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Celastrol is one of the most studied natural products. Our studies show for the first time that celastrol can bind to its target protein via specific noncovalent interactions that position celastrol next to the thiol group of the reactive cysteine for reversible covalent bond formation. Such specific noncovalent interactions confer celastrol binding specificity and demonstrate the feasibility of improving the efficacy and selectivity of celastrol for therapeutic applications.

UV-induced disulfide formation (UV-DF) and disulfide reduction (UV-DR) reactions for surface functionalization and dynamic photopatterning are presented. Both photochemical reactions allow for the spatially and temporally controlled, reversible transition

A process comprising reacting, in a reactor having a fixed bed containing a solid catalyst which contains a zeolite, hydrogen sulfide and an oxirane in the presence of the solid catalyst to yield a reaction product with contains a mercapto-alcohol. A reactor system includes the reactor, an oxirane feed stream, a hydrogen sulfide feed stream, a fixed bed containing the solid catalyst placed inside the reactor, and an effluent stream containing the reaction product. The hydrogen sulfide and the oxirane are present in a mole ratio in a range of about 5:1 to 50:1.

Vesicle lipid bilayers have been employed as templates to modulate the product distribution in a dynamic covalent library of Michael adducts formed by mixing a Michael acceptor with thiols. In methanol solution, all possible Michael adducts were obtained in similar amounts. Addition of vesicles to the dynamic covalent library led to the formation of a single major product. The equilibrium constants for formation of the Michael adducts are similar for all of the thiols used in this experiment, and the effect of the vesicles on the composition of the library is attributed to the differential partitioning of the library members between the lipid bilayer and the aqueous solution. The results provide a quantitative approach for exploiting dynamic covalent chemistry within lipid bilayers. This journal is

The invention belongs to field of mineral flotation collecting agent materials and in particular discloses a method for preparing thionocarbamates. The method comprises the following steps: carrying out esterification reaction on xanthogenate and 2-halogenated ethanol to obtain O-alkyl-S-hydroxyethyl xanthogenate; carrying out ammonolysis reaction on the O-alkyl-S-hydroxyethyl xanthogenate and fatty amine to obtain a mixture of the thionocarbamates and 2-mercaptoethanol; after carrying out alkali washing on the mixture of the thionocarbamates and the 2-mercaptoethanol, carrying out oil-water separation, wherein an oil phase is the thionocarbamates and a water phase is 2-hydroxyethanethiol salt; carrying out acid washing on the 2-hydroxyethanethiol salt to obtain 2-mercaptoethanol. The invention further provides O-alkylthioethyl xanthogenate which is prepared by enabling the 2-hydroxyethanethiol salt and alkyl halide to react to obtain 2-alkylthioethyl ethanol and enabling the 2-alkylthioethyl ethanol to react with carbon disulfide and alkali. According to the method provided by the invention, the yield of the prepared thionocarbamates, 2-mercaptoethanol and O-alkylthioethyl xanthogenate is high and the purity is high; a product is easy to separate and purity and co-production is realized; the cost is saved and the reaction efficiency is also improved; the method is green and environmentally friendly.

A process includes reacting, in a reactor having a fixed bed containing a solid catalyst which contains a heterogeneous ion exchange resin, hydrogen sulfide and ethylene oxide in the presence of the solid catalyst to yield a reaction product which contains beta-mercaptoethanol. A reactor system includes the reactor, an ethylene oxide stream, a hydrogen sulfide stream, a fixed bed containing the solid catalyst placed in the reactor, and an effluent stream containing the reaction product. During steady state operation of the reactor in the process and the reactor system, the hydrogen sulfide and the ethylene oxide are present in a mole ratio in a range of about 9:1 to about 20:1.

5-Methylene pyrrolones (5MPs) are highly thiol-specific and tracelessly removable bioconjugation tools. 5MPs are readily prepared from primary amines in one step. 5MPs exhibit significantly improved stability under physiologically relevant conditions and cysteine specificity compared to commonly used analogues, maleimides. Michael addition of thiol to 5MPs occurs rapidly, cleanly, and does not generate a stereocenter. The conjugates efficiently release thiols via retro-Michael reaction in alkaline buffer (pH 9.5) or via thiol exchange at pH 7.5. This unique property makes 5MPs valuable for the controlled release of conjugated cargo and temporary thiol protection. The utilization of 5MPs for protein immobilization and pull-down of active complexes is illustrated using E. coli. acetohydroxyacid synthase isozyme I.

