Sulfanyl Research Articles

Design of pH-responsive and amphiphilic pullulan-based biological macromolecule for gene delivery.

Nanomedicine, particularly gene delivery, holds immense potential and offers promising therapeutic options. Non-viral systems gained attention due to their binding capacity, stability and scalability. Among these, natural polysaccharides, such as pullulan, are advantageous in terms of sustainability, biocompatibility and potential degradability. In our study, a pH-responsive and amphiphilic pullulan derivative, pullulan norbornene carboxylate (PNC-DMA) was developed, by a two-step synthetic process involving esterification with hydrophobic norbornene group and radical thiol-ene reaction to introduce a pH-dependent cationic group. The molar mass of the polymer was systematically varied to adjust its hydrophobicity and pH-responsive properties, with DS values ranging from 0.4 to 1.4. The created pullulan library exhibited apparent pKa values between 6.5 and 7.1, which were inversely proportional to the degree of substitution (DS). This increase enhanced the polymer's affinity for genetic material, facilitated responsive complexation, provided protection against DNase, and boosted transfection efficiency. However, increased DS was associated with cytotoxicity and protein interaction. Thus, PNC-DMA(140) emerged as the most promising candidate for aqueous formulation and gene delivery in HEK293T cells, even in the presence of serum proteins. This structure-activity-relationship study paves the way for further exploration of the potential advantages of using polysaccharides in gene delivery applications.

Innocuous solvent-based, low-temperature curable, and highly transparent photosensitive polyimides developed using soluble polyimides containing bio-based magnolol moieties.

Traditional photosensitive polyimide (PSPI) materials require a high curing temperature and exhibit low transparency, limiting their applications in thermally sensitive optical devices. To overcome this challenge, soluble photosensitive polyimide resins were synthesized based on the structural design of a bio-based magnolol monomer. It is noteworthy that the PI photoresist, developed by using the as-prepared polyimides and non-toxic solvents (2-acetoxy-1-methoxypropane, PGEMA) and other additives, demonstrated an impressive low-temperature curing performance (180 °C). Furthermore, the solvent residue in the cured film prepared using PGEMA as solvent was markedly decreased compared to that prepared using N-methyl pyrrolidone (NMP). In addition, the C-PI-3 films cured by photoinitiated thiol-ene radical reactions exhibited high transparency with an average visible light transmittance of 87.8%, as well as excellent thermal stability, dielectric and breakdown properties, and photo-patterning capabilities. This partially bio-based and innocuous solvent-based PSPI with low-temperature curability and high transparency properties could be a pioneering example to resolve the challenges of energy efficiency and environmental sustainability and is expected to be used in the field of color filters.

A Comparative Study between Thiol-Ene and Acrylate Photocrosslinkable Hyaluronic Acid Hydrogel Inks for Digital Light Processing.

Photocrosslinkable formulations based on the radical thiol-ene reaction are considered better alternatives than methacrylated counterparts for light-based fabrication processes. This study quantifies differences between thiol-ene and methacrylated crosslinked hydrogels in terms of precursors stability, the control of the crosslinking process, and the resolution of printed features particularized for hyaluronic acid (HA) inks at concentrations relevant for bioprinting. First, the synthesis of HA functionalized with norbornene, allyl ether, or methacrylate groups with the same molecular weight and comparable degrees of functionalization is presented. The thiol-ene hydrogel precursors show storage stability over 15 months, 3.8 times higher than the methacrylated derivative. Photorheology experiments demonstrate up to 4.7-times faster photocrosslinking. Network formation in photoinitiated thiol-ene HA crosslinking allows higher temporal control than in methacrylated HA, which shows long post-illumination hardening. Using digital light processing, 4% w/v HA hydrogels crosslinked with a dithiol allowed printing of 13.5 × 4 × 1mm3 layers with holes of 100µm resolution within 2 s. This is the smallest feature size demonstrated in DLP printing with HA-based thiol-ene hydrogels. The results are important to estimate the extent to which the synthetic effort of introducing -ene functions can pay off in the printing step.

