Alkoxy Research Articles

Novel Suberoylanilide Hydroxamic Acid Analogs Inhibit Angiogenesis and Induce Apoptosis in Breast Cancer Cells.

Histone deacetylases (HDACs) are the enzymes that catalyze the removal of the acetyl group from lysine residues and regulate several biological processes. Suberoylanilide hydroxamic acid (SAHA) is a notable HDAC inhibitor that exhibited remarkable anti-proliferative efficiency by alleviating gene regulation against solid and hematologic cancers. The aim of this study was to develop new chemotherapeutic agents for breast cancer treatment, therefore, a novel series of Suberoylanilide hydroxamic acid (SAHA) analogs were investigated as anticancer agents. We designed and synthesized a novel series of analogs derived from SAHA by substituting alkyl, alkoxy, halo, and benzyl groups at different positions of the phenyl ring. The newly synthesized analogs were assessed for their cytotoxic potential against four human cancer cell lines in comparison with healthy cell lines, using several biological assays. SAHA analogs displayed significant cytotoxic potential with IC50 values ranging from 1.6 to 19.2 μM in various tumor cell lines. Among these analogs, 2d (containing 3-chloro, 4-floro substitutions on phenyl moiety), 2h (containing 3,4-di chloro substitutions on phenyl moiety), and 2j (containing 4-chloro, 3-methyl substitutions on phenyl moiety) showed significant cytotoxic potential with IC50 values ranging from 1.6 to 1.8 μM in MCF-7 (breast carcinoma) cell line. More importantly, these analogs were found to be non-toxic towards healthy primary human hepatocytes (PHH) and mouse fibroblast cells (NIH3T3), which represent their tumor selectivity. These analogs were further analyzed for their effect on cell migration, BrdU incorporation, Annexin V-FITC and cell cycle arrest (Sub-G1 phase). Remarkably, analogs 2d, 2h, and 2j displayed significant HDAC inhibition than the parent SAHA molecule. Further studies also confirmed that these SAHA analogs are efficient in inducing apoptosis, as they regulated the expression of several proteins involved in mitochondrial or intrinsic apoptosis pathways. Findings in the Chick Chorioallantoic Membrane (CAM) assay studies revealed anti-angiogenic properties of the currently described SAHA analogs. From anti-proliferative study results, it is clearly evident that 3,4-substitution at the SAHA phenyl ring improves the anti-proliferative activity of SAHA. Based on these findings, we presume that the synthesized novel SAHA analogs could be potential therapeutic agents in treating breast cancer.

Effective adsorptive removal of dyes and heavy metal using graphene oxide based Pre-treated with NaOH / H2SO4 rubber seed shells synthetic graphite Precursor: Equilibrium Isotherm, kinetics and thermodynamic studies

Graphene oxide (GO) has excellent adsorption capacity as a promising adsorbent due to its large surface area consisting of large number of oxygen-functional groups. Nonetheless, the properties of GO are heavily influenced by the graphite sources and the type of pretreatment. This study aims to investigate the effect of pre-treatment of graphite sourced from agricultural wastes on the properties of the GO for the adsorption of dyes and heavy metal ion. Two sources of graphite (pre-treated with NaOH and H2SO4) were synthesised using biomass wastes (rubber seed shells) and were utlilized to produce high-efficiency GO for the adsorption of Methylene blue (MB), Congo red (CR) and Cadmium (II) from aqueous solutions. The effect of pre-treatment on the GO properties, behavior and performance was evaluated through batch adsorption studies which were conducted under operational condition of activation temperature (25–55 ○C), contact time (2–20 min), dosage (0.02–0.1 g), pH (2–12) using impregnation ratio of 1:4. The morphological analysis revealed that GO pretreated with NaOH (GO-N) graphite source exhibited more porous surface area compared to GO pretreated with H2SO4 (GO-H) graphite source, the surface properties was attributed to higher oxygen ratio as indicated in the EDX mapping and as demonstrated in the BET analysis. In general, both GO demonstrated excellent adsorption capacity due to their single-layered planes with noticeable functional groups which included hydroxyl, alkoxy, and carboxyl groups along with the π − π interactions and hydrogen bonds. Maximum monolayer adsorption capacities for the effective removal of CR, MB and Cd (II) was achieved as 299.38, 311.54, and 107.65 mg g−1 respectively onto GO-N compared to GO-H as illustrated by the Langmuir isotherms. Furthermore, the results showed that the experimental data were well-fitted to the pseudo-second-order model for both CR and MB including Cd (II) with GO-N with higher correlation coeficient R2 (R2 > 0.9) recorded. Thermodynamic study signified that the enthalpy (ΔH) and Gibbs free energy (ΔG) values of the adsorption process for both pollutants were negative indicating that adsorption of CR, MB and Cd were spontaneous and exothermic in nature which suggests that the adsorption of dyes and heavy metal from an aqueous solution was attributed to the presence of active sites and functional groups on the GO surface. However, the study revealed that GO–N proved to be a better adsorbent compared to GO-H under same operational condition and can be considered as a promising and cost-effective adsorbent for the removal of dyes and metal ions from industrial wastewater.

