Quaternary Derivatives Research Articles

Recent Advances in Electron Donor‐Acceptor (EDA)‐Complex Reactions involving Quaternary Pyridinium Derivatives

AbstractQuaternary pyridinium compounds are valuable intermediates in organic synthesis, which have gained immense popularity in the synthetic community. The application of transition metal or photoredox catalysis in transforming quaternary pyridinium compounds into various C−C and C−X bonds is well established. A majority of these methods require high temperatures, expansive catalysts, and delicate conditions for successful execution. On the other hand, the use of transition metal‐free and photocatalysis‐free strategies in constructing C−C and C−X bonds using quaternary pyridinium derivatives has been sought‐after. In this context, the electron‐donor‐acceptor (EDA)‐complex reactions have emerged as a state‐of‐the‐art organic synthetic methodology, which do not require any photocatalyst for their successful execution. EDA‐complex photochemistry takes advantage of the electron‐acceptor ability of quaternary pyridinium derivatives, which can quickly generate a radical precursor via the deaminative process. These newly generated radical intermediates are useful in several valuable transformations. We hereby, in this review, discuss an area of major progress in EDA‐complex mediated reactions involving quaternary pyridinium compounds with mechanism, substrate scope, and limitations.magnified image

Complexation between poly (styrene-co-methacrylic acid) and polyquaternium for use in shampoo formulations

The complexation between poly (styrene-co-methacrylic acid) (P(St-co-MAA)) and a series of cationically substituted quaternary ammonium derivatives of hydroxyethylcellulose, JR and LR (polyquaternium) was investigated through the viscosity change of the complexes at different mixing ratios of the two polymers. The performance of the shampoo containing the complexes was also evaluated. The results show that the viscosity of the mixed aqueous solution increased as the ratio of (P(St-co-MAA)) to JR or LR increased. The maximum viscosity was obtained when the molar ratio (r) of St in P(St-co-MAA) to cations in polyquaternium was near 1. As the mixing ratio increased further, syneresis occurred when the charge stoichiometry between MAA and the quaternary ammonium cation was 1:1. This result reveals that cation-π electron interactions rather than electrostatic attraction play a key role in forming complexes between polyquaternium and P(St-co-MAA). The higher the molecular weight of polyquaternium is, the higher the viscosity of the complex solution. The complexes maintained a large apparent viscosity at a temperature of 70 °C, a shear rate of 1 s−1 and a NaCl concentration of 1.2 mol/L. The complexes had good tolerance to temperature, salt and shearing. The addition of the complexes in shampoo was beneficial to thickening, which is difficult in amino acid anionic surfactant systems. Compared with the shampoo containing the polyquaternium normally, the addition of P(St-co-MAA) helped to generate more flocculation earlier during washing of the hair. Unexpectedly, the wet carding performance of the shampoo was significantly better than that of commercial silicon-containing shampoo (P < 0.01). The complex has potential as a thickener and a conditioner in shampoo formulations.

Hybrid nanoparticles of quaternary ammonium cellulose derivatives and citric acid for enhancing the antibacterial activity of polyvinyl alcohol composites

Hybrid nanoparticles of quaternary ammonium cellulose derivatives and citric acid for enhancing the antibacterial activity of polyvinyl alcohol composites

Selective Serotonin Reuptake Inhibitors within Cells: Temporal Resolution in Cytoplasm, Endoplasmic Reticulum, and Membrane.

Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed treatment for individuals experiencing major depressive disorder. The therapeutic mechanisms that take place before, during, or after SSRIs bind the serotonin transporter (SERT) are poorly understood, partially because no studies exist on the cellular and subcellular pharmacokinetic properties of SSRIs in living cells. We studied escitalopram and fluoxetine using new intensity-based, drug-sensing fluorescent reporters targeted to the plasma membrane, cytoplasm, or endoplasmic reticulum (ER) of cultured neurons and mammalian cell lines. We also used chemical detection of drug within cells and phospholipid membranes. The drugs attain equilibrium in neuronal cytoplasm and ER at approximately the same concentration as the externally applied solution, with time constants of a few s (escitalopram) or 200-300 s (fluoxetine). Simultaneously, the drugs accumulate within lipid membranes by ≥18-fold (escitalopram) or 180-fold (fluoxetine), and possibly by much larger factors. Both drugs leave cytoplasm, lumen, and membranes just as quickly during washout. We synthesized membrane-impermeant quaternary amine derivatives of the two SSRIs. The quaternary derivatives are substantially excluded from membrane, cytoplasm, and ER for >2.4 h. They inhibit SERT transport-associated currents sixfold or 11-fold less potently than the SSRIs (escitalopram or fluoxetine derivative, respectively), providing useful probes for distinguishing compartmentalized SSRI effects. Although our measurements are orders of magnitude faster than the therapeutic lag of SSRIs, these data suggest that SSRI-SERT interactions within organelles or membranes may play roles during either the therapeutic effects or the antidepressant discontinuation syndrome.SIGNIFICANCE STATEMENT Selective serotonin reuptake inhibitors stabilize mood in several disorders. In general, these drugs bind to SERT, which clears serotonin from CNS and peripheral tissues. SERT ligands are effective and relatively safe; primary care practitioners often prescribe them. However, they have several side effects and require 2-6 weeks of continuous administration until they act effectively. How they work remains perplexing, contrasting with earlier assumptions that the therapeutic mechanism involves SERT inhibition followed by increased extracellular serotonin levels. This study establishes that two SERT ligands, fluoxetine and escitalopram, enter neurons within minutes, while simultaneously accumulating in many membranes. Such knowledge will motivate future research, hopefully revealing where and how SERT ligands engage their therapeutic target(s).

DOTAP: Structure, hydration, and the counterion effect

The cationic lipid 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) is one of the original synthetic cationic lipids used for the liposomal transfection of oligonucleotides in gene therapy. The key structural element of DOTAP is its quaternary ammonium headgroup that is responsible for interactions with both nucleic acids and target cell membranes. Because these interactions are fundamental to the design of a major class of transfection lipids, it is important to understand the structure of DOTAP and how it interacts with halide counterions. Here, we use x-ray and neutron diffraction techniques to examine the structure of DOTAP and how chloride (Cl−) and iodide (I−) counterions alter the hydration properties of the DOTAP headgroup. A problem of particular interest is the poor solubility of DOTAP/I− in water solutions. Our results show that the poor solubility results from very tight binding of the I− counterion to the headgroup and the consequent expulsion of water. The structural principles we report here are important for assessing the suitability of DOTAP and its quaternary ammonium derivatives for transfection.

Enhanced Photovoltaic Performance of Inverted Perovskite Solar Cells through Surface Modification of a NiOx-Based Hole-Transporting Layer with Quaternary Ammonium Halide–Containing Cellulose Derivatives

In this study, we positioned three quaternary ammonium halide-containing cellulose derivatives (PQF, PQCl, PQBr) as interfacial modification layers between the nickel oxide (NiOx) and methylammonium lead iodide (MAPbI3) layers of inverted perovskite solar cells (PVSCs). Inserting PQCl between the NiOx and MAPbI3 layers improved the interfacial contact, promoted the crystal growth, and passivated the interface and crystal defects, thereby resulting in MAPbI3 layers having larger crystal grains, better crystal quality, and lower surface roughness. Accordingly, the photovoltaic (PV) properties of PVSCs fabricated with PQCl-modified NiOx layers were improved when compared with those of the pristine sample. Furthermore, the PV properties of the PQCl-based PVSCs were much better than those of their PQF- and PQBr-based counterparts. A PVSC fabricated with PQCl-modified NiOx (fluorine-doped tin oxide/NiOx/PQCl-0.05/MAPbI3/PC61BM/bathocuproine/Ag) exhibited the best PV performance, with a photoconversion efficiency (PCE) of 14.40%, an open-circuit voltage of 1.06 V, a short-circuit current density of 18.35 mA/cm3, and a fill factor of 74.0%. Moreover, the PV parameters of the PVSC incorporating the PQCl-modified NiOx were further enhanced when blending MAPbI3 with PQCl. We obtained a PCE of 16.53% for this MAPbI3:PQCl-based PVSC. This PQCl-based PVSC retained 80% of its initial PCE after 900 h of storage under ambient conditions (30 °C; 60% relative humidity).