The transfer of the nitroso group from 1-nitroso-1-methyl-3-tolylsulfonylguanidine (NOTSG) and 1-nitroso-1-methyl-3-benzoylguanidine (NOBMG) to some thiols, including the amino acid cysteine, was studied in a pH range between 7 and 12. The measured apparent bimolecular rate constant of transnitrosation (ktrapp) revealed a bell-shaped pH dependence that clearly indicates that both nitrosoguanidines react through the corresponding neutral form, and the nucleophiles in the thiolate anion form to give the corresponding S-nitrosothiol. Regarding cysteine, the existence of three macroscopic acidity constants influenced the kinetic behavior of the transnitrosation reaction. Transnitrosation rates (ktr) of the two possible nucleophilic species were obtained and it was found that NOBMG has lower thiol transnitrosation capacity due to the lower electron-withdrawing effect of benzoyl group and to the possible stabilization of the anionic structure as a consequence of the establishment of the intramolecular hydrogen bond. The ktr values of the studied nucleophiles were calculated and a Br?nsted-type plot was established giving unexpected negatives βnuc(βnuc(NOBMG)=-0,17 and βnuc(NOTSG)=-0,11). The atypical βnuc values were attributed to the need for previous desolvation of the nucleophile.

Dynamic covalent chemistry (DCC) has become a powerful tool for the creation of molecular assemblies and complex systems in chemistry and materials science. Herein we developed for the first time quantitative reactivity scales capable of correlation and prediction of the equilibrium of dynamic covalent reactions (DCRs). The reference reactions are based upon universal DCRs between imines, one of the most utilized structural motifs in DCC, and a series of O-, N-, and S- mononucleophiles. Aromatic imines derived from pyridine-2-carboxyaldehyde exhibit capability for controlling the equilibrium through distinct substituent effects. Electron-donating groups (EDGs) stabilize the imine through quinoidal resonance, while electron-withdrawing groups (EWGs) stabilize the adduct by enhancing intramolecular hydrogen bonding, resulting in curvature in Hammett analysis. Notably, unique nonlinearity induced by both EDGs and EWGs emerged in Hammett plot when cyclic secondary amines were used. This is the first time such a behavior is observed in a thermodynamically controlled system, to the best of our knowledge. Unified quantitative reactivity scales were proposed for DCC and defined by the correlation log K = SN (RN + RE). Nucleophilicity parameters (RN and SN) and electrophilicity parameters (RE) were then developed from DCRs discovered. Furthermore, the predictive power of those parameters was verified by successful correlation of other DCRs, validating our reactivity scales as a general and useful tool for the evaluation and modeling of DCRs. The reactivity parameters proposed here should be complementary to well-established kinetics based parameters and find applications in many aspects, such as DCR discovery, bioconjugation, and catalysis.

Tris(3-hydroxypropyl)phosphine (THPP) is demonstrated to be a versatile, water-soluble and air-stable reducing agent, allowing for the rapid, irreversible reductive cleavage of disulfide bonds in both aqueous and buffered aqueous-organic media. The reagent shows exceptional stability at biological pH under which condition it permits the rapid reduction of a wide range of differentially functionalized small-molecule disulfides.

Background: Hydrogen sulfide (H2S) modulates physiological processes in mammals. Results: The reactivity of H2S toward disulfides (RSSR) and albumin sulfenic acid (RSOH) to form persulfides (RSSH) was assessed. Conclusion: H2S is less reactive than thiols. Persulfides have enhanced nucleophilicity. Significance: This kinetic study helps rationalize the contribution of the reactions with oxidized thiol derivatives toH2S biology.

For fifty years, dithiothreitol (DTT) has been the preferred reagent for the reduction of disulfide bonds in proteins and other biomolecules. Herein we report on the synthesis and characterization of 2,3-bis(mercaptomethyl)pyrazine (BMMP), a readily accessible disulfide-reducing agent with reactivity under biological conditions that is markedly superior to DTT and other known reagents. This journal is the Partner Organisations 2014.

An object of the present invention is to produce hepatic cells from non-hepatic cells that can be obtained less invasively and at low cost. The gene of HNF3α, HNF3β, or HNF3γ and the gene of HNF4α are transduced into non-hepatic cells. The present invention enables the production of induced hepatocytes from somatic cells that are non-hepatic cells, such as skin cells. The use of the induced hepatocytes obtained by the present invention can establish and develop, as general medical treatment, cell transplantation into the liver, artificial livers, and drug response tests, which are the areas that have not been generalized because of the difficulty of procuring hepatocytes.