High‐Performance All‐Small‐Molecule Organic Solar Cells Enabled by Regio‐Isomerization of Noncovalently Conformational Locks

AbstractThe power conversion efficiencies (PCEs) of organic solar cells (OSCs) have surpassed 19% thanks to the innovation of polymer donors and molecular acceptors. However, the batch‐to‐batch variations in polymer materials are detrimental to the reproducibility of the device performance. In comparison, small‐molecule donors (SMDs) possess some unique advantages, such as well‐defined molecular weights, easy purification, and excellent batch‐to‐batch repeatability. Herein, a pair of regioisomeric SMDs (BT‐O1 and BT‐O2) has been synthesized with alkoxy groups as S···O noncovalently conformational locks (NoCLs) at the inner and outer position, respectively. Theoretical and experimental results reveal that the regioisomeric effect has a significant influence on the light‐harvest ability, energy levels, molecular geometries, internal reorganization energy, and packing behaviors for the two SMDs. As a result, BT‐O2‐based binary device shows an impressive PCE of 13.99%, much higher than that of BT‐O1 based one (4.07%), due to the better‐aligned energy level, more balanced charge transport, less charge recombination, lower energy loss, and more favorable phase separation. Furthermore, the fullerene derivative PC71BM is introduced into BT‐O2:H3 as the third component to achieve a notable PCE of 15.34% (certified 14.6%). Overall, this work reveals that NoCLs is a promising strategy to achieve high‐performance SMDs for all‐small‐molecule OSCs.

Synthesis, Structure-Activity Relationships, and Antiviral Profiling of 1-Heteroaryl-2-Alkoxyphenyl Analogs as Inhibitors of SARS-CoV-2 Replication.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to a pandemic, that continues to be a huge public health burden. Despite the availability of vaccines, there is still a need for small-molecule antiviral drugs. In an effort to identify novel and drug-like hit matter that can be used for subsequent hit-to-lead optimization campaigns, we conducted a high-throughput screening of a 160 K compound library against SARS-CoV-2, yielding a 1-heteroaryl-2-alkoxyphenyl analog as a promising hit. Antiviral profiling revealed this compound was active against various beta-coronaviruses and preliminary mode-of-action experiments demonstrated that it interfered with viral entry. A systematic structure–activity relationship (SAR) study demonstrated that a 3- or 4-pyridyl moiety on the oxadiazole moiety is optimal, whereas the oxadiazole can be replaced by various other heteroaromatic cycles. In addition, the alkoxy group tolerates some structural diversity.

Synthesis and mesomorphic properties of laterally fluoro azo/ ester based on four ring compounds with a wide range mesophase thermal stability

ABSTRACT New series of compounds were prepared by replacing the lateral methyl and bromo substituents in the previously investigated 4-ring compounds by the strong electronegative and smaller size fluorine atom. The two wings of the rode-shaped molecules, one is a compact polar group (CH3O, CH3, H, and Br), while the other is an alkoxy group with varying chain length that varies between 6–16 carbon atoms. Transition temperatures and temperature ranges of the observed phases were determined by DSC and phases identified by PLM. Except for the terminally methoxy-substituted homologues, which were found to be purely nematogenic, homologues of all the remaining derivatives are dimorphic possessing both N and SmA phases with wide temperature range. The fluoro derivatives were compared with the previously investigated lateral Br and methyl analogues in order to evaluate the effect of the polarity and size of the lateral group on their mesomorphic behaviour and polarisability anisotropy (ΔαM). The comparison revealed that the replacement of lateral substituent by the small-sized strong electronegative fluorine atom is accompanied by an enhancement of thermal stability and temperature ranges of the mesophases compared with lateral Br and methyl substituents. The results were discussed in terms of molecular polarisability and steric effect.

Promoters for Improved Adhesion Strength between Addition-Cured Liquid Silicone Rubber and Low-Melting-Point Thermoplastic Polyurethanes.

