Silylating Reagent Research Articles

α-Selective Solid-Phase Synthesis of Glycosyl Phosphate Repeating Structure Via the Phosphoramidite Method.

Lipophosphoglycans (LPGs) are found on the surface of Leishmania, a protozoan parasite, and are immunologically important. Herein, disaccharide 1-phosphate repeating units of LPGs were successfully synthesized on a solid support with high anomeric purity using a disaccharide α-1-phosphoramidite building block. To enhance solubility in the reaction solvent, hydroxy-protecting groups in the form of para-t-butylbenzoyl were introduced to the building block. The saccharide chain was elongated via stable glycosyl boranophosphate linkages, followed by the conversion of inter-sugar linkages to phosphodiester counterparts using an oxaziridine derivative. The addition of a silylating reagent post-reaction with the oxaziridine derivative efficiently facilitated the conversion of boranophosohodiesters to phosphodiesters. This method enabled the α-selective synthesis of up to 15 repeating units, marking the longest homogeneous repeating units of LPGs synthesized chemically. Given the chain length equivalence to native LPGs, the method developed herein holds promise for advancing anti-Leishmanial pharmaceuticals and vaccines.

MSTFA as an Effective TMS Source for the TMSOTf-Catalzyed Synthesis of Cyclic Acetals.

Commercially and readily available MSTFA [2,2,2-trifluoro-N-methyl-N-(trimethylsilyl)acetamide] was identified as a highly effective TMS (trimethylsilyl) source for the convenient preparation of cyclic acetals under modified Noyori's conditions. The reactions proceeded smoothly under mild conditions, affording a wide range of the corresponding cyclic acetals with excellent yields in the presence of catalytic TMSOTf (trimethylsilyl trifluoromethanesulfonate). The present method does not require a large excess of diols that can be valuable and does not require presynthesized silylated diols. In contrast to other silylating reagents such as BSA [N,O-bis(trimethylsilyl)acetamide] and BSTFA [N,O-bis(trimethylsilyl)trifluoroacetamide], the application of MSTFA avoided the inhibition of catalytic acetalization by the side product 2,2,2-trifluoro-N-methylacetamide.

Simultaneous determination of 19 bromophenols by gas chromatography–mass spectrometry (GC-MS) after derivatization

Bromophenols (BPs) are a class of ubiquitous emerging halogenated pollutants. Their 19 congeners are problematically separated and detected. This work described the separation and detection of 19 BP congeners by gas chromatography-mass spectrometry (GC-MS). Investigations into the derivatization of bromophenols were carried out using two silylation reagents (N,O-bis(trimethylsilyl)trifluoroacetamide and N-methyl-N-(trimethylsily)trifluoroacetamide), two alkylation reagents (methyl iodide and trimethylsilyldiazomethane) and acetic anhydride prior to GC-MS analysis. Optimal chromatographic separation, sensitivity, and linearity were achieved after BP derivatization using acetic anhydride, featuring the equipment detection limits of 0.39–1.26 pg and correlation coefficients of 0.9948–0.9999 (linear range: 0.5–250 ng mL−1) for all 19 BP congeners. Furthermore, the simultaneous determination of 19 bromophenols and 19 bromoanisoles, common environmental transformation products of BPs, is also demonstrated. The improved analytical performance on GC-MS after derivatization would benefit investigations on the environmental origins, behaviors and fates of BPs and their environmental metabolites.

Enantioselective and Regiodivergent Synthesis of Propargyl‐ and Allenylsilanes through Catalytic Propargylic C−H Deprotonation

AbstractWe report a highly enantioselective intermolecular C−H bond silylation catalyzed by a phosphoramidite‐ligated iridium catalyst. Under reagent‐controlled protocols, propargylsilanes resulting from C(sp3)−H functionalization, as well the regioisomeric and synthetically versatile allenylsilanes, could be obtained with excellent levels of enantioselectivity and good to excellent control of propargyl/allenyl selectivity. In the case of unsymmetrical dialkyl acetylenes, good to excellent selectivity for functionalization at the less‐hindered site was also observed. A variety of electrophilic silyl sources (R3SiOTf and R3SiNTf2), either commercial or in situ‐generated, were used as the silylation reagents, and a broad range of simple and functionalized alkynes, including aryl alkyl acetylenes, dialkyl acetylenes, 1,3‐enynes, and drug derivatives were successfully employed as substrates. Detailed mechanistic experiments and DFT calculations suggest that an η3‐propargyl/allenyl Ir intermediate is generated upon π‐complexation‐assisted deprotonation and undergoes outer‐sphere attack by the electrophilic silylating reagent to give propargylic silanes, with the latter step identified as the enantiodetermining step.

