Deprotection Reaction Research Articles

One-dimensional nanochains consisting of magnetic core and mesoporous aluminosilicate for use as efficient nanocatalysts

Magnetic assembly at the nanoscale level brings potential possibilities in obtaining novel delicate nanostructures with unique physical, photonic or electronic properties. Interface surfactant micelle-directed assembly strategy holds great promising in fabricating ordered mesoporous materials with multifunctionality and pore parameter tunability. Combing these, herein, one-dimensional (1D) nanochains with well-aligned silica-coated magnetic particles as core and mesoporous aluminosilicate as shell are rational fabricated for the first time through magnetic field induced interface coassembly in biliquid system followed by the incorporation of Al species via in-situ chemical modification and transformation strategy. The obtained magnetic mesoporous aluminosilicate nanochains (MMAS-NCs) possess well-defined core-shell-shell sandwich nanostructure, tunable perpendicular mesopore channels in the shell (2.7–7.6 nm), high surface area (359 m2·g−1), abundant acidic sites, and superparamagnetism with a magnetization saturation of 13.8 emu·g−1. Thanks to the unique properties, the MMAS-NCs exhibit excellent performance in acting as magnetically recyclable superior solid acid catalysts and nanostirrers with high conversion of over 96.8%, selectivity of 95.0% in the deprotection reaction of benzaldehyde dimethylacetal to benzaldehyde. Moreover, MMAS-NCs exhibit an interesting pore size effect on the catalytic activity, namely, in the pore size range of 2–8 nm, the catalysts with larger pores show significantly enhanced catalytic activity due to the balanced mass transport and density of surface active sites.

Protecting-Group-Free Iterative Exponential Growth Method for Synthesizing Sequence-Defined Polymers.

As a main synthetic strategy for monodisperse sequence-defined polymers, the known iterative exponential growth (IEG) methods were all developed on protecting-group chemistry, where the additional deprotection reactions increased their synthetic steps and decreased their atom economy. In this study, we developed a protecting-group-free IEG method for the formation of sequence-defined polymers by combining three orthogonal click reactions of copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), sulfur-fluoride exchange reaction (SuFEx), and Ugi four-component reaction (Ugi-4CR). In this approach, oligomer synthesis began with three parallel CuAAC, SuFEx, and Ugi-4CR couplings among three monomers each with two orthogonal clickable end groups. By iteratively applying parallel CuAAC, SuFEx, and Ugi-4CR to couple three resultant oligomers, each having two orthogonal clickable terminals, this approach could exponentially grow three different sequence-defined polymers simultaneously with high efficiency, requiring no protecting-group chemistry. Additionally, each Ugi-4CR coupling reaction could introduce two external side groups to provide the molecular variation and side-chain functionalization for the resultant sequence-defined polymers.

A pH-responsive polyelectrolyte multilayer film with tunable interfacial properties

We report a facile and versatile approach to fabricate polyelectrolyte multilayer (PEM) films with a chemically modifiable outer surface. A PEM film was prepared by layer-by-layer assembly of poly (2-aminoethyl methacrylate) (PAMA) and polymethacrylic acid (PMAA), terminated with a partially tert-butyloxycarbonyl (Boc)-protected random copolymer (PAMA-co-PBocAMA) as the final layer. The obtained PEM film was then cross-linked and the free amino groups in the PEM film were quenched using EDC/NHS chemistry. The outer layer of the film was then treated via a deprotection reaction, affording free amino groups selectively located at the film surface. As a proof of concept study, these functional groups were used to modify the film surface with two model hydrophilic and hydrophobic compounds, which tuned the wettability of the PEM.

Chalice-Type Tridentate Silicon Lewis Acids of C3 Symmetry in a Single Step Starting from Hexadehydrotribenzo[12]annulene.

Tridentate Lewis acids with aligned functions were synthesized based on the rigid framework hexadehydrotribenzo[12]annulene. The backbone and its fluorinated analogue were synthesised in one‐pot syntheses, with alkyne deprotection and Sonogashira cross coupling reaction being carried out in one step. Hydrosilylation of the annulene with chlorohydrosilanes proceeded highly selectively and afforded rigid poly‐Lewis acids with three SiCl3 or SiCl2Me substituents perfectly oriented to one side of the molecule in a single step. The progress of hydrosilylation was investigated by time‐correlated NMR spectroscopic studies. The crystal structures show that the framework is symmetrically functionalised and the silyl substituents are aligned in one direction. To increase the acidity of the Lewis acids the chlorosilyl substituents were fluorinated with SbF3. Further investigation of hydrometallation reactions (M=B, Al, Ga, Sn) did not lead to corresponding structures.

