Silyl Ether Groups Research Articles

Combining Siloxane-Based polybenzoxazine with Poly(ethylene-co-vinyl acetate/hydroxyl) for tougher, more Stable, and Self-Healable materials

Cross-linked EVOH containing dynamic silyl ether bonds with improved toughness and processability have been prepared by taking advantage of both ethylene vinyl alcohol (EVOH) and benzoxazine chemistry. For that, the cross-linked EVOH was synthesized through a trans etherification reaction between siloxane mono-functional benzoxazine and pendant hydroxyl groups on ethylene vinyl alcohol (EVOH) copolymer. The precursor EVOH copolymer was obtained by hydrolysis of the commercially available and inexpensive ethylene–vinyl acetate copolymer (EVA). The chemical structures of polymers were analyzed by proton nuclear magnetic resonance (1H NMR) spectra and Fourier transform infrared (FTIR) spectroscopy. The curing and thermal stability were researched by using differential scanning calorimetry (DSC) and a thermogravimetric analyzer (TGA), respectively. The mechanical properties via the stress–strain analysis were examined to identify the effect of the benzoxazines with the silyl ether group on the toughness and self-healing ability of the modified EVOH.

Mechanically Tunable and Reconstructable Lignin Thermosets via “Click” Chemistry and Surface Functionalization

Among the most abundant biomass, lignin is an appealing yet challenging feedstock for manufacturing sustainable materials. The polyphenolic structure and globular architecture of lignin makes it a mechanically weak material for being incorporated in polymer composites. Upon surface modification with functionalized silyl ether groups via thiol-ene chemistry in this work, lignin was cross-linked to create reconstructable thermosets. These thermosets exhibit not only enhanced mechanical properties but also improved degradability. The synthesis of different cross-linkers was used to explore the structure–property relationship. Altering the cross-linking density and the size of cross-linkers has a large impact on the mechanical properties of the final thermosets. Furthermore, the chemical recycling of these thermosets was explored for the conversion to initial motifs under basic environments.

C2‐Cyanomethyl (CNMe) Ether‐Protected Glycosyl Trichloroacetimidate Donors for Stereoselective β‐O‐Glycosylations

AbstractStereoselective construction of glycosidic linkages have emerged as one of the pivotal aspects for the synthesis of complex oligosaccharide assemblies. We herein report C2‐cyanomethyl (CNMe) ether as a strong stereodirecting group on trichloroacetimidate glycosyl donors for the synthesis of 1,2‐trans‐β‐O‐glycosides. The developed donors bearing various arming and disarming protections along with C2‐CNMe ether delivered the glycosides in short reaction time, moderate to good yields and high to excellent stereoselectivities. Gluco‐ and galacto‐ configured donors were found compatible with an array of alcohols having varied reactivities. The orthogonality of the CNMe ether protection with silyl ether group has been further explored for sequential glycosylations.

Simultaneously Improving the Optical, Dielectric, and Solubility Properties of Fluorene-Based Polyimide with Silyl Ether Side Groups

Three fluorene-based polyimides with silyl ether groups (Si–PIs) were successfully synthesized by a simple and efficient silicon etherification reaction of hydroxyl-containing polyimides (OH–PIs) and tert-butylchlorodiphenylsilane (TBDPSCl), and their structures were confirmed by 1H NMR and IR spectra. The bulky nonpolar tert-butyldiphenylsilyl (TBDPS) side groups in the modified PI unit instead of the strong electron donor −OH group is conducive to decreasing electronic conjugation and charge transfer (CT) interaction along the PI chain. Accordingly, the optical, dielectric, and solubility properties of the modified Si–PI films are simultaneously improved compared with the precursor OH–PI films. The modified Si–PI films demonstrate a meaningful enhancement in the transmittances at a wavelength of 400 nm (T400) to 74–81% from 42 to 55% of OH–PI films and the regeneration of fluorescence characteristics. The dielectric constant and loss of Si–PI films are also obviously reduced to 2.63–2.75 and 0.0024–0.0091 at 1 kHz from 4.19 to 4.78 and 0.0173–0.0295 of OH–PI films, respectively, due to substituted with the bulky nonpolar TBDPS groups to increase the free volume and hydrophobicity of Si–PI films. The solubility of Si–PIs in low- or nonpolar solvents (such as CHCl3, CH2Cl2, acetone, and toluene) is significantly improved. Furthermore, Si–PI films still maintain relatively good thermal properties with the 5% weight loss temperature (T5%) in the range 470–491 °C under a nitrogen atmosphere and the glass transition temperature (Tg) in the range 245–308 °C.

