Amphiphilic Pyridinium Research Articles

Multi-Stimuli-Responsive Amphiphilic Pyridinium Salt and Its Application in the Visualization of Level 3 Details in Latent Fingerprints.

Organic luminescent materials that can simultaneously achieve multimode mechanochromism and its water-vapor-induced recovery are desirable for practical applications but rarely reported. Herein, an amphiphilic compound, 4-(9H-carbazol-9-yl)-1-(2-hydroxyethyl)pyridin-1-ium bromide (CPAB), was designed by integrating a lipophilic aromatic unit and hydrophilic end in the molecular architecture. Self-recovered mechanochromism from brown to cyan was observed upon mechanical grinding in air. Comprehensive research by X-ray diffraction, infrared spectroscopy, and single-crystal analysis revealed that the photoluminescence switch originated from the variation in intermolecular hydrogen bonds and molecular packing mode. The amphiphilic nature of CPAB allowed water molecules to enter the crystalline lattice, forming two polymorphs of the crystalline phase, namely CPAB-D and CPAB-W. The hydrosoluble CPAB exhibited excellent capability in probing the level 3 details of fingerprints because its lipophilic part could target the fatty acid residues of fingerprints, leading to strong aggregation-induced fluorescence. The research may inspire the design of latent fingerprint developers and application in forensics/anti-counterfeiting. This article is protected by copyright. All rights reserved.

Self-assemble nanostructured ensembles for detection of guanosine triphosphate based on receptor structure modulated sensitivity and selectivity

As one vital member of the biologically important nucleotides, guanosine-5′-triphosphate (GTP) monitoring in biological systems has become a key research field because its abnormal concentration promotes certain pathological states. Herein, we report two “cleft-form” amphiphilic pyridinium receptors based on isophthalamide (PyPh-C16) and 2,6-dicarboxamidopyridine (PyPy-C16) spacers for structure modulated sensitive and selective response to GTP via the indicator displacement assay (IDA) method. Both receptors bind with a fluorescent indicator uranine dye (UD) to form self-assembled non-fluorescent nano-aggregate ensembles, i.e.,PyPh-C16/UD and PyPy-C16/UD, which can be used for the nM detection of GTP in aqueous solution and also imaging GTP in complicated living cells environment. The non-fluorescent UD becomes fluorescent with releasing from the nano-ensembles displaced by GTP. With the aid of this phenomenon, the nano-ensembles could successfully discriminate GTP from other structurally related anions, including ATP, PPi, and most nucleotide polyphosphates (NPPs). In addition, the structure-related sensing properties of receptors toward GTP were detailly discussed. Thus, we believe that the present work will allow for many important developments in the future based on IDAs with advanced nano-ensembles and different indicators to recognize various types of essential nucleoside polyphosphates.

A computational estimation for alkyl chain effect in Schiff base pyridinium fluoride ionic liquid on chemical reactivity, thermophysical properties, pharmacokinetics, and biological activity by DFT approach

Amphiphilic pyridinium fluoride is the novel class of ionic liquid for drug discover for their biological and pharmacological activity. In this case, amphiphilic pyridinium cation was selected to this study. Changing the alkyl chain length, the effect was estimated on thermophysical, chemical, and biological activity. Using density functional theory (DFT), thermophysical and HOMO, LUMO were optimized and calculated. From HOMO, LUMO, the ionization energy, electronegativity, softness, hardness, electrophilicity (ω), and chemical potential (μ) were calculated. The HOMO, LUMO, and HOMO-LUMO gap are near to-8.85, -0.85, and 8.0. From QSAR study, the value of the Log P is from +1.5 to +2.6 as hydrophobic nature. As is observed the pharmacokinetics data, the Lipinski rule, bioavailability score, leadlikeness, solubility, and LogP o/w were calculated.