A polydimethylsiloxane armed with epoxy, alkoxy and acrylate groups was synthesized from silanol terminated-PDMS and epoxy and acrylate groups functionalized silane coupling agents, and utilized as the adhesion promoter (AP) to prepare addition-cured liquid silicone rubber that exhibited self-adhesion ability (SA-LSR) with biocompatible thermoplastic polyurethanes (TPU) sheets. The structural characteristics of AP were characterized by Fourier transform infrared (FTIR) spectroscopy, which demonstrated the strong adhesion to polyester-based TPU sheets due to a sufficient amount of acrylate groups, epoxy groups and silanol groups obtained by the hydrolysis of alkoxy groups. In detail, the peel-off strength of SA-LSR and TPU joints reached up to 7.63 N mm−1 after the optimization of adhesion promoter including type and content, and curing condition including time and temperature. The cohesive failure was achieved during the sample breakage process. Moreover, the SA-LSR showed a good storage stability under proper storage conditions. This design strategy provided the feasibility to combine the advantages of addition-cured liquid silicone rubber and plastics with low melting points, promoting the potential application range of those silicone-based materials.

The Evaluation of Counter Diffusion CVD Silica Membrane Formation Process by In Situ Analysis of Diffusion Carrier Gas.

A new evaluation method for preparing silica membranes by counter diffusion chemical vapor deposition (CVD) was proposed. This is the first attempt to provide new insights, such as the decomposition products, membrane selectivity, and precursor reactivity. The permeation of the carrier gas used for supplying a silica precursor was quantified during the deposition reaction by using a mass spectrometer. Membrane formation processes were evaluated by the decrease of the permeation of the carrier gas derived from pore blocking of the silica deposition. The membrane formation processes were compared for each deposition condition and precursor, and the apparent silica deposition rates from the precursors such as tetramethoxysilane (TMOS), hexyltrimethoxysilane (HTMOS), or tetraethoxysilane (TEOS) were investigated by changing the deposition temperature at 400–600 °C. The apparent deposition rates increased with the deposition temperature. The apparent activation energies of the carrier gas through the TMOS, HTMOS, and TEOS derived membranes were 44.3, 49.4, and 71.0 kJ mol−1, respectively. The deposition reaction of the CVD silica membrane depends on the alkoxy group of the silica precursors.

Palladium-Catalyzed Siloxycyclopropanation of Alkenes Using Acylsilanes.

Currently, catalytically transferable carbenes are limited to electron-deficient and neutral derivatives, and electron-rich carbenes bearing an alkoxy group (i.e., Fischer-type carbenes) cannot be used in catalytic cyclopropanation because of the lack of appropriate carbene precursors. We report herein that acylsilanes can serve as a source of electron-rich carbenes under palladium catalysis, enabling cyclopropanation of a range of alkenes. This reactivity profile is in sharp contrast to that of metal-free siloxycarbenes, which are unreactive toward normal alkenes. The resulting siloxycyclopropanes serve as valuable homoenolate equivalents, allowing rapid access to elaborate β-functionalized ketones.

Synthesis of C2-Alkoxy-Substituted 19-Nor Vitamin D3 Derivatives: Stereoselectivity and Biological Activity

The active form of vitamin D3 (D3), 1a,25-dihydroxyvitamn D3 (1,25D3), plays a central role in calcium and bone metabolism. Many structure–activity relationship (SAR) studies of D3 have been conducted, with the aim of separating the biological activities of 1,25D3 or reducing its side effects, such as hypercalcemia, and SAR studies have shown that the hypercalcemic activity of C2-substituted derivatives and 19-nor type derivatives is significantly suppressed. In the present paper, we describe the synthesis of 19-nor type 1,25D3 derivatives with alkoxy groups at C2, by means of the Julia–Kocienski type coupling reaction between a C2 symmetrical A ring ketone and a CD ring synthon. The effect of C2 substituents on the stereoselectivity of the coupling reaction was evaluated. The biological activities of the synthesized derivatives were evaluated in an HL-60 cell-based assay. The a-methoxy-substituted C2α-7a was found to show potent cell-differentiating activity, with an ED50 value of 0.38 nM, being 26-fold more potent than 1,25D3.

Effects of alkylthio groups on phase transitions of organic molecules and liquid crystals: a comparative study with alkyl and alkoxy groups

The effects of the alkylthio groups on the phase transition behavior of organic liquid crystal molecules were examined by comparing them with the effects of alkyl and alkoxy groups.

Facile synthesis of a glutathione-depleting Cu(II)-half-salamo-based coordination polymer for enhanced chemodynamic therapy.

