Coupling Of Thiols Research Articles

Why Not Trans? Inhibited Radical Isomerization Cycles and Coupling Chains of Lipids and Alkenes with Alkane -thiols.

Reversible addition of thiyl radicals to cis fatty acids converts them into trans fatty acids, L Z + S• ⇄ SL• ⇄ L E + S•, in a cycle that, uninterrupted, would rapidly isomerize lipids exposed to radicals and thiols. One reason this does not happen in foods and organisms is because the cycle is interrupted, by exothermic allylic abstraction, L + S• → L• + SH. Autoinhibition limits the cis-trans cycle length to around 400-500 (L E per S•) in a MUFA model (methyl oleate) and just ∼13-15 in a PUFA lipid model (methyl linoleate). The weak C-H bonds in bisallylic groups in PUFAs thereby act as the first line of defense against thiyl cis-trans cycles in biolipid solutions (±O2). With the intriguing exception of vitamin E in MUFA, thiyl-active antioxidants inhibit isomerization in much the same way as they protect against peroxidation. Applied to thiol-ene coupling (TEC), the allylic abstraction, degraded-chain paradigm resolved a raft of hitherto contradictory trends and findings in "click" TEC polymerization and organic synthesis methods.

Guanidines as Reagents in Proton-Coupled Electron-Transfer Reactions and Redox Catalysts

Redox-active guanidines are ideal proton-coupled electron-transfer (PCET) reagents, since they combine a high Brønsted basicity with a low and tunable redox potential. In this article, the development of redox-active guanidines (especially guanidino-functionalized aromatics, GFAs) in the last ten years is summarized, and their properties compared to other organic Brønsted bases and organic electron donors. First, some applications in organic chemistry that purely use the redox activity (formation of organic donor–acceptor materials and photochemical reductive C–C coupling reactions) are presented. Then, reactions that involve both proton and electron transfer are reviewed. In stoichiometric reactions, redox-active guanidines are used for the dehydrogenative coupling of thiols and phosphanes. The first redox catalytic applications are discussed, using dioxygen as green oxidizing reagent.1 Introduction2 Redox-Active Amines and Guanidines3 Brønsted Basicity of Amines and Guanidines4 Variations of GFA Compounds5 GFA Compounds in Organic Donor–Acceptor Materials and as Reducing Reagents in Organic Synthesis6 Stoichiometric Dehydrogenative Coupling Reactions with Redox-Active Guanidines7 Guanidines as Redox Catalysts8 Conclusions and Outlook

Bone Repair: High‐Performance Thiol–Ene Composites Unveil a New Era of Adhesives Suited for Bone Repair (Adv. Funct. Mater. 26/2018)

Adhesives suitable for fracture fixation can unfold a paradigm shift toward personalized bone repairs. In article number 1800372, Michael Malkoch and co-workers describe a surgically feasible adhesive system that capitalizes on visible light thiol–ene coupling chemistry. Preclinical validation, performed via fiber-reinforced adhesive patch methodology, reveals an unprecedented fixation strength that surpasses commercial dental systems or clinically used K-wires and matches metal plates and screw implants.

Cu-SBTU@MCM-41: As an Efficient and Reusable Nanocatalyst for Selective Oxidation of Sulfides an Oxidative Coupling of Thiols

Cu(II) complex with S-benzylisothiourea ligand was grafted into functionalized mesoporous MCM-41 (Cu-SBTU@MCM-41) and characterized by X-ray Diffraction (XRD), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FT-IR) and inductively Coupled Plasma (ICP-OES) techniques. After characterization of this catalyst its application has been studied in selective oxidation of sulfides to sulfoxides and oxidative coupling of thiols to disulfides using hydrogen peroxide (H2O2) as oxidant. This catalyst was shown good recyclability and reused for several consecutive runs without significant loss of its activity.

General Synthesis of Alkenyl Sulfides by Palladium-Catalyzed Thioetherification of Alkenyl Halides and Tosylates

The cross-coupling reaction of alkenyl bromides with thiols catalyzed by palladium complexes derived from inexpensive dppf ligand is reported. These reactions occur under low catalyst loading and in high yields and display wide scope, including the coupling of bulky thiols and trisubstituted bromoolefins, and functional group tolerance. In addition, the thioetherification of less reactive chloroalkenes and, for the first time, alkenyl tosylates was accomplished using a catalyst generated from CyPF tBu alkylbisphosphine ligand.