1,2-Arylboration of aliphatic alkenes by cooperative palladium/copper catalysis

A method for the 1,2-arylboration of aliphatic alkenes to afford alkylboronic esters by cooperative palladium/copper catalysis was developed. The reaction proceeds in a highly regioselective manner, and various functional groups such as silyl ether, alkoxycarbonyl, and cyano groups are tolerated under the applied reaction conditions.

Design and synthesis of novel quinic acid derivatives: invitro cytotoxicity and anticancer effect on glioblastoma.

Aim: Quinic acid (QA) is a cyclic polyol exhibiting anticancer properties on several cancers. However, potential role of QA derivatives against glioblastoma is not well established. Methodology & results: Sixteennovel QA derivatives and QA-16 encapsulated poly (lactic-co-glycolic acid)nanoparticles (QA-16-NPs) were screened for their anti-glioblastoma effect using standard cell and molecular biology methods. Presence of a tertiary hydroxy and silylether groups in the lead compound were identified for the antitumor activity. QA-16 have 90% inhibition with the IC50 of 10.66μM and 28.22μM for LN229 and SNB19, respectively. The induction of apoptosis is faster with the increased fold change of caspase 3/7 and reactive oxygen species. Conclusion: QA-16 and QA-16-NPs shows similar cytotoxicity effect, providing the opportunity to use QA-16 as a potential chemotherapeutic agent.

Deoxygenative Divergent Synthesis: En Route to Quinic Acid Chirons.

The installation of vicinal mesylate and silyl ether groups in a quinic acid derivative generates a system prone for stereoselective borane-catalyzed hydrosilylation through a siloxonium intermediate. The diversification of the reaction conditions allowed the construction of different defunctionalized fragments foreseen as useful synthetic fragments. The selectivity of the hydrosilylation was rationalized on the basis of deuteration experiments and computational studies.

The Synthesis, Anticancer Activity, Structure-Activity Relationships and Molecular Modelling Studies of Novel Isoindole-1,3(2H)-dione Compounds Containing Different Functional Groups.