New amphiphilic pyridinium ionic liquids for demulsification of water Arabic heavy crude oil emulsions

Recently ionic liquids (ILs) have been approved recognition as environmentally safe chemicals in a wide variety of applications including petroleum industry. In the present work, new amphiphilic pyridinium ILs were synthesized via the reaction of 4-amino pyridine with 1-bromotetradecane to form quaternized amino pyridinium bromide followed by ethoxylation of the amino group to form ethoxylate amino pyridinium bromide IL (QEP). Finally, QEP was quaternized using triflouroacetic acid to produce diquaternized pyridinium bromide IL (DQEP). The surface activities of the prepared pyridinium ILs were determined in their aqueous solutions to confirm the amphiphilicity of QEP and DQEP ILs. Zeta potential measurements were also carried out to verify the positive charges on the IL colloids in their aqueous solutions. Relative solubility number values of QEP and DQEP ILs were measured to show the higher hydrophobicity of DQEP than QEP. The prepared ILs were applied as demulsifiers for water in petroleum crude oil (W/O) emulsions having different compositions. The demulsification mechanism of QEP and DQEP ILs were investigated using optical microscope, interfacial tension (IFT), RSN measurements and ILs/asphaltene interactions. The presence of QEP and DQEP was reduced the IFT to confirm their abilities on interaction with the asphaltene layer at interface to successfully dehydrate W/O emulsions. The demulsification efficiencies of QEP and DQEP reached 100% for W/O emulsion (50/50 vol%) and (30/70 and 10/90 vol%), respectively to confirm the ability of these pyridinium ILs to be applied as demulsifiers for crude oil emulsions.

ChemInform Abstract: Two‐Phase Oxidations with Aqueous Hydrogen Peroxide Catalyzed by Amphiphilic Pyridinium and Diazinium Salts.

AbstractThis novel oxidation method takes advantage of interim covalent bonding of hydrogen peroxide to an amphiphilic pyridinium or diazinium salt to increase the lipophilicity of the hydroperoxide species which eventually allows for oxidation in a non‐polar medium.

Two‐Phase Oxidations with Aqueous Hydrogen Peroxide Catalyzed by Amphiphilic Pyridinium and Diazinium Salts

AbstractAmphiphilic pyridinium and diazinium salts were shown to be effective catalysts in two‐phase (water/chloroform or water/dichloromethane) sulfoxidations and N‐oxidations with hydrogen peroxide under mild conditions. This unprecedented oxidation method utilizes covalent bonding of hydrogen peroxide to a simple pyridinium or diazinium nucleus to increase the lipophilicity of the hydroperoxide species and to subsequently activate it for oxidations in a non‐polar medium. The catalytic efficiency was found to depend on the type of heteroarenium core and on the lipophilicity of the catalyst. Five series of heteroarenium catalysts were prepared and investigated: 1‐Alkyl‐3,5‐dicyanopyridinium, 1‐alkyl‐3,5‐dinitropyridinium, 1‐alkyl‐3‐cyanopyrazinium, 1‐alkyl‐4‐cyanopyrimidinium and 1‐alkyl‐4‐(trifluoromethyl)pyrimidinium triflates (alkyl=butyl, hexyl, octyl, decyl, dodecyl and hexadecyl). Among them, the 1‐octyl‐3,5‐dinitropyridinium and 1‐decyl‐4‐(trifluoromethyl)pyrimidinium triflates were found to be superior catalysts, showing the best stability and the highest catalytic activity, achieving acceleration by a factor of 350 relative to the non‐catalyzed reaction. In contrast to other organocatalytic two‐phase oxidations that use hydrogen peroxide, the presented method is characterized by high chemoselectivity and low catalyst loading (5 mol%) and with the reactions being performed under mild conditions, that is, at 25 °C using diluted hydrogen peroxide and a non‐basic aqueous phase. The catalysts have simple structures and are readily available from commercial materials. Practical applications are demonstratedviathe oxidation of several types of sulfides and amines.magnified image

Small molecule blockers of the Alzheimer Abeta calcium channel potently protect neurons from Abeta cytotoxicity.