Benzalcyanoacetamides were designed and synthesized as reversible thiol conjugate addition acceptors. These thia-conjugate additions can rapidly and reversibly achieve equilibrium under aqueous conditions at neutral pH. Kinetic studies show that electron-withdrawing groups at the 4-position of the phenyl ring of the benzalcyanoacetamides promote the conjugate addition at equilibrium. Dynamic thiol exchange of these conjugate acceptors is faster than singly activated α,β-unsaturated carbonyl compounds. These thia-conjugate additions can be assembled as potentially useful components in dynamic combinatorial chemistry. Benzalcyanoacetamides were studied with thiols as reversible thiol conjugate addition acceptors. These thia-conjugate additions can rapidly and reversibly achieve equilibrium under aqueous conditions at neutral pH, which verifies the ultimate use of these conjugate acceptors in dynamic combinatorial chemistry. Copyright

Pass them on! Dithiobutylamine immobilized on a resin is a useful reagent for the reduction of disulfide bonds. Its ability to reduce a disulfide bond in a protein is enhanced greatly if used along with a soluble strained cyclic disulfide or mixed diselenide that relays electrons from the resin to the protein. This electron-relay catalysis system provides distinct advantages over the use of excess soluble reducing agent alone. Copyright

Composite structures composed of a device as a core structure, being a medical device or article, and a porous polymeric coat and designed capable of encapsulating bioactive agents while retaining the activity of these agents are disclosed. Further disclosed are processes of preparing such composite structures.

The white rot fungus Phanerochaete chrysosporium, a saprophytic basidiomycete, possesses a large number of cytosolic glutathione transferases, eight of them showing similarity to the Omega class. PcGSTO1 (subclass I, the bacterial homologs of which were recently proposed, based on their enzymatic function, to constitute a new class of glutathione transferase named S-glutathionyl-(chloro)hydroquinone reductases) and PcGSTO3 (subclass II related to mammalian homologs) have been investigated in this study. Biochemical investigations demonstrate that both enzymes are able to catalyze deglutathionylation reactions thanks to the presence of a catalytic cysteinyl residue. This reaction leads to the formation of a disulfide bridge between the conserved cysteine and the removed glutathione from their substrate. The substrate specificity of each isoform differs. In particular PcGSTO1, in contrast to PcGSTO3, was found to catalyze deglutathionylation of S-glutathionyl-p-hydroquinone substrates. The three-dimensional structure of PcGSTO1 presented here confirms the hypothesis that it belongs not only to a new biological class but also to a new structural class that we propose to name GST xi. Indeed, it shows specific features, the most striking ones being a new dimerization mode and a catalytic site that is buried due to the presence of long loops and that contains the catalytic cysteine.

(Figure Presented) Photolysis of dihydroxy compounds (diols) protected as 2-nitrobenzylidene acetals (ONBA) and subsequent acid- or base-catalyzed hydrolysis of the 2-nitrosobenzoic acid ester intermediates result in an efficient and high-yielding release of the substrates. We investigated the scope and limitations of ONBA photochemistry and expanded upon earlier described two-step procedures to show that the protected diols of many structural varieties can also be liberated in a one-pot procedure. In view of the fact that the acetals of nonsymmetrically substituted diols are converted into one of the corresponding 2-nitrosobenzoic acid ester isomers with moderate to high regioselectivity, the mechanism of their formation was studied using various experimental techniques. The experimental data were found to be in agreement with DFT-based quantum chemical calculations that showed the preferential cleavage occurs on the acetal C-O bond in the vicinity of more electron-withdrawing (or less electron-donating) groups. The study also revealed considerable complexity in the cleavage mechanism and that the structural variations in the substrate can significantly alter the reaction pathway. This deprotection strategy was found to be also applicable for 2-thioethanol when released from the corresponding monothioacetal in the presence of a reducing agent, such as ascorbic acid.

Ethylene chlorohydrin when reacted with elemental chalcogens or dimethyl dichalcogenides in the hydrazine hydrate-alkali system forms chalcogen-containing analogs of ethylene glycol and its derivatives (dichalcogenated β-diglycols, chalcogenated ethanols, and chalcogenated methyl cellosolves).

