Sulfanyl Group Research Articles

Metabolic dysfunction-associated steatohepatitis treated by poly(ethylene glycol)-block-poly(cysteine) block copolymer-based self-assembling antioxidant nanoparticles

Non-alcoholic steatohepatitis (NASH), now known as metabolic dysfunction-associated steatohepatitis (MASH), involves oxidative stress caused by the overproduction of reactive oxygen species (ROS). Small-molecule antioxidants have not been approved for antioxidant chemotherapy because of severe adverse effects that collapse redox homeostasis, even in healthy tissues. To overcome these disadvantages, we have been developing poly(ethylene glycol)-block-poly(cysteine) (PEG-block-PCys)-based self-assembling polymer nanoparticles (NanoCyses), releasing Cys after in vivo degradation by endogenous enzymes, to obtain antioxidant effects without adverse effects. However, a comprehensive investigation of the effects of polymer design on therapeutic outcomes has not yet been conducted to develop our NanoCys system for antioxidant chemotherapy. In this study, we synthesized different poly(L-cysteine) (PCys) chains whose sulfanyl groups were protected by tert-butyl thiol (StBu) and butyryl (Bu) groups to change the reactivity of the side chains, affording NanoCys(SS) and NanoCys(Bu), respectively. To elucidate the importance of the polymer design, these NanoCyses were orally administered to MASH model mice as a model of oxidative stress-related diseases. Consequently, the acyl-protective NanoCys(Bu) significantly suppressed hepatic lipid accumulation and oxidative stress compared to NanoCys(SS). Furthermore, we substantiated that shorter PCys were much better than longer PCys for therapeutic outcomes and the effects related to the liberation properties of Cys from these nanoparticles. Owing to its antioxidant functions, NanoCyses also significantly attenuated hepatic inflammation and fibrosis in the MASH mouse model.

Tuning Fluorescence and Singlet Oxygen Quantum Yields of Subporphyrazines by Axial Functionalization.

The axial functionalization of Subporphyrazines (SubPzs) with unreported alkoxy groups, carboxy and carboperoxy rests, as well as sulfanyl, aryl and amino groups, forming B-O, B-S, B-C, and B-N bonds, respectively, has been investigated. The studied oxygen nucleophiles include aromatic and sterically demanding aliphatic alcohols, along with carboxylic acids and peracids. In general, direct substitution of the chloro-SubPz by oxygen nucleophiles of diverse nature proceeds smoothly, with yields of the isolated alkoxy and carboxy-substituted SubPzs ranging from 49 to 100 %. Conversely, direct substitution with sulphur, carbon and nitrogen nucleophiles do not afford the corresponding substituted SubPzs. In these cases, a stepwise procedure involving an axial triflate-SubPz intermediate was employed, affording only the phenyl-SubPz in 8 % yield. The major compound under these conditions was the unreported SubPz μ-oxo dimer, presumably arising from substitution of the triflate-SubPz by the in situ generated hydroxy-SubPz. This result indicates a quite low reactivity of the TfO-SubPz intermediate with carbon, sulphur and nitrogen nucleophiles. All SubPzs prepared in this work exhibited fluorescence at 510-515 nm with quantum yields ranging from 0.1 to 0.24. Additionally, all SubPzs generated singlet oxygen, with ΦΔ values ranging from 0.15 to 0.57, which show no apparent correlation with the axial substituents.

A Survey of the Angular Distortion Landscape in the Coordination Geometries of High-Spin Iron(II) 2,6-Bis(pyrazolyl)pyridine Complexes.

