its alternatives, including chlorinated polyfluorinated ether sulfonates (Cl-PFESAs), are mainly detected per- and polyfluoroalkyl substances (PFAS) in human samples such as milk. However, the mechanism of their blood to milk transfer was not well studied. Here, 145 paired maternal serum and human milk samples were analyzed for six PFOS isomers and Cl-PFESAs to evaluate the transfer efficiency from maternal serum to human milk (TEHM/MS). Besides physicochemical properties, this study for the first time evaluated the influencing effects of the primary components in human milk (carbohydrate, lipid, and protein) on TEHM/MS of PFAS. No significant association was observed between TEHM/MS and the albumin binding affinity of the compounds (p = 0.601), but TEHM/MS was significantly negatively correlated with the logarithmic octanol-water partition coefficients (r2 = 0.853, p = 0.001), the logarithmic membrane-water partition coefficients (r2 = 0.679, p = 0.012), and the carbohydrate contents in human milk. The effect of carbohydrate was further confirmed using in vitro tests. The negative associations between TEHM/MS and hydrophobicity, membrane passive permeability, and the carbohydrate content in human milk consistently indicated that passive diffusion through the paracellular route might be the main transfer pathway for PFOS and Cl-PFESAs from blood to milk in humans.

Prenatal exposures to per- and polyfluoroalkyl substances and epigenetic aging in umbilical cord blood: The Healthy Start study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous, environmentally persistent chemicals, and prenatal exposures have been associated with adverse child health outcomes. Prenatal PFAS exposure may lead to epigenetic age acceleration (EAA), defined as the discrepancy between an individual's chronologic and epigenetic or biological age. OBJECTIVES: We estimated associations of maternal serum PFAS concentrations with EAA in umbilical cord blood DNA methylation using linear regression, and a multivariable exposure-response function of the PFAS mixture using Bayesian kernel machine regression. METHODS: Five PFAS were quantified in maternal serum (median: 27 weeks of gestation) among 577 mother-infant dyads from a prospective cohort. Cord blood DNA methylation data were assessed with the Illumina HumanMethylation450 array. EAA was calculated as the residuals from regressing gestational age on epigenetic age, calculated using a cord-blood specific epigenetic clock. Linear regression tested for associations between each maternal PFAS concentration with EAA. Bayesian kernel machine regression with hierarchical selection estimated an exposure-response function for the PFAS mixture. RESULTS: In single pollutant models we observed an inverse relationship between perfluorodecanoate (PFDA) and EAA (-0.148 weeks per log-unit increase, 95% CI: -0.283, -0.013). Mixture analysis with hierarchical selection between perfluoroalkyl carboxylates and sulfonates indicated the carboxylates had the highest group posterior inclusion probability (PIP), or relative importance. Within this group, PFDA had the highest conditional PIP. Univariate predictor-response functions indicated PFDA and perfluorononanoate were inversely associated with EAA, while perfluorohexane sulfonate had a positive association with EAA. CONCLUSIONS: Maternal mid-pregnancy serum concentrations of PFDA were negatively associated with EAA in cord blood, suggesting a pathway by which prenatal PFAS exposures may affect infant development. No significant associations were observed with other PFAS. Mixture models suggested opposite directions of association between perfluoroalkyl sulfonates and carboxylates. Future studies are needed to determine the importance of neonatal EAA for later child health outcomes.

Sodium α-Olefin Sulfonates.

The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 1998, along with updated information regarding product types and concentrations of use, and confirmed that sodium α-olefin sulfonates are safe as cosmetic ingredients in the practices of use and concentration as described in this report.

Copper-Catalyzed Enantioselective Trifluoromethoxylation of Propargyl Sulfonates.

Due to the strong electron-withdrawing nature and high lipophilicity of trifluoromethoxy group (OCF3 ), methods for introducing OCF3 into organic molecules are in high demand. However, the research area of direct enantioselective trifluoromethoxylation is still in the embryonic stage, with limited enantioselectivity and/or reaction types. Here, we describe the first copper-catalyzed enantioselective trifluoromethoxylation of propargyl sulfonates using trifluoromethyl arylsulfonate (TFMS) as the trifluoromethoxy source in up to 96 % ee.

