Quaternary Ammonium Molecules Research Articles

In-situ synthesis of quaternary alkylammonium ligand capped organic-inorganic hybrid halide perovskite for high pure green luminescence in display application

This study delves into the intricate dynamics of ligand engineering for the synthesis of Methyl Ammonium Lead Bromide (MAPbBr3) nanocrystals (NCs), which exhibit immense potential in optoelectronic and photovoltaic applications. Our focus centres on the role of the quaternary ammonium molecule CTAB as a ligand in stabilizing MAPbBr3 NCs. This also addresses the challenges related to the stability and surface defects of NCs that hinder their commercial viability. Employing a modified ligand-assisted reprecipitation technique (LARP) with a dual solvent system, we optimized the CTAB concentration to 0.05 mmol, resulting in MAPbBr3 NCs with an impressive 88% quantum yield. XPS and FTIR analyses confirm the presence and binding of CTAB on the NC surface. The MAPbBr3-CTAB NCs exhibit higher exciton–phonon binding energy, enhancing their optical properties. Despite an unfavourable geometric fit, CTAB is effective in surface defect passivation due to its binding, solvation, and desorption energy during the dynamic binding process. 2D-DOSY NMR reveals approximately 66% CTAB bound to the NC surface. A comparative study involving MAPbBr3-OA, OLA, and MAPbBr3-CTAB deposited on LEDs demonstrates the superior performance of the latter, achieving a luminous efficiency of 42.18 lm W−1 at 1.2 ml deposition. These findings highlight the efficacy of CTAB in achieving high-purity green luminescence, aligning with BT.2020 display colour standards and paving the way for advanced optoelectronic applications. The successful synthesis and improved performance of MAPbBr3-CTAB NCs underscore their potential as a promising material for future optoelectronic and photovoltaic technologies.

Advancements in developing biomaterials for 3D printing photosensitive resins containing quaternary ammonium molecules for enhanced oral healthcare

In this study, we investigated the development of biomaterials tailored for UV-cured 3D printing technology in oral healthcare. Traditionally, 3D-printed oral healthcare products have exhibited imperfections in antimicrobial and anti-pollution properties, limiting their utility. To address this challenge, we synthesised antimicrobial agents incorporating quaternary ammonium groups through a combination of isophorone diisocyanate (IPDI), hydroxyethyl methacrylate (HEMA), and choline chloride. These agents were then blended with diluents, resins, and photoinitiators to create raw materials suitable for UV-curing 3D printing photosensitive resins. Subsequently, the resins were subjected to digital light processing (DLP) 3D printing for curing. The resulting 3D-printed material underwent rigorous mechanical and antimicrobial testing. Our findings demonstrate that the 3D printed compounds, cured through this process, exhibited exceptional hardness, tensile properties, antimicrobial characteristics, and long-lasting antimicrobial durability. These developments promise widespread adoption and application within the oral healthcare field.

Tunable functionalization of poly(ethylene terephthalate) with short-chained quaternary ammonium salt and N-chloramine to enhance conversion of N-H to N-Cl and the antibacterial activity of the resulting N-Cl

Cross-contamination mediated by fomites such as textiles has been identified as one of the major pathways of infectious disease transmission. It is therefore critical to endow those substrates with rechargeable potent antimicrobial activity. N -chloramines, compounds with N-Cl bonds, are a typical group of broad-spectrum effective antimicrobials. Once immobilized onto a substrate, N -chloramines can attain repeated cycles of killing pathogens (loss of active chlorine) and regeneration (recovery of the original N -chloramine structure). However, relatively high levels of free chlorine are needed to recharge the biocidal function on N -chloramine containing textile substrates especially on such hydrophobic ones such as poly(ethylene terephthalate) (PET). We found the introduction of a short-chained quaternary ammonium group to N -chloramines could lead to higher conversion rate of surface bound N-H to N-Cl. Here, we separately clicked an azido N -chloramine precursor (AzH) and a short chain QAS (AzQAS) onto a previously established clickable PET platform to explore the effect of such surface bound QAS on the conversion of surface N-H to N-Cl and the antibacterial activity of the resulting N-Cl. Despite not being covalently bonded to hydantoin, the source of a cyclic N-H, the positive charge center dramatically facilitates the conversion of the hydantoin N-H to N -chloramine in dilute chlorine bleach (<250 ppm Cl 0 ). At a 5 0 :50 ratio to the cyclic N -chloramine precursor (hydantoin), the surface bound QAS enables the PET substrate, after being activated with dilute chlorine bleach (100 ppm Cl 0 ), to achieve 5.81 log reduction of MDR- E. coli within 10 minutes of contact. • A new way to achieve tunable functionalization of poly(ethylene terephthalate) (PET) with short-chained quaternary ammonium salt (QAS) and N-chloramine at varying ratios • Despite being separately bonded to PET surface with an N-chloramine precursor hydantoin, a quaternary ammonium molecule can dramatically facilitate the conversion of the hydantoin N-H to N-chloramine in dilute chlorine bleach (<250 ppm Cl0). • At a 50:50 ratio to the cyclic N-chloramine precursor (hydantoin), the surface bound QAS enables the PET substrate, after being activated with dilute chlorine bleach (100 ppm Cl0), to achieve 5.81 log reduction of MDR-E. coli within 10 minutes of contact. • Positive charge contributes to faster killing of MDR-E. coli by N-chloramine immobilized on PET.

