Addition Of Thiol Group Research Articles

Synthesis of sugar enones and their use as powerful synthetic precursors of thiodisaccharides

Monosaccharide derivatives having a double bond conjugated to a carbonyl (sugar enones or enuloses) are relevant synthetic tools. They are also suitable starting materials, or versatile intermediates, for the synthesis of a wide variety of natural or synthetic compounds with a broad spectrum of biological and pharmacological activities. The preparation of enones is mainly focused on the search for more efficient and diastereoselective synthetic methodologies. The usefulness of enuloses relies on the diverse reaction possibilities offered by alkene and carbonyl double bonds, which are prone to undergo varied reactions such as halogenation, nitration, epoxidation, reduction, addition, etc. The addition of thiol groups that led to sulfur glycomimetics, such as thiooligosaccharides, is particularly relevant. Therefore, the synthesis of enuloses and the Michael addition of sulfur nucleophiles to give thiosugars or thiodisaccharides are discussed here. Chemical modifications of the conjugate addition products to afford biologically active compounds are also reported.

Synthesis of Alternating Polyisocyanate Copolymers by Anionic Polymerization for Mimicking Amphiphilic Helical Peptides.

The amphiphilic conformation of α-helical peptides has important biological functions, such as ion transport, antifreeze, and innate immunity, which can be mimicked by alternating polyisocyanate copolymers. We synthesized poly(allyl isocyanate-alt-(S)-(-)-α-methylbenzyl isocyanate (P(AIC-alt-SMBIC)) and ammonium-containing P(AIC-alt-SMBIC) (N-P(AIC-alt-SMBIC)), ensuring the amphiphilic helical conformation. The benzyl group of SMBIC plays an important role in alternating copolymerization with its steric and electron-withdrawing effects, while AIC provides an alkene group capable of introducing a customized functional group. The P(AIC-alt-SMBIC) with predominantly alternating sequence was acquired at fSMBIC /fAIC =8 with a controlled molecular weight and narrow dispersity. N-P(AIC-alt-SMBIC)s were synthesized from thiol-ene radical addition with P(AIC-alt-SMBIC).

Consecutive Alkylation, "Click", and "Clip" Reactions for the Traceless Methionine-Based Conjugation and Release of Methionine-Containing Peptides.

"Click" reactions have revolutionized research in many areas of science. However, a disadvantage of the high stability of the Click product is that identifying simple treatments for cleanly dissociating the latter under the same guiding principles, i.e., a "Clip" reaction, remains a challenge. This study demonstrates that electron-deficient alkynes, conveniently installed on methionine residues, can participate in well-known Click (nucleophilic thiol-allene addition) and subsequent Clip reactions (radical thiol-ene addition). To illustrate this concept, a variety of bioconjugates (peptide-peptide; peptide-fluorophore; peptide-polymer; and peptide-protein) were prepared. Interestingly, the Clip reaction of these bioconjugates releases the original peptides concurrent with regeneration of their unmodified methionine residue, in minutes. Moreover, the conjugates demonstrate substantial stability toward endogenous levels of reactive species in bacteria, illustrating the potential for this chemistry in the biosciences. The reaction conditions employed in the Click and Clip steps are compatible with the preservation of the integrity of biomolecules/fluorophores and involve readily accessible reagents and the natural functional groups on peptides/proteins.