Thioglucopyranose Ligands Promote Phase‐Transfer of Cadmium Selenide Quantum Dots from Organic Solvents to Water

AbstractThe attainment of water‐dispersible cadmium selenide quantum dots (CdSe QDs) with bright luminescence and tunable optical properties represents a great challenge to improve their biological applications. Indeed, over the last years, fluorescent materials have been widely applied for sensing and bioimaging, thus promoting research in the field of life science. Herein, we present the functionalization of CdSe QDs with peracetylated thioglucopyranose (2,3,4,6‐Tetra‐O‐acetyl‐1‐thio‐β‐D‐glucopyranose) and the subsequent deprotection reaction. This novel protocol performed at room temperature and under mild conditions allows the phase‐transfer of the functionalized nanoparticles from organic solvents into water. The CdSe QDs in water showed higher photoluminescent efficiency than their nanoparticle precursors in organic solvents. Our results represent an effective methodology useful to obtain water‐soluble QDs to foster the potential uses for glycobiological studies.

Deep Learning for Prediction and Optimization of Fast-Flow Peptide Synthesis.

The chemical synthesis of polypeptides involves stepwise formation of amide bonds on an immobilized solid support. The high yields required for efficient incorporation of each individual amino acid in the growing chain are often impacted by sequence-dependent events such as aggregation. Here, we apply deep learning over ultraviolet–visible (UV–vis) analytical data collected from 35 427 individual fluorenylmethyloxycarbonyl (Fmoc) deprotection reactions performed with an automated fast-flow peptide synthesizer. The integral, height, and width of these time-resolved UV–vis deprotection traces indirectly allow for analysis of the iterative amide coupling cycles on resin. The computational model maps structural representations of amino acids and peptide sequences to experimental synthesis parameters and predicts the outcome of deprotection reactions with less than 6% error. Our deep-learning approach enables experimentally aware computational design for prediction of Fmoc deprotection efficiency and minimization of aggregation events, building the foundation for real-time optimization of peptide synthesis in flow.

Free volume manipulation of a 6FDA-HAB polyimide using a solid-state protection/deprotection strategy

Tert-butoxycarbonyl (t-BOC) is a thermally labile moiety that can be used to protect hydroxyl groups on polymers. In this study, t-BOC was appended onto a polyimide consisting of 2,2′-bis-(3,4-dicarboxyphenyl) hexafluoropropane dianhydride (6FDA) and 3,3′-dihydroxy-4,4′-diamino-biphenyl (HAB), after which the polymer was formed into self-standing films. Solid-state thermal treatments were performed to systematically remove t-BOC moieties to alter the physical packing structure and concomitant gas transport properties of the polymer. Despite performing deprotection reactions well below the glass transition temperature of 6FDA-HAB (~300 °C), this free volume manipulation (FVM) approach produced only subtle differences in polymer density, fractional free volume, average free volume element size, and gas transport properties relative to the unprotected polymer. While these findings suggest that thermally removing covalently bound functional groups from polymer films can be used to manipulate free volume and gas transport performance for glassy polymers, more robust polymer systems than linear polyimides are required to preserve the nascent free volume architecture generated from this approach.

A Novel Camphor-Based “Turn-on” Fluorescent Probe with High Specificity and Sensitivity for Sensing Mercury(II) in Aqueous Medium and Its Bioimaging Application

Precise detection of Hg2+ in an ecological environment and biological system is of great importance. Hence, in this paper, we have constructed a simple fluorescent turn-on probe CP-Hg toward Hg2+ based on natural and renewable camphor. A significantly enhanced green fluorescence was clearly observed only with the participation of Hg2+ due to the Hg2+-mediated deprotection reaction of thioacetal. The probe CP-Hg could also sensitively detect Hg2+ with a detection limit of 19.3 nM and a large Stokes shift of 153 nm in a near-perfect aqueous solution. The reaction mechanism was fully analyzed through 1H NMR (proton nuclear magnetic resonance), ESI-MS (electrospray ionization mass spectrometry), and DFT (density functional theory) calculations. Moreover, the CP-Hg-coated test strips were successfully fabricated for naked-eye detection of Hg2+. Furthermore, the cell imaging experiment manifested that the probe CP-Hg is suitable for labeling intracellular Hg2+.

A Highly Selective Fluorescent Probe for Hg2+ Based on a 1,8-Naphthalimide Derivative.