Reaction of 2,4,6-trifluoropyridine with sodium 3,4-dimethoxybenzenethiolate and 2 equiv of sodium pyrazolate in tetrahydrofuran at room temperature affords 4-(3,4-dimethoxyphenylsulfanyl)-2,6-di(pyrazol-1-yl)pyridine (L), in 30% yield. The iron(II) complexes [FeL2][BF4]2 (1a) and [FeL2][ClO4]2 (1b) are high-spin with a highly distorted six-coordinate geometry. This structural deviation from ideal D2d symmetry is common in high-spin [Fe(bpp)2]2+ (bpp = di{pyrazol-1-yl}pyridine) derivatives, which are important in spin-crossover materials research. The magnitude of the distortion in 1a and 1b is the largest yet discovered for a mononuclear complex. Gas-phase DFT calculations at the ω-B97X-D/6-311G** level of theory identified four minimum or local minimum structural pathways across the distortion landscape, all of which are observed experimentally in different complexes. Small distortions from D2d symmetry are energetically favorable in complexes with electron-donating ligand substituents, including sulfanyl groups, which also have smaller energy penalties associated with the lowest energy distortion pathway. Natural population analysis showed that these differences reflect greater changes to the Fe-N{pyridyl} σ-bonding as the distortion proceeds, in the presence of more electron-rich pyridyl donors. The results imply that [Fe(bpp)2]2+ derivatives with electron-donating pyridyl substituents are more likely to undergo cooperative spin transitions in the solid state. The high-spin salt [Fe(bpp)2][CF3SO3]2, which also has a strong angular distortion, is also briefly described and included in the analysis.

Multifarious characteristics of sulfur-oxidizing bacteria residing in rice rhizosphere.

Sulfur-oxidizing bacteria (SOB) are versatile microorganisms known for their ability to oxidize various reduced sulfur compounds, namely, elemental sulfur (S0), hydrogen sulfide (H2S), tetrathionate (S4O62-), and trithionate (S3O62-) to sulfate (SO42-). In this study, out of twelve SOB isolates from rice rhizosphere, five were screened based on their sulfur oxidation potential, viz., SOB1, SOB2, SOB3, SOB4, and SOB5, and were identified as Ochrobactrum soli SOB1, Achromobacter xylosoxidans SOB2, Stenotrophomonas maltophilia SOB3, Brucella tritici SOB4, and Stenotrophomonas pavanii SOB5, respectively. All the isolates displayed chemolithotrophic nutritional mode by consuming thiosulfate and accumulating trithionate and tetrathionate in the growth medium which is ultimately oxidized to sulfate. The strains were authenticated with the production of thiosulfate oxidizing enzymes such as rhodanese and sulfite oxidase. Despite their tendency to oxidize reduced sulfur compounds, B. tritici SOB4 and S. pavanii SOB5 were also found to possess phosphate and zinc solubilization potential, acetic acid, and indole acetic acid (IAA) production and 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity. The presence of sulfanyl (R-SH) groups was noticed in the A. xylosoxidans SOB2. Elemental sulfur conversion into sulfate was noted in the S. maltophilia SOB3, and hydrogen sulfide conversion into sulfate was observed in the Ochromobacter soli SOB1. Sulfur oxidation potential coupled with beneficial properties of the isolates widen the knowledge on SOB.

Autocatalytic Mechanism in the Anaerobic Reduction of Metmyoglobin by Sulfide Species.

The mechanism of the metal centered reduction of metmyoglobin (MbFeIII) by sulfide species (H2S/HS-) under an argon atmosphere has been studied by a combination of spectroscopic, kinetic, and computational methods. Asymmetric S-shaped time-traces for the formation of MbFeII at varying ratios of excess sulfide were observed at pH 5.3 < pH < 8.0 and 25 °C, suggesting an autocatalytic reaction mechanism. An increased rate at more alkaline pHs points to HS- as relevant reactive species for the reduction. The formation of the sulfanyl radical (HS•) in the slow initial phase was assessed using the spin-trap phenyl N-tert-butyl nitrone. This radical initiates the formation of S-S reactive species as disulfanuidyl/ disulfanudi-idyl radical anions and disulfide (HSSH•-/HSS•2- and HSS-, respectively). The autocatalysis has been ascribed to HSS-, formed after HSSH•-/HSS•2- disproportionation, which behaves as a fast reductant toward the intermediate complex MbFeIII(HS-). We propose a reaction mechanism for the sulfide-mediated reduction of metmyoglobin where only ferric heme iron initiates the oxidation of sulfide species. Beside the chemical interest, this insight into the MbFeIII/sulfide reaction under an argon atmosphere is relevant for the interpretation of biochemical aspects of ectopic myoglobins found on hypoxic tissues toward reactive sulfur species.