Enantioselective and Regiodivergent Synthesis of Propargyl- and Allenylsilanes through Catalytic Propargylic C-H Deprotonation.

We report a highly enantioselective intermolecular C-H bond silylation catalyzed by a phosphoramidite-ligated iridium catalyst. Under reagent-controlled protocols, propargylsilanes resulting from C(sp3)-H functionalization, as well the regioisomeric and synthetically versatile allenylsilanes, could be obtained with excellent levels of enantioselectivity and good to excellent control of propargyl/allenyl selectivity. In the case of unsymmetrical dialkyl acetylenes, good to excellent selectivity for functionalization at the less-hindered site was also observed. A variety of electrophilic silyl sources (R3SiOTf and R3SiNTf2), either commercial or in situ-generated, were used as the silylation reagents, and a broad range of simple and functionalized alkynes, including aryl alkyl acetylenes, dialkyl acetylenes, 1,3-enynes, and drug derivatives were successfully employed as substrates. Detailed mechanistic experiments and DFT calculations suggest that an η3-propargyl/allenyl Ir intermediate is generated upon π-complexation-assisted deprotonation and undergoes outer-sphere attack by the electrophilic silylating reagent to give propargylic silanes, with the latter step identified as the enantiodetermining step.

Capillary electrophoresis using triple layer modified capillary facilitating salivary ion analyses: Application to search for potential stress markers induced by cold pressure test

In this study, we introduce a novel approach for the analysis of salivary ions using capillary electrophoresis (CE) with a triple-layer coated capillary. The capillary is sequentially coated with cationic silylating reagents, poly(vinylsulfonate), and polybrene to form a custom designed surface that effectively inhibits adsorption of protein matrix on the capillary inner wall and allows for reproducible ion analysis. For the CE with capacitively coupled contactless conductivity detection, we used suitable background electrolytes (BGEs) for salivary ion analysis. Anions were separated using a mixture of 2-(N-morpholino)ethanesulfonic acid and l-arginine, and cations were separated using that with 18-crown-6. This setup enabled rapid separation, within 4 min, together with sensitive detection. We quantified nine common anions and five cations typically found in saliva samples using this CE method, both before and after a cold pressure test (CPT, a standard stress test). The CE system demonstrated consistent ion separation across 30 consecutive measurements without requiring capillary replacement. Notably, the salivary ion balance remained predominantly anion-rich, regardless of the CPT. Cold water exposure induced greater variation in the total anion concentration than in the total cation concentration. Further analysis using multiple regression analysis revealed strong relationships between nitrate and nitrite, formate and phosphate, and potassium and nitrate, before and after the CPT. Notably, potassium and nitrate ions exhibited variations in response to stress. These results provided a method for assessing salivary ion composition and insights into the potential of salivary ions as biomarkers for stress.

One-step formation of functionalized mesoporous shell on silica core for chromatography

Since stationary phase is the key to chromatographic separations, it is worth pursuing simpler and more efficient methods for preparing chromatographic stationary phases. In this work, co-condensation and pseudomorphic transformation were combined to prepare a functionalized shell on the surface of the silica core in one step, and different kinds of silylation reagents were used to investigate the self-assembly mechanism. 3-Mercaptopropyltriethoxysilane facilitated the formation of the shell during pseudomorphic transformation, and sulfhydryl groups were distributed in the shell uniformly. These core-shell particle were applied in hydrophilic chromatography and ion-exchange chromatography successfully after the oxidation of the sulfhydryl groups to sulfonic acid groups. Pseudomorphic transformation with silylated reagents has the advantage of rapid preparation of chromatographic stationary phases with good reproducibility.

Heterodifunctionalization of Electron-Rich Alkynes Catalyzed by in Situ Generated Silylium Ions.

Silylium ions are versatile Lewis acids in organic synthesis. While they have been well-known for the activation of σ donors, catalysis initiated by the activation of π donors remains underdeveloped, particularly for alkynes. Herein, we demonstrate an example of silylium-catalyzed alkyne heterodifunctionalization. The silylium ion generated in situ from HNTf2 and the silyl reagent serve as superior catalysts in the efficient silylphosphination and silylcyanation of electron-rich alkynes with excellent regio- and stereoselectivity. The compatibility of this protocol with strongly coordinating ligands (Ph2P and CN) not only complements the metal-catalyzed systems but also expands the scope of silylium-catalyzed reactions.

Molecularly imprinted polymer-based SERS sensing of transferrin in human serum.