Trends in PhysChem Properties of Newly Approved Drugs over the Last Six Years; Predicting Solubility of Drugs Approved in 2021

For the ‘small-molecule’ NMEs (new molecular entities) approved in 2021 by the US FDA, quantitative solubility values were found for 28 drugs, nearly all from published New Drug Applications (NDAs). Comparisons of physicochemical properties over the last six years indicate that the NMEs are slowly continuing to increase in size and decrease in solubility. Since 2016, the intrinsic solubility values (S0) have decreased on average by 0.50 log10 unit, the calculated octanol–water partition coefficients (clogP) have increased by 0.34 log10 unit, and the molecular weights (MW) have increased by 22 g·mol−1 (to 477, compared to 298 in older drugs). The average number of H-bond acceptors has remained constant, while the average number of H-bond donors and the Kier Φ molecular flexibility indices have decreased slightly. The reported solubility data for the 2021 small-molecule NMEs were processed using the program pDISOL-X to obtain S0 values, normalized to 25 °C. The S0 values ranged from 2 ng·mL−1 (avacopan) to 43 mg·mL−1 (viloxazine). In the new set, MW spanned from 233 g·mol−1 (dexmethylphenidate) to 1215 g·mol−1 (voclosporin). Values of clogP ranged from − 0.3 (serdexmethylphenidate, a quaternary ammonium molecule) to 8.1 (avacopan). Five different in-silico models were used to predict the aqueous intrinsic log10 solubility of the 28 novel NMEs: (i) Yalkowsky’s General Solubility Equation (GSE(classic)), (ii) Abraham’s Linear Solvation Equation (ABSOLV), (iii) Avdeef–Kansy ‘Flexible-Acceptor’ General Solubility Equation ((GSE(Φ,B)), (iv) Breiman’s Random Forest Regression (RFR), and (v) consensus model based on (ii) and (iii) above. The various models were retrained with an enlarged version of the Wiki-pS0 database (currently at 7655 log10 S0 entries of drug-relevant molecules). The consensus model (r2 = 0.67, RMSE = 1.08) just slightly outperformed the other four models. The relatively simple consensus prediction equation can be easily incorporated into spreadsheet calculations. As new drugs are approved, it will be important to continue monitoring the quality of measured solubility. Matching prediction to measurement is valuable when prediction methods are applied to virtual libraries, in order to seek opportunities to minimize pharmacokinetic risks of large, but otherwise promising, candidate molecules.

Properties of Bromine Fused Salts Based on Quaternary Ammonium Molecules and Their Relevance for Use in a Hydrogen Bromine Redox Flow Battery.

Bromine complexing agents (BCA) in aqueous electrolytes for hydrogen bromine flow batteries are used to reduce bromine‘s vapour pressure, while an insoluble and liquid fused salt is formed. The properties (concentrations, composition, conductivity and viscosity) of this fused salt are investigated in this study systematically ex situ by using 7 BCAs at different state of charge in HBr/Br2/H2O electrolytes with a theoretical capacity of 179.6 Ah L−1. Bromine is stored in the fused salt at concentrations up to 13.6 M, reaching theoretical volumetrical capacities up to 730 Ah L−1 in fused salts. The fused salt consists of a pure, bromine‐ and water‐free ionic liquid of organic [BCA]+ cations and polybromides, and its conductivity bases on a hopping mechanism among the polybromides. Alkyl side chain length of the BCAs and distribution of polybromides influence strongly the conductivity and viscosity of the fused salts. 1‐ethylpyridin‐1‐iumbromide results to be favoured BCA for application.