Nature of Luminescence and Pharmacological Activity of Sulfaguanidine.

Sulfonamides are one of the oldest groups of veterinary chemotherapeutic agents. Physico-chemical properties, the concentration and the nature of the environment are the factors responsible for the distribution of sulfonamides in the living organism. Although these drug compounds have been in use for more than half a century, knowledge about their behavior is still limited. Physiological activity is currently attributed to the sulfanyl radical. Our study is devoted to the spectral properties of aqueous solutions of sulfaguanidine, in which the formation of complexes with an H-bond and a protonated form takes place. The nature of the fluorescent state of sulfaguanidine was interpreted using computational chemistry, the electronic absorption method and the luminescence method. The structure of sulfaguanidine includes several active fragments: aniline, sulfonic and guanidine. To reveal the role of fragments in the physiological activity of the studied antibiotic, we calculated and compared the effective charges of the fragments of aniline and sulfaguanidine molecules. Chromophore groups were identified in molecules, which determine the intermolecular interaction between a molecule and a proton-donor solvent. The study also revealed the impact of sulfone and guanidine groups, as well as complexation, on the effective charge of the antibiotic fragment responsible for physiological activity and luminescent ability.

New Aminobiphenylcysteine Derivatives in Globin and Urine of Rats Dosed with 4-Aminobiphenyl, a Tobacco Smoke Carcinogen.

The 4-biphenylnitrenium ion (BPN), a reactive metabolic intermediate of the tobacco smoke carcinogen 4-aminobiphenyl (4-ABP), can react with nucleophilic sulfanyl groups in glutathione (GSH) as well as in proteins. The main site of attack of these S-nucleophiles was predicted using simple orientational rules of aromatic nucleophilic substitution. Thereafter, a series of presumptive 4-ABP metabolites and adducts with cysteine were synthesized, namely, S-(4-amino-3-biphenyl)cysteine (ABPC), N-acetyl-S-(4-amino-3-biphenyl)cysteine (4-amino-3-biphenylmercapturic acid, ABPMA), S-(4-acetamido-3-biphenyl)cysteine (AcABPC), and N-acetyl-S-(4-acetamido-3-biphenyl)cysteine (4-acetamido-3-biphenylmercapturic acid, AcABPMA). Then, globin and urine of rats dosed with a single ip dose of 4-ABP (27 mg/kg b.w.) was analyzed by HPLC-ESI-MS2. ABPC was identified in acid-hydrolyzed globin at levels of 3.52 ± 0.50, 2.74 ± 0.51, and 1.25 ± 0.12 nmol/g globin (mean ± S.D.; n = 6) on days 1, 3, and 8 after dosing, respectively. In the urine collected on day 1 (0-24 h) after dosing, excretion of ABPMA, AcABPMA, and AcABPC amounted to 1.97 ± 0.88, 3.09 ± 0.75, and 3.69 ± 1.49 nmol/kg b.w. (mean ± S.D.; n = 6), respectively. On day 2, excretion of the metabolites decreased by one order of magnitude followed by a slower decrease on day 8. Regarding the possible formation of AcABPC from ABPC, N-acetylation of the amino group at the biphenyl moiety prior to that at cysteine appears to be very unlikely. Thus, the structure of AcABPC indicates the involvement of N-acetyl-4-biphenylnitrenium ion (AcBPN) and/or its reactive ester precursors in in vivo reactions with GSH and protein-bound cysteine. ABPC in globin might become an alternative biomarker of the dose of toxicologically relevant metabolic intermediates of 4-ABP.

Sulforaphane and Its Bifunctional Analogs: Synthesis and Biological Activity.

