Chloromethyl Research Articles

Fabrication of charged and zwitterionic nanofiltration membranes and anti-adhesion analysis using quartz crystal microbalance with dissipation and atomic force microscopy

Three nanofiltration (NF) membranes (positive charge, negative charge and near charge neutrality) were fabricated to investigate the anti-adhesion mechanism. Among them, the NF membrane with positive charge was synthesized through an electrophilic substitution reaction between the amino group of polyethyleneimine (PEI) and the chloromethyl groups of chloromethyl polysulfone (CMPSf) on a supporting polysulfone (PSf)/CMPSf blend membrane. The NF membrane with negative charge was fabricated through polycondensation using 1, 3, 5-benzenetricarbonyl trichloride (TMC) as a reactive monomer on the positive charge NF membrane. Subsequently, the near charge neutral zwitterion NF membrane (ZNF) was prepared by grafting 3-((2-aminoethyl) dimethylammonio) propane-1-sulfonate (sulfobetaine) (ADSS) onto the negative charge NF membrane. The anti-adhesion behaviors of the NF membranes during the dye selective separation were analyzed by Atomic force microscopy (AFM) and quartz crystal microbalance with dissipation (QCM-D). The results demonstrated that the near charge neutral ZNF membrane displayed a higher dyes rejection (>94.4 %) and higher flux recovery rates (>88.1 %) than charged NF membranes. Meanwhile, the near charge neutral ZNF membrane demonstrated the lowest amounts of dye deposition compared with charged NF membranes, such as reactive blue 4 (R4) for 509.9 ng/cm2, basic blue 24 (BB 24) for 269.0 ng/cm2, rhodamine B (RB) for 197.4 ng/cm2). Additionally, the near charge neutral ZNF membrane with the thicker hydration layer (121.7 nm) displayed weaker interaction forces (−4.8 nN to −7.4 nN) with the dyes than the charged membranes (−10.4 nN to −28.6 nN). Finally, an anti-adhesion mechanism involved charged shielding effect and hydration layer formation was proposed. These observations provide comprehensive insights into the anti-adhesion mechanism of ZNF membrane.

Homopolymerization of substituted styrenes and their copolymerization with carbon monoxide catalyzed by iminopyridine palladium catalyst

Homopolymerization of styrenic monomer featuring different functional group and their copolymerization with carbon monoxide were investigated by imine-pyridine palladium complex with the assistance of AgSbF6. Poly(4-vinylbenzyl chloride) and poly(4-N,N-dimethylaminostyrene) were produced probably according to coordination-insertion mechanism. In the presence of carbon monoxide, substituted styrenes except for the 4-N,N-dimethylaminostyrene were copolymerized with CO to yield polyketones by the same catalysts. Thus, polyketones featuring chloromethyl group, diphenylaminomethyl group and quaternary ammonium salt were produced for the first time by direct alternating copolymerization. DSC results disclosed that glass transition temperature of the resulting polyketones was significantly affected by the substituents. The Tg of polyketone featuring quaternary ammonium salt was 160 °C.

Two New Polymorphs of Meso-Chlorinated BODIPY Dyes

New polymorphs of (2-(chloro(pyrrol-2-ylidene)methyl)pyrrole)-difluoro-borane (1) and (2-(chloro(4-ethyl-3,5-dimethyl-2H-pyrrol-2-ylidene)methyl)pyrrole)-4-ethyl-3,5-dimethyl-1H-pyrrolato)-difluoro-borane (2) were identified using single crystal X-ray diffraction. The new polymorph of 1 crystallises in the triclinic, P-1 space group with an asymmetric unit comprising two crystallographically-independent molecules (Z′ = 2). The differences between this structure and that of the known polymorph of 1 are attributed to the formation of two distinct dimer motifs in each polymorph and the packing between these dimer units. The new polymorph structure of 2, exhibits a similar asymmetric unit to the known form, comprising 3 molecules (Zʹ = 3). The two structures differ in the orientation of the molecules within the trimeric asymmetric unit and the manner in which these trimers pack along the crystallographic [010] direction.Graphical The triclinic polymorph of 8-chloro BODIPY exhibits an asymmetric unit with two crystallographically-independent molecules.