Hg2+ has a significant hazardous impact on the environment and ecosystem. There is a great demand for new methods with high selectivity and sensitivity to determine mercury in life systems and environments. In this paper, a novel turn-on Hg2+ fluorescent probe has been reported with a naphthalimide group. The Hg2+ fluorescent probe was designed by the inspiration of the well-known specific Hg2+-triggered thioacetal deprotection reaction. A 1,2-dithioalkyl group was chosen as the specific recognition site of Hg2+. The probe showed weak fluorescence without Hg2+, and the color of the solution was light yellow. In the presence of Hg2+, the probe reacted specifically with the mercury ion to produce an aldehyde and emitted strong fluorescence, and the color of the solution also turned light green, thus realizing the monitoring of the mercury ion. The Hg2+ fluorescent probe showed outstanding sensitivity and selectivity toward Hg2+. Furthermore, the Hg2+ fluorescent probe could work in a wide pH range. The linear relationship between the fluorescence intensity at 510 nm and the concentration of Hg2+ was obtained in a range of Hg2+ concentration from 2.5 × 10–7 to 1.0 × 10–5 M. The detection limit was found to be 4.0 × 10–8 M for Hg2+. Furthermore, with little cell toxicity, the probe was successfully applied to the confocal image of Hg2+ in PC-12 cells.

Gem-Dinitromethyl-Functionalized 5-Amino-1,3,4-oxadiazolate Derivatives: Alternate Route, Characterization, and Property Analysis.

A new, safer, and more cost-effective methodology to synthesize salts based on gem-dinitromethyl-functionalized 5-amino-1,3,4-oxadiazolate is given. Cyclization, deprotection, nitration, and neutralization reactions were conducted to obtain products in high yield. All compounds were fully characterized by NMR and IR spectroscopy, elemental analysis, and differential scanning calorimetry. Crystal structure analysis, property tests, and theoretical calculations confirm good detonation performance and high mechanical stabilities of the salts.

Hybrid Injectable Sol-Gel Systems Based on Thermo-Sensitive Polyurethane Hydrogels Carrying pH-Sensitive Mesoporous Silica Nanoparticles for the Controlled and Triggered Release of Therapeutic Agents.

Injectable therapeutic formulations locally releasing their cargo with tunable kinetics in response to external biochemical/physical cues are gaining interest in the scientific community, with the aim to overcome the cons of traditional administration routes. In this work, we proposed an alternative solution to this challenging goal by combining thermo-sensitive hydrogels based on custom-made amphiphilic poly(ether urethane)s (PEUs) and mesoporous silica nanoparticles coated with a self-immolative polymer sensitive to acid pH (MSN-CS-SIP). By exploiting PEU chemical versatility, Boc-protected amino groups were introduced as PEU building block (PEU-Boc), which were then subjected to a deprotection reaction to expose pendant primary amines along the polymer backbone (PEU-NH2, 3E18 -NH2/gPEU–NH2) with the aim to accelerate system response to external acid pH environment. Then, thermo-sensitive hydrogels were designed (15% w/v) showing fast gelation in physiological conditions (approximately 5 min), while no significant changes in gelation temperature and kinetics were induced by the Boc-deprotection. Conversely, free amines in PEU-NH2 effectively enhanced and accelerated acid pH transfer (pH 5) through hydrogel thickness (PEU-Boc and PEU-NH2 gels covered approximately 42 and 52% of the pH delta between their initial pH and the pH of the surrounding buffer within 30 min incubation, respectively). MSN-CS-SIP carrying a fluorescent cargo as model drug (MSN-CS-SIP-Ru) were then encapsulated within the hydrogels with no significant effects on their thermo-sensitivity. Injectability and in situ gelation at 37°C were demonstrated ex vivo through sub-cutaneous injection in rodents. Moreover, MSN-CS-SIP-Ru-loaded gels turned out to be detectable through the skin by IVIS imaging. Cargo acid pH-triggered delivery from PEU-Boc and PEU-NH2 gels was finally demonstrated through drug release tests in neutral and acid pH environments (in acid pH environment approximately 2-fold higher cargo release). Additionally, acid-triggered payload release from PEU-NH2 gels was significantly higher compared to PEU-Boc systems at 3 and 4 days incubation. The herein designed hybrid injectable formulations could thus represent a significant step forward in the development of multi-stimuli sensitive drug carriers. Indeed, being able to adapt their behavior in response to biochemical cues from the surrounding physio-pathological environment, these formulations can effectively trigger the release of their payload according to therapeutic needs.