The conjugate addition of aliphatic and aromatic thiols to ethynyl p-tolyl sulphone (tosylacetylene) has been managed to afford Tosvinyl derivatives chemoselectively (in the presence of oxygen nucleophiles) and stereoselectively (isomers Z) in practically quantitative yields. The conditions of choice are: catalytic amounts of Et3N (only 0.5-1.0 mol%), a reaction temperature around 0°C and, for the less acidic thiols, CF3CH2OH or CH3CN/CF3CH2OH as the solvent. Thus, N-Boc-Cys-OMe has been quantitatively protected as its S-Tosvinyl derivative in the presence of N-Boc-Ser-OMe and N-Boc-Tyr-OMe. This novel protecting group is stable to several basic and acidic conditions; its removal is achieved at rt by treatment with an excess of pyrrolidine or at 0°C with alkanethiolate ions.

Aqueous ink for ink-jet recording which contains at least a water-insoluble coloring matter, water and a resin as main components and which takes the form of an emulsion, in which is characterized by containing at least one yellow hue coloring matter selected from the group consisting of a quinophthalone compound represented by the formula (1); and a pyridone azo compound represented by the formula (2); The ink is ink for ink-jet recording having excellent light resistance and storage stability, and enables formation of a high quality image without blotting, and obtained recording image is excellent in water resistance as ink for ink-jet recording.

The invention relates to a dental material with at least one polymerizable binder and at least one filler containing a redox-initiator system for the radical polymerization, which comprises an initiator and an activator. The material is characterized in that the filler contains a homogeneous mixture of a first part of the filler, which is mixed with the initiator, a second part of the filler, which is mixed with the activator, and a third part of the filler, which does not contain a component of the initiator system. The materials are particularly suitable as cements and filling materials.

A room-temperature deprotection method of trityl amines, -ethers, and -thioethers is presented, based on coupling of metal acid catalysis (HgX2, with X- = Cl- or OAc-) and sodium borohydride reduction. The results of its application to monotritylated compounds (ethanethiol, ethanol, and piperidine) and to mono- and ditritylated 1,2-bifunctional compounds (mercaptoethanol, aminoethanethiol, and ethanolamine) are compared with those obtained with early methods based on the use of strong Bronsted acids (pure TFA and MeCN solutions of HCl). Trityl thioethers of simple thiols and amino and hydroxy thiols are promptly cleaved by reductive detritylation, and one-pot procedures can be employed to produce free thiols. In contrast, dilution with water of these same compounds in solutions of strong Bronsted acids leaves them unaffected. O-Tr and N-Tr bonds are broken by this latter treatment. However, trityl ethers are rapidly cleaved by even dilute HCl solutions, while cleaving of trityl amines is modulated by HCl concentration. Addition of NaBH4 to solutions of monofunctional trityl ethers in HgCl2/MeCN leads to complete deprotection. Monofunctional trityl amines are partially deprotected only if the complexation reaction is allowed to reach equilibrium. Combination of H+- with HgX+-catalyzed detritylation methods allows selective deprotection of pertritylated amino and hydroxy thiols. The results appear to be due to the strong difference in the affinity of the donor atoms present in the pertritylated substrates for H+ and HgX+. Catalysis based on Bronsted acids leads to cleaving of the N- and O-trityl bonds with recovering of the S-trityl group; that based on mercury salts allows recovering of N- and O-trityl groups with deprotection of the -SH function. Selectivity in deprotection of pertritylated amino alcohols seems to be severely hampered by similarity in the affinity of N- and O-atoms for H+ and HgX+, and, taking advantage of the lower HgX+-complexation rate of the N-trityl with respect to the O-trityl group, only preservation of the N-trityl bond has been achieved.

Using UV-vis spectrometrical measurements, equilibrium constants for NO transfer between S-nitroso-N-acetyl-penicillamine (SNAP) and different thiols as well as kinetic data for NO transfer from S-nitroso bovine serum albumin (BSANO) to thiols have been obtained. NO transfer from SNAP to other primary/secondary thiols are thermodynamically favorable, whereas other S-nitrosothiols exhibit similar NO transfer potential. The obtained Gibbs free energy, enthalpy and entropy data indicated that NO transfer reactions from SNAP to four thiols are exothermic with entropy loss. The kinetic behavior of BSANO/RSH transfer can be related to both the acidity of sulfhydryl group and the electronic structure in thiol.

Aqueous ink for ink jet recording which contains at least a water-insoluble coloring matter, water and a resin as main components and which takes the form of an emulsion, the coloring matter being represented by formula (1) The coloring matter for ink jet recording of the invention is excellent in water resistance in particular and also excellent in light resistance and compatibility with the resin. Thus, it is suited for ink jet recording. Further, the aqueous ink for ink jet recording of the invention which is produced using the coloring matter is excellent in light resistance and storage stability. Especially, when it is used as ink for ink jet recording system, the use of the ink composition can provide excellent aqueous ink that enables formation of a high-quality image without blotting and a recorded image having an excellent water resistance.