Visible-Light-Promoted Reduction of Nitroarenes with Formate Salts as Reductants.

A visible-light-promoted reduction of nitrobenzenes using formate salts as the reductant was developed. A wide range of nitrobenzenes can be converted into aniline products in a transition metal free fashion. Mechanistic studies revealed that radical species (carbon dioxide radical anion and thiol radical) are key intermediates for the transformation. We anticipate that this method will provide a valuable and green strategy for the reduction of nitrobenzenes.

Bio-sourced tartaric acid-derived tartarimides as diol counterparts towards renewable polyurethanes

The depletion of petroleum-based fossil resources and ever-increasing environmental problems are serious issues in the production of polymeric materials. An increasingly important approach is to obtain the building blocks used in the production of these materials from renewable sources of natural origin. In the present study, bio-sourced tartaric acid-based tartarimides were evaluated as monomeric diol compounds to synthesize polyurethane polymers. Structurally diverse tartarimides were conveniently obtained from the condensation reactions of tartaric acid with various primary amine compounds. The diol structure of the generated tartarimides allowed to access polyurethanes along with the polymerizations of diisocyanate monomers. Copolymers in the range of 22.9 kDa to 29.3 kDa molecular weights were obtained with moderately high total monomer conversions (up to 96%). Depending on the tartarimide and diisocyanate monomers employed during polymerization, copolymers with different physical and thermal properties were generated. By utilizing tartarimides carrying furan and alkene functionalities, side chain reactive polyurethanes were synthesized. These reactive polymers were evaluated in post-polymerization modification and crosslinking processes by using radical thiol-ene and Diels-Alder based click reactions. The results obtained in this study demonstrated that the bio-sourced tartarimides could provide a convenient access to structurally tailorable polyurethane polymers that are important materials in various applications.

Synthesis and Characterization of Thiol-Ene Networks Derived from Levoglucosenone.

Levoglucosenone (LGO), a renewable compound obtained from cellulose biomass, has been utilized to prepare novel monomers bearing alkene functional groups. These monomer derivatives of LGO were subsequently cured via ultraviolet (UV)-initiated radical thiol-ene "click" chemistry with commercially available multifunctional thiols to obtain colourless, optically transparent cross-linked thermosets. The monomers prepared in this work are unique due to utilising the internal double bond of the LGO ring during polymerization as part of the cross-linked network. The thermal and mechanical properties along with the degradation of thermosets containing both ether and ester linkages within the LGO monomers were studied. These thermosets had tensile strengths of 1.3-3.3 MPa, glass transition temperatures between 23.2 and 27.2 °C, and good thermal stability of up to 300 °C.

Stability of a Multiresponsive Sulfonium Vinyl Sulfide Linker toward Nucleophilic/Radical Thiols, Reactive Nitrogen Species, and in Cells under Pro-inflammatory Stimulation.

Chemical linkages that respond to biological stimuli are important for many pharmaceutical and biotechnological applications, making it relevant to explore new variants with different responsivity profiles. This work explores the responsiveness of a TAT peptide-based sulfonium vinyl sulfide probe that responds to nucleophilic thiols, radical thiol species (RTS), and reactive nitrogen species (RNS). Under model conditions, response to nucleophilic thiols was very slow (hours/days), though fast with down to molar equivalents of either RTS or RNS (minutes). These reactions led to the traceless release of a methionine-containing peptide in the first two cases and to a hydroxy nitration adduct in the third case. Despite the sensitive nature of the probe, it remained stable for at least ∼2 h in the presence of cells during TAT-mediated trafficking, even under pro-inflammatory stimulation. The thiol-responsiveness is intermediate to that observed for disulfide linkers and conventional cysteine-maleimide linkers, presenting opportunities for biotechnological applications.

Multi-Stimuli-Responsive, Topology-Regulated, and Lignin-Based Nano/Microcapsules from Pickering Emulsion Templates for Bidirectional Delivery of Pesticides.