Chemodynamic therapy (CDT), utilizing Fenton catalysts to convert intracellular H2O2 into toxic hydroxyl radicals (˙OH) to kill cancer cells, has a wide application prospect in tumor treatment because of its high selectivity. Its anticancer effect, however, is unsatisfactory due to the overexpressed glutathione (GSH). Herein, a GSH-depleting Cu(II)-half-salamo-based coordination polymer (CuCP) was prepared and validated by single crystal X-ray crystallography, Hirshfeld surface analyses and DFT calculations. The Cu(II) ions in the coordination polymer are five-coordinated bearing slightly twisted square pyramidal coordination environments and are bridged by phenoxy and alkoxy groups. After internalization by tumor cells, the CuCP could be biodegraded and reduced by GSH to generate a large amount of Cu(I), simultaneously depleting GSH. Subsequently, the Cu(I) ions interact with H2O2 to generate toxic ˙OH through a Fenton-like reaction to enhance their anticancer efficacy. Our study provides useful insights into designing smarter metal-based anticancer agents to improve the CDT efficiency in cancer therapy.

Binary system of alkyl polyether carboxylate and quaternary ammonium with ultra-low interfacial tension at high temperature and a wide range of salinity

A novel formula of anionic surfactants with propoxy (PO) and ethoxy(EO) groups and cationic surfactants was developed and temperature and salt resistance performance of the formula has been studied with both model oil and crude oil. An obvious synergistic effect was evidenced by CMC values and interaction parameters of nonylphenol polyether carboxylate, hexadecyltrimethylammonium chloride and their mixtures. Effect of molar ratio of anionic surfactant and cationic surfactant, temperature, salinity, concentration and oil-water ratio on phase behavior and interfacial tension were investigated systematically. The results demonstrate that ultra-low interfacial tension and excellent phase behavior were obtained at temperature up to 120 °C and a wide range of salinity, which shows promising for enhanced oil recovery.

Reductive Elimination of Alkoxy Group in Anthraquinone Derivatives

Reductive Elimination of Alkoxy Group in Anthraquinone Derivatives

Axial-ligand-cleavable silicon phthalocyanines triggered by near-infrared light toward design of photosensitizers for photoimmunotherapy

Near-infrared photoimmunotherapy (NIR-PIT) is a novel phototherapy for the treatment of cancer that uses NIR light and conjugates of antibody-IR700, a silicon phthalocyanine photosensitizer. A key feature of NIR-PIT is light-induced axial ligand cleavage of IR700, which finally causes cytotoxicity. Here, we focused on protonation of the axial ligand on the IR700 anion radical during the photochemical process. The Gibbs energy in the protonation reaction of IR700 derivatives with different axial ligands was calculated. These calculations suggested the order of the cleavage efficiency corresponds to the basicity of the axial ligand (i.e. alkoxy > siloxy (IR700) > phenoxy > oxycarbonyl), which was confirmed by the photoirradiation experiments with synthesized compounds. Thus, axial ligand cleavage is significantly dependent on the basicity of the axial ligand. Our findings suggest that PIT reagent with an IR700 derivative bearing alkoxy group would show better efficacy than IR700.

One-pot synthesis of double silane-functionalized carbon dots with tunable emission and excellent coating properties for WLEDs application

Silane-functionalized carbon dots (SiCDs) can be exploited as effective color converting materials for the solid-state light-emitting devices. However, most of SiCDs reported thus far have shown photoluminescence emissions in the blue and green spectral range, which limit them to construct an efficient white light-emitting diodes (WLEDs) due to the lack of long-wavelength emission. Herein, a series of double silane-functionalized carbon dots (DSiCDs) were prepared via a one-step solvothermal method. The results show that the organic functional group of the silane has great influence on the optical properties of DSiCDs and the number of alkoxy group in the silane has great influence on coating properties of DSiCDs. In addition, the DSiCDs prepared by (3-aminopropyl)triethoxysilane and N-[3-(trimethoxysilyl)propyl]ethylenediamine with molar ratio of 7:3 show excellent optical properties with the maximum emission at 608 nm under 570 nm excitation. Furthermore, they can be completely cured within 1 h at room temperature to form fluorescent coating with high stability and strong adhesion to the substrate. Together with their excellent optical and coating properties, they can be directly coated on LED chips to prepare WLEDs, with a CIE coordinate of (0.33,0.31), color rendering index of 81.6, and color temperature of 5774 K.

Hydrogen Bonds Dominate Brønsted Acid Sites in Zeolite SSZ-42: A Classification of Their Diversity.