Arylene Diimide Derivatives as Anolyte Materials with Two-Electron Storage for Ultrastable Neutral Aqueous Organic Redox Flow Batteries

Arylene Diimide Derivatives as Anolyte Materials with Two-Electron Storage for Ultrastable Neutral Aqueous Organic Redox Flow Batteries

Synthesis of iron oxide nanoparticles, characterization, uses as nanozyme and future prospects

Iron oxide nanoparticles (IONPs) have recently attracted wider attention because of their unique properties, such as superparamagnetism, larger surface area, surface-to-volume ratio and simple manufacturing process. Several chemical, physical and biological techniques have been employed to synthesize nanoparticles (NPs) with acceptable surface chemistry. This paper summarizes the approaches for producing IONPs, managing their shape and size and tailoring their properties for bioengineering, pharmaceutical and modern applications. Iron oxides have significant potential in biology, climate change mitigation and horticulture, among several fields. Surface coatings with organic or inorganic particles are one of a kind. The surface coatings of IONPs are critical to their performance because they prevent NP aggregation, reduce the risk of immunogenicity and limit non-specific cellular uptake. Chitosan is a biodegradable polymer that is applied on IONPs to coat them. Chitosan derivatives such as O-(2-hydroxyl)propyl-3-trimethyl ammonium chitosan chloride (O-HTCC; an ammonium quaternary chitosan derivative) have a long-lasting positive charge that allows them to work in different pH ranges, allowing them to interact with cell layers at physiological pH. By reacting epoxypropyltrimethylammonium chloride with chitosan, the hydro-solvent HTCC is formed. For hyperthermic treatment of patients, NPs can also be coordinated to an organ, tissue or tumor through an external attractive field. Given the increasing interest in iron NPs, the purpose of this review is to present data on IONPs, particularly chitosan-capped iron NPs, for different biomedical fields.

Bergamot Essential Oil: A Method for Introducing It in Solid Dosage Forms.

Bergamot essential oil (BEO) possess antimicrobial, antiproliferative, anti-inflammatory, analgesic, neuroprotective, and cardiovascular effects. However, it is rich in volatile compounds, e.g., limonene, that are susceptible to conversion and degradation reactions. The aim of this communication was to prepare a conjugate based on a quaternary ammonium chitosan derivative (QA-Ch) and methyl-βCD (MCD), coded as BEO/QA-Ch-MCD, to encapsulate BEO in order to stabilize its volatile compounds, eliminate its unpleasant taste, and convert the oil in a solid dosage form. The obtained conjugate, BEO/QA-Ch-MCD, was highly soluble and had a percentage of extract association efficiency (AE %), in terms of polyphenols and limonene contents, of 22.0 ± 0.9 and 21.9 ± 1.2, respectively. Moreover, stability studies under UV stress in simulated gastric fluid showed that BEO/QA-Ch-MCD was more able to protect polyphenols and limonene from degradation compared to free BEO or BEO complexed with MCD (BEO/MCD). The complexation and subsequent lyophilization allowed the transformation of a liquid into a solid dosage form capable of eliminating the unpleasant taste of the orally administered oil and rendering the solid suitable to produce powders, granules, tablets, etc. These solid oral dosage forms, as they come into contact with physiological fluids, could generate nanosized agglomerates able to increase the stability of their active contents and, consequently, their bioavailability.

Design of Photoredox-Catalyzed Giese-Type Reaction for the Synthesis of Chiral Quaternary α-Aryl Amino Acid Derivatives via Clayden Rearrangement.

Chiral quaternary α-aryl amino acids are biologically valued but synthetically challenging building blocks. Herein, we report a strategy for the synthesis of molecular architectures by unifying a photoredox catalytic asymmetric Giese-type reaction and Clayden rearrangement. A new class of chiral Karady-Beckwith dehydroalanines is designed and serves as a versatile handle for the photoredox-mediated highly stereoselective Giese-type reaction with feedstock carboxylic acids and tertiary amines. Subsequent Clayden rearrangement delivers chiral quaternary α-aryl amino acid derivatives with high stereoselectivity. The versatile approach offers a reliable source for the assembly of highly demanding chiral building blocks.