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A kinetic study of the acid-catalyzed loss of alkoxide and thiolate ions from alkoxide and thiolate ion adducts, respectively, of benzylidene Meldrum's acid (1-H), methoxybenzylidene Meldrum's acid (1-OMe), and thiomethoxybenzylidene Meldrum's acid (1-SMe) is reported. The reactions appear to be subject to general acid catalysis, although the catalytic effect of buffers is weak and the bulk of the reported data refers to H+-catalysis. α-Carbon protonation and, in some cases, protonation of one of the carbonyl oxygens to form an enol compete with alkoxide or thiolate ion expulsion. This rendered the kinetic analysis more complex but allowed the determination of pK(a) values and of proton-transfer rate constants at the α-carbon. In conjunction with previously reported data on the nucleophilic addition of alkoxide and thiolate ions to the same Meldrum's acid derivatives, rate constants for nucleophilic addition by the respective neutral alcohols and thiols could also be calculated. Various structure-reactivity relationships are discussed that help define transition-state structures. Comparisons with similar reactions of alkoxide ion adducts of β-alkoxy-α-nitrostilbenes provide additional insights.

The nucleophilic vinylic substitution (S(N)V) reactions of methoxybenzylidene Meldrum's acid (5-OMe) follow the common two-step mechanism involving a tetrahedral intermediate. With thiolate and alkoxide ions, this intermediate is shown to accumulate to detectable levels and a detailed kinetic study allowed the determination of the rate constants of the various elementary steps. With OH- as the nucleophile, the intermediate cannot be observed; it is shown that this is the result of the intermediate rapidly breaking down to products by a pathway not available in the reactions with the thiolate or alkoxide ions. Comparison of structure-reactivity data for the reactions of 5-OMe with those of benzylidene Meldrum's acid (5-H) and β-methoxy-α-nitrostilbene (4-OMe) reveal a complex interplay of steric effects, π-donor and π-acceptor resonance effects, and anomeric effects.

Prostaglandins (PGs) such as Δ12-PGJ2 and Δ7-PGA1 methyl ester that possess a cross-conjugated dienone unit exhibit unique antitumor and antiviral activities independent of intracellular cAMP levels. These compounds are transported reversibly into cultured cells and accumulate in nuclei via covalent interaction, eliciting growth inhibition. PGA1 methyl ester, a simple cyclopentenone analog, is less potent. The unique cellular behavior of the dienone PGs correlates well with their chemical properties. The PGs react specifically with thiol nucleophiles such as glutathione. Michael addition of thiols to Δ7-PGA1 methyl ester, an alkylidenecyclopentenone derivative, occurs facilely at the endocyclic C(11) position rather than at the C(7) position. This process is reversible, and in solution phase, the adducts are in equilibrium with considerable amounts of free PG and thiols. However, the reaction of this PG with Sepharose-bound thiols, regarded to be plausible mimics of protein thiols, is irreversible, and the resulting adducts are dissociated only by alkali treatment. On the other hand, PGA1 methyl ester reacts with soluble or polymer-anchored thiols at lower rates than Δ7-PGA1 methyl ester, but the resulting thiol adducts are substantially more stable than those of the dienone PGs. This tendency of the PGA1 methyl ester causes its equilibrium to shift to the adduct formation. The reversibility of the Michael reaction of PGs with thiols is consistent with their intracellular behavior and biological activities. Since glutathione adducts of PGs have no antiproliferative activities for cancer cells, the intracellular free PGs are presumed to interact with target molecules to cause cell growth inhibition. The involvement of the ATP-dependent glutathione S-conjugate export pump (GS-X pump) in the efflux of PGs is discussed. Thus, the marked difference in potency of the dienone and enone PGs is explained by considering the combined kinetic and thermodynamic properties and the action of the GS-X pump.

The technique of combined pulse radiolysis/laser photolysis has been used to investigate the disulfide radical anion formation reactions for mercaptoethanol, cysteamine, and N-acetyl-L-cysteine over the pH range 7.0-13.0. The photolysis of the transient radical anions, formed by the one electron oxidation of the sulfhydryl, perturbs the disulfide radical anion/thiyl radical equilibrium, allowing rate constants for thiyl radical reaction with the parent sulfhydryl to be uniquely determined from the absorption bleach and subsequent recovery. These pH-dependent values were combined with measured disulfide radical anion equilibrium constants to calculate first-order disulfide radical anion dissociation rate constants. By computer modeling of established mechanisms for the disulfide radical anion growths, rate constants for the reaction of hydroxyl radicals with individual sulfhydryl species were calculated. These values are contrasted with previously reported values determined by using competition kinetics.

