Trimethylammonium Group Research Articles

Raman scattering-based multiconformational analysis for probing the structural differences between acetylcholine and acetylthiocholine

Acetylcholine is the first discovered neurotransmitter that has received a great attention regarding its capability of binding to several cellular targets. The chemical composition of acetylcholine, including a positively charged trimethylammonium and a carbonyl group, as well as its conformational flexibility was pointed out as the key factors in the stabilization of its interactions. Here, the possibilities offered by a Raman scattering-based multiconformatioal analysis to access the most stable conformers of acetylcholine, is discussed. To control the validity of this protocol, acetylcholine and one of its closely structured analogues, acetylthiocholine, were simultaneously analyzed. Solution Raman spectra revealed distinct and well resolved strong markers for each molecule. Density functional theory calculations were consistent with the fact that the energy order of the low energy conformers is considerably affected by the acyloxy oxygen→sulfur atom substitution. Raman spectra were calculated on the basis of the thermal average of the spectra arising from the low energy conformers. It has been evidenced that the carbonyl and trimethylammonium groups are the most favorable hydration sites in aqueous environment. Taking into account the large gap between the carbonyl bond-stretch and aliphatic bending bands, Raman spectra also allowed separation of the HOH bending vibrations arising from the bound and bulk water molecules.

Degradation of radiation grafted hydroxide anion exchange membrane immersed in neutral pH: removal of vinylbenzyl trimethylammonium hydroxide due to oxidation

Degradation tests in deionised water of radiation grafted anion exchange membranes for fuel cell/electrolyser operation showed loss of vinylbenzyl trimethylammonium groups.

Conformational flexibility and pseudosymmetric aggregation in a betainium salt hydrate

The cation of 3-(trimethylammonium)-benzoic acid exhibits a considerable conformational flexibility connected to the orientation of carboxyl group, coupled to the proton position, and rotations of the trimethylammonium group. This conformational flexibility considerably affects the aggregation of ions and molecules of 3-(trimethylammonium)-benzoic acid iodide hydrate, which crystallizes in a low-symmetry structure with four symmetry-independent formula units (monoclinic space group Pc, Z’ = 4, model I). However this structure approximates the symmetry of space group P21/c in the same unit cell (Z’ = 2, model II), and also even a still more highly symmetric structure of space group P21/c in a half-smaller unit cell (Z’ = 1, model III). The independent formula units are differentiated by the conformations of trimethylammonium groups (ordered in model I, but disordered in models II and III), conformations of the carboxyl groups and positions of OH···O bonded water molecules (ordered in molecules I and II, and disordered in model III), while the bulks of the cations and iodide anions are consistent for all models. While the calorimetric study and varied-temperature structural determinations exclude phase transitions of the highly pseudosymmetric model I. This pseudosymmetry is independent of temperature between 100 K and the m.p. at 463 K, and illustrates subtle structural effects leading complex molecular aggregation in the crystal. Theoretical computations confirm the low energy differences between the conformers.Graphical abstractᅟ

Plasmonic detection and visualization of directed adsorption of charged single nanoparticles to patterned surfaces.

It has recently been shown that surface plasmon microscopy (SPM) allows single nanoparticles (NPs) on sensor surfaces to be detected and analyzed. The authors have applied this technique to study the adsorption of single metallic and plastic NPs. Binding of gold NPs (40, 60 and 100 nm in size) and of 100 nm polystyrene NPs to gold surfaces modified by differently ω-functionalized alkyl thiols was studied first. Self-assembled monolayers (SAM) with varying terminal functions including amino, carboxy, oligo(ethylene glycol), methyl, or trimethylammonium groups were deposited on gold films to form surfaces possessing different charge and hydrophobicity. The affinity of NPs to these surfaces depends strongly on the type of coating. SAMs terminated with trimethylammonium groups and carboxy group display highly different affinity and therefore were preferred when creating patterned charged surfaces. Citrate-stabilized gold NPs and sulfate-terminated polystyrene NPs were used as negatively charged NPs, while branched polyethylenimine-coated silver NPs were used as positively charged NPs. It is shown that the charged patterned areas on the gold films are capable of selectively adsorbing oppositely charged NPs that can be detected and analyzed with an ~1 ng⋅mL−1 detection limit. Graphical abstractSelf-assembled monolayers of ω-functionalized alkyl thiols were deposited on a gold layer of a patterned sensor array. The charge-selective binding of single nanoparticles to such surfaces was registered by wide-field surface plasmon microscopy. Electronic supplementary materialThe online version of this article (doi:10.1007/s00604-016-1956-7) contains supplementary material, which is available to authorized users.