Highly Efficient Oxidative Coupling of Thiols and Oxidation of Sulfides in the Presence of MCM-41@Tryptophan-Cd and MCM-41@Tryptophan-Hg as Novel and Recoverable Nanocatalysts

Two heterogeneous catalysts, MCM-41@Tryptophan-Cd and MCM-41@Tryptophan-Hg, were synthesized by immobilization of Cd or Hg complexes on MCM-41 as novel, efficient, recoverable and stable nanocatalysts for Oxidation of sulfides to sulfoxides and oxidative coupling of thiols into their corresponding disulfides. These functionalized complexes were characterized by FT-IR spectroscopy, thermogravimetric analysis (TGA), powder X-ray diffraction (XRD) and N2 adsorption–desorption isotherms. The designed catalysts successfully oxidized a variety of sulfides and thiols with short reaction times in high to excellent yields at room temperature and recovered for several times without significant loss of their catalytic activity. Synthesis of Cd and Hg tryptophan complexes immobilized on to surface of mesoporous MCM-41 under mild reaction conditions has been presented. After characterization of these catalysts, their catalytic activity has been investigated for the synthesis of sulfoxide and disulfides derivatives.

High‐Performance Thiol–Ene Composites Unveil a New Era of Adhesives Suited for Bone Repair

AbstractThe use of adhesives for fracture fixation can revolutionize the surgical procedures toward more personalized bone repairs. However, there are still no commercially available adhesive solutions mainly due to the lack of biocompatibility, poor adhesive strength, or inadequate fixation protocols. Here, a surgically realizable adhesive system capitalizing on visible light thiol–ene coupling chemistry is presented. The adhesives are carefully designed and formulated from a novel class of chemical constituents influenced by dental resin composites and self‐etch primers. Validation of the adhesive strength is conducted on wet bone substrates and accomplished via fiber‐reinforced adhesive patch (FRAP) methodology. The results unravel, for the first time, on the promise of a thiol–ene adhesive with an unprecedented shear bond strength of 9.0 MPa and that surpasses, by 55%, the commercially available acrylate dental adhesive system Clearfil SE Bond of 5.8 MPa. Preclinical validation of FRAPs on rat femur fracture models details good adhesion to the bone throughout the healing process, and are found biocompatible not giving rise to any inflammatory response. Remarkably, the FRAPs are found to withstand loads up to 70 N for 1000 cycles on porcine metacarpal fractures outperforming clinically used K‐wires and match metal plates and screw implants.

Nickel Schiff base complex anchored on Fe3O4@MCM-41 as a novel and reusable magnetic nanocatalyst and its application in the oxidation of sulfides and oxidative coupling of thiols using H2O2

GRAPHICAL ABSTRACT

Glycopeptide ligation via direct aminolysis of selenoester

Direct aminolysis of selenoester in aqueous media was investigated as a glycopeptide ligation strategy. This strategy allows the peptide and glycopeptide ligation to proceed smoothly (even with hindered amino acids) without the need of cysteine residue, N-terminal thiol auxiliary or coupling additive, and to afford the corresponding amide products in excellent yields. No epimerization was observed during ligation reations. In this work, the selenoester of unprotected glycopeptide was readily prepared, and the direct aminolysis of glycopeptide selenoester was successfully applied to synthesize MUC1 mucin sequence efficiently.

Palladium-catalyzed heteroaryl thioethers synthesis overcoming palladium dithiolate resting states inertness: Practical road to sulfones and NH-sulfoximines

We provide efficient synthetic access to heteroaryl sulfones in two-steps using a simple palladium–1,1′-bis[(diphenyl)phosphanyl]ferrocene catalyst to form in high yields variously functionalized heteroaromatic thioethers. Pyridinyl-containing substrates can be subsequently selectively oxidized into sulfones and NH-sulfoximines by using very mild oxidation conditions with a high functional group tolerance. In the palladium-catalyzed C–S coupling of heteroaromatic thiols, reactivity limitation is attached with electron-deficient thiols. We show that this limitation can be resolved by the successful use of 2-bromoheteroarenes in the C–S coupling. We established herein that this choice of heteroaryl electrophilic reagent in palladium-catalyzed C–S bond formation allows overcoming palladium dithiolate out-of-cycle resting state inertness. This was illustrated in the stoichiometric reactivity study of the palladium dithiolate formed from 4-trifluoromethylbenzen-1-thiol –isolated and characterized by multinuclear NMR and XRD– with both 2-chloropyridine and 2-bromopyridine.

Selective N-acetylation with concurrent S-oxidation of o-amino thiol at ambient conditions over Ce doped ZnO composite nanocrystallites