Synthesis of an oligomeric thickener for supercritical carbon dioxide and its properties

The applications of supercritical CO2 as a solvent are limited by its very low viscosity. A four-armed oligomeric CO2 thickener containing fluorine 1,6-bis(1,3-perfluorooctanoic acid biester-2-Urea)Hexane (BPFAUH) was synthesized with 2-amino-1,3-propanediol, (Boc)2D, pentadecafluorooctanoic acid, thionyl chloride, hexamethylene-1,6-diisocyanate (HMDI) as crude materials by using amino protection, esterification, deprotection, and nucleophilic addition reaction. and characterized using FTIR, 13C NMR and elemental analysis. TG analysis showed that the oligomeric thickener was thermally stable below 473.15 K. Its solubility in CO2 correlated well with the pressure. The viscosity of the system increased with increasing thickener concentration, but the viscosity of the thickener decreased with increasing temperature and shear rate. The system viscosity reached 19.2 mPa·s, a 480-fold increase compared to the initial viscosity, when 2.0 wt% thickener was added; this increase greatly exceeds that of other reported thickeners. The CO2-philic fluorocarbon groups promoted the solubility of the thickener; while intra-molecular thickener crosslinking occurred via O···H bonds. Thus, the molecule with four fluorocarbon groups and two urea groups formed a network structure to achieve superstrong CO2-thickening ability.

Investigation of Parameters that Affect Resin Swelling in Green Solvents.

The influence of various physical and chemical factors on the swelling of polystyrene and PEG based resins in greener organic solvents has been systematically investigated. In general, chemical factors: the nature of the functionality/linker and the degree of loading were found to have a far larger influence on the swelling of the resins than physical parameters such as bead size. The results are interpreted in terms of Hansen solubility parameters for the solvents and there is evidence that some solvents interact with the polymeric core of a resin whilst others interact with the functionality. The results are extended to a study of the changes in resin swelling observed during both deprotection and chain elongation reactions during solid phase peptide synthesis.

Polymer Stabilized Cholesteric Liquid Crystal Siloxane for Temperature-Responsive Photonic Coatings.

Temperature-responsive photonic coatings are appealing for a variety of applications, including smart windows. However, the fabrication of such reflective polymer coatings remains a challenge. In this work, we report the development of a temperature-responsive, infrared-reflective coating consisting of a polymer-stabilized cholesteric liquid crystal siloxane, applied by a simple bar coating method. First, a side-chain liquid crystal oligosiloxane containing acrylate, chiral and mesogenic moieties was successfully synthesized via multiple steps, including preparing precursors, hydrosilylation, deprotection, and esterification reactions. Products of all the steps were fully characterized revealing a chain extension during the deprotection step. Subsequently, the photonic coating was fabricated by bar-coating the cholesteric liquid crystal oligomer on glass, using a mediator liquid crystalline molecule. After the UV-curing and removal of the mediator, a transparent IR reflective polymer-stabilized cholesteric liquid crystal coating was obtained. Notably, this fully cured, partially crosslinked transparent polymer coating retained temperature responsiveness due to the presence of non-reactive liquid-crystal oligosiloxanes. Upon increasing the temperature from room temperature, the polymer-stabilized cholesteric liquid crystal coating showed a continuous blue-shift of the reflection band from 1400 nm to 800 nm, and the shift was fully reversible.

Bithiophene-based fluorescent sensor for highly sensitive and ultrarapid detection of Hg2+ in water, seafood, urine and live cells.

Using Hg2+-promoted deprotection reaction, we have developed a new fluorescent turn-on sensor 2TS based on bithiophene fluorophore for Hg2+ detection. The sensing mechanism of 2TS towards Hg2+ was strongly proved by 1H NMR, FTIR, HRMS, UV-vis and fluorescence spectra. Remarkly, 2TS towards Hg2+ in 100% aqueous solution shows high sensitivity with a low detection limit of 19nM, superior selectivity and ultra-rapid response of 20s during a wide sensing pH range from 4 to 10. Taking advantage of the excellent properties, the low-cost sensor 2TS-based filter paper/TLC test strips were fabricated for visual, immediate and quantitative detection of Hg2+ in water, proving its applicability towards sensitive in-situ and on-site detection. Meanwhile, 2TS showed high analytical performance for Hg2+ detection in water, seafood as well as human urine samples. Moreover, thanks to the good water solubility, negligible cytotoxicity, good biocompatibility and cell-membrane permeability, 2TS was further applied to effectively image Hg2+ in live cells. Furthermore, the developed sensor 2TS acted as good fluorescent display material for Hg2+ with obvious color change.

Enantioselective Synthesis of a Tricyclic, sp3 -Rich Diazatetradecanedione: an Amino Acid-Based Natural Product-Like Scaffold.