Synthesis of Anion Exchange Membranes with Side-Chain-Type Benzylic Cationic Groups Using Chloromethylbenzoylation

To circumvent the shortcomings of traditional synthetic routes relying on chloromethylation or bromination of benzylic methyl groups, a novel approach, chloromethylbenzoylation, has been proposed to synthesize commercially available poly(aryl ether)s (PAEs) with side-chain-type benzylic cationic groups for anion exchange membranes (AEMs). Previous works have demonstrated that adding alkyl side chain to PAE backbones can improve the alkaline stability of the AEMs. In this work, side-chain-type benzylchloride groups have been directly introduced onto poly resorcinol ketone (PRK) via an acylation reaction between 4-(chloromethyl)benzoic acid and PRK in P2O5/CH3SO3H at 60 oC. 1H NMR and GPC confirm that 100% substitution occurred, without side reactions such as crosslinking or degradation. Robust AEMs were then obtained through amination upon introduction of trimethylammonium (TMA+) groups. The chloride ionic conductivity of the AEM was 8.8 mS/cm at 30 °C, which is competitive with that of a commercial TokuyamaÒ A201 membrane at similar IEC values. In summary, this approach represents a simple and straightforward route capable of quantitative introduction of side-chain-type benzylchloride groups without using expensive or toxic reagents, with potential applications of the resultant AEMs in energy conversion and storage and other fields.

Reversible, partial inactivation of plant betaine aldehyde dehydrogenase by betaine aldehyde: mechanism and possible physiological implications.

In plants, the last step in the biosynthesis of the osmoprotectant glycine betaine (GB) is the NAD(+)-dependent oxidation of betaine aldehyde (BAL) catalysed by some aldehyde dehydrogenase (ALDH) 10 enzymes that exhibit betaine aldehyde dehydrogenase (BADH) activity. Given the irreversibility of the reaction, the short-term regulation of these enzymes is of great physiological relevance to avoid adverse decreases in the NAD(+):NADH ratio. In the present study, we report that the Spinacia oleracea BADH (SoBADH) is reversibly and partially inactivated by BAL in the absence of NAD(+)in a time- and concentration-dependent mode. Crystallographic evidence indicates that the non-essential Cys(450)(SoBADH numbering) forms a thiohemiacetal with BAL, totally blocking the productive binding of the aldehyde. It is of interest that, in contrast to Cys(450), the catalytic cysteine (Cys(291)) did not react with BAL in the absence of NAD(+) The trimethylammonium group of BAL binds in the same position in the inactivating or productive modes. Accordingly, BAL does not inactivate the C(450)SSoBADH mutant and the degree of inactivation of the A(441)I and A(441)C mutants corresponds to their very different abilities to bind the trimethylammonium group. Cys(450)and the neighbouring residues that participate in stabilizing the thiohemiacetal are strictly conserved in plant ALDH10 enzymes with proven or predicted BADH activity, suggesting that inactivation by BAL is their common feature. Under osmotic stress conditions, this novel partial and reversible covalent regulatory mechanism may contribute to preventing NAD(+)exhaustion, while still permitting the synthesis of high amounts of GB and avoiding the accumulation of the toxic BAL.

ARSENIC SORPTION USING MIXTURES OF ION EXCHANGE RESINS CONTAINING N-METHYL-D-GLUCAMINE AND QUATERNARY AMMONIUM GROUPS

The method of synthesis and the arsenic removal properties of ion-exchange resins based on N -methyl-D-glucamine and trimethylammonium groups are presented. The N-methyl-D-glucamine based monomer was synthesized by the reaction of 4-vinyl benzyl chloride with N-methyl-D-glucamine, along with the use of N,N -methylene- bis -acrylamide as a crosslinker reagent for polymerization. In addition, poly(4-vinylbenzyl)trimethylammonium was synthesized. Arsenate sorption studies were conducted and the pH effect, kinetics, sorption capacity, and elution performance were studied. The experimental data were fitted to kinetic models, such as the pseudo-first order and pseudo-second order models. The pseudo-second order model exhibited the best correlation with the experimental data. The Langmuir and Freundlich isotherms were fitted to the experimental data, and the Freundlich isotherm exhibited the best fit.