Isoindole-1,3(2H)-dione derivatives are known to have cytotoxic effects on many cancer cells. The anticancer activity of these compounds varies depending on the substituents attached to them. Therefore, the effect of substituents is very important when determining the anticancer activities of molecules. We have recently reported an example of the substituent effect. According to that work, the anticancer activity against HeLa, C6, and A549 cancer cell lines of isoindole- 1,3(2H)-dione compounds containing tert-butyldiphenylsilyl ether, azido, and hydroxyl groups was examined by our group. It was found that an isoindole-1,3(2H)-dione compound containing both tert-butyldiphenylsilyl ether group and azido groups showed higher anticancer activity than 5-fluorouracil and another isoindole-1,3(2H)- dione compound containing both azido and hydroxyl groups. After we discovered that tert-butyldiphenylsilyl ether group in the skeletal structure of isoindole-1,3(2H)-dione exhibits anticancer activity against HeLa, C6, and A549 cancer cell lines, we wanted to examine the anticancer activities of different silyl ether groups, i.e., OTMS, -OTBDPS, and -OTBDMS groups, and also -OH and -Br groups, by comparing them with each other according to the structure-activity relationship. All of the synthesized compounds were characterized by 1H and 13C NMR spectra, IR spectroscopy, and mass spectra measurements. The IC50 values of these compounds were calculated for all cancer cell lines and compared with each other and cisplatin, which is a platinum-containing chemotherapeutic drug. Molecular modelling studies were carried out using the MOE software package. It was found that compounds 13 and 16, containing both silyl ether (-OTBDMS) and -Br groups, showed higher anticancer activity than cisplatin against both Caco-2 and MCF-7 cell lines. Compounds 20 and 23 showed anticancer activity in MCF-7 cells and compounds 8, 9, 20, and 23 in Caco-2 cells. While compounds 20 and 23 have only a silyl ether (-OTMS) group, compounds 8 and 9 have only a -OH group. Molecular modelling studies indicated that compounds 8 and 13, as well as their analogs, may bind to the active site of hRS6KB1 (pdb: 4l3j), compound 11 may bind to the active site of human mTOR (pdb: 4jt5) and additionally, compounds 10-17 are expected to be both mutagenic and reactive according to the mutagenicity and reactivity calculations. According to these results, the anticancer activities of isoindole-1,3(2H)-dione compounds (8 - 23) vary depending on the groups they contain and these groups affect each other's activities. Silyl ethers (-OTBDMS and -OTMS) and -OH and -Br groups in the skeletal structure of isoindole-1,3(2H)-dione can be regarded as anticancer agents. In this sense, compounds 13 and 16, containing both silyl ether (-OTBDMS) and - Br groups, may be regarded as alternative chemotherapeutic drugs. This work may lead to the synthesis of new isoindole-1,3(2H)-dione compounds containing different silyl ether groups and studies evaluating their anticancer activities or other biological properties.

A study of silylated tris(styryl)benzenes as potential fluorescent sensors for aqueous fluoride

Different tris(styryl)benzenes bearing a tert-butyldimethylsilyl (TBDMS) group at the periphery have been efficiently prepared by a straightforward protocol. The potential of these compounds as fluorescent sensors for fluoride has been studied. In all cases, this anion caused significant quenching of the emission intensity upon cleavage of the silyl ether group and the formation of the corresponding phenolate anion. All compounds displayed good selectivity over a variety of other anions. They could sense fluoride ions in aqueous solutions with sensitivity in the lower μM range when dissolved in DMSO, demonstrating the validity of this approach.

Catalytic Dehydrogenative Cyclization of o‐Teraryls under pH‐Neutral and Oxidant‐Free Conditions

AbstractA cobaloxime‐catalyzed acceptorless dehydrogenative cyclization of o‐teraryls was developed. In stark contrast to the established methods such as the Scholl or Mallory reactions, this method does not require any strong acids or oxidants, and shows high atom economy and a broad substrate scope. It operates at near room temperature with light as the source of energy. Acid‐ or oxidant‐sensitive functional groups, such as 4‐methoxyphenyl, unprotected benzyl alcohol, silyl ether, and thiophene groups are tolerated. Remarkably, aryls with electron‐withdrawing groups, and electron‐poor heteroarenes, such as pyridine and pyrimidine, can also react. Preliminary mechanistic study reveals that hydrogen gas is released during the reaction, and both light and the cobalt catalyst are important for the dehydrogenation step.

Catalytic Dehydrogenative Cyclization of o-Teraryls under pH-Neutral and Oxidant-Free Conditions.

A cobaloxime-catalyzed acceptorless dehydrogenative cyclization of o-teraryls was developed. In stark contrast to the established methods such as the Scholl or Mallory reactions, this method does not require any strong acids or oxidants, and shows high atom economy and a broad substrate scope. It operates at near room temperature with light as the source of energy. Acid- or oxidant-sensitive functional groups, such as 4-methoxyphenyl, unprotected benzyl alcohol, silyl ether, and thiophene groups are tolerated. Remarkably, aryls with electron-withdrawing groups, and electron-poor heteroarenes, such as pyridine and pyrimidine, can also react. Preliminary mechanistic study reveals that hydrogen gas is released during the reaction, and both light and the cobalt catalyst are important for the dehydrogenation step.