Multifunctional Polymer Particles Containing Quaternary Ammonium for Antimicrobial Particulate Surfactants and Defoaming

The preparation of multifunctional polymer particles containing quaternary ammonium molecules by emulsion iodine transfer polymerization (emulsion ITP) via polymerization-induced self-assembly was proposed for the first time. Poly(2-methacryloyloxy ethyl trimethyl ammonium chloride-dimethylamino ethyl methacrylate 12 alkyl chain length)-iodide (P(MTMA-QAC12)12-I) was first synthesized by solution iodine transfer polymerization. It was simultaneously used as a macro-chain transfer agent and emulsifier in emulsion ITP. All conditions smoothly proceeded without coagulation, where the polymerization reached high conversion within only 4 h. When the methyl methacrylate-styrene (P(MMA-S)) copolymer was synthesized in the second block as P(MTMA-QAC12)12-b-P(MMA-S)462, the water contact angle of the obtained particles was close to 90°, which was the most appropriate to use as the particulate surfactant. The P(MTMA-QAC12)12-b-P(MMA-S)462 particles represented a good antimicrobial property based on the positive charge quaternary ammonium groups existing on surfaces. Using such P(MTMA-QAC12)12-b-P(MMA-S)462 nanoparticles (∼90 nm) at 1 wt %, the obtained cutting oil emulsion model represented high colloidal stability with approximately 50 μm oil droplet size without any coalescence. Moreover, foam formation was significantly reduced compared to the commercial cutting oil. According to their excellent properties, P(MTMA-QAC12)12-b-P(MMA-S)462 nanoparticles would be effectively used as a particulate surfactant in Pickering emulsion, including defoamers and antimicrobial agents.

Oral Bioavailability of Deuterated L‐carnitine in Healthy Volunteers

BACKGROUND Deuterium, the stable isotope of hydrogen was discovered in 1931. Since then the use of deuterated molecules have allowed several advancements in the field of chemical biology. For example: in elucidating mechanisms of reactions, tracking metabolic products, and more recently, the enhancement of pharmacokinetic parameters in already existing drugs. L-carnitine is an amino acid derivative, quaternary ammonium molecule with hygroscopic properties that displays an essential role in the fatty acid metabolism in mammals. L-carnitine is an example of a molecule that is both endogenously synthetized and exogenously administered in the forms of dietary products, supplements, and medicine. This poses a challenge differentiating the source of L-carnitine measured in plasma. OBJECTIVES Our study, aims to use deuterated molecules in pharmacokinetics, for distinguishing endogenous synthesized molecules from exogenously administered ones, like L-carnitine. We have developed a method based on deuteration and posterior detection of L- carnitine using high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). METHODS The study was conducted over an open, four period with a 1-week washout interval and six healthy subjects were recruited. Capsules containing 500 mg of L-carnitine which contained different doses of deuterated (D3) L-carnitine (10,30,100 and 100mg of D3 L-carnitine and 490,470 and 400mg of L-carnitine) in each period were administered to each participant. Plasma L-carnitine D3 concentrations were analysed by liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) with multiple reactions monitoring (MRM). The method linearity ranged from 10 to 1000 ng/mL. RESULTS The following pharmacokinetic parameters were obtained from the L-carnitine D3 plasma concentration vs. time curves: AUClast (72.16, 613.48, 2450.29ng*h/mL [mean]), Cmax (19.25, 75.59, 216.79 ng/mL[mean]) and Tmax (3.5, 3.5, 3.5 h [median]) for 10 mg, 30 mg and 100 mg, respectively. The coefficient of variation for rate and extent of absorption were 55.37% and 65.10% (ratio 3/4 period; 100 mg), respectively. Linearity between the pharmacokinetic parameters was demonstrated by Pearson Correlation. The plasma concentrations showed correlation with dose (10, 30 and 100 mg). CONCLUSION This shows that deuterated L-carnitine displays a high variability coefficient and demonstrates linearity among doses of 10, 30 and 100 mg. These results are consistent with previous literature. The method presented here adds to the existing consensus that deuteration is valuable in studying the pharmacokinetics of endogenously synthesized substances.