Controllable synthesis of naphthalene-derived isotropic pitch with linear molecular structure via Blanc chloromethylation–dechlorination reaction

Isotropic pitches with high softening points were controllably synthesized using naphthalene (NAP) via Blanc chloromethylation–dechlorination. Under mild conditions, chloromethyl was introduced into the NAP ring in the presence of chloromethylation reagent. The chloromethylation products of NAP are mainly composed of 1-chloromethylnaphthalene (1-CMNP) and a small amount of 1,4-dichloromethylnaphthalene (1,4-DCMNP). The results of the thermodynamic and kinetic calculations confirmed that the alpha-hydrogen on the NAP ring was more susceptible to being substituted by chloromethyl during chloromethylation, resulting in the formation of 1-CMNP and 1,4-DCMNP. High-quality isotropic pitches with linear methylene-bridged NAP ring structures, characterized by high purity, a high H/C ratio, 100 % solubility in quinoline, and excellent spinnability, were obtained after thermal dechlorination polymerization. Due to their homogeneous isotropic phase, appropriate viscosity, and outstanding spinnability, the as-synthesized pitches were adopted as precursors to prepare isotropic pitch-based carbon fibers via melt spinning. Additionally, the investigation of the carbonization behavior of the as-synthesized pitches showed that the naphthalene-derived isotropic pitch obtained at a polymerization temperature of 380 °C had a 57 % carbon yield at 800 °C, and its derived semi-cokes displayed an isotropic texture, even when carbonized at 550 °C.

Rotational spectrum, structure, and quadrupole coupling of cyclopropylchloromethyldifluorosilane.

Cyclopropylchloromethyldifluorosilane, c-C3H5SiF2CH2Cl, has been synthesized, and its rotational spectrum has been recorded by chirped-pulse Fourier transform microwave spectroscopy. The spectral analysis of several isotopologues indicates the presence of two distinct conformations in the free-jet expansion, which are interconvertible through a rotation of the chloromethyl group. A partial substitution structure is presented for the lower energy conformation and is compared to the equilibrium structure obtained from quantum chemical calculations. Additionally, the presence of the chlorine nucleus leads to the rotational transitions splitting into multiple hyperfine components and χaa, a measure of the electric field gradient along the a axis, is unusually small at merely +0.1393(73) MHz. Various common abinitio and density functional theory methods fail to predict good quadrupole coupling constants (in the principal axis system) that adequately reproduce the observed hyperfine splitting, although diagonalizing the quadrupole coupling tensor from the principal axis system into a nucleus-centered axis system reveals that, overall, these methods calculate reasonably the electric field gradient about the chlorine nucleus. Finally, a total of nine electric dipole forbidden, quadrupole allowed transitions are observed in the rotational spectra of the parent species of the higher energy conformation and the 37Cl isotopologue of the lower energy conformation. These include those of x-type (no change in parity of Ka or Kc), which, to our knowledge, is the first time such transitions have been observed in a chlorine-containing molecule.

Covalently crosslinked poly(biphenyl dimethylamino benzene) membranes for high temperature proton exchange membrane fuel cells

The electrolyte membrane plays a pivotal role in high temperature proton exchange membrane fuel cells (HT-PEMFCs). Herein, we develops a new triarylmethane-backboned polymer, poly (biphenyl dimethylamino benzene) (PBDAB), synthesized through a facile one-step Friedel-Crafts reaction using biphenyl and 4-(dimethylamino) benzaldehyde as monomers. The presence of tertiary amine groups in PBDAB facilitates strong interactions with phosphoric acid (PA) molecules. To enhance the membrane's dimensional and mechanical stabilities, covalent crosslinking is performed via the Menshutkin reaction between the tertiary amine groups in PBDAB and chloromethyl groups in various crosslinkers. In order to study the influence of crosslinker chemical structure on the properties of PBDAB-based membranes, five different crosslinkers are employed, including small-molecule types such as 1,2-bis(2-chloroethoxy) ethane (BCE) and 1,4-bis(chloromethyl) benzene (BCB), siloxane type 3-chloropropyl (trimethoxy) silane (CTS), polymer types such as poly (vinylbenzyl chloride) (PVBC) and polyepichlorohydrin (PECH). Results reveal that the flexible and ether containing polymer crosslinker of PECH crosslinked membrane, denoted as CL-y%PECH, exhibits superior overall performance. When doped in an 85 wt% PA solution, the CL-5%PECH membrane achieves a PA uptake of 201%, resulting in an anhydrous proton conductivity of 0.064 S cm−1 at 180 °C and a mechanical strength of 7.2 MPa at room temperature. Using H2 and O2 as fed gases without humidification and backpressure, a single cell with abovementioned membrane attains a peak power density of 302 mW cm−2 at 160 °C. This work offers a kind of promising PBDAB based membranes for HT-PEMFC applications.