Specific detection of glycoproteins such as transferrin (TRF) related to neurological diseases, hepatoma and other diseases always plays an important role in the field of disease diagnosis. We designed an antibody-free immunoassay sensing method based on molecularly imprinted polymers (MIPs) formed by the polymerization of multiple functional monomers for the sensitive and selective detection of TRF in human serum. In the sandwich surface-enhanced Raman spectroscopy (SERS) sensor, the TRF-oriented magnetic MIP nanoparticles (Fe3O4@SiO2-MIPs) served as capture units to specifically recognize TRF and 4-mercaptophenylboronic acid-functionalized gold nanorods (MPBA-Au NRs) served as SERS probes to label the targets. In order to achieve stronger interaction between the recognition cavities of the prepared MIPs and the different amino acid fragments that make up TRF, Fe3O4@SiO2-MIPs were obtained through polycondensation reactions between more silylating reagents, enhancing the specific recognition of the entire TRF protein and achieving high IF. This sensing method exhibited a good linear response to TRF within the TRF concentration range of 0.01 ng mL-1 to 1 mg mL-1 (R2 = 0.9974), and the LOD was 0.00407 ng mL-1 (S/N = 3). The good stability, reproducibility and specificity of the resulting MIP based SERS sensor were demonstrated. The determination of TRF in human serum confirmed the feasibility of the method in practical applications.

Murchison Meteorite Analysis Using Tetramethylammonium Hydroxide (TMAH) Thermochemolysis Under Simulated Sample Analysis at Mars (SAM) Pyrolysis‐Gas Chromatography‐Mass Spectrometry Conditions

AbstractThe Sample Analysis at Mars (SAM) instrument aboard the Curiosity Rover at Gale crater can characterize organic molecules from scooped and drilled samples via pyrolysis of solid materials. In addition, SAM can conduct wet chemistry experiments which enhance the detection of organic molecules bound in macromolecules and convert polar organic compounds into volatile derivatives amenable to gas chromatography‐mass spectrometry analyses. Specifically, N‐tert‐butyldimethylsilyl‐N‐methyltrifluoroacetamide (MTBSTFA) is a silylation reagent whereas tetramethylammonium hydroxide (TMAH) is a thermochemolysis methylation reagent. Shortly after arriving at Mars, the SAM team discovered that at least one of the MTBSFTA cups was leaking, contributing to a continuous background inside SAM with the potential to interfere with future TMAH reactions. Therefore, here we characterized possible interactions between the two reagents to determine byproducts and implications for the detection of indigenous organics. SAM‐like pyrolysis experiments supplemented with flash pyrolysis were accordingly conducted with fragments of the Murchison meteorite as a reference for exogenous organic matter delivered to Mars. Flash TMAH experiments yielded various aromatic acids, dicarboxylic acids, and amino acids while SAM‐like pyrolysis presented mixtures of methylated and non‐methylated compounds due to decreased reaction efficiency at slower ramp rates. All experiments in the presence of simulated MTBSTFA vapor produced pervasive silylated byproducts which co‐elute and obscure the identification of Murchison‐derived compounds. Despite challenges, a significant diversity of pyrolyzates and TMAH derivatives could still be identified in flash pyrolysis in presence of MTBSTFA. However SAM‐like experiments with TMAH and MTBSTFA are hindered by both decreased methylation yields and additional co‐eluting compounds.

Silylation of thymol extracted from Thymus migricus essential oil, improvement of lipophilicity properties, and investigation of its pharmacological properties

Thymus species are well known as medicinal plants because of their biological and pharmacological properties. Thymus migricus Klokov & Desj. -Shos belongs to Lamiaceae. Young branches of this plant produce an essential oil that is abundant in potent and volatile compounds that have a variety of therapeutic uses. In this study, the natural composition of thymol in this plant’s essential oil was first detected with HPLC and Mass, and then the essential oil was extracted. The increase in the lipophilicity of the synthesized silylated derivatives was then examined by HPLC after numerous silylated derivatives of this phenolic compound were synthesized using various silylation reagents. These derivatives were then analyzed by FT-IR and 1HNMR analysis. The antibacterial activity of thymol with its silylated derivatives against gram-negative and gram-positive bacteria was next tested by diffusion method, after which the antioxidant activity of thymol with its silylated derivatives was assessed by two DPPH and FRAP methods.