Solution-processable 2D semiconductors for high-performance large-area electronics

Two-dimensional (2D) materials, consisting of atomically thin crystal layers bound by the van der Waals force, have attracted much interest because of their potential in diverse technologies, including electronics, optoelectronics and catalysis1-10. In particular, solution-processable 2D semiconductor (such as MoS2) nanosheets are attractive building blocks for large-area thin-film electronics. In contrast to conventional zero- and one-dimensional nanostructures (quantum dots and nanowires, respectively), which are typically plagued by surface dangling bonds and associated trapping states, 2D nanosheets have dangling-bond-free surfaces. Thin films created by stacking multiple nanosheets have atomically clean van der Waals interfaces and thus promise excellent charge transport11-15. However, preparing high-quality solution-processable 2D semiconductor nanosheets remains a challenge. For example, MoS2 nanosheets and thin films produced using lithium intercalation and exfoliation are plagued by the presence of the metallic 1T phase and poor electrical performance (mobilities of about 0.3 square centimetres per volt per second and on/off ratios of less than 10)2,12, and materials produced by liquid exfoliation exhibit an intrinsically broad thickness distribution, which leads to poor film quality and unsatisfactory thin-film electrical performance (mobilities of about 0.4 square centimetres per volt per second and on/off ratios of about 100)14,16,17. Here we report a general approach to preparing highly uniform, solution-processable, phase-pure semiconducting nanosheets, which involves the electrochemical intercalation of quaternary ammonium molecules (such as tetraheptylammonium bromide) into 2D crystals, followed by a mild sonication and exfoliation process. By precisely controlling the intercalation chemistry, we obtained phase-pure, semiconducting 2H-MoS2 nanosheets with a narrow thickness distribution. These nanosheets were then further processed into high-performance thin-film transistors, with room-temperature mobilities of about 10 square centimetres per volt per second and on/off ratios of 106 that greatly exceed those obtained for previous solution-processed MoS2 thin-film transistors. The scalable fabrication of large-area arrays of thin-film transistors enabled the construction of functional logic gates and computational circuits, including an inverter, NAND, NOR, AND and XOR gates, and a logic half-adder. We also applied our approach to other 2D materials, including WSe2, Bi2Se3, NbSe2, In2Se3, Sb2Te3 and black phosphorus, demonstrating its potential for generating versatile solution-processable 2D materials.

Monolayer atomic crystal molecular superlattices.

Artificial superlattices, based on van der Waals heterostructures of two-dimensional atomic crystals such as graphene or molybdenum disulfide, offer technological opportunities beyond the reach of existing materials. Typical strategies for creating such artificial superlattices rely on arduous layer-by-layer exfoliation and restacking, with limited yield and reproducibility. The bottom-up approach of using chemical-vapour deposition produces high-quality heterostructures but becomes increasingly difficult for high-order superlattices. The intercalation of selected two-dimensional atomic crystals with alkali metal ions offers an alternative way to superlattice structures, but these usually have poor stability and seriously altered electronic properties. Here we report an electrochemical molecular intercalation approach to a new class of stable superlattices in which monolayer atomic crystals alternate with molecular layers. Using black phosphorus as a model system, we show that intercalation with cetyl-trimethylammonium bromide produces monolayer phosphorene molecular superlattices in which the interlayer distance is more than double that in black phosphorus, effectively isolating the phosphorene monolayers. Electrical transport studies of transistors fabricated from the monolayer phosphorene molecular superlattice show an on/off current ratio exceeding 107, along with excellent mobility and superior stability. We further show that several different two-dimensional atomic crystals, such as molybdenum disulfide and tungsten diselenide, can be intercalated with quaternary ammonium molecules of varying sizes and symmetries to produce a broad class of superlattices with tailored molecular structures, interlayer distances, phase compositions, electronic and optical properties. These studies define a versatile material platform for fundamental studies and potential technological applications.

UV-Curable Contact Active Benzophenone Terminated Quaternary Ammonium Antimicrobials for Applications in Polymer Plastics and Related Devices.