An unprecedented function for a tungsten-containing oxidoreductase.

Five tungstopterin-containing oxidoreductases were characterized from the hyperthermophile Pyrococcus furiosus. Each enzyme catalyzes the reversible conversion of one or more aldehydes to the corresponding carboxylic acid, but they have different specificities. The physiological functions of only two of these enzymes are known: one, termed GAPOR, is a glycolytic enzyme that oxidizes glyceraldehyde-3-phosphate, while the other, termed AOR, oxidizes multiple aldehydes generated during peptide fermentation. Two of the enzymes have known structures (AOR and FOR). Herein, we focus on WOR5, the fifth tungstopterin enzyme to be discovered in P. furiosus. Expression of WOR5 was previously shown to be increased during cold shock (growth at 72 â„ƒ), although the physiological substrate is not known. To gain insight into WOR5 function, we sought to determine both its structure and identify its intracellular substrate. Crystallization experiments were performed with a concentrated cytoplasmic extract of P. furiosus grown at 72 â„ƒ and the structure of WOR5 was deduced from the crystals that were obtained. In contrast to a previous report, WOR5 is heterodimeric containing an additional polyferredoxin-like subunit with four [4Fe-4S] clusters. The active site structure of WOR5 is substantially different from that of AOR and FOR and the significant electron density observed adjacent to the tungsten cofactor of WOR5 was modeled as an aliphatic sulfonate. Biochemical assays and product analysis confirmed that WOR5 is an aliphatic sulfonate ferredoxin oxidoreductase (ASOR). A catalytic mechanism for ASOR is proposed based on the structural information and the potential role of ASOR in the cold-shock response is discussed.

Legacy and Emerging Poly- and Perfluoroalkyl Substances in Finless Porpoises from East China Sea: Temporal Trends and Tissue-Specific Accumulation.

Perfluoroalkyl sulfonates (PFSAs), perfluoroalkyl carboxylates (PFCAs), and emerging alternatives and precursors of these compounds were determined in tissues of finless porpoise (Neophocaena asiaeorientalis sunameri) collected from East China Sea in 2009-2010 and 2018-2019. The median hepatic concentrations of emerging poly- and perfluoroalkyl substances (PFASs), including 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFESA), 2,3,3,3-tetrafluoro-2-propanoate (HFPO-DA), and 4,8-dioxa-3H-perfluorononanoate (ADONA) were 16.2, 2.16, < LOQ (limit of quantification) and < LOQ ng/g ww (wet weight), respectively. The concentrations of legacy substances, perfluorooctanesulfonate (PFOS), and perfluorooctanoate (PFOA), were 86.9 and 1.95 ng/g ww, respectively. The liver concentrations of 6:2 Cl-PFESA, HFPO-DA, and perfluorohexanesulfonate (PFHxS) increased with time between 2009-2010 and 2018-2019. Further, concentrations of PFOA showed a declining trend in finless porpoise, whereas PFOS and its precursor (i.e., perfluorooctane sulfonamide [FOSA]) showed an increasing trend with time between 2009-2010 and 2018-2019. Analysis of PFASs in nine different tissues/organs of finless porpoise (i.e., liver, heart, intestine, spleen, kidney, stomach, lung, muscle, and skin) revealed a similar distribution pattern between 6:2 Cl-PFESA and PFOS; however, the tissue distribution patterns differed between HFPO-DA and PFOA. The concentrations of PFAS alternatives in kidney were similar or lower than the prototype compounds PFOS and PFOA (i.e., 8:2 Cl-PFESA < 6:2 Cl-PFESA ≈ PFOS; HFPO-DA < PFOA), implying slow renal excretion of PFAS alternatives as that of legacy PFASs. The estimates of body burdens of PFASs in porpoises suggested comparable accumulation of PFAS alternatives and legacy PFSAs and PFCAs. This study provides novel information on temporal trends and tissue distribution of emerging PFASs in marine mammals in China.