For decades, various plants have been studied as sources of biologically active compounds. Compounds with anticancer and antimicrobial properties are the most frequently desired. Cruciferous plants, including Brussels sprouts, broccoli, and wasabi, have a special role in the research studies. Studies have shown that consumption of these plants reduce the risk of lung, breast, and prostate cancers. The high chemopreventive and anticancer potential of cruciferous plants results from the presence of a large amount of glucosinolates, which, under the influence of myrosinase, undergo an enzymatic transformation to biologically active isothiocyanates (ITCs). Natural isothiocyanates, such as benzyl isothiocyanate, phenethyl isothiocyanate, or the best-tested sulforaphane, possess anticancer activity at all stages of the carcinogenesis process, show antibacterial activity, and are used in organic synthesis. Methods of synthesis of sulforaphane, as well as its natural or synthetic bifunctional analogues with sulfinyl, sulfanyl, sulfonyl, phosphonate, phosphinate, phosphine oxide, carbonyl, ester, carboxamide, ether, or additional isothiocyanate functional groups, and with the unbranched alkyl chain containing 2–6 carbon atoms, are discussed in this review. The biological activity of these compounds are also reported. In the first section, glucosinolates, isothiocyanates, and mercapturic acids (their metabolites) are briefly characterized. Additionally, the most studied anticancer and antibacterial mechanisms of ITC actions are discussed.

UV Photolysis of C2H5SH in Solid CO and Ar

Ethanethiol (C2H5SH) contains the −SH group, a functional group considered to be crucial for the prebiotic polymerization of amino acids. Ethanethiol is also one of about 250 molecules detected in the interstellar medium or circumstellar shells. We irradiated C2H5SH embedded in carbon monoxide (CO) as well as argon (Ar) ices. Using spectroscopy, we detected methane (CH4), ethane (C2H6), ethylene (C2H4), acetylene (C2H2), carbon monosulfide (CS), carbonyl sulfide (OCS), dihydrogen sulfide (SH2), thioformaldehyde (H2CS), ethanethial (CH3CHS), thiirane, ethenethione (H2CCS), ethynethiol (HCCSH), thiirene, ethenedithione (SCCS), methylene radical (CH2), ethylthiyl radical (C2H5S), thioketenyl radical (HCCS), sulfanyl radical (SH), and sulfur atoms. Additionally, we observed OCS luminescence during annealing of the Ar matrix sample, which indicates the existence of a free sulfur atom. All products contain fewer atoms than the parent. CH3CHS was the main organic product in CO; OCS is the only product detected that formed due to a reaction with CO. Quantum chemical computations show that the S–H bond can easily be broken upon electronic excitation. Although more experimental and theoretical data are needed, we suggest that C2H5SH can exist only in interstellar clouds shielded from UV radiation like G+0.693-0.027 but not in Orion KL.

Hapten Synthesis and Monoclonal Antibody Preparation for Simultaneous Detection of Albendazole and Its Metabolites in Animal-Origin Food.

Albendazole (ABZ) is one of the benzimidazole anthelmintics, and the overuse of ABZ in breeding industry can lead to drug resistance and a variety of toxic effects in humans. Since the residue markers of ABZ are the sum of ABZ and three metabolites (collectively referred to as ABZs), albendazole-sulfone (ABZSO2), albendazole-sulfoxide (ABZSO), and albendazole-2-amino-sulfone (ABZNH2SO2), an antibody able to simultaneously recognize ABZs with high affinity is in urgent need to develop immunoassay for screening purpose. In this work, an unreported hapten, 5-(propylthio)-1H-benzo[d]imidazol-2-amine, was designed and synthesized, which maximally exposed the characteristic sulfanyl group of ABZ to the animal immune system to induce expected antibody. One monoclonal antibody (Mab) that can simultaneously detect ABZs was obtained with IC50 values of 0.20, 0.26, 0.77, and 10.5 μg/L for ABZ, ABZSO2, ABZSO, and ABZNH2SO2 in ic-ELISA under optimized conditions respectively, which has been never achieved in previous reports. For insight into the recognition profiles of the Mab, we used computational chemistry method to parameterize cross-reactive molecules in aspects of conformation, electrostatic fields, and hydrophobicity, revealing that the hydrophobicity and conformation of characteristic group of molecules might be the key factors that together influence antibody recognition with analytes. Furthermore, the practicability of the developed ic-ELISA was verified by detecting ABZs in spiked milk, beef, and liver samples with recoveries of 60% to 108.8% and coefficient of variation (CV) of 1.0% to 15.9%.