Pairs of thiol-substituted 1,2,4-triazole-based isomeric covalent inhibitors with tunable reactivity and selectivity

Covalent bioactive compounds are successfully used in clinic and attracted intense research efforts in the fundamental study as well as drug development. The advantageous effects of covalent compounds compared with non-covalent ones are highly dependent on electrophilic warheads. Hence, electrophilic warheads with tunable reactivity and selectivity are highly demanded in fields of medicinal chemistry and chemical biology. Herein, we report a novel electrophilic warhead, chloromethyl group activated by thiol-substituted 1,2,4-triazole. Interestingly, a pair of regioisomers could be simultaneously occurred in the step of alkylation during the synthesis of this unique motif. This is a rare example that the alkylation could simultaneously generate these two separable regioisomers of 1,2,4-triazole at the nitrogen or sulfur atom. The covalent-working mechanism of this new warhead is confirmed by various chemoproteomics experiments including target identification and binding site mapping. Importantly, the reactivity and selectivity of this new electrophilic warhead could be efficiently tuned by virtue of stereo effect. Interestingly, one pair of regioisomers (19S and 19X) induced distinct modes of cell death. Isomer 19S could induce apoptosis of colon cancer cells while 19X could induce both apoptosis and ferroptosis. Together, this study provides pairs of novel electrophilic warheads that could be useful not only in supporting the design of covalent compounds for drug discovery but also in providing chemical probes for the fundamental biological study.

Evidence for Reactivity of Decamethylcobaltocene with Dichloromethane

Decamethylcobaltocene (Cp*2Co) is commonly encountered in organometallic chemistry, where it is often used as a one-electron reductant under inert atmosphere and considered to be a stable metallocene in both its reduced [CoII] and oxidized [CoIII] forms. Here, we report that Cp*2Co is not stable in dichloromethane (CH2Cl2), a finding that contrasts markedly with the robustness of this compound in other solvents used for redox chemistry, such as neat acetonitrile (CH3CN). Parallel chemical and electrochemical studies show that when Cp*2Co comes into contact with CH2Cl2, both [Cp*2Co]+ (A) and Cp*Co(η4-C5Me5CH2Cl) (B), a species in which a chloromethyl group has been added to one Cp* ring, are generated. B subsequently undergoes a ring-expanding rearrangement if exposed to MeOH, yielding Cp*Co(η5-C6Me5CH2) (C) that is detectable by mass spectrometry (MS). [Cp*Co]3(μ3-CH)2 (D) could also be detected by MS, adding to the array of products arising from Cp*2Co that do not maintain the expected metallocene motif. Taken together, these findings suggest that Cp*2Co should be used with caution in CH2Cl2, particularly in cases in which one-electron transfer and/or clean reactivity are desired.

A new hydrocyanine probe for imaging reactive oxygen species in the mitochondria of live cells

A new hydrocyanine probe containing a ROS-responsive element and a mitochondrial-targeting moiety, as well as a thiol-reactive chloromethyl group, has been designed for imaging reactive oxygen species (ROS) in the mitochondria of live cells. This hydrocyanine probe is cell-permeable, selectively targets mitochondria and responds to superoxide and hydroxyl radical, and can be used for detection of ROS production in the mitochondria of live cells caused by an oxidative stress.