N,N,N′,N′,N′′-Pentamethyl-N′′-[2-(trimethylazaniumyl)ethyl]guanidinium bis(tetraphenylborate) acetone monosolvate

The asymmetric unit of the title solvated salt, C11H28N42+·2C24H20B−·C3H6O, comprises two cations, four tetraphenylborate anions and two acetone molecules. One cation shows an orientational disorder at the CN3moiety and two sets of N-atom positions were found related by a 60° rotation, with a refined occupancy ratio of 0.935 (1):0.065 (1). The respective nitrogen-bonded –CH2and –CH3groups are included in the disorder model. The C—N bond lengths in the central CN3units of both guanidinium ions range between 1.3329 (17) and 1.364 (16) Å, indicating a degree of double-bond character. The central C atom is bonded to the three N atoms in a nearly ideal trigonal–planar geometry and one positive charge is delocalized in the CN3plane. The C—N bond lengths in the terminal trimethylammonium groups have values close to a typical single bond, and the second positive charge is localized there. In the crystal, the guanidinium ions are connected by C—H...O hydrogen bonds with the acetone molecules. C—H...π interactions are present between the guanidinium and acetone hydrogen atoms and the phenyl rings of the tetraphenylborate ions, leading to the formation of a two-dimensional supramolecular pattern along thebcplane.

N,N,N′,N′-Tetramethyl-N′′-[2-(trimethylazaniumyl)ethyl]guanidinium bis(tetraphenylborate) acetone disolvate

The asymmetric unit of the title solvated salt, C10H26N42+·2C24H20B−·2C3H6O, comprises one cation, two tetraphenylborate ions and two acetone solvent molecules. The N and methyl C atoms of the terminal trimethylammonium group are disordered over two sets of sites, with a refined occupancy ratio of 0.846 (3):0.154 (3). The C—N bond lengths in the central C3N unit of the guanidinium ion range between 1.3308 (16) and 1.3508 (16) Å, indicating a degree of double-bond character. The central C atom is bonded to the three N atoms in a nearly ideal trigonal–planar geometry and the positive charge is delocalized in the CN3plane. The C—N bond lengths in the terminal trimethylammonium group have values close to that of a typical single bond, and the second positive charge is localized there. In the crystal, the guanidinium ion is connected by N—H...O and C—H...O hydrogen bonds with the acetone molecules. C—H...π interactions are present between the guanidinium H atoms and the phenyl rings of the tetraphenylborate ions, leading to the formation of a two-dimensional supramolecular pattern along thebcplane.

Effect of ammonium groups on the properties of anion conductive membranes based on partially fluorinated aromatic polymers

Anion exchange membranes based on partially fluorinated segment and oligophenylene with a variety of ammonium cations were synthesized. The copolymer with trimethylammonium groups seemed most promising in terms of the conductivity and the stability.

Cation-π Interactions Contribute to Substrate Recognition in γ-Butyrobetaine Hydroxylase Catalysis.

γ‐Butyrobetaine hydroxylase (BBOX) is a non‐heme FeII‐ and 2‐oxoglutarate‐dependent oxygenase that catalyzes the stereoselective hydroxylation of an unactivated C−H bond of γ‐butyrobetaine (γBB) in the final step of carnitine biosynthesis. BBOX contains an aromatic cage for the recognition of the positively charged trimethylammonium group of the γBB substrate. Enzyme binding and kinetic analyses on substrate analogues with P and As substituting for N in the trimethylammonium group show that the analogues are good BBOX substrates, which follow the efficiency trend N+>P+>As+. The results reveal that an uncharged carbon analogue of γBB is not a BBOX substrate, thus highlighting the importance of the energetically favorable cation–π interactions in productive substrate recognition.