The increasing demand for improving pesticide utilization efficiency has prompted the development of sustainable, targeted, and stimuli-responsive delivery systems. Herein, a multi-stimuli-responsive nano/microcapsule bidirectional delivery system loaded with pyraclostrobin (Pyr) is prepared through interfacial cross-linking from a lignin-based Pickering emulsion template. During this process, methacrylated alkali lignin nanoparticles (LNPs) are utilized as stabilizers for the tunable oil-water (O/W) Pickering emulsion. Subsequently, a thiol-ene radical reaction occurs with the acid-labile cross-linkers at the oil-water interface, leading to the formation of lignin nano/microcapsules (LNCs) with various topological shapes. Through the investigation of the polymerization process and the structure of LNC, it was found that the amphiphilicity-driven diffusion and distribution of cyclohexanone impact the topology of LNC. The obtained Pyr@LNC exhibits high encapsulation efficiency, tunable size, and excellent UV shielding to Pyr. Additionally, the flexible topology of the Pyr@LNC shell enhances the retention and adhesion of the foliar surface. Furthermore, Pyr@LNC exhibits pH/laccase-responsive targeting against Botrytis disease, enabling the intelligent release of Pyr. The in vivo fungicidal activity shows that efficacy of Pyr@LNC is 53% ± 2% at 14 days postspraying, whereas the effectiveness of Pyr suspension concentrate is only 29% ± 4%, and the acute toxicity of Pyr@LNC to zebrafish is reduced by more than 9-fold compared with that of Pyr technical. Moreover, confocal laser scanning microscopy shows that the LNCs can be bidirectionally translocated in plants. Therefore, the topology-regulated bidirectional delivery system LNC has great practical potential for sustainable agriculture.

Radical polymerisation and thiol–ene post-polymerisation functionalisation of terpenoid acrylates in conventional and renewably sourced organic solvents

Geranyl acrylate has been synthesized and polymerized by various radical polymerisation techniques.

Physically crosslinked polyacrylates by quadruple hydrogen bonding side chains.

Dynamic polymer materials can be obtained by introducing supramolecular interactions between the polymer chains. Here we report on the preparation and mechanical properties of poly(methyl acrylate) (PMA) and poly(n-butyl acrylate) (PBA) funcionalized with ureidopyrimidinone (UPy) in the side chains. In contrast to the traditional UPy with a methyl group, the selected UPy motif contained a branched alkyl side chain, which enhances solubility, compatibility with the polymer matrix and potentially prevents stacking of UPy dimers. Low molar mass PMA and PBA were synthesized via Cu(0)-mediated radical polymerization and allyl bonds were introduced with different degrees of functionalization by stoichiometrically controlled transesterification with allyl alcohol. The allyl esters served as functional handles for UPy attachment via UV-initiated radical thiol-ene coupling. The PMA-UPy materials displayed a more glassy appearance, in contrast to the rubbery PBA-UPy polymer networks, associated to its higher glass transition temperature. The mechanical properties of the resulting hydrogen bonded polymer networks were assessed by thermogravimetric analysis, differential scanning calorimetry, dynamic mechanical thermal analysis and tensile testing, followed by rheological analysis of the network dynamics. Furthermore, the effect of associative groups on the linear viscoelastic response is discussed based on a modified sticky Rouse model indicating the absence of significant aggregation or phase separation of the UPY units.

Multifunctionalization of polybutadiene by RAFT/MADIX technology

A new strategy for the multi-functionalization of polybutadiene has been developed using reversible addition–fragmentation chain transfer polymerization/macromolecular design by interchange of xanthates (RAFT/MADIX) technology.

A Versatile Platform to Generate Shell-Cross-Linked Uniform Π-Conjugated Nanofibers with Controllable Length, High Morphological Stability, and Facile Surface Tailorability.