High‐Permittivity Polysiloxanes for Solvent‐Free Fabrication of Dielectric Elastomer Actuators

AbstractDielectric elastomer actuators (DEAs) are a class of soft transducers with broad potential applications in soft robotics. DEAs consist of two stretchable electrodes on a dielectric elastomer, which deform and generate force when charged. The generated force is increased by placing many DEAs on top of one another to form a stack actuator. Next‐generation stack actuators require high permittivity inks that are solvent‐free processable and cross‐linkable into thin elastic films. Here, a process toward elastomers with tuneable permittivity that can be prepared solvent‐free is reported. Polycondensation of chlorosilanes yields polymers with vinyl end‐groups and cross‐linkers with multiple hydrosilane groups that both carry polar chloromethyl groups. Their dielectric permittivity and mechanical properties are tuned by changing the polar group content and the molar mass of the vinyl‐terminated polymer, respectively. Solvent‐free doctor blading provides thin films, which are cross‐linked by heating. DEAs prepared from the films reach a lateral actuation of promising 4.6% at a low electric field of 11.2 V µm‐1 and can be operated at frequencies up to 5 Hz. The high‐permittivity polymer ink is used in a solvent‐free layer‐by‐layer stack actuator fabrication, which yields an actuator with three active layers that gives a thickness strain of 1.0% at 12.4 V µm‐1.

Further Development of Polyepichlorohydrin Based Anion Exchange Membranes for Reverse Electrodialysis by Tuning Cast Solution Properties.

Recently, there have been several studies done regarding anion exchange membranes (AEMs) based on polyepichlorohydrin (PECH), an attractive polymer enabling safe membrane fabrication due to its inherent chloromethyl groups. However, there are still undiscovered properties of these membranes emerging from different compositions of cast solutions. Thus, it is vital to explore new membrane properties for sustainable energy generation by reverse electrodialysis (RED). In this study, the cast solution composition was easily tuned by varying the ratio of active polymer (i.e., blend ratio) and quaternary agent (i.e., excess diamine ratio) in the range of 1.07-2.00, and 1.00-4.00, respectively. The membrane synthesized with excess diamine ratio of 4.00 and blend ratio of 1.07 provided the best results in terms of ion exchange capacity, 3.47 mmol/g, with satisfactory conductive properties (area resistance: 2.4 Ω·cm2, electrical conductivity: 6.44 mS/cm) and high hydrophilicity. RED tests were performed by AEMs coupled with the commercially available Neosepta CMX cation exchange membrane (CEMs).

Noscapine-Amino Acid Conjugates Suppress the Progression of Cancer Cells.

Lung cancer is the leading cause of cancer deaths globally; 1 in 16 people are diagnosed with lung cancer in their lifetime. Microtubules, a critical cytoskeletal assembly, have an essential role in cell division. Interference with the microtubule assembly leads to genetic instability during mitosis and cancer cell death. Currently, available antimitotic drugs such as vincas and taxanes are limited due to side effects such as alopecia, myelosuppression, and drug resistance. Noscapine, an opium alkaloid, is a tubulin-binding agent and can alter the microtubule assembly, causing cancer cell death. Amino acids are fundamental building blocks for protein synthesis, making them essential for the biosynthesis of cancer cells. However, the ability of amino acids in drug transportation has yet to be exploited in developing noscapine analogues as a potential drug candidate for cancer. Hence, in the present study, we have explored the ninth position of noscapine by introducing a hydroxymethylene group using the Blanc reaction and further coupled it with a series of amino acids to construct five target conjugates in good yields. The synthesized amino acid conjugate molecules were biologically evaluated against the A549 lung cancer cell line, among which the noscapine-tryptophan conjugate showed IC50 = 32 μM, as compared to noscapine alone (IC50 = 73 μM). Morphological changes in cancer cells, cell cycle arrest in the G1 phase, and ethidium bromide/acridine orange staining indicated promising anticancer properties. Molecular docking confirmed strong binding to tubulin, with a score of -41.47 kJ/mol with all 3D coordinates and significant involvement of molecular forces, including the hydrogen bonds and hydrophobic interactions. Molecular dynamics simulations demonstrated a stable binding of noscapine-tryptophan conjugate for a prolonged time (100 ns) with the involvement of free energy through the reaction coordinates analyses, solving the bioavailability of parent noscapine to the body.