Oxidation of Dithia Compounds: Comparative Experimental and Theoretical Studies on 1,3‐Bis(methylthio)propane, Bis(methylthio)methane, and meso‐4,6‐Dimethyl‐1,3‐dithiane

Abstract1,3‐Bis(methylthio)propane, bis(methylthio)methane, and meso‐4,6‐dimethyl‐1,3‐dithiane were oxidized with 1–4 equivalents of hydrogen peroxide, meta‐chloroperbenzoic acid, sodium periodate, or potassium permanganate, respectively, and the amounts of oxidized substrates (sulfoxides and/or sulfones) were determined by NMR spectroscopy. Sulfanyl groups in the former starting material turned out to behave like independent functions, while a mutual influence of the sulfur functions was verified in the latter compounds. A meaningful investigation was possible in the conformationally constrained dithiane derivative. Oxidation of the dithiane with stoichiometric amounts of periodate led to exclusive formation of bissulfoxides, while hydrogen peroxide and meta‐chloroperbenzoic acid yielded the possible products less specifically and permanganate preferentially furnished sulfones. The experimental investigations were supported by calculations on energies and stereoelectronic effects of starting materials, products, and transition states. The unique property of permanganate to exclusively yield sulfones might be due to its special oxidation mechanism, where the sulfur is not only acting as nucleophile, but concomitantly as electrophilic moiety.

Quamtum Mechanical Approach to Gas Phase Reaction of Isopropanol with Sulfanyl Radical

i-C3H7OH (IPA) is one of the potential fuel additives. The reaction mechanism of isopropanol with sulfanyl radical was investigated at the CCSD(T)//B3LYP/6-311+G(3df,2p) level of theory. Ten possible reaction pathways giving PR1-PR10 including three H-abstraction reactions and seven substitution reactions were considered. Based on the determined potential energy surface and molecular parameters, the rate constants and branching ratios of each reaction pathway were calculated at the temperature range of 298K - 2000K by using the transition state theory considering the Eckart tunnel effect. The kinetics results showed that at 298K, the reaction products were mainly PR2 ((CH3)2COH + H2S) (~ 100%). However, at 2000K, the contribution of PR2 decreased to 77.8% of the total product, while, PR3 (CH3CH(CH2)OH + H2S) and PR1 ((CH3)2CHO + H2S) accounted for 16.7% and 5.5% of the total product, respectively.

Synthesis and Cytotoxicity of Sulfanyl, Sulfinyl and Sulfonyl Group Containing Ursane Conjugates with 1,3,4‐Oxadiazoles and 1,2,4‐Triazoles

AbstractA library of novel sulfanyl, sulfinyl, and sulfonyl group‐containing ursane conjugates with 1,3,4‐oxadiazoles and 1,2,4‐triazoles were designed and obtained. The target compounds were synthesized by alkylation of the corresponding azole‐based thiones followed by S‐selective oxidation. The expected sulfoxides and sulfones were obtained depending on the applied excess of mCPBA without oxidation of the ursane double bond. The novel products were studied for their antiproliferative activity on cell lines MCF7 (breast cancer), U‐87 MG (glioblastoma multiform cells), A549 (lung carcinoma), and U‐87 MG (hepatocarcinoma), using immortalized human fibroblasts hTERT as non‐cancer control. Oxadiazole‐derived methylsulfones possessed the most notable cytotoxicity, while the sulfanyl group containing ursane conjugates with 1,2,4‐triazoles 7 g, 7 h exhibited the best selectivity and antiproliferative activity, superior to ursolic acid and starting azole‐based thiones. Possible mechanism of action of thioethers 7 g, 7 h was studied using molecular modeling.