Living crystallization-driven self-assembly (CDSA) has emerged as an efficient route to generate π-conjugated-polymer-based nanofibers (CPNFs) with promising applications from photocatalysis to biomedicine. However, the lack of efficient tools to endow CPNFs with morphological stability and surface tailorability becomes a frustrating hindrance for expanding application spectrum of CPNFs. Herein, a facile strategy to fabricate length-controllable OPV-based (OPV = oligo(p-phenylenevinylene)) CPNFs containing a cross-linked shell with high morphological stability and facile surface tailorability through the combination of living CDSA and thiol-ene chemistry by using OPV5 -b-PNAAM32 (PNAAM = poly(N-allyl acrylamide)) as a model is reported. Uniform fiber-like micelles with tunable length can be generated by self-seeding of living CDSA. By taking advantage of radical thiol-ene reaction between vinyls of PNAAM corona and four-arm thiols, the shell of micelles can be cross-linked with negligible destruction of structure of vinylene-containing OPV core. The resulting micelles show high morphological stability in NaCl solution and PBS buffer, even upon heating at 80°C. The introduced extra thiol groups in the cross-linked shell can be further employed to install extra functional moieties via convenient thiol-Michael-type reaction. Given the negligible cytotoxicity of resulting CPNFs, this strategy opens an avenue to fabricate various CPNFs of diverse functionalities for biomedicine.

Difunctionalization of 1,3-Butadiene via Sequential Radical Thiol-ene Reaction and Allylation by Dual Photoredox and Titanium Catalysis.

Recently, radical difunctionalization of the feedstock 1,3-butadiene has become an attractive strategy for increasing molecular complexity. Herein, we present a novel approach that effectively combines radical thiol-ene chemistry with TiIII catalysis to enable a three-component aldehyde allylation using 1,3-butadiene as an allyl group source under visible light conditions. This sustainable and straightforward method has facilitated the rapid production of diverse allylic 1,3-thioalcohols with exceptional regio- and diastereoselectivity.

Post-coordination photoinitiated macromolecular thiol-ene coupling reaction for construction of metallo-supramolecular complexes of ABCL2-type miktoarm star copolymers and self-assembly of the complexes in water

In this paper, we focus on investigating synthesis of metallo-supramolecular architectures of ABCL2-type miktoarm star copolymers PCL(-b-PDPA)-b-[(Tpyp)2-b-PMPC] (A, PCL; B, PDPA; C, PMPC; L, Tpyp) with ruthenium(II) (Ru(II)) ions and exploring self-assembly behavior of the complexes in water. Direct coordination of PCL(-b-PDPA)-b-[(Tpyp)2-b-PMPC] to Ru(II) ions and post-coordination photoinitiated macromolecular thiol-ene coupling reaction strategies were explored to construct Ru(II) coordination complexes, respectively. The result indicates that the post-coordination coupling reaction was more suitable strategy for constructing this kind of coordination complexes, which may avoid a larger steric hindrance generated from the coexistence of the three arms of PCL(-b-PDPA)-b-[(Tpyp)2-b-PMPC] leading to the disadvantageous influence on the formation of the bis(terpyridine)-Ru(II) complex. It should be mentioned that, however, although a photoinitiated macromolecular thiol-ene radical coupling reaction is facile, so far to achieve complete reaction of the target groups (i.e., alkene groups) has remained a challenge. Therefore, herein a post-coordination thiol-ene coupling reaction was explored carefully and an appropriate condition for the complete reaction of the alkene groups was given. Interestingly, the Ru(II) coordination complexes could self-assemble to form 2D platelets. This should be attributed to the unique metallo-supramolecular architecture. It is expected that the exploration can provide strategies for construction of complicated and exquisite metallo-supramolecular architectures and novel self-assemblies.