Theoretical studies on the reaction of mono- and ditriflate derivatives of 1,4:3,6-dianhydro-D-mannitol with trimethylamine--Can a quaternary ammonium salt be a source of the methyl group?

DFT studies on the mechanism of the formation of "gemini" quaternary ammonium salts in the reaction of 1,4:3,6-dianhydro-D-mannitol ditriflate derivative with trimethylamine and its subsequent conversion to tertiary amine through the methyl-transfer reaction are discussed. Two alternative reaction pathways are presented in the gas phase and in ethanol. Additionally, the transformation of the monotriflate derivative of 1,4:3,6-dianhydro-D-mannitol into the single quaternary ammonium salt is presented. Two functionals (B3LYP, M062X) and two basis sets (6-31+G** and 6-311++G**) were used for the calculations. The effect of the substituent attached to the five-membered rings at the C2 (and/or C5) carbon atom on the activation barrier is described. The trimethylammonium group bond to the five-membered ring greatly reduces the activation barrier height. The preferred reaction pathway for the conversions was established. Including the London dispersion in the calculations increases the stabilization of all the points on the potential energy surface in relation to individual reactants.

Enhanced Antitumor Efficacy by 808 nm Laser‐Induced Synergistic Photothermal and Photodynamic Therapy Based on a Indocyanine‐Green‐Attached W18O49 Nanostructure

A novel nanoplatform based on tungsten oxide (W18O49, WO) and indocyanine green (ICG) for dual‐modal photothermal therapy (PTT) and photodynamic therapy (PDT) has been successfully constructed. In this design, the hierarchical unique nanorod‐bundled W18O49 nanostructures play roles in being not only as an efficient photothermal agent for PTT but also as a potential nanovehicle for ICG molecules via electrostatic adsorption after modified with trimethylammonium groups on their surface. It is found that the ability of ICG to produce cytotoxic reactive oxygen species for PDT is well maintained after being attached on the WO, thus the as‐obtained WO@ICG can achieve a synergistic effect of combined PTT and PDT under single 808 nm near‐infrared (NIR) laser excitation. Notably, compared with PTT or PDT alone, the enhanced HeLa cells lethality of the 808 nm laser triggered dual‐modal therapy is observed. The in vivo animal experiments have shown that WO@ICG has effective solid tumor ablation effect with 808 nm NIR light irradiation, revealing the potential of these nanocomposites as a NIR‐mediated dual‐modal therapeutic platform for cancer treatment.

Interaction Study of Phospholipid Membranes with an N-Glucosylated β-Turn Peptide Structure Detecting Autoantibodies Biomarkers of Multiple Sclerosis.

The interaction of lipid environments with the type I’ β-turn peptide structure called CSF114 and its N-glucosylated form CSF114(Glc), previously developed as a synthetic antigenic probe recognizing specific autoantibodies in a subpopulation of multiple sclerosis patients’ serum, was investigated by fluorescence spectroscopy and electrochemical experiments using large unilamellar vesicles, mercury supported lipid self-assembled monolayers (SAMs) and tethered bilayer lipid membranes (tBLMs). The synthetic antigenic probe N-glucosylated peptide CSF114(Glc) and its unglucosylated form interact with the polar heads of lipid SAMs of dioleoylphosphatidylcholine at nonzero transmembrane potentials, probably establishing a dual electrostatic interaction of the trimethylammonium and phosphate groups of the phosphatidylcholine polar head with the Glu5 and His9 residues on the opposite ends of the CSF114(Glc) β-turn encompassing residues 6-9. His9 protonation at pH 7 eliminates this dual interaction. CSF114(Glc) is adsorbed on top of SAMs of mixtures of dioleoylphosphatidylcholine with sphingomyelin, an important component of myelin, whose proteins are hypothesized to undergo an aberrant N-glucosylation triggering the autoimmune response. Incorporation of the type I’ β-turn peptide structure CSF114 into lipid SAMs by potential scans of electrochemical impedance spectroscopy induces defects causing a slight permeabilization toward cadmium ions. The N-glucopeptide CSF114(Glc) does not affect tBLMs to a detectable extent.