The kinetics of NO-group transfer have been measured for the reaction between a nitrosothiol (HOCH2CH2SNO) and nine thiols, mostly based on the cysteine structure.The reaction is second-order and there is evidence for a steric effect for thiols containing 1,1-dimethyl substituents (penicillamine derivatives).Reaction occurs via the thiolate anion as shown by the pH-rate constant profile, and a full kinetic analysis for the reactions of two thiols (N-acetylcysteine and glutathione) is quantitatively in agreement with this mechanism.Variation of the nitrosothiol structure for reaction with N-acetylcysteine shows that electron-withdrawing substituents in the nitrosothiol promote reaction; there is a similarity with the corresponding reactions of alkyl nitrites.

Oligomers with polydiene sequences and crosslinkable grafts are useful as coatings for protecting metal surfaces as well as inking buffers. The oligomers contain a polydiene sequence of 1-100 diene links, from 1 to 20 polar functional groups, and from 1-20 acrylic or methacrylic groups. The oligomers have the general formula: STR1

Equilibrium constants (Keq) for the thiol-disulfide interchange reactions between dithiothreitol (DTT) and lipoic acid (14.2 +/- 0.7), lipoic acid (Lip) and mercaptoethanol (13.3 M +/- 1.0 M), and mercaptoethanol (ME) and glutathione (GSH or GSSG) (1.20 +/- 0.10) were measured in D2O at pD 7.0 by 1H NMR spectroscopy.Two of these equilibrium constants were also measured in D2O/CD3OD.These values are compared with those obtained by other methods.A coherent set of values for the equilibrium constants between DTT or ME and thiols having a range of structures was assembled (Table III).The recommended value for the equilibrium constant between DTT and GSH is 210 M (Keq = ox>2/(red>)).

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6,6′-Dithiosucrose (sucrose dithiol, Suc(SH)2) is a weakly reducing species. The equilibrium constant for reduction of mercaptoethanol disulfide, MEox, by sucrose dithiol in aqueous solution is Keq = 0.3 M = {[SucS2][Mered]2}/{[Suc(SH) 2][MEox]}, where SucS2 (6,6′-dithiosucrose cyclic disulfide, sucrose disulfide) is the cyclic disulfide formed from the oxidation of sucrose dithiol. Measurements of values of T1, and J using 1H NMR spectroscopy indicate that sucrose and sucrose dithiol adopt indistinguishable conformations in water. The conformations of sucrose dithiol and sucrose disulfide are similar but distinguishable. Molecular mechanics calculations indicate that two of the possible structures of sucrose disulfide have relatively low energies. Comparison of coupling constants calculated for these structures with experimental coupling constants from 1H NMR spectra indicated that one of the two structures was more probable; this more probable structure had the conformation more similar to that of sucrose. The reduction potential of the Suc(SH)2/SucS2 (an 11-membered ring) couple is similar to that of an n-alkane-1,n-dithiol/cyclic disulfide (n = 5 or 6) couple; the value of EC (effective concentration = Keq = 0.3 M) characterizing oxidation of the two thiols of SuC(SH)2 to a disulfide is similar to that for oxidation of the two thiols of hexane-1,6-dithiol (Keq = 0.2 M) and pentane-1,5-dithiol (Keq = 3.6 M). The similarity of these values of EC suggests that SucS2 is a relatively strain-free structure and reflects the proximity of the two thiol groups in this carbohydrate.

Rate constants for reaction of coenzyme A and cysteine with oxidized glutathione (GSSG) and equilibrium constants for the reaction of coenzyme A, cysteine, homocysteine, cysteamine, and related thiols with GSSG by thiol/disulfide interchange were determined over a range of pD values by NMR spectroscopy.The rate constants for reaction of the thiolate anion forms of coenzyme A and cysteine with GSSG suggest that reduction of GSSG by coenzyme A and cysteine is a mechanistically uncomplicated SN2 reaction.Equilibrium constants for the thiol/disulfide interchange reactions show a strong dependence on the Bronsted basicity of the thiolate anion.In a similar way, ΔE0', the difference between the half-cell potentials for the RSSR/RSH and GSSG/GSH redox couples, is linearly dependent on the difference between the pKA values of RSH and glutathione: ΔE0' = 64ΔpKA - 7.7 where ΔE0' is in units of mV.The reducing strength at a given pH is also determined by the fraction of the thiol present in the reactive thiolate form.At pD 7, the half-cell potentials for coenzyme A, cysteine, homocysteine, and cysteamine are close to that of glutathione, the major intracellular thiol redox system, which suggests that small changes in the intracellular redox potential can cause significant changes in the intracellular distribution of these biological thiols between their reduced and oxidized forms.