Experimental (Raman and IR) and computational (DFT, MP2) studies of the conformational diversity of 1-chloromethyl-1-fluorosilacyclopentane molecule

1-chloromethyl-1-fluorosilacyclopentane (1-ClM-1-FSiCP) was synthesized for the first time and investigated by means of vibrational spectroscopy and theoretical calculations. FT-IR and Raman spectroscopic methods were implemented to collect vibrational spectra of 1-ClM-1-FSiCP. The conformational analysis was performed utilizing FT-IR matrix isolation technique and theoretical methods such as density functional theory and ab initio calculations. The spectra of the 1-ClM-1-FSiCP isolated in the argon and nitrogen matrices, were collected before and after the annealing process. During the conformational analysis the envelope (E) and twisted (T) ring shapes with the position of the fluorine atom and chloromethyl group in terms of axial/equatorial and cis/trans/gauche-/gauche+ positions were investigated utilizing MP2/aug-cc-pVTZ and DFT/B3LYP/aug-cc-pVTZ level of theory. Results indicate three stable conformers: twisted trans (global energy minimum), twisted gauche– and twisted gauche+. The potential energy surface scans were performed to trace the energy changes and the presence of transition state structures during ring conversion and rotation of the CH2Cl group.

The Bifunctional Silyl Reagent Me2(CH2Cl)SiCF3 Enables Highly Enantioselective Ketone Trifluoromethylation and Related Tandem Processes

AbstractWe report the development of bifunctional trifluoromethylsilyl reagents for selective trifluoromethylation. The newly developed reagent, Me2(CH2Cl)SiCF3, allows highly enantioselective trifluoromethylations of ketones with broad scope. Notably, by taking advantage of the chloromethyl group, a tandem synthesis of chiral trifluoromethylated oxasilacyclopentanes is developed, paving way to α‐CF3 tertiary alcohols with vicinal tertiary or quaternary stereocenters. Theoretical studies revealed the important role of nonclassical C−H⋅⋅⋅F−C interactions in stabilizing the transition state, and that the presence of the chlorine atom enhances such interactions for better enantiofacial control.

The Bifunctional Silyl Reagent Me2 (CH2 Cl)SiCF3 Enables Highly Enantioselective Ketone Trifluoromethylation and Related Tandem Processes.

We report the development of bifunctional trifluoromethylsilyl reagents for selective trifluoromethylation. The newly developed reagent, Me2 (CH2 Cl)SiCF3 , allows highly enantioselective trifluoromethylations of ketones with broad scope. Notably, by taking advantage of the chloromethyl group, a tandem synthesis of chiral trifluoromethylated oxasilacyclopentanes is developed, paving way to α-CF3 tertiary alcohols with vicinal tertiary or quaternary stereocenters. Theoretical studies revealed the important role of nonclassical C-H⋅⋅⋅F-C interactions in stabilizing the transition state, and that the presence of the chlorine atom enhances such interactions for better enantiofacial control.

Synthesis and Characterization of Anthraquinone Analog and Studies on its bioassay

The current study concerns with the synthesis of anthraquinone analogs involving the reaction of 2- chloro 5-amino anthraquinone and methylation. Toluene and potassium carbonate (K2CO3) were used to obtain the target molecule (TM). The obtained products were colorless crystals. The yield of the product was found to be ~ 81%. The product so obtained was characterized by IR and 1H NMR. Finally, these molecules were found to exhibit antiinflammatory and anti-oxidant property.

Synthesis of Inherently Fluorescent Core–Shell Nanoparticles for Cell Imaging and Targeting Therapy: An In Vitro Evaluation