Removal of micro-stickies from model wastewaters of the paper industry by amphiphilic starch derivatives

Abstract Biologically degradable polymers based on renewable raw materials, such as polysaccharides, represent promising alternatives to synthetic polymers used as flocculants or stabilizing agents. Polysaccharides derived from potato starch have been modified with benzyl- and additionally cationic hydroxypropyl trimethyl ammonium groups of different degrees of substitution (DS). In this work these amphiphilic starch derivatives have been used to remove substances which impact negatively the paper production process when using recycled paper, so called stickies. Model suspensions have been studied using a multitude of different measurement techniques with the aim to predict a “sticky potential” and to reduce dissolved and colloidal substances such as micro-stickies. Systematic experiments studying the interactions between the novel amphiphilic starch derivatives and the model suspension have shown that dynamic surface tension is a very suitable property to characterize the surface active compounds in the model suspension giving additional information about the sticky potential of waste water, e.g. white water and offering a new and sensitive way to describe the parameter “hydrophobicity”. Moderately cationic and hydrophobic starch derivatives proved to be the most effective ones for sticky removal.

Synthesis and study of the complex formation of a cationic alkyl-chain bola amino alcohol with DNA: in vitro transfection efficiency

Recent studies point out that bolaamphiphiles can be used in nonviral gene therapy. Due to their bipolar character, they may span a membrane and thus stabilize or destabilize it which could be relevant for DNA transfer across a biological membrane. Since there are only very few studies on bolaamphiphile application in DNA transfection, it is difficult to assess whether they will bring additional advantages to the class of nonviral vectors. A bolaamphiphile with a hydrophobic chain of 22 carbon atoms with trimethylammonium and hydroxyl groups at each end was synthesized (22-hydroxydocos-1-yl-N,N,N-trimethylammonium bromide). The bolaamphiphile conferred stability and lowered the zeta potential of vesicles of a cationic lipid. Confocal laser scanning microscopy and flow cytometry experiments have shown that this bolaamphiphile can transfect the green fluorescent protein plasmid in cells if mixed with a cationic lipid. It can compete with standard cationic lipids in terms of transfection but is at the same time less toxic. The potential of this class of molecules in gene delivery results from the fact that they will confer high stability to the DNA vector.

Mechanically Stable Poly(aryl ether) Anion Exchange Membranes for Alkaline Applications

The alkaline stability of poly(aryl ether) backbones in anion exchange polymer electrolyte membranes (AEMs) featuring quaternary benzyl N, N- dimethylhexylammmonium (DMH+) and trimethylammonium (TMA+) groups were investigated in poly(2,6-dimethyl 1,4-phenylene) oxide (PPO) and Udel® polysulfone (PSF) polymers. Previous works have demonstrated that quaternary ammonium and phosphonium groups trigger polymer backbone degradation in commercially available poly(aryl ethers) despite the non-cation functionalized polymers being resilient in alkaline media. Recently, DMH+ cations in PPO was shown to eliminate cation triggered backbone degradation, but it was unknown whether or not implementation of this cation would also eliminate cation triggered backbone degradation in PSF. Herein, we demonstrate that the electron withdrawing or donating character in the poly(aryl ether) backbone, ultimately decides whether or not the prepared AEMs will become brittle in alkaline media. For instance, DMH+ at the benzyl position in Udel® PSF does not mitigate cation triggered backbone degradation. PPO backbones functionalized with bromine at the aryl position in addition to having DMH+ cations did not prevent cation triggered backbone degradation either. Mitigation of cation triggered backbone degradation was only achieved when electron withdrawing substituents (not including the cation), such as sulfone or bromine, were not incorporated in the polymer backbone. PPO AEMs prepared through chloromethylation, rather than free radical bromination, were resistant to backbone hydrolysis in alkaline media because each cation functionalized repeat unit had two electron donating methyl groups rather than a single methyl group. In closing, some design rules will be presented for preparing mechanically stable poly(aryl ether) AEMs from low cost, commercially available polymers for alkaline applications.

Charge-controlled nanoprecipitation as a modular approach to ultrasmall polymer nanocarriers: making bright and stable nanoparticles.