Determination of methionine and selenomethionine in food matrices by gas chromatography mass spectrometry after aqueous derivatization with triethyloxonium salts

A novel analytical method for the simultaneous gas chromatography–mass spectrometry (GC–MS) determination of methionine and selenomethionine in food samples is described. Samples were digested with methanesulfonic acid in a closed vessel without the need for reflux. A single step derivatization using triethyloxonium tetrafluoroborate was optimized for the conversion of the analytes into their ethyl derivatives, followed by their extraction with hexane and GC–MS analysis.. This derivatization approach was simpler and/or safer with respect to current methods based on alkyl chloroformate or silylating reagents and it yielded very clean chromatography. A design of experiment approach, based on an open source chemometric software, was used to optimize the experimental conditions. When analysis of a 1 mL volume of aqueous standard was performed, detection limits of 1 ng/g methionine and 10 ng/g for selenomethionine were obtained.The method was validated by analysis of a selenized yeast Certified Reference Material NRC SELM-1.

GC-MS Silylation Derivative Method to Characterise Black BIC® Ballpoint 2-Phenoxyethanol Ratio Evaporation Profile-A Contribution to Ink Ageing Estimation.

One of the major challenges in forensic document analysis is estimating the age of ink deposition on a manually written document. The present work aims to develop and optimise a methodology, based on the evaporation of 2-phenoxyethanol (PE) over time, that can contribute to ink age estimation. A black BIC® Crystal Ballpoint Pen was purchased in a commercial area, and ink deposition began in September 2016 over 1095 days. For each ink sample, 20 microdiscs were subjected to n-hexane extraction in the presence of an internal standard (ethyl benzoate) followed by derivatisation with a silylation reagent. A gas chromatography-mass spectrometry (GC/MS) method was optimised for PE-trimethylsilyl (PE-TMS) to characterise the ageing curve. The developed method presented good linearity between 0.5 and 50.0 μg mL-1, as well as limits of detection and quantification of 0.026 and 0.104 μg mL-1, respectively. It was possible to characterise PE-TMS concentration over time, which reveals a two-phase decay behaviour. First, there was a substantial decline between the 1st and the 33rd day of deposition, followed a by a stabilisation of the signal, which allowed to detect the presence of PE-TMS up to 3 years. Two unknown compounds were also present and allowed to identify three dating time frames for the same ink stroke: (i) between time 0 and 33 days, (ii) between time 34 and 109 days, and (iii) more than 109 days. The developed methodology allowed to characterise the behaviour of PE over time and to establish a relative dating of three-time frames.

Hydrosilylation of alkenes with acylhydrosilanes.

Acylsilanes are an important class of organosilicon compounds that have gained increased attention recently. Their various reaction modes in particularly their ability to generate carbenes under thermal or photochemical conditions render them valuable reagents in organic synthesis. In this communication, an unprecedented route towards acylsilanes is reported by introducing the acylsilane moiety directly in a single step through alkene hydrosilylation. In this context, acylhydrosilanes representing a novel class of acylsilanes are introduced and applied as silylation reagents in rhodium catalyzed alkene hydrosilylations to access a great variety of acylsilanes. These reactions occur in good to excellent yields under mild conditions and show high functional group tolerance and atom economy.

Intermolecular 1,2-Difunctionalization of Terminal Alkynes to Access Trisubstituted Alkenes via Copper/Photoredox Dual Catalysis.

We report a copper metallaphotocatalytic 1,2-difunctionalization of terminal alkynes with N-hydroxyphthalimide (NHP) esters and readily available silyl reagents (TMSCN and TMSNCS) to access stereodefined trisubstituted alkenes, including (E)-alkenyl nitriles and thiocyanates. The reaction proceeds with excellent anti-stereoselectivity and demonstrates broad compatibility with a wide range of terminal alkynes and NHP esters as alkyl radical precursors. Experimental and computational studies have been performed to gain insight into the reaction mechanism.

Multi-step Strategies Toward Regioselectively Sulfated M-Rich Alginates.

Sulfated alginates (ASs), as well as several artificially sulfated polysaccharides, show interesting bioactivities. The key factors for structure-activity relationships studies are the degree of sulfation and the distribution of the sulfate groups along the polysaccharide backbone (sulfation pattern). The former parameter can often be controlled through stoichiometry, while the latter requires the development of suitable chemical or enzymatic, regioselective methods and is still missing for ASs. In this work, a study on the regioselective installation of several different protecting groups on a d-mannuronic acid enriched (M-rich) alginate is reported in order to develop a semi-synthetic access to regioselectively sulfated AS derivatives. A detailed structural characterization of the obtained ASs revealed that the regioselective sulfation could be achieved complementarily at the O-2 or O-3 positions of M units through multi-step sequences relying upon a silylating or benzoylating reagent for the regioselective protection of M-rich alginic acid, followed by sulfation and deprotection.