A series of UV active benzophenone ([C6H5COC6H4-O-(CH2)n-N+Me2R][X-]; 4, R = C12H25, n = 3, X- = Br-; 5a-c, R = C18H37, n = 3, X- = Cl-, Br-, I-; 6a-c, R = C18H37, n = 4, X- = Cl-, Br-, I-; 7a-c, R = C18H37, n = 6, X- = Cl-, Br-, I-) terminated C12 and C18 quaternary ammonium salts (QACs) were prepared by thermal or microwave-driven Menshutkin protocols of the appropriate benzophenone alkyl halide (1a-c, 2a-c, 3a-c) with the corresponding dodecyl- or octadecyl N,N-dimethylamine. All new compounds were characterized by NMR spectroscopy, HRMS spectrometry, and, in one instance (4), by single-crystal X-ray crystallography. Representative C12 and C18 benzophenone QACs were formulated into 1% (w/v) water or water/ethanol-based aerosol spray coatings and then UV-cured onto plastic substrates (polypropylene, polyethylene, polystyrene, polyvinyl chloride, and polyether ether ketone) with exposure to low to moderate doses of UV (20-30 J cm-2). Confirmation as to the presence of the coatings was detected by advancing water contact angle measurements, which revealed a more hydrophilic surface after coating. Further confirmation was gained by X-ray photoelectron spectroscopy analysis, time of flight secondary ion mass spectrometry, and bromophenol blue staining, all of which showed the presence of the attached quaternary ammonium molecule. Analysis of surfaces treated with the C18 benzophenone 5b by atomic force microscopy and surface profilometry revealed a coating thickness of ∼350 nm. The treated samples along with controls were then evaluated for their antimicrobial efficacy against Gram-positive (Arthrobacter sp., Listeria monocytogenes) and Gram-negative (Pseudomonas aeruginosa) bacteria at a solid/air interface using the large drop inoculum protocol; this technique gave no evidence for cell adhesion after a 3 h time frame. These antimicrobial materials show promise for their use as coatings on plastic biomedical devices with the aim of preventing biofilm formation and preventing the spread of hospital acquired infections.

Structures of KcsA in complex with symmetrical quaternary ammonium compounds reveal a hydrophobic binding site.

Potassium channels allow for the passive movement of potassium ions across the cell membrane and are instrumental in controlling the membrane potential in all cell types. Quaternary ammonium (QA) compounds block potassium channels and have long been used to study the functional and structural properties of these channels. Here we describe the interaction between three symmetrical hydrophobic QAs and the prokaryotic potassium channel KcsA. The structures demonstrate the presence of a hydrophobic pocket between the inner helices of KcsA and provide insight into the binding site and blocking mechanism of hydrophobic QAs. The structures also reveal a structurally hidden pathway between the central cavity and the outside membrane environment reminiscent of the lateral fenestration observed in sodium channels that can be accessed through small conformational changes in the pore wall. We propose that the hydrophobic binding pocket stabilizes the alkyl chains of long-chain QA molecules and may play a key role in hydrophobic drug binding in general.

Electroformed Giant Vesicles from a Binary Mixture of Phospholipids and Quaternary Ammonium Salts

In this article, positively charged GVs were electroformed in a binary system of quaternary ammonium salts and egg phosphatidylcholine (EggPC) under an alternative current (AC) electric field. The diameter and charge density of the GVs is controlled by doping suitable cationic quaternary ammonium molecules into the EggPC bilayer. By developing positively charged GVs, there will be expanded the applications for phospholipids vesicles, especially the investigation of charge-induced interactions between cationic lipid membranes and macromolecules, such as colloidal particles or proteins.

Improvement of the adsorption of quaternary ammonium on polypropylene affinity membrane through the control of its surface properties

Polypropylene fiber meshes were plasma-treated in order to attach new chemical functions corresponding to acidic or basic groups without altering the roughness of such thin material. An almost complete wettability of these plasma-treated materials is obtained. Because of the plasma-grafting of acid or amino moieties, such surface treatment allows increasing the adsorption rate of quaternary ammonium molecule like Aliquat 336. This increase was explained by specific interactions of ammonium head of the Aliquat 336 and hydrophilic group of plasma-treated PP, followed by the adsorption of a further layer of Aliquat 336 through hydrophobic interactions of its hydrocarbon chain. These interactions between the carrier and the polymeric surface were characterized leading to physisorption mechanism. Such new material could be applied to the extraction process since no evidence of aging was given.