The oxidative SS coupling of thiol to disulfide is an imperative chemical transformation in the domain of biological processes and also finds numerous chemical applications. The CeO2 and ZnO are significant catalysts for oxidation of thiol to disulfide and N-acetylation of amines respectively. Dithiobis(phenylene)bis(benzyldeneimine) moiety containing N-acetyl and disulfide functional groups is a potential antimicrobial agent with Leishmanicidal and antihyperlipidemic activities. Herein, we report a synchronized catalytic application of Ce doped ZnO (Ce-ZnO) and CeO2-Ce-ZnO composites for selective synthesis of Dithiobis(phenylene)bis(benzyldeneimine) from o-amino thiol. The Ce-ZnO samples were synthesized by simple co precipitation method by calcination of hydroxide precursors at 400 °C to get 0–10% Ce-ZnO nanocrystallites. The formation of CeO2-Ce-ZnO composite material was observed beyond 1.5% Ce concentration. The synthesized materials were well characterized by IR, XRD, DRS spectroscopy and SEM-EDS analysis. The application of Ce doped ZnO as an efficient catalyst towards the selective N-acetylation and concurrent S-oxidation of o-amino thiol to afford Dithiobis(phenylene)bis(benzyldeneimine) at ambient temperature in acetonitrile was deliberated. Among all screened catalysts, the maximum selectivity was found for 7.5% Ce-ZnO as CeO2-Ce-ZnO composite catalyst. Lewis acidic property of catalyst supported probable mechanism for achieved dual transformations. Also, the 7.5% Ce-ZnO catalyst has demonstrated a versatile SS coupling ability for variety of thiol substrates with excellent stability.

Synthesis of new zirconium complex supported on MCM‐41 and its application as an efficient catalyst for synthesis of sulfides and the oxidation of sulfur containing compounds

In the present work, we report synthesis of new zirconium complex supported on mesoporous silica by anchoring of adenine on the wall of functionalized MCM‐41, then reacted with ZrOCl2. The resultant MCM‐41‐Adenine‐Zr was characterized by FT‐IR, XRD, TEM, SEM, TGA, EDX, ICP and BET techniques. It was exhibited that the MCM‐41‐Adenine‐Zr can be used as an efficient and thermally stable nanocatalyst for the oxidation of sulfides, oxidative coupling of thiols and synthesis of sulfides. Moreover, this heterogeneous catalyst can be easily recovered from the reaction mixture by simple filtration and reused for several consecutive cycles without noticeable change in its catalytic activity.

Synthesis and characterization of oxo-vanadium complex anchored onto SBA-15 as a green, novel and reusable nanocatalyst for the oxidation of sulfides and oxidative coupling of thiols

The present work describes the synthesis of a new oxo-vanadium complex immobilized on SBA-15 nanostructure as an efficient catalyst for oxidation of sulfides and oxidative coupling of thiols. Characterization of the resultant AMPD@SBA-15 nanostructure was performed by various physico-chemical techniques such as Fourier transform infrared spectroscopy, transmission and scanning electron microscopies, energy-dispersive X-ray spectroscopy, inductively coupled plasma optical emission spectroscopy, X-ray diffraction, thermal gravimetric analysis, and N2 adsorption and desorption. The results of the developed procedure bring several benefits such as the use of commercially available, ecologically benign, operational simplicity, and cheap and chemically inert reagents. It shows good reaction times, practicability and high efficiency, and is easily recovered from the reaction mixture by simple filtration and reused for several consecutive cycles without noticeable change in its catalytic activity. More importantly, high efficiency, simple and an inexpensive procedure, commercially available materials, easy separation, and an eco-friendly procedure are the several advantages of the currently employed heterogeneous catalytic system.

Promotion of a Reaction by Cooling: Stereoselective 1,2-cis-α-Thioglycoconjugation by Thiol-Ene Coupling at -80 °C.

The photoinitiated thiol-ene coupling reactions of 2-substituted glycals were studied as a generally applicable strategy for stereoselective 1,2-cis-α-thioconjugation. Although all glycals reacted with full α-selectivity, the efficacy of the reactions varied in a broad range depending on their configuration and glycals bearing axial acetoxy substituents reacted with very low efficacy at room temperature. The study revealed that the reaction progress could be promoted by cooling and inhibited by heating. At -80 °C, the equilibrium of the rapidly reversible addition of the thiyl radical to alkenes is shifted almost completely toward products, leading to efficient addition reactions. By exploiting this unique temperature effect a series of α-thio-l-fucosides, -d-galactosides, and d-GlcNAc derivatives were prepared with high efficacy and complete stereoselectivity.

Functional siloxanes with photo-activated, simultaneous chain extension and crosslinking for lithography-based 3D printing

A novel, poly(dimethyl siloxane)-based photopolymer that exhibits simultaneous linear chain extension and crosslinking was suitable for vat photopolymerization additive manufacturing. Photopolymer compositions consisted of dithiol and diacrylate functional poly(dimethyl siloxane) oligomers, where simultaneous thiol-ene coupling and free radical polymerization provided for linear chain extension and crosslinking, respectively. Compositions possessed low viscosity before printing and the modulus and tensile strain at break of a photocured, higher molecular weight precursor after printing. Photorheology and soxhlet extraction demonstrated highly efficient photocuring, revealing a calculated molecular weight between crosslinks of 12,600 g/mol and gel fractions in excess of 90% while employing significantly lower molecular weight precursors (i.e. < 5300 g/mol). These photocured objects demonstrated a 2× increase in tensile strain at break as compared to a photocured 5300 g/mol PDMS diacrylamide alone. These results are broadly applicable to the advanced manufacturing of objects requiring high elongation at break.