Preparation of magnetic fluorescent nanoparticles with quaternary ammonium chitosan derivatives and its properties

To explore a novel solution to the challenges in constructing polymer coated magnetic fluorescent nanoparticles, HTCC/Fe3O4/CdTe magnetic fluorescent nanoparticles (MFCNPs) that can be well dispersed in water were prepared via the electrostatic interaction of the cationic N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) and the anion precoated water-soluble cadmium telluride (CdTe) quantum dots (QDs) and the sodium citrate-coated Fe3O4 (SC-Fe3O4) magnetic nanoparticles (MNPs), which overcame the performance defects of hydrophobic polymer for surface coating and the possible toxicity of cross-linking agent induced by the hydrophilic polymer coating materials. The structural characterizations by FTIR, XRD and XPS reveal that the surfaces of SC-Fe3O4 MNPs and CdTe QDs are coated with HTCC. TEM imaging suggests that the MFCNPs are spherical particles with the diameters of ∼15–20 nm. The MFCNPs exhibit good biocompatibility. Further investigation suggests that the UV-Vis and fluorescence spectral properties and surface electrical properties of HTCC/Fe3O4/CdTe MFCNPs are mainly affected by the relative ratios of SC-Fe3O4 MNPs, CdTe QDs and HTCC. The adsorption and release properties of the MFCNPs were studied using bovine serum albumin (BSA) as the model. The results indicate that the chitosan-based magnetic fluorescent composite is a promising delivery carrier candidate with excellent comprehensive properties for both magnetic response and fluorescence imaging.

Local Delivery of Metronidazole-loaded N-Trimethyl Quaternary Ammonium Chitosan Nanoparticles for Periodontitis Treatment

Background: Recent findings suggest that chitosan has shown antibacterial activity acting through various mechanisms, but when the amine group in chitosan is converted to quaternary ammonium compound, the antibacterial activity of chitosan is elevated due to the increase in its solubility in an acidic environment. Objectives:: The purpose of this study was to formulate and standardize metronidazole-loaded Ntrimethyl quaternary ammonium chitosan nanoparticles for the treatment of periodontitis. Method: N-trimethyl quaternary ammonium chitosan derivative was synthesized, and nanoparticles (NPs) were prepared by ionic gelation methodology followed by 32 full factorial designs. Particle size, zeta potential, polydispersity index (PDI), surface morphology, thermal properties, in vitro drug release as well as antimicrobial activity, stability study, ex vivo, and acute toxicity of NPs were evaluated. Results: The optimized batches of NPs were in the size range of 150 to 237 nm with a mean size of 117.01 ± 0.03 nm. Entrapment efficiency (EE) of 81.45 ± 0.03 % was obtained with a zeta potential (mV) of 28.19 ± 0.03 mV. Almost 98.97 ± 7.17% of the drug was released within 24 hours in vitro to obtain a sustained release drug; the optimized batches exhibited a smooth surface with appreciable in vitro, ex vivo antibacterial, and acute toxicity, and it was found that the formulation could be stored for up to 6 months. Conclusion: The present study revealed that metronidazole-loaded N-trimethyl quaternary ammonium chitosan nanoparticles exhibit enhanced antibacterial activity against periodontal infections.

Preparation of chitosan-rosmarinic acid derivatives with enhanced antioxidant and anti-inflammatory activities

In present study, several chitosan derivatives grafted with rosmarinic acid，including chitosan-rosmarinic acid conjugate (CS-RA), chitosan rosmarinic acid salt (CSRA), N,N,N-trimethylated chitosan rosmarinic acid salt (TMCRA), and N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan rosmarinic acid salt (HACRA), were prepared and the effects of different grafting methods on bioactivity of these derivatives were investigated. The structural characterization was identified by FTIR and 1H NMR spectroscopy. The chitosan derivatives were also evaluated biologically for antioxidant, cytotoxic, and anti-inflammatory activities. Derivatives CSRA, TMCRA, and HACRA prepared through ion exchange method exhibited significant antioxidant ability. All derivatives remarkably inhibited lipopolysaccharide-induced nitric oxide and TNF-α production in RAW 264.7 cells without cytotoxicity, especially derivative TMCRA, whose inhibition rate was >50 % at only 250 μg/mL. The results suggested that chitosan quaternary ammonium derivatives grafted with rosmarinic acid possessed better antioxidant and anti-inflammatory properties than chitosan, which could be used as drug materials against oxidative and inflammation-related pathological processes.