Effect of Functional Group on the Monolayer Structures of Biodegradable Quaternary Ammonium Surfactants

The monolayer structures and conformational ordering of cationic surfactants including the biodegradable quaternary ammonium molecules have been systematically characterized by π-A isotherm, surface potential, atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and sum frequency generation (SFG) vibrational spectroscopy. It was found that the monolayer of the typical dialkyl dimethylammonium on the water surface was less densely packed along with many conformational gauche defects. The packing density and ordering of these monolayers were improved as halide ions were added to the subphase. A similar condensation effect was also observed when amide or ester groups are present in the alkyl tails of the surfactant. These results are discussed on the basis of the repulsive electrostatic interactions between the terminal ammonium moieties, the hydrogen bonding between the functional groups in the alkyl chains, as well as the flexibility of the alkyl chains in these surfactants. The present study is crucial to understanding the relationship between the interfacial structures and the functionalities of the biodegradable quaternary ammonium surfactants.

Affinities of bispyridinium non-oxime compounds to [3H]epibatidine binding sites of Torpedo californica nicotinic acetylcholine receptors depend on linker length

The toxicity of organophosphorus nerve agents or pesticides arises from accumulation of acetylcholine and overstimulation of both muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs) due to inhibition of acetylcholinesterase (AChE). Standard treatment by administration of atropine and oximes, e.g., obidoxime or pralidoxime, focuses on antagonism of mAChRs and reactivation of AChE, whereas nicotinic malfunction is not directly treated. An alternative approach would be to use nAChR active substances to counteract the effects of accumulated acetylcholine. Promising in vitro and in vivo results were obtained with the bispyridinium compounds SAD-128 (1,1′-oxydimethylene bis(4-tert-butylpyridinium) dichloride) and MB327 (1,1′-(propane-1,3-diyl)bis(4-tert-butylpyridinium) di(iodide)), which were partly attributed to their interaction with nAChRs. In this study, a homologous series of unsubstituted and 4-tert-butyl-substituted bispyridinium compounds with different alkane linker lengths was investigated in competition binding experiments using [3H]epibatidine as a reporter ligand. Additionally, the effect of the well-characterised MB327 on the [3H]epibatidine equilibrium dissociation (KD) constant in different buffers was determined. This study demonstrated that divalent cations increased the affinity of [3H]epibatidine. Since quaternary ammonium molecules are known to inhibit AChE, the obtained affinity constants of the tested bispyridinium compounds were compared with the inhibition of human AChE. In competition experiments, bispyridinium derivatives of longer linker length displaced [3H]epibatidine and inhibited AChE strongly. Bispyridinium compounds with short linkers, at most, have an allosteric interaction with the [3H]epibatidine binding sites and barely inhibited AChE. In dependence on alkane linker length, the bispyridinium compounds seemed to interact at different binding sites. However, the exact binding sites of the bispyridinium compounds responsible for the positive pharmacological effects have still not been identified, making predictive drug design difficult.

Wood Protective Fungicidal Treatment: Quaternary Ammonium Molecules Grafting on Cellulose Assisted by Afterglows at Atmospheric Pressure

AbstractWood or cellulosic materials protection against fungi is possible by binding covalent molecules as quaternary ammonium compounds (QAC) on the hydroxyl reactive groups present in cellulose. This work firstly consists in the synthesis of a specific quaternary ammonium molecule containing a long aliphatic chain and an epoxide reactive group: Glycidyldimethyldodecylammonium chloride (GDDAC). Fungicidal properties of this molecule have been proven. Secondly, afterglows issued from atmospheric pressure Dielectric Barrier Discharges (DBDs), can assist QAC grafting on cellulose. The efficiency of the reaction is improved by adding a few percentage of oxygen in nitrogen DBD. Antifungal efficiency of GDDAC grafting on wood sawdust is finally shown demonstrating the great interest of such process. magnified image

Multiple inhibitory actions of lidocaine on Torpedo nicotinic acetylcholine receptors transplanted to Xenopus oocytes