Inhibition of Urease, a Ni‐Enzyme: The Reactivity of a Key Thiol With Mono‐ and Di‐Substituted Catechols Elucidated by Kinetic, Structural, and Theoretical Studies

AbstractThe inhibition of urease from Sporosarcina pasteurii (SPU) and Canavalia ensiformis (jack bean, JBU) by a class of six aromatic poly‐hydroxylated molecules, namely mono‐ and dimethyl‐substituted catechols, was investigated on the basis of the inhibitory efficiency of the catechol scaffold. The aim was to probe the key step of a mechanism proposed for the inhibition of SPU by catechol, namely the sulfanyl radical attack on the aromatic ring, as well as to obtain critical information on the effect of substituents of the catechol aromatic ring on the inhibition efficacy of its derivatives. The crystal structures of all six SPU‐inhibitors complexes, determined at high resolution, as well as kinetic data obtained on JBU and theoretical studies of the reaction mechanism using quantum mechanical calculations, revealed the occurrence of an irreversible inactivation of urease by means of a radical‐based autocatalytic multistep mechanism, and indicate that, among all tested catechols, the mono‐substituted 3‐methyl‐catechol is the most efficient inhibitor for urease.

Tuning of organic heterojunction conductivity by the substituents’ electronic effects in phthalocyanines for ambipolar gas sensors

Exploiting organic heterojunction effects in electrical devices are an important strategy to improve the electrical conductivity, which can be utilized into improving the conductometric gas sensors performances. In this endeavor, the present article reports fabrication of organic heterostructures in a bilayer device configuration incorporating octa-substituted nickel phthalocyanines (NiPc) and radical lutetium bis-phthalocyanine (LuPc2) and investigates their sensing properties towards NH3 vapor. NiPc having hexyl sulfanyl, hexyl sulfonyl and p-carboxyphenoxy moieties are synthesized, which electronic effects are electron donating, accepting and moderate accepting, respectively, also validated by cyclic voltammetry. The electronic effects of substituents in NiPc modulate the interfacial electrical conductivity and the type of the organic heterojunction formed. The electron acceptor and donor groups favor the formation of accumulation and accumulation/depletion heterojunctions, which are also correlated to negative and positive response towards NH3, respectively. Among the studied heterojunction devices, the one based on hexyl sulfanyl groups, revealed the highest and the most stable response in 10−90 ppm of NH3 and under variable relative humidity (rh) (10–70 %). Interestingly, the bilayer device having p-carboxyphenoxy substituted NiPc, exhibited ambipolar behavior such that its p-type semiconducting nature is changed into n-type at higher rh values, also demonstrated by change in its negative response into positive towards NH3.

Combination therapy of N-acetyl-L-cysteine and S-2(2-aminoethylamino) ethylphenyl sulfide for sulfur mustard induced oxidative stress in mice.

Sulfur mustard (SM) is chemically, bis(2-chloroethyl) sulfide and a strong alkylating agent that causes cytotoxicity and blisters on skin. In laboratory animal models, SM is extremely lethal. Since no specific antidote has been proposed, decontamination upon contact is the recommended procedure. Several antidotes have been screened for SM, and in that sulfanyl compounds, N-acetyl-l-cysteine (NAC) and S-2(2-aminoethylamino) ethylphenyl sulfide (DRDE-07) showed good protection. Since they showed protection at high doses, the aim of this study was to evaluate the efficacy in combination at low dose, for percutaneously administered SM in mice. 4 LD50 of SM (32.4 mg/kg) was administered, and NAC (50 mg/kg), DRDE-07 (25 and 50 mg/kg) and their combinations were evaluated as 30 min pre-treatment by single oral administration. After 72 h of SM exposure, significant decrease in body weight, decrease in hepatic reduced glutathione, and increase in hepatic malondialdehyde were observed (P < 0.001), showing oxidative stress. The combination of NAC (100 mg/kg) and DRDE-07 (50 mg/kg) showed significant protection (P < 0.01). The severe histopathological lesions induced by SM in liver, spleen and skin were also considerably reduced by the combination. The combination of NAC and DRDE-07 having sulfanyl groups, will be promising antioxidants and an effective antidote for SM toxicity.