Functionalization and soft photoreduction of graphene oxide triggered by the photoinitiator during thiol-ene radical addition

Thiol-ene radical addition (TERA) is a powerful reaction for the chemical functionalization of the reactive alkenes of GO with thiols. To trigger TERA, a photoinitiator (PI) is added to ensure high yields associated with fast conversion rates. However, the inappropriate use of PIs might affect the GO functionalization leading to photoreduction as well as low conversion rates. Herein, we explored the GO functionalization with cysteamine (CA) by TERA and its reduction influenced by Irgacure® 369, a commercial PI. We focused to analyze the reaction conditions that promote an orthogonal GO functionalization finding the limits where the photoreduction began. UV-spectroscopy, Raman spectroscopy, fluorescence labeling and XPS were used to characterize the functionalized GO. The data indicate three possible scenarios depending on the PI/CA molar ratio: i) orthogonal GO functionalization by TERA, ii) side reactions between GO and the radicals formed upon the PI photocleavage, and iii) soft photoreduction of the GO with alcohols and carboxylic acids as the functional groups mainly affected. However, we found that the GO functionalization by TERA was still occurring, but in less favorable conditions despite the side reactions and by-products. Therefore, photo-initiated TERA was confirmed as a powerful reaction to functionalize the reactive alkenes of GO, and by tuning the PI/CA molar ratio an orthogonal GO functionalization can be achieved, limiting side reactions and particularly GO reduction.

Functionalization and Soft Photoreduction of Graphene Oxide Triggered by the Photoinitiator During Thiol-Ene Radical Addition

Functionalization and Soft Photoreduction of Graphene Oxide Triggered by the Photoinitiator During Thiol-Ene Radical Addition

Thioacetate-Based Initiators for the Synthesis of Thiol-End-Functionalized Poly(2-oxazoline)s.

New functional initiators for the cationic ring-opening polymerization of 2-alkyl-2-oxazolines are described to introduce a thiol moiety at the α terminus. Both tosylate and nosylate initiators carrying a thioacetate group are obtained in multigram scale, from commercial reagents in two steps, including a phototriggered thiol-ene radical addition. The nosylate derivative gives access to a satisfying control over the cationic ring-opening polymerization of 2-ethyl-2-oxazoline, with dispersity values lower than 1.1 during the entire course of the polymerization, until full conversion. Cleavage of the thioacetate end group is rapidly achieved using triazabicyclodecene, thereby leading to a mercapto terminus. The latter gives access to a new subgeneration of α-functional poly(2-oxazoline)s (butyl ester, N-hydroxysuccinimidyl ester, furan) by Michael addition with commercial (meth)acrylates. The amenability of the mercapto-poly(2-ethyl-2-oxazoline) for covalent surface patterning onto acrylated surfaces is demonstrated in a microchannel cantilever spotting (µCS) experiment, characterized by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary-ion mass spectrometry (ToF-SIMS).

Thiol-ene photo-click immobilization of a chiral chromatographic ligand on silica particles

This work reports procedures for the immobilization of vinyl ligands on silica particles by UV-initiated thiol-ene radical addition reaction (photo-click immobilization). tert‑Butylcarbamoyl quinine was the functional ligand (ene component) for the synthesis of chiral stationary phases. Two distinct surface chemistries were evaluated. In one approach, the ligand was directly attached to 3-mercaptopropyl-silica triggered by radicals generated by UV irradiation from a photoinitiator. In another approach, the ligand was immobilized onto vinyl silica via poly(3-mercaptopropyl-methylsiloxane) (PMPMS) as crosslinker by a photoinitiated double click reaction in which functionalization with chiral ligand and crosslinking to vinylsilica occurred simultaneously in one synthesis step. PMPMS-bonded CSPs were prepared from suspension (slurry method) or solventless after coating of the polythiol onto the vinylsilica surface (film method). Optimization by a design of experiment approach showed that the reaction time is the prime variable to optimize the surface coverage of chiral selector which also increased with PMPMS concentration. When the film formation of the latter approach was assisted by a minute volume of toluene during photo-click immobilization, selector coverage could be significantly increased to 0.73 µmol/m2 in a 2 h synthesis compared to 0.44 µmol/m2 by the solventless film method and 0.47 µmol/m2 by the slurry method under otherwise comparable conditions. The solvent assistance improved the chromatographic efficiency of the film method and resulted equal minimal reduced plate height of 2.6 as the slurry method for a chiral probe (Fmoc-Phe). The mass transfer resistance was around factor 2 smaller with the solvent-assisted film method as compared to the film approach without toluene, presumably due to a more homogenous distribution of the thin polymer film owing to lower dynamic viscosity in presence of toluene.