Lidocaine is a local anaesthetic that blocks sodium channels, but also inhibits several ligand-gated ion-channels. The aim of this work was to unravel the mechanisms by which lidocaine blocks Torpedo nicotinic receptors transplanted to Xenopus oocytes. Acetylcholine-elicited currents were reversibly blocked by lidocaine, in a concentration dependent manner. At doses lower than the IC(50) , lidocaine blocked nicotinic receptors only at negative potentials, indicating an open-channel blockade; the binding site within the channel was at about 30% of the way through the electrical field across the membrane. In the presence of higher lidocaine doses, nicotinic receptors were blocked both at positive and negative potentials, acetylcholine dose-response curve shifted to the right and lidocaine pre-application, before its co-application with acetylcholine, enhanced the current inhibition, indicating all together that lidocaine also blocked resting receptors; besides, it increased the current decay rate. When lidocaine, at low doses, was co-applied with 2-(triethylammonio)-N-(2,6-dimethylphenyl) acetamide bromide, edrophonium or 1,5-bis(4-allyldimethylammoniumphenyl)pentan-3-one dibromide, which are quaternary-ammonium molecules that also blocked nicotinic receptors, there was an additive inhibitory effect, indicating that these molecules bound to different sites within the channel pore. These results prove that lidocaine blocks nicotinic receptors by several independent mechanisms and evidence the diverse and complex modulation of this receptor by structurally related molecules.

Asymmetrical Ligands in the Potassium Channel Cavity

Quaternary ammonium (QA) compounds are the most extensively studied class of potassium channel blockers. Molecules such as tetraethylammonium (TEA) and tetrabutylammonium (TBA) have long been used in functional experiments designed to elucidate the drug-binding, ion-binding and gating behaviors of a wide variety of potassium channels. More recently, the development of potassium channel crystallization techniques has allowed co-crystal structures of KcsA in complex with QAs to be solved. The four-fold symmetry of potassium channels, however, has limited such experiments to symmetrical QA molecules, meaning that the binding sites for pharmacological important molecules remain unknown. Molecules such as octyltriethylammonium (C8), local anesthetics and anti-arrhythmics likely bind at or near the known QA binding site, but the hydrophobic interactions that stabilize these molecules have yet to be resolved due to a symmetry mismatch between the channel and its blockers. Here we present several strategies for overcoming this symmetry mismatch and solving the structure of KcsA in complex with asymmetrical molecules. We have used these strategies to solve the structure of KcsA in complex with a number of asymmetrical ligands - including C8, C10, several arsenic-containing derivatives of asymmetrical QA molecules and amiodarone. Our structures demonstrate the existence of a hydrophobic binding site located between the inner helices of two KcsA monomers and suggest this region of the channel may be important for the stabilization of “drug-like” ligands in the potassium channel cavity.

Branched quaternary ammonium amphiphiles: nematic ionic liquid crystals near room temperature

Branched quaternary ammonium molecules were synthesized and characterized by calorimetric, optical and X-ray diffraction studies; two of the molecules exhibited interesting nematic liquid crystalline behavior close to room temperature.

Nanoporous Organosilicate Films Prepared in Acidic Conditions Using Tetraalkylammonium Bromide Porogens

AbstractOrganosilicate films with narrow pore size distribution tunable in the range of 1–3.4 nm were prepared by spin‐coating of silicon wafers with sols prepared in acidic conditions using tetraethyl orthosilicate, methyltrimethoxysilane, and tetraalkylammonium bromide (TAABr) porogen. The pore size was defined by the alkyl chain length of the quaternary ammonium molecule and the porogen concentration. The pore network in the films and the hydrophobicity of the pore surfaces were characterized using ellipsometric porosimetry with toluene and water adsorbates. In the absence of TAABr, the pore volume was 9 vol% and the pore size 1 nm. By using TAABr porogens, monomodal pore size distributions were obtained in the range of 1.2–3.5 nm. The pore volume was in the range from 18 vol% at 1.2 nm pore diameter up to 54 vol% at 3.5 nm diameter. The hydrophobicity of the pores was dependent on the pore diameter, with smaller pores being the least hydrophobic. The increase of hydrophobicity with pore size was explained by an increased distance between silanol groups on the curved pore surfaces. The mechanical properties and dielectric constant of these films were comparable to reference materials prepared using more sophisticated porogens reported in the literature.