Silylation of piroxicam with some silylating reagents, and characterization of them to improve some properties of this drug

In this work, we synthesized some organosilicon derivatives of piroxicam. Due to some properties of organosilicon compounds, including increased lipophilicity and thermal stabilization and prodrug for drugs, some silyl ethers of this drug were synthesized and characterized. Increasing of the lipophilic properties of this drug can be very important in the rate of absorption and its effectiveness. We synthesized silyl ethers of this drug, in the next step some copolymers this drug was synthesized. All of compounds were identified by spectroscopic methods.

Identification and quantification of IEPOX in ambient aerosols, using electron and chemical ionization sources GC/MS as their trimethylsilyl ethers, and using H-NMR

Isoprene is the most abundant non-methane hydrocarbon (NMHC) emitted by vegetation, and the precursor that makes the greatest contribution to secondary organic aerosols (SOA) in the troposphere. Atmospheric oxidation of isoprene produces a series of reactive intermediates, isoprene epoxydiols (IEPOX). The reactive uptake of IEPOX is the significant formation pathway of atmospheric SOA. In this work, four isomers of IEPOX were synthesized, derivatized by silylation reagents, and measured by gas chromatography/mass spectrometry (GC/MS). The electron-impact (EI) and methane chemical ionization (CI) sources mass spectra of trimethylsilyl ester (TMS) derivatives of IEPOX isomers were obtained and the fragmentation behaviors of the derivatives were examined. Moreover, the hydrogen nuclear magnetic resonance (H-NMR) spectra of IEPOX isomers were also obtained and the peak intensities in the H-NMR spectra were analyzed. Based on the standard spectra, IEPOX isomers were identified in ambient PM2.5 aerosols in the Gongga Mountain (China). The peak sequence of TMS derivatives of IEPOX isomers in GC/MS chromatogram was δ4-IEPOX, δ1-IEPOX, cis-β-IEPOX and trans-β-IEPOX. The isomers with the highest concentrations were δ1-IEPOX (threo- and erythro-). The mass ratios of IEPOX to 2-methyltetrols were 0.02–6.0 and the concentrations of IEPOX were 0.8–41.6 ng/m3 in the PM2.5 aerosols. The current study verified the core roles of IEPOX as active intermediates in photo oxidation of isoprene in ambient atmosphere.

Use of Trifluoro-Acetate Derivatives for GC-MS and GC-MS/MS Quantification of Trace Amounts of Stera-3β,5α,6β-Triols (Tracers of Δ5-Sterol Autoxidation) in Environmental Samples.

Stera-3β,5α,6β-triols make useful tracers of the autoxidation of Δ5-sterols. These compounds are generally analyzed using gas chromatography-mass spectrometry (GC-MS) after silylation. Unfortunately, the 5α hydroxyl groups of these compounds, which are not derivatized by conventional silylation reagents, substantially alter the chromatographic properties of these derivatives, thus ruling out firm quantification of trace amounts. In this work, we developed a derivatization method (trifluoroacetylation) that enables derivatization of the three hydroxyl groups of 3β,5α,6β-steratriols. The derivatives thus formed present several advantages over silyl ethers: (i) better stability, (ii) shorter retention times, (iii) better chromatographic properties and (iv) mass spectra featuring specific ions or transitions that enable very low limits of detection in selected ion monitoring (SIM) and multiple reaction monitoring (MRM) modes. This method, validated with cholesta-3β,5α,6β-triol, was applied to several environmental samples (desert dusts, marine sediments and particulate matter) and was able to quantify trace amounts of 3β,5α,6β-steratriols corresponding to several sterols: not only classical monounsaturated sterols (e.g., cholesterol, campesterol and sitosterol) but also, and for the first time, di-unsaturated sterols (e.g., stigmasterol, dehydrocholesterol and brassicasterol).

Stability Effects of Selective Anion Abstraction from Cesium Lead Halide Perovskite Nanocrystals

The dynamic surface chemistry and stabilization of cesium lead halide perovskite nanocrystals (NCs) remain principal challenges for the use of these materials in many applications. Here, trimethylsilyl trifluoromethanesulfonate (Me3SiOTf) was used as a Lewis acidic reagent for quantitative and irreversible silylation and removal of anionic ligands from colloidal oleate- and oleylamine-capped CsPbBr3 and CsPbCl3 NCs. 1H NMR and FTIR spectroscopies, combined with elemental analysis, show strong binding of a population of anionic ligands to the NC surfaces. Surface anion exchange for trifluoromethanesulfonate also results in an increase in photoluminescence quantum yields. For CsPbCl3 NCs, Me3SiOTf treatment abstracts chlorides and destabilizes the NC lattice. The thermodynamic differences between these reactions and their implications are discussed.