Development of a 1,3a,6a-triazapentalene derivative as a compact and thiol-specific fluorescent labeling reagent

For the fluorescence imaging of biologically active small compounds, the development of compact fluorophores that do not perturb bioactivity is required. Here we report a compact derivative of fluorescent 1,3a,6a-triazapentalenes, 2-isobutenylcarbonyl-1,3a,6a-triazapentalene (TAP-VK1), as a fluorescent labeling reagent. The reaction of TAP-VK1 with various aliphatic thiols proceeds smoothly to afford the corresponding 1,4-adducts in high yields, and nucleophiles other than thiols do not react. After the addition of thiol groups in dichloromethane, the emission maximum of TAP-VK1 shifts to a shorter wavelength and the fluorescence intensity is substantially increased. The utility of TAP-VK1 as a compact fluorescent labeling reagent is clearly demonstrated by the labeling of Captopril, which is a small molecular drug for hypertension. The successful imaging of Captopril, one of the most compact drugs, in this study demonstrates the usefulness of compact fluorophores for mechanistic studies.

Enrichment and Distribution of Pb2+ Ions in Zwitterionic Poly(cysteine methacrylate) Brushes at the Solid-Liquid Interface.

Cysteine-based polyzwitterionic brushes have been prepared via a two-step route. First, poly(allyl methacrylate) (PAMA) brushes have been grown from the surface of silicon substrates using surface-initiated atom transfer radical polymerization. The obtained PAMA brushes with free pendant vinyl groups were further modified via radical thiol-ene addition reaction to attach l-cysteine moieties. Surface ζ potential investigations on pH-responsiveness of these poly(cysteine methacrylate) (PCysMA) brushes confirm their zwitterionic character at intermediate pH range, while at pH values either below pH 3.50 or above pH 8.59, they exhibit polyelectrolyte character. Under acid (pH < 3.50) or base (pH > 8.59) conditions, they possess either cationic or anionic character, respectively. In the zwitterionic region, these PCysMA brushes show positive surface ζ potential in the presence of Pb(CH3COO)2 solutions of various concentrations. The results are in line with microscopic investigations using anomalous X-ray reflectivity (AXRR) carried out along the absorption edge of Pb2+ ions. When the photon energies were varied around the absorption L3 edge of lead (13037 eV), the Pb2+ concentration normal to the silicon substrates, as a function of depth inside PCysMA brushes, could be revealed at the nanoscale. Both ζ potential and AXRR measurements confirm the enrichment of Pb2+ ions inside PCysMA brushes, indicating the potential of PCysMA to be used as a water purification material.

New hybrid materials based on cyclophosphazene and polysiloxane precursors: Synthesis and properties

New cross-linked polymers with different morphology based on cyclotriphosphazene and polysiloxane precursors were obtained by the thiol-ene radical addition. A series of samples such as aerogels with various density, a xerogel, a monolith and a film were prepared and their physico-mechanical properties were studied. Phosphazene-containing polymeric aerogels were prepared directly in supercritical carbon dioxide (scCO2) media. The morphology of the samples was investigated by scanning electron microscopy (SEM). The average particle size in the aerogels was in the range of 2–15 μm. The mechanical properties of all the samples were studied by the compression test. It was shown that the Young modulus of the monolith (95 MPa) was 7 times larger than that of the xerogel (14 MPa). The aerogels are porous elastic polymers with the Young modulus of 0.032 and 0.257 MPa, correspondingly. The thermal stability of the samples was evaluated by thermal gravimetric analysis (TGA). Weight loss was observed in the range of 255–298 °C in air and 251–295 °C in argon for all the samples. Aerogel samples have a greater water contact angle (130° for A1 and 136° for A2) than xerogel (122°), monolith (121°) and film samples (84°), which can be explained by the lotus effect.