Alzheimer's disease (AD) is a common, chronic neurodegenerative disease that is thought to be caused by the neurotoxic effect of the Amyloid beta peptides (Abeta). We have hypothesized that the intrinsic Abeta calcium channel activity of the oligomeric Abeta polymer may be responsible for the neurotoxic properties of Abeta, and that Abeta channel blockers may be candidate AD therapeutics. As a consequence of a rational search paradigm based on the model structure of the Abeta channel, we have identified two compounds of interest: MRS2481 and an enatiomeric species, MRS2485. These are amphiphilic pyridinium salts that both potently block the Abeta channel and protect neurons from Abeta toxicity. Both block the Abeta channel with similar potency (approximately 500 nM) and efficacy (100%). However, we find that inhibition by MRS2481 is easily reversible, whereas inhibition by MRS2485 is virtually irreversible. We suggest that both species deserve consideration as candidates for Alzheimer's disease drug discovery.

De Novo Biosynthetic Profiling of High Abundance Proteins in Cystic Fibrosis Lung Epithelial Cells

In previous studies with cystic fibrosis (CF) IB3-1 lung epithelial cells in culture, we identified 194 unique high abundance proteins by conventional two-dimensional gel electrophoresis and mass spectrometry (Pollard, H. B., Ji, X.-D., Jozwik, C. J., and Jacobowitz, D. M. (2005) High abundance protein profiling of cystic fibrosis lung epithelial cells. Proteomics 5, 2210-2226). In the present work we compared the IB3-1 cells with IB3-1/S9 daughter cells repaired by gene transfer with AAV-(wild type)CFTR. We report that gene transfer resulted in significant changes in silver stain intensity of only 20 of the 194 proteins. However, simultaneous measurement of de novo biosynthetic rates with [(35)S]methionine of all 194 proteins in both cell types resulted in the identification of an additional 31 CF-specific proteins. Of the 51 proteins identified by this hybrid approach, only six proteins changed similarly in both the mass and kinetics categories. This kinetic portion of the high abundance CF proteome, hidden from direct analysis of abundance, included proteins from transcription and signaling pathways such as NFkappaB, chaperones such as HSC70, cytoskeletal proteins, and others. Connectivity analysis indicated that approximately 30% of the 51-member hybrid high abundance CF proteome interacts with the NFkappaB signaling pathway. In conclusion, measurement of biosynthetic rates on a global scale can be used to identify disease-specific differences within the high abundance cystic fibrosis proteome. Most of these kinetically defined proteins are unaffected in expression level when using conventional silver stain analysis. We anticipate that this novel hybrid approach to discovery of the high abundance CF proteome will find general application to other proteomic problems in biology and medicine.

Cleavage of 4-Nitrophenyl Diphenyl Phosphate by Isomeric Quaternary Pyridinium Ketoximes - How Can Structure and Lipophilicity of Functional Surfactants Influence Their Reactivity in Micelles and Microemulsions?

Amphiphilic pyridinium ketoximes 4-[1-(hydroxyimino)alkyl]-1-methylpyridinium bromides (1) and 1-alkyl-4-[1-(hydroxyimino)ethyl]pyridinium bromides (2) are isomeric cationic surfactants bearing the nucleophilic hydroxyimino group. They differ in the position of the nucleophilic function relative to polar head group and hydrophobic alkyl chain. The 4-nitrophenyl diphenyl phosphate (PNPDPP) cleavage by the oximate anions generated from 1 and 2 was used as a model reaction for the investigation of the influence of the structure and lipophilicity of functional surfactants on their reactivity in micelles and microemulsions. The investigation of the model reaction in cationic micelles of hexadecyltrimethylammonium bromide (CTAB), in non-ionic micelles (Triton X-100 and Brij 35) and in o/w microemulsion (isooctane/phosphate buffer/CTAB and butan-1-ol) has revealed that it is the lipophilicity which is the most important factor influencing the localization and reactivity of functional surfactants in nanoaggregates.