6‐, 7‐, and 8‐membered rings are assembled from a linear precursor by successive cyclisation reactions to construct a tricyclic diazatricyclo[6.5.1.04, 9]‐tetradecanedione scaffold. Advanced building blocks based on d‐aspartic acid and l‐pyroglutamic acid were combined by a sp3−sp2 Negishi coupling. A carbamate‐guided syn‐diastereoselective epoxidation followed by an intramolecular epoxide opening allowed the construction of the piperidine ring. An efficient one‐pot hydroxyl‐group protection twofold deprotection reaction prepared the ground for the cyclisation to the bicycle. A final deprotection of the orthogonal protecting groups and lactamisation led to the novel, sp3‐rich tricycle. The final compound is a substrate mimic of peptidyl‐prolyl cis‐trans isomerases featuring a locked trans‐amide bond. Cheminformatic analysis of 179 virtual derivatives indicates favourable physicochemical properties and drug‐like characteristics. As proof of concept we, show a low micromolar activity in a fluorescence polarisation assay towards the FK506‐binding protein 12.

Modulation of Prins Cyclization by Vibrational Strong Coupling.

Light-molecule strong coupling has emerged within the last decade as a new method to control chemical reactions. A few years ago it was discovered that chemical reactivity could be altered by vibrational strong coupling (VSC). Only a limited number of reactions have been investigated under VSC to date, including solvolysis and deprotection reactions. Here the effect of VSC on a series of aldehydes and ketones undergoing Prins cyclization, an important synthetic step in pharmaceutical chemistry, is investigated. A decrease of the second-order rate constant with VSC of the reactant carbonyl stretching groups is observed. We also observe an increased activation energy due to VSC, but proportional changes in activation enthalpy and entropy, suggesting no substantive change in reaction pathway. The addition of common cycloaddition reactions to the stable of VSC-modified chemical reactions is another step towards establishing VSC as a genuine tool for synthetic chemistry.

Modulation of Prins Cyclization by Vibrational Strong Coupling

AbstractLight‐molecule strong coupling has emerged within the last decade as a new method to control chemical reactions. A few years ago it was discovered that chemical reactivity could be altered by vibrational strong coupling (VSC). Only a limited number of reactions have been investigated under VSC to date, including solvolysis and deprotection reactions. Here the effect of VSC on a series of aldehydes and ketones undergoing Prins cyclization, an important synthetic step in pharmaceutical chemistry, is investigated. A decrease of the second‐order rate constant with VSC of the reactant carbonyl stretching groups is observed. We also observe an increased activation energy due to VSC, but proportional changes in activation enthalpy and entropy, suggesting no substantive change in reaction pathway. The addition of common cycloaddition reactions to the stable of VSC‐modified chemical reactions is another step towards establishing VSC as a genuine tool for synthetic chemistry.

Highly selective tetrahydropyranylation/dehydropyranylation of alcohols and phenols using porous phenolsulfonic acid-formaldehyde resin catalyst under solvent-free condition

An efficient protocol for solvent-free chemoselective tetrahydropyranylation/depyranylation of alcohols and phenols is reported herein using mesoporous Phenolsulfonic Acid Formaldehyde Resins as a heterogeneous acid catalyst. The catalyst successfully performed chemoselective protection and deprotection reactions of a wide range of substrates ranging from primary to secondary and tertiary alcohols and also phenols. The reactions were carried out at ambient temperature under solvent-free condition (SolFC) which resulted in high yields within a very short time. FT-IR, TEM, SEM, EDS and TG-DSC analysis techniques were employed to characterize the synthesized polymeric catalyst. The chemoselective nature of our method was confirmed using 13C DEPT-135 NMR studies. The polymer catalyst was found to be recoverable even after 10th catalytic cycle without much depreciation in its activity. The heterogeneity of the catalyst was verified by hot filtration method. Good yield, energy and cost- effective method, solvent-free protocol, mild reaction conditions, no inert atmosphere, metal-free heterogeneous polymer catalyst and excellent recoverability of the catalyst are notable milestones of the reported protocol.

Synthesis of glucosamine derivative with double caffeic acid moieties at N– and 6-O-positions for developments of natural based materials

Glucosamine derivatives with double caffeic acid moieties were synthesized for developments of natural based materials. Caffeic acids were introduced to glucosamine derivatives through the synthesis roots as protection and de-protection reactions. Firstly, the silyl groups and tert-butoxycarbonyl groups were selected for the protection of each hydroxyl group and amino group. The designed glucosamine derivative showed reactivity of the double bonds, which was confirmed by UV spectra. Photoresponsivity was observed both in solution and heterogeneous suspension. The oligomerization was also confirmed in water suspension. The solubility and thermal stability were changed after the UV irradiation. This results show the potential of great progress a natural based material development.