Polyester fabric-based nano copper-polyhedral oligomeric silsesquioxanes sorbent for thin film extraction of non-steroidal anti-inflammatory drugs

In this study, in-situ preparation of copper nanoparticles under sonoheating conditions followed by coating on commercial polyester fabric is reported. Through the self-assembly interaction of thiol groups and copper nanoparticles, the modified polyhedral oligomeric silsesquioxanes (POSS) was deposited on the fabric's surface. In the next step, radical thiol–ene click reactions were implemented to create more layers of POSSs. Subsequently, the modified fabric was applied for sorptive thin film extraction of non-steroidal anti-inflammatory drugs (NSAIDs) including naproxen, ibuprofen, diclofenac, and mefenamic acid from urine samples, followed by high-performance liquid chromatography equipped with a UV detector. The morphology of the prepared fabric phase was characterized by scanning electron microscopy, water angle contact, energy dispersive spectrometry mapping, analysis of nitrogen adsorption-desorption isotherms, and attenuated total reflectance Fourier transform infrared spectroscopy. The significant extraction parameters, including the acidity of the sample solution, desorption solvent and its volume, extraction time, and desorption time, were investigated using the one-variable-at-a-time approach. Under the optimal condition, NSAIDs' detection limit was 0.3–1 ng mL−1 with a wide linear range of 1–1000 ng mL−1. The recovery values were between 94.0% and 110.0%, with relative standard deviations of less than 6.3%. The prepared fabric phase exhibited acceptable repeatability, stability, and sorption property toward NSAIDs in urine samples.

Cysteine-Selective Installation of Functionally Diverse Boronic Acid Probes on Peptides.

The current methods for direct late-stage and residue-selective installation of a versatile boronic acid (BA) repertoire on peptides are inadequate for a wide range of applications. Here, we show the suitability and efficiency of thiol-ene radical click chemistry to install functionally versatile BA derivatives on numerous bioactive, native peptides. Our work highlights that the methodology is operationally simple and adaptable for applications with BA-modified peptides, such as cyclization, conjugation, and functional group alteration.

Mechanical Evaluation of Hydrogel-Elastomer Interfaces Generated through Thiol-Ene Coupling.

The formation of hybrid hydrogel-elastomer scaffolds is an attractive strategy for the formation of tissue engineering constructs and microfabricated platforms for advanced in vitro models. The emergence of thiol-ene coupling, in particular radical-based, for the engineering of cell-instructive hydrogels and the design of elastomers raises the possibility of mechanically integrating these structures without relying on the introduction of additional chemical moieties. However, the bonding of hydrogels (thiol-ene radical or more classic acrylate/methacrylate radical-based) to thiol-ene elastomers and alkene-functional elastomers has not been characterized in detail. In this study, we quantify the tensile mechanical properties of hybrid hydrogel samples formed of two elastomers bonded to a hydrogel material. We examine the impact of radical thiol-ene coupling on the crosslinking of both elastomers (silicone or polyesters) and hydrogels (based on thiol-ene crosslinking or diacrylate chemistry) and on the mechanics and failure behavior of the resulting hybrids. This study demonstrates the strong bonding of thiol-ene hydrogels to alkene-presenting elastomers with a range of chemistries, including silicones and polyesters. Overall, thiol-ene coupling appears as an attractive tool for the generation of strong, mechanically integrated, hybrid structures for a broad range of applications.

Spectroscopic identification of the ammonia-mercapto radical complex.

The elusive hydrogen-bonded radical complex (˙SH⋯NH3) consisting of ammonia (NH3) and a mercapto radical (˙SH) has been generated through the 193 nm laser photolysis of the molecular complex between NH3 and hydrogen sulfide (H2S) in solid Ar- and N2-matrixes at 10 K. The identification of ˙SH⋯NH3 with matrix-isolation IR spectroscopy and UV-vis spectroscopy is supported by 15N- and D-isotope labeling experiments and quantum chemical calculations at the B3LYP-D3(BJ)/6-311++G(3df,3pd) level of theory. In line with a large red shift of -172.2 cm-1 for the frequency of the S-H stretching mode observed in ˙SH⋯NH3 (cf. free ˙SH), the radical ˙SH acts as a hydrogen donor, and NH3 acts as an acceptor. According to the calculations at the CCSD(T)/aug-cc-pVTZ level, the SH⋯N bonded structure ˙SH⋯NH3 (binding energy De = 3.9 kcal mol-1) is more stable than the isomeric amidogen radical complex HSH⋯˙NH2 (De = 2.8 kcal mol-1) by 16.6 kcal mol-1. This is in sharp contrast to the photochemistry of the closely related HOH⋯NH3 complex, since the water-amidogen radical complex HOH⋯˙NH2 (De = 5.1 kcal mol-1) was generated under similar photolysis conditions, whereas the ammonia-hydroxyl radical complex ˙OH⋯NH3 (De = 7.9 kcal mol-1) is higher in energy by 9.3 kcal mol-1.