Interfacial Cross-Link Inhomogeneity of a Phenolic Resin on a Silica Surface As Revealed by X-ray and Neutron Reflection Measurements

The interfacial structure of a hexamethylenetetramine-cured phenolic resin on a silica surface was investigated by the complementary use of X-ray and neutron reflectivity (XRR and NR, respectively). The contrast-variation technique was applied using D2O for the NR analysis in which the coherent neutron scattering length density (SLD) largely changed owing to the D2O absorption of the dry phenolic resin and the hydrogen-to-deuterium exchange of phenolic hydroxyl groups. The XRR profile indicated no clear interfacial structure in terms of the mass density, whereas the NR profile indicated the presence of an interfacial nanolayer on the native silica surface according to the SLD. The thickness of the interfacial layer was 1–2 nm, which was independent of the thickness of the bulk resin layer. The formation of the interfacial layer on the silica surface could be caused by preferential adsorption of the novolac resin on the silica surface via strong hydrogen bonding between phenolic units in the novolac resin and silica surface comprising silanol and silyl ether groups resulting in interfacial cross-link inhomogeneity of the phenolic resin on the silica surface in the thickness direction. To the best of our knowledge, this is the first report of an experimental elucidation of the buried interfacial structure between the phenolic resins on the silica surface at a nanometer level.

Addressing Multiple Ions Using Single Optical Probe: Multi‐Color Response via Mutually Independent Sensing Pathways

AbstractMultiresponsive smart optical probe based on p‐phenylene vinylene backbone is designed for simultaneous sensing of multiple ions, such as Cu2+, Zn2+ and F− at pH 7.4. A rapid color change from colorless to deep yellow is observed upon addition of both Cu2+ and Zn2+ ion. However, under long UV lamp, the green‐colored emission of the probe is specifically quenched in the presence of Cu2+, while Zn2+ induces change in the emission color from green to yellow. On the contrary, F−, unlike Cu2+ and Zn2+, does not render any change in visible color, however, an emission quenching, similar to that of Cu2+ addition, was noticed. The binding of metal ions to the central bipyridine core diminishes the ‘conformational flexibility’ and facilitates ‘ligand to metal ion’ charge transfer. On the contrary, addition of fluoride triggers the cleavage of silyl ether groups and results in the photo‐induced electron transfer from free hydroxyl groups to the core aromatic unit. Thus, we can detect as well as discriminate these three ions (Cu2+, Zn2+ and F−) simultaneously by comparing the respective output signals. Further, a sustainable strategy has been developed for on‐site detection of toxic ions using reusable, low‐cost paper strips. Most importantly, the current method is found to be fairly effective in quantifying (as evident by relatively smaller standard deviation values) the presence of toxic metal ions, above permissible levels, in a wide range of natural water samples. Further, estimation of fluoride is achieved in commercially available toothpaste and mouthwash products.

Novel Silyl Ether-Based Acid-Cleavable Antibody-MMAE Conjugates with Appropriate Stability and Efficacy.

Antibody-drug conjugate (ADC) is a novel efficient drug delivery system that has been successfully used in clinical practice, and it has become a research hotspot in the anti-tumor drug field. Acid-cleavable linkers were first used in clinical ADCs, but their structural variety (e.g., hydrazone and carbonate) is still limited, and their stability is usually insufficient. Designing novel acid-cleavable linkers for the conjugation of the popular cytotoxin monomethyl auristatin E (MMAE) has always been a significant topic. In this paper, we generate a novel, silyl ether-based acid-cleavable antibody-MMAE conjugate, which skillfully achieves efficient combination of amino-conjugated MMAE with the acid-triggered silyl ether group by introducing p-hydroxybenzyl alcohol (PHB). The stability, acid-dependence cleavage, effective mechanism, efficacy and safety of the resulting ADC were systematically studied; the results show that it exhibits a significant improvement in stability, while maintaining appropriate efficacy and controlled therapeutic toxicity. This strategy is expected to expand a new type of acid-cleavable linkers for the development of ADCs with highly potent payloads.

Mechanistic Perspectives in the Regioselective Indole Addition to Unsymmetrical Silyloxyallyl Cations.