Novel mitomycin derivatives are characterized by a substituent on the C6 -methyl group. The mitomycin derivatives exhibit anti-tumor and antibacterial activity and have low toxicity.

meso-2,5-Dimercapto-N,N,N',N'-tetramethyladipamide (meso-DTA) reduces disulfide bonds up to 8 times faster (kinetic) than does dithiothreitol (DTT) in aqueous solution at pH 7.0. meso-DTA is easily synthesized in five steps (39percent overall yield) from adipic acid. meso-DTA, which forms a cyclic disulfide, is less reducing than DTT by approximately 56 mV, but is much more reducing than mercaptoethanol.

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We have synthesized a new reagent - N,N'-dimethyl-N,N'-bis(mercaptoacetyl)hydrazine (DMH) - for the reduction of disulfide bonds in proteins.DMH reduces disulfide bonds 7 times faster than does dithiothreitol (DTT) in water at pH 7.DMH reduces mixed disulfides of cysteine proteases (papain and ficin) especially rapidly (30 times faster than DTT).DMH (ε0 = -0.300 V) reduces noncyclic disulfides completely, although it is less strongly reducing than DTT (ε0 = -0.356 V).

There are provided alkyl esters of 5-heterocyclic-pyridine-2,3-dicarboxylic acids useful as intermediates for the preparation of highly effective 5-heterocyclic-2-(2-imidazolin-2-yl)pyridine herbicidal agents and methods for the preparation thereof.

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The reduction potential for the .CO2- radical anion has been determined by equilibration of formate with sulfhydryl radicals of β-mercaptoethanol, penicillamine, and lipoamide in aqueous solutions at pH 3-6.The reaction .CO2- + e- + H+ = HCO2- yields the value E09 = 1.49 V with an uncertainty of +/-0.06 V.On the basis of this value and the known free energies of CO2(aq) and HCO2-(aq), E019 for CO2 + e- = .CO2- was found to be -1.85 V.

The addition reactions of thiol anions to form adducts with acrylonitrile (1), 1-chloroacrylonitrile (2), and fumaronitrile (3) and the corresponding elimination reactions were examined in aqueous solution, generally containing 8.3percent Me2SO at 25 deg C.Deuterium exchange into the methanethiol and thiosalicylate adducts of 1 is faster than elimination.Deuterium exchange causes biphasic kinetics for elimination reactions in D2O of the p-nitrothiophenol, but not of the pentafluorothiophenol, adducts 1 and 2.The kinetic solvent deuterium isotope effects of knHOH/knDOD = 2.0 for addition of thiosalicylate to form 3 and 1.1-1.2 for addition of β-mercaptoethanol and thioacetic acid anions to form 1 are smaller than the product discrimination isotope effects of kH/kD = 3.2, 2.8 and 3.2 for these reactions.These differences show that the reactions proceed through a carbanion intermediate that is protonated faster than it expels basic thiol anions.These results exclude a concerted mechanism for addition-elimination with a concurrent, separate exchange reaction.The solvent kinetic deuterium isotope effect is 3.9 for the addition of thionitrobenzoate dianion to form 3.Buffer catalysis of elimination becomes more significant with more acidic leaving groups and is larger for 3 than for 1 with a given leaving group.The results show that the rate-limiting step changes from addition-elimination of the thiol anion to proton transfer with decreasing pKa of the thiol; the same change is favored by addition of CN to the α-position for a given thiol.The effect of the α-CN group is attributed to conjugation with the developing double bond in the transition state for elimination.The Broensted slope is β = 0.90 for rate-limiting deprotonation of the pentafluorothiophenol adduct 3 and Broensted-type plots against the pKa of the leaving group have slopes of β1g = -0.25 and -0.54 for predominantly rate-limiting deprotonation and leaving group expulsion, respectively.