The zeolite catalyst SSZ‐42 shows a remarkable high abundance (≈80 %) of hydrogen‐bonded Brønsted acid sites (BAS), which are deshielded from the 1H chemical shift of unperturbed BAS at typically 4 ppm. This is due to their interaction with neighboring oxygen atoms in the zeolite framework when oxygen alignments are suitable. The classification and diversity of hydrogen bonding is assessed by DFT calculations, showing that oval‐shaped 6‐rings and 5‐rings allow for a stronger hydrogen bond to oxygen atoms on the opposite ring side, yielding higher experimental chemical shifts (δ (1H)=6.4 ppm), than circular 6‐rings (δ(1H)=5.2 ppm). Cage‐like structures and intra‐tetrahedral interactions can also form hydrogen bonds. The alignment of oxygen atoms is expected to impact their role in the stabilization of intermediates in catalytic reactions, such as surface alkoxy groups and possibly transition states.

Effects of side alkoxy groups on the arylacetylene unit on properties of Poly(silylene arylacetylene)s

A series of poly(dimethylsilylene arylacetylene)s with different side alkoxy groups on the arylacetylene unit (named as PSA-(AO) resins), including methoxy (MO), ethoxy (EO), pentyloxy (PO), and decyloxy (DO), were synthesized from corresponding disubstituted diethynylbenzene and dichlorodimethylsilane. The processability, heat resistance and mechanical properties, and the effects of side alkoxy groups were investigated. The results show the processability of PSA-(AO) resins is improved, while the flexural properties and heat resistance of the relative cured resins decrease with the increase in the length of side alkoxy groups. The flexural strength and degradation temperature of 5% weight loss for the cured PSA-(EO) resin with side ethoxy groups reach 20.8 MPa and 415℃, respectively.

Exploring steric effect of electron-donating group in palladium and nickel mediated ethylene polymerization and copolymerization with polar monomers

The influence of steric effect of electron-donating substituents on the phosphine-sulfonate palladium and nickel catalysts was rarely studied in olefin (co)polymerizations. In this contribution, a family of flexible cyclohexyl/rigid aromatic phosphine-sulfonate palladium and nickel catalysts was designed, synthesized, and comprehensively identified by varying number, position, and size of alkoxy groups on aromatic substituents of phosphine. In ethylene polymerization, the steric effect of alkoxy substituents in palladium and nickel catalysts plays an important role on tuning polymer molecular weight, which gives the high molecular weight of 380 kg mol−1 at 80 °C in the palladium system and also provides very high catalytic activity of 16000 kg mol-1 h−1 at 70 °C in the nickel system. In ethylene copolymerization with polar monomers, the decrease of steric bulk leads to an increase on the co-monomer incorporation in the obtained copolymers. As a result, the copolymerization of ethylene with methyl acrylate, and acrylic acid using palladium catalysts affords the high incorporation of 9.5 mol% and 8.3 mol%, respectively; and the nickel promoted ethylene copolymerization with vinyl trimethoxysilane, and 6-chloro-1-hexene gives the incorporation of 3.7 mol% and 5.0 mol%, respectively.

Intermolecular C-O Bond Formation with Alkoxyl Radicals: Photoredox-Catalyzed α-Alkoxylation of Carbonyl Compounds.

Due to the high reactivity of alkoxyl (RO·) radicals and their propensity to easily undergo β-scission or Hydrogen Atom Transfer (HAT) reactions, intermolecular alkoxylations involving RO· radicals are barely described. We report herein for the first time the efficient intermolecular trapping of alkoxyl radicals by silyl enol ethers. This photoredox-mediated protocol enables the introduction of both structurally simple and more complex alkoxy groups into a wide range of ketones and amides.

An Alkoxy Modified N‐Heterocyclic Carbene‐Palladacycle: Synthesis, Characterization and Application towards Buchwald‐Hartwig and Suzuki‐Miyaura Coupling Reactions

AbstractA well‐defined N‐heterocyclic carbene‐palladacycles (NHC‐Pdcycle) by introducing alkoxy group was synthesized, and its structure was confirmed using single‐crystal X‐ray diffraction. The complex as catalyst exhibited high catalytic activity in Buchwald‐Hartwig and Suzuki‐Miyaura coupling reactions involving (hetero)aryl chlorides. Remarkably, the protocol with a wide range of substrate compatibility is suitable for the gram‐scale synthesis of Piribedil, a clinical drug for the treatment of Parkinson's disease, highlighting its potential applications in pharmaceutical synthesis.