Our investigations on the reaction mechanism to account for regioselectivity on the addition of indoles to unsymmetrical silyloxyallyl cations are reported. Using both experimental and computational methods, we confirmed the significance of steric effects from the silyl ether group toward directing the inward approach of indoles, leading to nucleophilic attack at the less substituted electrophilic α'-carbon. The role of residual water toward accelerating the rate of reaction is established through stabilization of the participating silyloxyallyl cation.

Total Synthesis of Scytonemide A Employing Weinreb AM Solid-Phase Resin.

The human 20S proteasome inhibitor scytonemide A (1), a macrocyclic imine originally isolated from the cyanobacterium Scytonema hofmanni, was synthesized via a biomimetic solid-phase peptide synthesis (SPPS) approach employing the Weinreb AM resin. Utilizing this approach, cyclization of the protected heptapeptide via formation of the imine bond occurred spontaneously upon cleavage from the resin in the presence of a reducing agent and subsequent aqueous workup. The final deprotection step necessary to produce the natural product was accomplished under slightly basic conditions, facilitating cleavage of the silyl ether group while leaving the macrocycle intact. Purification of the synthetic scytonemide A was accomplished via normal-phase flash column chromatography, potentially facilitating larger scale preparation of the compound necessary for future mechanistic and SAR studies. The structure of the target compound was confirmed by NMR spectroscopy, which also shed light on differences in the spectroscopic data obtained for the synthetic and natural scytonemide A samples for some of the amide and alcohol signals in the 1H NMR spectrum.

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.

Comparison of monomethoxy‐, dimethoxy‐, and trimethoxysilane anchor groups for surface‐initiated RAFT polymerization from silica surfaces

ABSTRACTThe immobilization of reversible addition–fragmentation chain transfer (RAFT) agents on silica for surface‐initiated RAFT polymerizations (SI‐RAFT) via the Z‐group approach was studied systematically in dependence of the functionality of the RAFT‐agent anchor group. Monoalkoxy‐, dialkoxy‐, and trialkoxy silyl ether groups were incorporated into trithiocarbonate‐type RAFT agents and bound to planar silica surfaces as well as to silica nanoparticles. The immobilization efficiency and the structure of the bound RAFT‐agent film varied strongly in dependence of the used solvent (toluene vs. 1,2‐dimethoxyethane) and the anchor group functionality, as evidenced by atomic force microscopy, transmission electron microscopy, dynamic light scattering, and UV/Vis spectroscopy. Surface‐initiated RAFT polymerizations using functionalized silica nanoparticles revealed that grafted oligomers, which often occur in SI‐RAFT, are not formed within the crosslinked structures that originate from the immobilization, and that RAFT‐agent films that show less aggregation during the immobilization are more efficient during SI‐RAFT in terms of polymer grafting density. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015, 53, 103–113

ChemInform Abstract: Convergent Access to Bis‐Spiroacetals Through a Sila‐Stetter—Ketalization Cascade.

AbstractThe NHC‐catalyzed title reaction between aliphatic acylsilanes and vinylketones bearing silyl ether groups affords bis‐spiroacetals (IV) and (XV) in two steps.

4-[(tert-Butyl-diphenyl-sil-yloxy)meth-yl]pyridazin-3(2H)-one.

In the title compound, C21H24N2O2Si, the carbonyl group of the heterocyclic ring and the O atom of the silyl ether group are placed toward opposite sides and the tert-butyl and pyridazinone moieties are anti-oriented across the Si—O bond [torsion angle = −168.44 (19)°]. In the crystal, mol­ecules are assembled into inversion dimers through co-operative N—H⋯O hydrogen bonds between the NH groups and O atoms of the pyridazinone rings of neighbouring mol­ecules. The dimers are linked by π–π inter­actions involving adjacent pyridazinone rings [centroid–centroid distance = 3.8095 (19) Å], generating ladder-like chains along the b-axis direction. The chains are further linked into a two-dimensional network parallel to the ab plane through weak C—H⋯π inter­actions.