Chlorinated Polyfluorinated Ether Sulfonates and Thyroid Hormone Levels in Adults: Isomers of C8 Health Project in China.

Chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) are one kind of replacement chemistry for perfluorooctanesulfonate (PFOS). Recent studies have shown that Cl-PFESAs could interfere with thyroid function in animal models. However, epidemiological evidence on the link between Cl-PFESAs and thyroid function remains scarce. In this study, we focused on two representative legacy perfluoroalkyl substances (PFAS), including PFOS and perfluorooctanoic acid (PFOA), and two PFOS alternatives (6:2 and 8:2 Cl-PFESAs) in the general adult population from a cross-sectional study, the "Isomers of C8 Health Project in China". Three serum thyroid hormones (THs), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were measured. We fitted generalized linear regression, restricted cubic spline regression, and Bayesian kernel machine regression models to assess associations of individual Cl-PFESAs, legacy PFAS, and PFAS mixtures with THs, respectively. We found individual PFAS and their mixtures were nonlinearly associated with THs. The estimated changes of the TSH level (µIU/mL) at the 95th percentile of 6:2 Cl-PFESA and PFOS against the 5th percentile were -0.74 (95% CI: -0.94, -0.54) and -1.18 (95% CI: -1.37, -0.98), respectively. The present study provided epidemiological evidence for the association of 6:2 Cl-PFESA with thyroid hormone levels in the general adult population.

Separation and characterization of sulfonates in dissolved organic matter from industrial wastewater by solid phase extraction and high-resolution mass spectrometry.

Electrospray ionization (ESI) source combined with high-resolution mass spectrometry (HRMS) has been successfully used to characterize the molecular composition of dissolved organic matter (DOM) in industrial wastewaters. However, sulfonates are commonly presenting in these wastewaters and showing strong ionization suppression for the ESI analysis, which seriously affects the characterization of other DOM components. In this paper, a novel method based on polymer anion exchange (PAX) solid phase extraction (SPE) was proposed to separate DOMs from petroleum refining and coal coking wastewaters into hydrophobic neutral, hydrophobic acids, and hydrophobic strong acids; the fractions were analyzed by negative-ion ESI Fourier transform ion cyclotron resonance mass spectrometry. The results show that PAX-SPE separated sulfonates from wastewaters and enabled the molecular characterization of oxygen-containing compounds, which are the major component of DOM in the wastewaters. Semi-quantitative analysis of sulfonates in the wastewaters was carried out and the results show that these compounds account for 11% and 2% in total organic carbon for the refinery and coal coking wastewaters, respectively. PAX-SPE with stepwise elution and followed by high-resolution mass spectrometry analysis enables a comprehensive characterization for the molecular composition of industrial wastewater DOM. The method has potential for extensive application and the results are instructive for the understanding of the molecular composition of DOM in industrial wastewaters.

Fluoro-functionalized ionic covalent organic frameworks (F-iCOFs) for highly selective enrichment and sensitive determination of perfluorinated sulfonates by MALDI-MS.

An easily prepared fluoro-functionalized ionic covalent organic framework (F-iCOF) has been implemented into MALDI-TOF MS, enabling the highly selective enrichment and sensitive determination of perfluorinated sulfonate (PFS) contaminants in a rapid and convenient manner. The good thermal stability and excellent optical absorption properties of F-iCOF makes it a brilliant matrix with no background noise. Moreover, benefitting from the large surface area, appropriate pore size, good water dispersibility, and abundant fluorine atom and cationic characteristic of F-iCOF, it exhibited superior adsorption capacity and enrichment selectivity towards PFSs. Good signal responses for PFSs were obtained in the presence of various interfering compounds such as BSA, HA, or even more than 100-fold excess of glutamic acid and similar in structure sodium alkyl sulfonates, highlighting the specific selectivity of F-iCOF. Calibration curves for potassium perflurobutane sulfonate (PFBSK) in tap water and whole blood were established with good linear correlation in the range 1-500 pg mL-1. The limits of detection and quantification for PFBSK were as low as 0.04 pg mL-1 and 0.05 pg mL-1, respectively, which are comparable or better than the existing methods for the determination of PFSs.