Click-based thiol-ene photografting of COOH groups to SiO2 nanoparticles: Strategies comparison

We present the study of the anchoring of carboxylic groups on SiO2 nanoparticles from different approximations based on the photochemical radical thiol-ene addition (PRTEA) reaction: a photografting approach between mercaptosuccinic acid (MSA) and vinyl-modified SiO2 nanoparticles and the post-grafting on the surface of silica colloids of the silane precursor 2-((2-(trimethoxysilyl)ethyl)thio)succinic acid (TMSMSA), obtained from the PRTEA. These synthetic strategies were compared with a widely common derivatization methodology based on the nucleophilic attack of surface-anchored amino groups with succinic anhydride. The successful functionalization of the colloidal silica was confirmed by infrared spectroscopy (FTIR), zeta potential at different pH and contact angle measurements. We found that although these three approaches were valid for −COOH immobilization, they had a noticeable impact on the dispersability and agglomeration of the colloidal suspension at the end of the synthesis. Scanning electron microscopy, dynamic light scattering (DLS) and fluorescence correlation spectroscopy (FCS) measurements indicated that the PRTEA photografting between MSA and vinyl-modified SiO2 resulted in highly dispersed colloidal particles. On the other hand, the presence of surface −COOH groups was highly beneficial for redispersion of the colloidal material after lyophilization or freeze-drying procedures.

Interrupted CuAAC Ligation: An Efficient Approach to Fluorescence Labeled Three-Armed Mikto Star Polymers

We introduce a powerful variant of the copper(I)-mediated azide–alkyne cycloaddition (CuAAC) for the synthesis of miktoarm block copolymers with a fluorescently labeled core. Via the simple addition of a functional azirine to a conventional CuAAC reaction of an azide and alkyne terminal polymer strand, a vinyl functionality is introduced at the focal point of the two polymers, which can subsequently be modified, via, e.g., radical thiol–ene addition. Concomitantly, a second functionality–a pyrene chromophore–stemming from the functional azirine is introduced enabling fluorescence detection and unimolecular micelle formation. Thus, by virtue of thiol terminal polymers an efficient two-step synthesis of midchain functional mikto-three armed star polymers is possible. Detailed NMR, SEC, DSC, UV–vis, and fluorescence studies underpin the successful formation of the functional miktoarm star with a fluorescence labeled core. Finally, yet importantly, dynamic light scattering (DLS) results demonstrate that the miktoarm polymers form self-fluorescent micelles in aqueous media and display robust micellar stability with unimolecular micellar characteristics.

Cationic Poly(benzyl ether)s as Self-Immolative Antimicrobial Polymers.

Self-immolative polymers (SIMPs) are macromolecules that spontaneously undergo depolymerization into small molecules when triggered by specific external stimuli. We report here the first examples of antimicrobial SIMPs with potent, rapid, and broad-spectrum bactericidal activity. Their antibacterial and hemolytic activities were examined as a function of cationic functionality. Polymers bearing primary ammonium cationic groups showed more potent bactericidal activity against Escherichia coli, relative to tertiary and quaternary ammonium counterparts, whereas the quaternary ammonium polymers showed the lowest hemolytic toxicity. These antibacterial polycations undergo end-to-end depolymerization when triggered by an externally applied stimulus. Specifically, poly(benzyl ether)s end-capped with a silyl ether group and bearing pendant allyl side chains were converted to polycations by photoinitiated thiol-ene radical addition using cysteamine HCl. The intact polycations are stable in solution, but they spontaneously unzip into their component monomers upon exposure to fluoride ions, with excellent sensitivity and selectivity. Upon triggered depolymerization, the antibacterial potency was largely retained but the hemolytic toxicity was substantially reduced. Thus, we reveal the first example of a self-immolative antibacterial polymer platform that will enable antibacterial materials to spontaneously unzip into biologically active small molecules upon the introduction of a specifically designed stimulus.