Fifty-five new five-membered cyclic organophosphorus compounds including oazaphospholidines, thiazaphospholidines, and oxathiaphospholanes were synthesized, which have substituents at 4- or/and 5-positions besides at the 2-position.The thiazaphospholidines showed the highest insecticidal activity followed by oxathiaphospholanes and oxazaphospholidines.The position preference of substituents in insecticidal activity was most obvious in the oxazaphospholidines.It was preferable for insecticidal activity to have the substituent near the more basic atom: the 4-position for thiazaphospholidine and oxazaphospholidine, the 5-position for oxathiaphospholane, with the exception of 4- or 5-phenyl oxazaphospholidine.

Redox equilibria between RS. and -S-S-- radicals, and between these types of radical and phenoxyl and chlorpromazine (ClPz.2+) radicals, have been investigated in aqueous solutions at pHs over the range 6-10 to obtain a self-consistent set of redox potentials for the reactions PhO. + H+ + e- = PhOH (4), RSS.R + 2H+ + e- = 2RSH (11), and RS. + H+ + e- = RSH (18), in sulfur systems with alkyl R groups.Absolute standard potentials were calculated on the of E0 = 0.83 V for the chlorpromazine couple.The results for E04 (=1.35 +/- 0.02 V) and E018 (=1.33 +/- 0.02 V) were in agreement with values calculated from thermodynamic data within the known uncertainties.E018 was found to exhibit a falloff when electron-rich groups, such as the two methyls of penicillamine or the CO2- of β-mercaptoacetic acid, were present on the carbon adjacent to the S atom.However, the effect was relatively small (ca. 10-14 mV).E011 was 1.72 +/- 0.02 V for β-mercaptoethanol.The corresponding potentials for the cyclic anions of dithiothreitol, dithioerythritol, and lipoamide were the same within experimental error, but the uncertainties were larger (+/- 0.04 V).For the reaction e- + -S-S- = -S-S-- (22), the magnitude of E022 was calculated to be -1.60 V, showing that only strongly reducing species could donate electrons to disulfide.Rate constants for several of the forward and backward reactions in the equilibria were also determined.

Treatment of 2H-azirines with mercaptosubstituted acids and their derivatives leads to β-ketoamides and 2-aziridinyl alkyl sulfides, respectively. 2-Aziridinyl alkyl sulfides, in turn, react with carboxylic acids to give β-ketoamides and substituted ethanethiol derivatives.Acylation of 2-aziridinyl alkyl sulfides with acyl halides generates a variety of products, depending on the reaction conditions; either products derived from cleavage and isomerization of the aziridinyl ring or (1-acylaziridinyl-2) alkyl sulfides are obtained.

2-(p-Methoxyphenyl)-1,3-dithiolan-2-yl cation (1) was isolated as a perchlorate and its reaction with water was examined kinetically in 10percent aqueous acetonitrile at 30 oC.Hydration of 1 to form a 2-hydroxydithiolane intermediate 2 is rate determining at pH >6, but the decomposition of 2 to lead to a thiolester product becomes a slow step at pH R (4.1) of 1, both of the steps become partially rate determining.Hydration of 1 is unusually slow as compared with that of the oxygen analogues and is catalyzed by general bases with wide ranges of basicity (pKa = 1.3-7.7); the Bronsted β = 0.18.In the presence of nucleophiles like thiol and primary and secondary amines, they can complete with water to form an adduct, 4.At higher acidity, the nucleophilic reaction becomes a rapid equilibrium which is followed by the slow hydrolysis of 1; biphasic kinetics were observed.

In an inert atmosphere (argon) in reaction with ferrous sulfate and hydrogen peroxide in a saturated aqueous solution of ferric sulfate at 5-10 deg C 2-ethoxy-1,3-dioxolane and 2-ethoxy-1,3-oxathiolane change after 15 min into ethylene glycol monoformate and 2-mercaptoethyl formate with yields of 49 and 32percent respectively and with cca 50percent conversion in the substrate.

Equilibrium constants Kh for the addition of 2-mercaptoethanol and glutathione to phenylglyoxal to form hemithioacetals were determined spectrophotometrically over the pH range 7-10.The observed Kh values decrease sigmoidally with pH as the thiol ionizes.Rearrangement of hemithioacetals formed from phenylglyoxal and various thiols was kinetically investigated.The rates increase with thiol concentration following a saturation curve to give Kh identical with the spectrophotometric value.The rearrangement is subject to general base catalysis.The solvent isotope effect on the rate of the rearrangement, kH2O/kd2O, is nearly 1.0; that on the equilibrium, KH2Oh/KD2Oh, is 0.38.The results strongly support the mechanism involving proton transfers through an enediol intermediate.