Photohomolysis and Photoheterolysis in Aryl Sulfonates and Aryl Phosphates.

The photochemical behaviour of selected aryl sulfonates and phosphates (ArOX) in polar and nonpolar media has been investigated by laser flash photolysis (LFP) experiments. Two main pathways have been identified, namely the photohomolysis of the ArO-X bond or the photoheterolysis of the Ar-OX bond depending on the nature of the leaving group (OX) and on the nature of the substituents on the aromatic ring. In nonpolar solvents the esters are quite photostable due to an efficient triplet deactivation. In polar solvents, the homolytic fragmentation of the ArO-S bond from the exited singlets was found in aryl sulfonates bearing moderately electron-donating groups as well as electron-withdrawing groups. In electron-rich aryl phosphates and sulfonates photoheterolysis of the Ar-OP/Ar-OS bond took place as the exclusive pathway.

Iron-Catalyzed Cross-Coupling Reactions of Alkyl Grignards with Aryl Chlorobenzenesulfonates.

Aryl sulfonate esters are versatile synthetic intermediates in organic chemistry as well as attractive architectures due to their bioactive properties. Herein, we report the synthesis of alkyl-substituted benzenesulfonate esters by iron-catalyzed C(sp2)-C(sp3) cross-coupling of Grignard reagents with aryl chlorides. The method operates using an environmentally benign and sustainable iron catalytic system, employing benign urea ligands. A broad range of chlorobenzenesulfonates as well as challenging alkyl organometallics containing ß-hydrogens are compatible with these conditions, affording alkylated products in high to excellent yields. The study reveals that aryl sulfonate esters are the most reactive activating groups for iron-catalyzed alkylative C(sp2)-C(sp3) cross-coupling of aryl chlorides with Grignard reagents.

An Active-Site Sulfonate Group Creates a Fast Water Oxidation Electrocatalyst That Exhibits High Activity in Acid.

The storage of solar energy in chemical bonds will depend on pH-universal catalysts that are not only impervious to acid, but actually thrive in it. Whereas other homogeneous water oxidation catalysts are less active in acid, we report a catalyst that maintained high electrocatalytic turnover frequency at pH values as low as 1.1 and 0.43 (kcat =1501±608 s-1 and 831±254 s-1 , respectively). Moreover, current densities, related to catalytic reaction rates, ranged from 15 to 50 mA cm-2 mM-1 comparable to those reported for state-of-the-art heterogeneous catalysts and 30 to 100 times greater than those measured for two prominent literature homogeneous catalysts at pH 1.1 and 0.43. The catalyst also exhibited excellent durability when a chemical oxidant was used (CeIV , 7400 turnovers, TOF 0.88 s-1 ). Preliminary computational studies suggest that the unusual active-site sulfonate group acts a proton relay even in strong acid, as intended.

Enantioselective Intermolecular Heck and Reductive Heck Reactions of Aryl Triflates, Mesylates, and Tosylates Catalyzed by Nickel.

Nickel-catalyzed intermolecular Heck reaction of cycloalkenes proceeds well with aryl triflates, mesylates and tosylates in excellent enantiomeric ratios. The asymmetric reductive Heck reaction also works with a 2-cyclopentenone ketal, which is equivalent to conjugate arylation of the enone itself.

Generation of Organozinc Reagents by Nickel Diazadiene Complex Catalyzed Zinc Insertion into Aryl Sulfonates.

The generation of arylzinc reagents (ArZnX) by direct insertion of zinc into the C-X bond of ArX electrophiles has typically been restricted to iodides and bromides. The insertions of zinc dust into the C-O bonds of various aryl sulfonates (tosylates, mesylates, triflates, sulfamates), or into the C-X bonds of other moderate electrophiles (X=Cl, SMe) are catalyzed by a simple NiCl2 -1,4-diazadiene catalyst system, in which 1,4-diazadiene (DAD) stands for diacetyl diimines, phenanthroline, bipyridine and related ligands. Catalytic zincation in DMF or NMP solution at room temperature now provides arylzinc sulfonates, which undergo typical catalytic cross-coupling or electrophilic substitution reactions.