AbstractFluorescent polymer nanoparticles (NPs) have great potential as bioimaging and therapeutic agents in the biomedical field. Here, a subtle method is developed to synthesize inherently fluorescent core–shell NPs with diameters less than 100 nm. The permanent fluorescence comes from the rigid conjugated structure between benzene and chloromethyl groups in the crosslinked poly(chloromethylstyrene) (PCMSt) core, which is able to be applied for the determination of Fe3+ with a detection limit of 1.39 × 10−6 m. It is further demonstrated that the galactose modification (poly (6‐O‐acryloyl‐d‐galactose), PADGal) shell can efficiently· facilitate the selective internalization of NPs by human hepatocellular carcinoma cells (HepG2), and the cells are more prone to uptake the NPs with medium crosslinking degree. The hydrophobic anticancer drug 10‐hydroxycamptothecin (HCPT) is then loaded onto PADGal@PCMSt NPs. Benefiting from the specific interactions between asialoglycoprotein (ASGP) receptors and the galactose moiety, the PADGal@PCMSt NPs can deliver HCPT with the highest efficiency to HepG2 cells in comparison with the human cervical cancer cells (HeLa), the human alveolar adenocarcinoma basal epithelial cells (A549), the mouse breast cancer cells (4T1), and the mouse fibroblast cells (NIH3T3). The present study provides a new strategy to build small‐size fluorescent polymer NPs with both bioimaging and therapeutic functions.

Synthesis Docking Studies and Antitubercular Activity of Ofloxacin Scaffold using Blanc Reaction

Synthesis, molecular docking and characterization of ofloxacin derivatives and in vitro evaluation for their antitubercular action were carried out. Synthesis ofloxacin derivatives viz. O+TRI, O+MEL, O+NAP, O+SUL, O+METF, O+IBU, O+ASP, O+DNP, O+SSA, O+PH, O+MC (where TRI = trimethoprim, MEL = meloxicam, NAP = naproxen, SUL = sulfamethoxazole, METF = metformin, IBU = ibuprofen, ASP = aspirin, DNP = 2,4-dinitrophenyl hydrazine, SSA = 5-sulpho salicylic acid, PH = phenyl hydrazine, MC = 7-hydroxy-4-methyl coumarin) were carried using Blanc reaction and purified by using of ethanol by recrystallization. The reaction products consist of methylene group linkage between two moieties and the molecules were characterized by analytical methods TLC, solubility, melting point, spectroscopic methods (FT-IR, mass and 1H NMR, 13C NMR). In silico methods were adopted for synthetic derivatives by Autodock vina software. Determined physico-chemical parameters (in silico studies) and docking studies have been performed using protein (5BS8) with designed ligands, binding energy scores were noted for different derivatives. Derivatives O+TRI, O+NAP shown good activity at 0.8 μg/mL. In docking studies, all the compounds shown promising results when compared to standard drugs.

Activation of Dichloromethane by a Bis-NHC Cp*Ru Complex: Formation of a Pentamethyl(chloromethyl)cyclopentadiene Ligand

The dinitrogen complex [{Cp*Ru(L)}2(μ-N2)][BPh4]2 (L = bis(3-methylimidazol-2-ylidene) reacts with dichloromethane at room temperature, furnishing the diene derivative [Ru(η4, κ1-Cl-C5Me5CH2Cl)Cl(L)][BPh4] as result of CH2Cl2 oxidative addition and subsequent migration of the chloromethyl group into the Cp* ring. Mechanistic insight provided by DFT computations indicate that while the cleavage of the C–Cl bond is not thermodynamically favored, the subsequent migration step is largely exergonic and thus provides the driving force for the formation of the observed product.

Synthesis and Applications of Polymeric Reagent p-Substituted Triphenylamine

Chemical modification of chloromethylstyrene - styrene copolymer throughout reaction of p-substituted carboxylic acid group of bis-(4,4`-dibromo)-4``-triphenylamine carboxylic acid with the chloromethyl group attached to a phenyl group was carried out on soluble copolymer and polymeric cross-linked copolymer. Chemical oxidation of the neutral p-substituted triphenylamine with antimony pentachloride in dichloromethane solvent gives the corresponding cation - radical salt with the counter ion antimony hexachloride (SbCl6-). The isolated deep blue color cation radical salt is soluble or in insoluble (resin) form in the copolymer was used as a thermal cationic initiator for the polymerization of epoxy and vinyl monomers at room temperature. The cation radical resin showed good activity and stability compared to the soluble polymeric cation radical, both can initiate the cationic polymerization of cyclohexene oxide and N-vinylcarbazole in dichloromethane at room temperature.