Branched Hydroxyl Modification of SBS Using Thiol-Ene Reaction and Its Subsequent Application in Modified Asphalt

Based on the thiol-ene radical addition reaction, the branched hydroxyl functionalized modified styrene-butadiene-styrene triblock copolymer (SBS-g-OH) was prepared using a commercially available SBS with high molecular weight and low content of 1,2-vinyls as substrate polymer, 2-mercaptoethanol (MCH) as modifying agent, 2,2-azodiisobutyronitrile (AIBN) as initiator, and 1,4-dioxane (DOA) as solvent. By the characterization of Fourier transform-infrared spectroscopy (FT-IR), and 1H nuclear magnetic resonance spectroscopy (1H NMR), the order of reactivity was proved that 1,2-vinyls had a priority to react with MCH at low functionalization degree of SBS-g-OH. A novel reaction kinetics model was set up to only describe the addition reaction between MCH and 1,2-vinyls, but not 1,4-units of PB segments, with this reaction kinetics model, the effect of reaction time, temperature, and initial concentration ratio of MCH to 1,2-vinyls on functionalization degree of SBS-g-OH were investigated, besides the desired o...

One-Step Synthesis of Mesoporous Silica Thin Films Containing Available COOH Groups.

Inorganic–organic hybrid mesoporous silica thin films with covalently bonded carboxylic acid groups were synthesized in a one-step procedure, using carboxylic-derivatized alkoxysilanes obtained by photochemical radical thiol-ene addition (PRTEA). The organosilanes were synthesized by clicking mercaptosuccinic or mercaptoacetic thioacids with vinyltrimethoxysilane, using benzophenone as the photoradical initiator. The films were synthesized by evaporation-induced self-assembly of a sol containing a mixture of tetraethoxysilane and different quantities of the organosilanes, without any further treatment after the PRTEA reaction. Two nonionic surfactants were used as templates to produce different pore sizes. Different aging times were also applied. Structural characterization with electron microscopy, porosimetry measurements, and small angle X-ray scattering with two-dimensional detection demonstrated the obtention of mesoporous phases whose degree of ordering depended on the amount of added organosilane. The incorporation of the functional silanes was shown by X-ray photoelectron spectroscopy, and the presence of the COOH groups was confirmed by Fourier transform infrared (FTIR). Finally, the availability of the COOH groups for further chemical modification was demonstrated by FTIR by following the changes in the typical carbonyl IR bands during proton exchange and metal complexation. The proposed simple methodology allows obtaining COOH-modified silica thin films in one step, without the need of hard reaction conditions or deprotection steps. Functionalization with carboxyl groups brings a pH-dependent switch-ability to the pore surface that can be used for multifunctional mesoporous materials design.

A new reactive polymethacrylate bearing pendant furfuryl groups: Synthesis, thermoreversible reactions, and self-healing

We report a new methacrylate copolymer having pendant furfuryl groups (PFu) reactive to maleimide-bearing compounds to form thermally-induced crosslinked networks exhibiting self-healability through thermoreversible Diels-Alder (DA)/Retro-DA reactions. The PFu is synthesized by a combination of a facile radical polymerization with post-modification methods through a base-catalyzed coupling reaction and a thermally-induced thiol-ene radical addition reaction. The resulting PFu is effective toward DA reaction with a maleimide-bearing crosslinker at moderate or elevated temperatures, yielding highly crosslinked films through DA linkages. Thermal analysis and spectroscopic studies along with NMR model study with small molecular weight precursors suggest the formation of DA-crosslinked networks at 50–100 °C and the occurrence of retro-DA reaction at >125 °C. The resulting DA-crosslinked network is dynamic, exhibiting self-healing through the occurrence of thermoreversible DA/retro-DA reactions, confirmed with sol-gel transition and optical microscopy.