Anticancer effects of sodium and potassium quercetin-5'-sulfonates through inhibition of proliferation, induction of apoptosis, and cell cycle arrest in the HT-29 human adenocarcinoma cell line.

In the present study, we compared the anticancer potential of quercetin (3,3',4',5,7-pentahydroxyflavone, I) and its sulfonic derivatives sodium/potassium quercetin-5'-sulfonates (described as II and III) against several human carcinoma cell lines. Quercetin (I) was used as a starting compound for synthesis of II and III. In this work, a modified and more efficient method of synthesizing derivatives II and III has been described. The molecular structures of the compounds were characterized in a solution and in the solid state using 1H NMR, 13C NMR, 2D NMR, and XPS spectroscopy, respectively. The stoichiometry of these complexes was determined by elemental analysis as well as thermogravimetric and X-ray fluorescence methods. The spectral data allowed complete characterization of the investigated compounds in the solution and in the solid state and unambiguous determination of the place of substitution of the sulfonic group in the phenyl ring in the C-5' position. Our in vitro studies revealed that II and III prominently reduced the viability of the HT-29 colon cancer cell line. Additionally, we observed that sulfonic derivatives decreased proliferation of colon (HT-29, LS180), lung (A549), and breast (T47D) cancer cell lines. Moreover, we detected a lower cytotoxic effect of II and III on several normal cell lines (colon epithelial CCD 841 CoTr, mouse subcutaneous connective tissue L-929, and human skin fibroblasts HSF cell lines) than that exerted by pure quercetin. The anticancer properties were especially evident in the HT-29 colon cancer cell line, where cell cycle inhibition in the G2-M phase and prominent apoptosis induced by II and III were observed. In conclusion, the sodium/potassium quercetin-5'-sulfonates prepared from quercetin showed promising anti-proliferative and pro-apoptotic activity against colon cancer cells. Therefore, we support the opinion that sodium/potassium quercetin-5'-sulfonates should be considered as promising organometallic compounds for possible clinical applications.

Evaluation of sulfonate and sulfamate derivatives possessing benzofuran or benzothiophene nucleus as inhibitors of nucleotide pyrophosphatases/phosphodiesterases and anticancer agents.

Ectonucleotidases are a broad family of ectoenzymes that play a crucial role in purinergic cell signaling. Ecto-nucleotide pyrophosphatases/phosphodiesterases (NPPs) belong to this group and are important drug targets. In particular, NPP1 and NPP3 are known to be druggable targets for treatment of impaired calcification disorders (including pathological aortic calcification) and cancer, respectively. In this study, we investigated a series of sulfonate and sulfamate derivatives of benzofuran and benzothiophene as potent and selective inhibitors of NPP1 and NPP3. Compounds 1c, 1g, 1n, and 1s are the most active NPP1 inhibitors (IC50 values in the range 0.12-0.95 µM). Moreover, compounds 1e, 1f, 1j, and 1l are the most potent inhibitors of NPP3 (IC50 ranges from 0.12 to 0.95 µM). Compound 1d, 1f and 1t are highly selective inhibitors of NPP1 over NPP3, whereas compounds 1m and 1s are found to be highly selective towards NPP3 over NPP1. Structure-activity relationship (SAR) study has been discussed in detailed. With the aid of molecular docking studies, a common binding mode of these compounds and suramin (the standard inhibitor) was revealed, where the sulfonate group acts as a cation-binding moiety that comes in close contact with the zinc ion of the active site. Moreover, cytotoxic evaluation against MCF-7 and HT-29 cancer cell lines revealed that compound 1r is the most cytotoxic towards MCF-7 cell line with IC50 value of 0.19 µM. Compound 1r is more potent and selective against cancer cells than normal cells (WI-38) as compared to doxorubicin.