Amphiphilic pyridinium salts block TNFα/NFκB signaling and constitutive hypersecretion of interleukin-8 (IL-8) from cystic fibrosis lung epithelial cells

Cystic fibrosis (CF) is a common, lethal genetic disease, which is due to mutations in the CFTR gene. The CF lung expresses a profoundly proinflammatory phenotype, due to constitutive hypersecretion of IL-8 from epithelial cells lining the airways. In a systematic search for candidate drugs that might be used therapeutically to suppress IL-8 secretion from these cells, we have identified a potent and efficacious series of amphiphilic pyridinium salts. The most potent of these salts is MRS2481, an ( R)-1-phenylpropionic acid ester, with an IC 50 of ca. 1 μM. We have synthesized 21 analogues of MRS2481, which have proven sufficient to develop a preliminary structure–activity relationship (SAR). For optimal activity, we have found that the ester must be connected to the pyridinium derivative by an eight-carbon chain. An optical isomer of the lead compound, containing an ( S)-1-phenylpropionic acid ester, has been found to be a much less active. The mechanism of action of MRS2481 appears to involve inhibition of signaling of the NFκB and AP-1 transcription factors to the IL-8 promoter. MRS2481 is a potent inhibitor of TNFα-induced phosphorylation and proteosomal destruction of IκBα. Inasmuch as IκBα is the principal inhibitor of the NFκB signaling pathway, preservation of intact IκBα would serve to keep the IL-8 promoter silent. We also find that MRS2481 blocks TNFα-activated phosphorylation of JNK, the c-JUN kinase. The IL-8 promoter is also activated by an AP-1 site, which requires a phospho-c-JUN/c-FOS dimer for activity. We therefore interpret these data to suggest that the mechanism of MRS2481 action is to inhibit both NFκB and AP-1 signaling on the IL-8 promoter. Given the medicinally promising properties of water-solubility, potency in the low μM concentration range, and high efficacy, we anticipate that MRS2481, or a further optimized derivative, may find an important place in the armamentarium of pharmaceutical strategies yet to be arrayed against the inflammatory phenotype of the CF lung.

A2-rhodopsin: a new fluorophore isolated from photoreceptor outer segments.

A2E and iso-A2E are fluorescent amphiphilic pyridinium bisretinoids involved in age-related macular degeneration (AMD). It is now shown that the presence of high exogenous concentrations of all-trans-retinal in photoreceptor outer segments leads to the formation of A2-rhodopsin (A2-Rh), an unprecedented fluorescent rhodopsin adduct which consists of bisretinoids (A2) linked to each of three lysine residues in rhodopsin (Rh) and which exhibits an emission spectrum similar to A2E. The fluorophore to protein ratio was determined by MALDI-TOF-MS and UV-VIS spectroscopy. Enzymatic degradation with thermolysin and cathepsin D showed that two of the A2 moieties were located in the region of the third cytoplasmic loop and 8th helix of Rh. Examination of A2-Rh and A2-PE (the precursor of A2E) fluorescence in relation to all-trans-retinal concentration indicated that whereas A2-PE formation is favored over that of A2-Rh, for a single rhodopsin molecule only one phosphatidylethanolamine molecule is available to react with all-trans-retinal; this phosphatidylethanolamine is probably tightly associated with the protein.

Preparation and characterisation of conductive Langmuir–Blodgett films of amphiphilic pyridinium–ni(dmit)2salts

The behaviour of (N-octadecylpyridinium)–Ni(dmit)2 at the air/water interface has been investigated, and Langmuir–Blodgett (LB) films have been built up on a variety of substrates. LB layers deposited from freshly spread, floating films are composite structures, containing aggregates of micrometre dimensions. True monolayers are obtained only if the floating film is left for several hours on the subphase surface in its uncompressed state. The spectroscopic and electrical properties of both types of LB film are reported. For the composite layers, stable, in-plane do conductivity values of up to 0.2 S cm–1 are obtained after doping in iodine vapour. However, LB films built up from floating monolayers are not conductive, either in their as-deposited state or following iodine doping.