Синтез и исследование строения 2-алкенилсульфанил-1-метилимидазолов

Derivatives of 1-methylimidazole-2-thiol (1) bearing substituents of various kinds are prom-ising ligands for modeling various enzymatic systems and structures with pharmacological activity. They are widely used as intermediates in the synthesis of organic compounds possessing biological activity (antitumor, antimicrobial, antidiabetic, antithyroid, antihistamine, antiprotozoal, and antiviral) as well as agrochemicals, dyes, photochemicals, corrosion inhibitors, epoxy hardeners, adhesives, and plastic modifiers. In the present paper we have studied the interaction between 1-methylimidazole-2-thiol 1 and prenyl bromide (2a), trans-cinnamyl chloride (2b), and butenyl bromide under various conditions for the first time. It has been found that selectivity of the alkylation reactions of compound 1 depends on the reaction conditions (alkylating agent, solvent, and base). Synthesis of individual 1-methyl-2-prenylsulfanylimidazole (3a) (yielding 78–86 %), 1-methyl-2-cinnamylsulfanylimidazole (3b) (yielding 94–97 %), and 2-(3-butenyl)sulfanyl-1-methyl-imidazole (4) (yielding 33–75 %) has been carried out by alkylation of 1-methylimidazole-2-thiol 1 with prenyl bromide 2a, trans-cinnamyl chloride 2b, and butenyl bromide, respectively, in the following systems: i-PrOH–i-PrONa, K2CO3–Me2CO (for 3а), MeOH–MeONa, i-PrOH–i PrONa, K2CO3–Me2CO, K2CO3–MeCN and i-PrOH–i-PrOК (for 3b), MeOH–MeONa, i PrOH–i-PrONa, K2CO3–Me2CO, K2CO3–MeCN, i-PrOH–i-PrOК and КОН–H2O–BTEAC (for 4). The structure of the synthesized compounds 3a,b and 4 has been studied and proved by mass spectrometry (GC–MS), as well as ¹H, ¹³C NMR spectroscopy. General predictable directions for fragmentation of the molecular ions of S-derivatives 3a,b and 4, which are accompanied by elimination of methyl/phenyl and thiol radicals, have been revealed. The evidence that alkylation reactions occur at the sulfur atom is the presence of signals for the –SCH2– protons in the region of 3.12–3.84 ppm in the 1Н NMR spectra of compounds 3a,b and 4. According to the 1Н NMR data, it has been found that alkylation of 1-methylmimidazole-2-thiol 1 at other conditions leads to formation of small quantities of by-products, such as N-alkenyl and S,N-dialkenyl derivatives, due to its thione-thiol tautomerism.

Visible-light driven electron-donor-acceptor (EDA) complex-initiated synthesis of thio-functionalized pyridines.

A visible/solar-light-induced electron-donor-acceptor (EDA)-aggregated/mediated radical cyclization between (E)-2-(1,3-diarylallylidene)malononitriles and thiophenols leads to poly-functionalized pyridines. The two reacting partners form an EDA complex that absorbs light and triggers the single-electron transfer (SET) to generate a thiol radical, which undergoes addition/cyclization with dicyanodiene through the formation of C-S and C-N bonds.