Investigation of a novel fluorinated surfactant-based system for the design of spherical wormhole-like mesoporous silica

In contrast to hydrogenated based systems that led to many studies, fluorinated surfactants have been little reported. Thanks to their high chemical and thermal stability, these compounds are considered as suitable candidates for the synthesis of porous materials with an enhanced hydrothermal stability. This study reports the synthesis of a new fluorinated surfactant, 2-trifluoromethyl-7,7,8,8,9,9,10,10,11,11,12,12,12-tridecafluoro-4-thia-1-dodecanoic acid (FSC) obtained from the thiol-ene radical addition of 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octanethiol onto 2-trifluoromethyl acrylic acid in 85% yield. In the aim of achieving micelles in water to design mesoporous materials according to the cooperative templating mechanism, FSC was modified with water-soluble telechelic diamine (Jeffamine) ED-600. The modified surfactant was deeply characterized by spectroscopic methods and the FSC-Jeffamine ED-600 micellar system was used as porogen to prepare mesoporous materials via the cooperative templating mechanism. Spherical wormhole-like mesostructured silica materials of high specific surface area (850m2/g) and homogeneous pore size distribution (ca. 3.4nm) were obtained by conveniently adjusting the porogen/silica molar ratio and the hydrothermal conditions.

Postpolymerization Modifications of Alkene-Functional Polycarbonates for the Development of Advanced Materials Biomaterials.

Functional aliphatic polycarbonates have attracted significant attention as materials for use as biomedical polymers in recent years. The incorporation of pendent functionality offers a facile method of modifying materials postpolymerization, thus enabling functionalities not compatible with ring-opening polymerization (ROP) to be introduced into the polymer. In particular, polycarbonates bearing alkene-terminated functional groups have generated considerable interest as a result of their ease of synthesis, and the wide range of materials that can be obtained by performing simple postpolymerization modifications on this functionality, for example, through radical thiol-ene addition, Michael addition, and epoxidation reactions. This review presents an in-depth appraisal of the methods used to modify alkene-functional polycarbonates postpolymerization, and the diversity of practical applications for which these materials and their derivatives have been used.

Preactivated thiomers for intranasal delivery of apomorphine: In vitro and in vivo evaluation

The purpose of this study was to synthesize preactivated thiomers with different degrees of preactivation and to evaluate their potential as novel excipient for nasal apomorphine administration. The thiomer (PAA-cys) was synthesized by addition of thiol groups on poly(acrylic acid) with various molecular mass including 100, 250and450kDafollowed by immobilization of 2-mercaptonicotinic acid (2MNA) to thiol groups by disulfide bond formation resulting in PAA-cys-2MNA. These thiomers (PAA100-cys, PAA250-cys and PAA450-cys) were in the next step preactivated by 56.3, 59.5 and 46.5% (medium degree), and 80.1, 81.6 and 87% (high degree), respectively. Apomorphine permeation across porcine nasal mucosa in the presence of PAA100-cys-2MNA, PAA250-cys-2MNA and PAA450-cys-2MNA with high degree of preactivation was 3.1-, 4.4- and 4.1-fold, while 2.7-, 3.4- and 3.0-fold higher than control for medium degree of preactivation, respectively. Administration of apomorphine in the presence of PAA250-cys-2MNA showed in rats 9 and ∼2-fold improvement of relative bioavailability compared with oral and intranasal administration of apomorphine solution, respectively. Because of the pronounced improvement among other polymers, PAA250-cys-2MNA with high degree of preactivation could be considered as promising excipient for nasal delivery of apomorphine.

ChemInform Abstract: Photochemical Radical Thiol—Ene Click‐Based Methodologies for Silica and Transition Metal Oxides Materials Chemical Modification: A Mini‐Review

AbstractReview: 137 refs.