Application of Azide-Tetrazole Tautomerism and Arylsulfanyl Group Dance in the Synthesis of Thiosubstituted Tetrazoloquinazolines

AbstractNucleophilic aromatic substitution reaction between 4-aryl­thio-2-chloroquinazolines and NaN3 takes place with an unusual sulfanyl group dance and leads to the formation of 5-(arylthio)tetrazolo[1,5-c]-quinazolines, which do not form the azide tautomer and do not undergo CuAAC reactions with alkynes. On the other hand, 5-azidotetrazolo[1,5-a]quinazoline (formally described as 2,4-diazidoquinazoline) undergoes regioselective nucleophilic aromatic substitution with thiols at C5 and forms 5-(alkyl/arylthio)tetrazolo[1,5-a]quinazolines, the structure of which has been proved by X-ray crystallography. The latter exist in tautomeric equilibrium with their 2-azidoquinazoline form, which provides possibility for copper-catalyzed azide–alkyne 1,3-dipolar cyclo­addition reaction, leading to the 4-alkyl/arylthio-2-(1H-1,2,3-triazol-1-yl)quinazolines.

Mass Spectra of New Heterocycles: XXI. Study of Alkyl [(5-Amino-1H-pyrrol-2-yl)sulfanyl]acetates by Electron and Chemical Ionization Mass Spectrometry

The fragmentation of previously inaccessible alkyl [(5-amino-1H-pyrrol-2-yl)sulfanyl]acetates under electron (70 eV) and chemical (reactant gas methane) ionization conditions was studied for the first time. Under electron ionization, all the studied compounds form a molecular ion (Irel 7–100%), the main primary fragmentation pathway of which is associated with the C–S bond cleavage in the sulfanyl group and elimination of the ester fragment (R4OCOCH2) in the form of a radical. The chemical ionization of alkyl [(5-amino-1H-pyrrol-2-yl)sulfanyl]acetates is characterized by protonation, recharging, and electrophilic addition. The base peak belongs to an [M + H]+ ion. Chemical ionization is accompanied by the elimination of an R4OCOCH2 radical from the M+• and [M + Et]+ ions and an R4OCOCHS molecule from the M+• and [M + H]+ ions.

Halogenated and di-substituted benzenesulfonamides as selective inhibitors of carbonic anhydrase isoforms

By applying an approach of a “ring with two tails”, a series of novel inhibitors possessing high-affinity and significant selectivity towards selected carbonic anhydrase (CA) isoforms has been designed. The “ring” consists of 2-chloro/bromo-benzenesulfonamide, where the sulfonamide group is as an anchor coordinating the Zn(II) in the active site of CAs, and halogen atom orients the ring affecting the affinity and selectivity. First “tail” is a substituent containing carbonyl, carboxyl, hydroxyl, ether groups or hydrophilic amide linkage. The second “tail” contains aryl- or alkyl-substituents attached through a sulfanyl or sulfonyl group. Both “tails” are connected to the benzene ring and play a crucial role in selectivity. Varying the substituents, we designed compounds selective for CA VII, CA IX, CA XII, or CA XIV.Since due to binding-linked protonation reactions the binding-ready fractions of the compound and protein are much lower than one, the “intrinsic” affinities were calculated that should be used to study correlations between crystal structures and the thermodynamics of binding for rational drug design. The “intrinsic” affinities together with the intrinsic enthalpies and entropies of binding together with co-crystal structures were used demonstrate structural factors determining major contributions for compound affinity and selectivity.

Comprehensive study of nitrofuroxanoquinolines. New perspective donors of NO molecules

The goal of present work is the study of NO releasing mechanisms in nitrofuroxanoquinoline (NFQ) derivatives. Mechanisms of their structural non-rigidity and pathways of NO donation - spontaneous or under the action of sulfanyl radicals or photoirradiation - were considered in details, both experimentally and quantum chemically. Furoxan-containing systems of the discussed type are not capable of spontaneous or photoinduced decomposition under mild conditions, and sulfanyl (radical) induced processes are the most preferable. It was shown that appropriate modification of NFQ through [3 + 2] cycloaddition and subsequent aromatization is a powerful tool to design new prospective donors of NO molecule. Two newly obtained NFQ derivatives were proven to have unusually high NO activity in full accordance with the theoretical model. We hope that these examples will encourage community to seek for new NO active molecules among cycloadducts and modified furoxanes.