Construction of Quaternary Allylic Amino Acid Derivatives through Palladium-Catalyzed Allylic Alkylation Reaction of Azlactones with Vinyl Aziridine

AbstractA highly efficient Pd-catalyzed allylic alkylation reaction of azlactones with vinyl aziridine has been achieved for the first time to access­ functionalized quaternary allylic amino acid derivatives (17 examples, up to 89% yield and 80% ee). Moreover, the broad scope and easy transformations of the products reinforce the value of this approach, which can enrich the chemistry of quaternary allylic amino acid derivatives.

A super sensitive fluorescent probe for imaging endogenous hydrogen sulfide in living cells

Hydrogen sulfide (H2S) that typically performs biphasic biological functions in organisms plays an opposite role at the concentrations above or below normal level of the organism. Therefore, it is significant to develop a fluorescent probe with high sensitivity and selectivity and rapid response for the detection of hydrogen sulfide in vivo. The work describes the design and biological applications of a novel turn-on fluorescence probe SS-N3 in which the quinoline quaternary ammonium salt derivative is introduced as the fluorescent skeleton and azide is employed as the detection group of H2S. The probe SS-N3 shows strong fluorescence at 610 nm, as the azide group is reduced to an amino group by H2S. The probe SS-N3 shows high selectivity to H2S than other anions and some biological mercaptans, and strong anti-interference capacity. In addition, the probe SS-N3 exhibits little cytotoxicity, improved photostability and large Stokes shift (135 nm), as well as can be effectively used as an indicator of H2S level in living cells.

Novel anesthetics in pediatric practice: is it time?

Steadily mounting evidence of anesthesia-induced developmental neurotoxicity has been a challenge in pediatric anesthesiology. Considering that presently used anesthetics have, in different animal models, been shown to cause lasting behavioral impairments when administered at the peak of brain development, the nagging question, 'Is it time for the development of a new anesthetic' must be pondered. The emerging 'soft analogs' of intravenous anesthetics aim to overcome the shortcomings of currently available clinical drugs. Remimazolam, a novel ester-analog of midazolam, is a well tolerated intravenous drug with beneficial pharmacological properties. Two novel etomidate analogs currently in development are causing less adrenocortical suppression while maintaining equally favorable hemodynamic stability and rapid metabolism. Quaternary lidocaine derivatives are explored as more potent and longer lasting alternatives to currently available local anesthetics. Xenon, a noble gas with anesthetic properties, is being considered as an anesthetic-sparing adjuvant in pediatric population. Finally, alphaxalone is being reevaluated in a new drug formulation because of its favorable pharmacological properties. Although a number of exciting anesthetic drugs are under development, there is currently no clear evidence to suggest their lack of neurotoxic properties in young brain. Well designed preclinical studies are needed to evaluate their neurotoxic potential.