Ultrasmall polymer nanoparticles are rapidly gaining importance as nanocarriers for drugs and contrast agents. Here, a straightforward modular approach to efficiently loaded and stable sub-20-nm polymer particles is developed. In order to obtain ultrasmall polymer nanoparticles, we investigated the influence of one to two charged groups per polymer chain on the size of particles obtained by nanoprecipitation. Negatively charged carboxylate and sulfonate or positively charged trimethylammonium groups were introduced into the polymers poly(d,l-lactide-co-glycolide) (PLGA), polycaprolactone (PCL), and poly(methyl methacrylate) (PMMA). According to dynamic light scattering, atomic force and electron microscopy, the presence of one to two charged groups per polymer chain can strongly reduce the size of polymer nanoparticles made by nanoprecipitation. The particle size can be further decreased to less than 15 nm by decreasing the concentration of polymer in the solvent used for nanoprecipitation. We then show that even very small nanocarriers of 15 nm size preserve the capacity to encapsulate large amounts of ionic dyes with bulky counterions at efficiencies >90%, which generates polymer nanoparticles 10-fold brighter than quantum dots of the same size. Postmodification of their surface with the PEG containing amphiphiles Tween 80 and pluronic F-127 led to particles that were stable under physiological conditions and in the presence of 10% fetal bovine serum. This modular route could become a general method for the preparation of ultrasmall polymer nanoparticles as nanocarriers of contrast agents and drugs.

Synthesis of guanidinylated chitosan with the aid of multiple protecting groups and investigation of antibacterial activity

A new synthetic approach employing two types of protecting groups, tertiarybutyldimethylsilyl (TBDMS) and tertiarybutyloxycarbonyl (Boc) was developed to obtain a series of guanidinylated chitosan derivatives. The synthesis was carried out in organic solvents which allowed quantitative reaction, a good control on the degree of substitution, and 100% substitution of the chitosan amino groups. Similar derivatives carrying the trimethylammonium group were also synthesized as reference compounds. All the derivatives were characterized using 1H and COSY NMR and IR spectroscopy. The antibacterial effect against clinically relevant strains of S. aureus and E. coli was found to increase with increase in the degree of substitution and decrease in the spacer length of the derivatives in both the series. An optimum activity could be obtained at a degree of substitution above 0.5 for most derivatives. The trimethylammonium derivatives showed slightly higher activity than the corresponding guanidinium derivatives but a similar structure–activity relationship was obtained.

Novel Anion Exchangers with Spatially Distant Trimethylammonium Groups in Linear and Branched Hydrophilic Functional Layers

Novel polystyrene–divinylbenzene (PS-DVB) based anion exchangers having branched structure of ion exchange functional groups are prepared and characterised. Two proposed synthetic methods include acylation of PS-DVB microspherical particles followed by reductive amination with dimethylamine or methylamine, which results in obtaining tertiary or secondary amino groups on the surface, respectively. Further alkylation of amino groups was provided by reaction with either (3-chloro-2-hydroxypropyl)trimethylammonium chloride or glycidyltrimethylammonium chloride, which allowed the simultaneous insertion of trimethylammonium functional group and hydrophilic spacer into the structure. The other considered option is reaction with diglycidyl ethers, which requires further amination of terminal epoxide rings with trimethylamine. The proposed approaches resulted in preparation of the ion exchangers with extended linear or branched anion exchange structure with trimethylammonium groups located at a distance from the surface and connected via hydrophilic linkers. The ion exchange selectivity and separation efficiency of obtained anion exchangers are studied for the model mixture of inorganic anions (F−, HCOO−, Cl−, NO2−, Br−, NO3−, H\( {\text{PO}}_{ 4}^{2 - } \) and \( {\text{SO}}_{4}^{ 2- } \)) using hydroxide eluents. The adsorbents with branched ion exchange layer having three positively charged sites in the structure of attached groups demonstrate superior column efficiencies and better peak symmetry as compared with anion exchanger having linear structure with two positively charged sites in the chain. In case of branched anion exchangers the calculated values of column efficiencies for polarisable NO3− and Br− are 44,000 and 50,000 N/m, respectively, and significantly higher than 7,000 and 8,000 N/m obtained for anion exchanger with linear structure of the ion exchange layer.