Diisopropylamine as a single catalyst in the synthesis of aryl disulfides

AbstractThe search for less time-consuming and inexpensive methods for the synthesis of disulfides continues to be a hot subject of research. Herein, we report that diisopropylamine (iPr2NH) can act as a very effective catalyst for this process. The oxidative coupling of aryl thiols was carried out in the presence of catalytic amount ofiPr2NH in air (room temperature) in acetonitrile, without metal catalyst, additives, or external activators. This procedure opens a low-cost, green, and industrially applicable synthetic pathway to obtain aryl disulfides.

Amine Induced Retardation of the Radical-Mediated Thiol-Ene Reaction via the Formation of Metastable Disulfide Radical Anions.

The effect of amines on the kinetics and efficacy of radical-mediated thiol-ene coupling (TEC) reactions was investigated. By varying the thiol reactant and amine additive, it was shown that amines retard thiyl radical-mediated reactions when the amine is adequately basic enough to deprotonate the thiol affording the thiolate anion, e.g., when the weakly basic amine tetramethylethylenediamine was incorporated in the TEC reaction between butyl 2-mercaptoacetate and an allyl ether at 5 mol %, the final conversion was reduced from quantitative to <40%. Alternatively, no effect is observed when the less acidic thiol butyl 3-mercaptopropionate is employed. The thiolate anion was established as the retarding species through the introduction of ammonium and thiolate salt additives into TEC formulations. The formation of a two-sulfur three-electron bonded disulfide radical anion (DRA) species by the reaction of a thiyl radical with a thiolate anion was determined as the cause for the reduction in catalytic radicals and the TEC rate. Thermodynamic and kinetic trends in DRA formations were computed using density functional theory and by modeling the reaction as an associative electron transfer process. These trends correlate well with the experimental retardation trends of various thiolate anions in TEC reactions.

One Scaffold, Many Possibilities – Copper(I)‐Catalyzed Azide–Alkyne Cycloadditions, Strain‐Promoted Azide–Alkyne Cycloadditions, and Maleimide–Thiol Coupling of Ruthenium(II) Polypyridyl Complexes

The applicability of RuII polypyridyl complexes with appropriate functionalities as substrates for biorthogonal coupling reactions is investigated. In detail, copper(I)‐catalyzed azide–alkyne cycloadditions (CuAAC), strain‐promoted azide–alkyne cycloadditions (SPAAC), and maleimide–thiol coupling reactions of ruthenium complexes are examined. The first examples of SPAAC in which the organic azide is provided by the metal complex are presented. All of the chromophores belong to one easy‐to‐synthesize scaffold, which has proven to be convenient for the application of metal chromophores. The fundamental photophysical properties of the examined compounds do not change with substitution, which is important for the design of chromophore conjugates. Furthermore, the limitations of CuAAC reactions will be discussed with regard to copper impurities in the products formed.

Biofunctionalized Patterned Polymer Brushes via Thiol-Ene Coupling for the Control of Cell Adhesion and the Formation of Cell Arrays.

Thiol-ene radical coupling is increasingly used for the biofunctionalization of biomaterials. Thiol-ene chemistry presents interesting features that are particularly attractive for platforms requiring specific reactions with peptides or proteins and the patterning of cells, such as reactivity in physiological conditions and photoactivation. In this work, we synthesized alkene-functionalized (allyl and norbornene residues) antifouling polymer brushes (based on poly(oligoethylene glycol methacrylate)) and studied thiol-ene coupling with a series of thiols including cell adhesive peptides RGD and REDV. The adhesion of umbilical vein endothelial cells (HUVECs) to these interfaces was studied and highlighted the absence of specific integrin engagement to REDV, in contrast to the high level of cell spreading observed on RGD-functionalized polymer brushes. This revealed that α4β1 integrins (binding to REDV sequences) are not sufficient on their own to sustain HUVEC spreading, in contrast to αvβ3 and α5β1 integrins. In addition, we photopatterned peptides at the surface of poly(oligoethylene glycol methacrylate) (POEGMA) brushes and characterized the quality of the resulting arrays by epifluorescence microscopy and atomic force microscopy (AFM). This allowed the formation of cell patterns and demonstrated the potential of thiol-ene based photopatterning for the design of cell microarrays.

Thiol-ene click chemistry towards easy microarraying of half-antibodies.

A UV light-induced thiol-ene coupling reaction (TEC) between half-antibodies (hIgG) and vinyl functionalized glass surfaces was run for biosensing in the microarray format. The accomplished performance improved that obtained with whole antibodies.