The Notable Articles Project

Studies are presented of the interaction of aromatic amine noncompetitive antagonists with the receptor-rich (post-synaptic) membranes isolated from <i>Torpedo marmorata</i> electric organ. When present at micromolar concentrations, methyl iodide quaternary derivatives of the potent non-competitive antagonists proadifen and dimethisoquin increase the affinity of the membrane-bound nicotinic receptor for [³H]acetylcholine and [¹⁴C]dimethyltubocurarine. The equilibrium binding of [¹⁴C]meproadifen (2-(diethylmethylamino)ethyl-2,2-diphenyl valerate) to the receptor-rich membranes is characterized by an ultracentrifugatiom assay. When all acetylcholine binding sites are occupied by the agonist carbamylcholine or the antagonist tubocurarine, [¹⁴C]meproadifen is bound with a dissociation constant <i>K_D</i> = 0.5 µM to a number of sites equal to one-quarter the number of α-neurotoxin binding sites. That high affinity binding site is found in the receptor-rich membranes and not in other membrane fractions isolated from <i>Torpedo</i> electric organ. Other non-competitive aromatic amino antagonists including dimethisoquin, proadifen, and prilocaine displace [¹⁴C]meproadifen, as does perhydrohistrionicotoxin. It is concluded that there is a specific site of binding for the aromatic amine non-competitive antagonists in the isolated nicotinic post-synaptic membrane that is distinct from the site of binding of acetylcholine. Analysis of the interaction of [¹⁴C]meproadifen with the receptor-rich membranes in the absence of cholinergic ligands indicates that under these circumstances the ligand binds weakly to both the anesthetic binding site and the acetylcholine binding site (<i>K_D</i> = 5 µM). The functional significance of the specific binding site for the aromatic amine non-competitive antagonists is discussed in terms of its possible relation to the site of ion translocatiom and to the mechanism of receptor desensitization.

Topical Antibiofilm Agents With Potential Utility in the Treatment of Chronic Rhinosinusitis: A Narrative Review

The role of bacterial biofilms in chronic and recalcitrant diseases is widely appreciated, and the treatment of biofilm infection is an increasingly important area of research. Chronic rhinosinusitis (CRS) is a complex disease associated with sinonasal dysbiosis and the presence of bacterial biofilms. While most biofilm-related diseases are associated with highly persistent but relatively less severe inflammation, the presence of biofilms in CRS is associated with greater severity of inflammation and recalcitrance despite appropriate treatment. Oral antibiotics are commonly used to treat CRS but they are often ineffective, due to poor penetration of the sinonasal mucosa and the inherently antibiotic resistant nature of bacteria in biofilms. Topical non-antibiotic antibiofilm agents may prove more effective, but few such agents are available for sinonasal application. We review compounds with antibiofilm activity that may be useful for treating biofilm-associated CRS, including halogen-based compounds, quaternary ammonium compounds and derivatives, biguanides, antimicrobial peptides, chelating agents and natural products. These include preparations that are currently available and those still in development. For each compound, antibiofilm efficacy, mechanism of action, and toxicity as it relates to sinonasal application are summarised. We highlight the antibiofilm agents that we believe hold the greatest promise for the treatment of biofilm-associated CRS in order to inform future research on the management of this difficult condition.

Interleukin-12 Plasmid DNA Delivery by N-[(2-Hydroxy-3-trimethylammonium)propyl]chitosan-Based Nanoparticles.

Cationic polysaccharides are capable of forming polyplexes with nucleic acids and are considered promising polymeric gene carriers. The objective of this study was to evaluate the transfection efficiency and cytotoxicity of N-[(2-hydroxy-3-trimethylammonium)propyl] chitosan salt (HTCS), a quaternary ammonium derivative of chitosan (CS), which benefits from non-ionizable positive charges. In this work, HTCS with a full quaternization of amino groups and a molar mass of 130,000 g·mol−1 was synthesized to use for delivery of a plasmid encoding the interleukin-12 (IL-12) gene. Thus, a polyplex based on HTCS and the IL-12 plasmid was prepared and then was characterized in terms of particle size, zeta potential, plasmid condensation ability, and protection of the plasmid against enzymatic degradation. We showed that HTCS was able to condense the IL-12 plasmid by the formation of polyplexes in the range of 74.5 ± 0.75 nm. The level of hIL-12 production following the transfection of the cells with HTCS polyplexes at a C/P ratio of 8:1 was around 4.8- and 2.2-fold higher than with CS and polyethylenimine polyplexes, respectively. These findings highlight the role of HTCS in the formation of polyplexes for the efficient delivery of plasmid DNA.

Chiral Bicyclic Imidazole-Catalyzed Direct Enantioselective C -Acetylation of Indolones

Chiral Bicyclic Imidazole-Catalyzed Direct Enantioselective <i>C</i> -Acetylation of Indolones