Organic Counterions Research Articles

Pharmaceutical Salts of Piroxicam and Meloxicam with Organic Counterions.

Piroxicam (PRM) and meloxicam (MEL) are two nonsteroidal anti-inflammatory drugs, belonging to the Biopharmaceutics Classification System Class II drugs. In this study, six novel pharmaceutical salts of PRM and MEL with three basic organic counterions, that is, 4-aminopyridine (4AP), 4-dimethylaminopyridine (4DMP), and piperazine (PPZ), were prepared by both slurrying and slow evaporation. These salts were characterized by single-crystal and powder X-ray diffraction, thermal analysis, and Fourier transform infrared spectroscopy. All six salts, especially MEL-4DMP and MEL-4AP, showed a significantly improved apparent solubility and dissolution rate in sodium phosphate solution compared with the pure APIs. Notably, PRM-4AP and PRM-4DMP salts exhibited enhanced fluorescence, and the PRM-PPZ salt showed weaker fluorescence compared with that of pure PRM due to different luminescence mechanisms.

Enhanced electrorheological effectiveness and temperature effect of suspensions based on poly(ionic liquid)s neutralized with mixed counterions

A series of random co-poly(ionic liquid)s (co-PILs) neutralized with mixed counterions of organic bis(trifluoromethane sulfonyl)imide ([TFSI]) and inorganic tetrafluoroborate ([BF 4 ]) of different mole ratio had been synthesized for use as electrorheological (ER) particles. The temperature-modulated ER effect of the co-PIL particles had been investigated and compared with that of homo-poly(ionic liquid)s neutralized with single organic [TFSI] counteranions. This work demonstrated that the ER effectiveness and temperature effect of electrorheological fluid based on neat organic counteranions-typed PILs can be significantly improved by a simple substitution of inorganic counteranions with a suitable mole ratio. The higher electrorheological effectiveness with suppressed leakage current density and enhanced temperature stability originated from that the substitution of inorganic counteranions for organic counteranions could systematically elevate the glass transition temperature and modulate the activation energy of ion movement in PILs matrix. Linear polymeric ionic liquids (PILs) neutralized with mixed counteranions of organic ([TFSI]) and inorganic ([BF 4 ]) could exhibit higher ER effectiveness and broader working temperatures range than the analogous PILs neutralized with single organic counteranions. • PILs containing organic and inorganic counterions of various mole ratio was prepared for use as electrorheological particles. • Partial replacement of [TFSI] by [BF 4 ] could improve the electrorheological effectiveness and thermal stability of PILs. • Partial replacement of [TFSI] by [BF 4 ] could modulate the glass temperature and ionic shifting activation energy of PILs.

The novel U(VI) and Np(VI) mixed-ligand complexes based on quinaldic acid zwitterion

Interaction of U(VI) and Np(VI) with quinaldic acid in the presence of various inorganic (nitrate, chloride, bromide, perrhenate, selenate, sulfate) or organic (dipicolinic acid) counter-ions allowed obtaining a series of complexes where quinaldic acid presents in the zwitterionic form. In all compounds, except one complex, quinaldic acid acts as a monodentate ligand and coordinates metal centers via one of the carboxylic oxygen atoms. In all these cases, isolated molecular complexes are formed. In contrast, uranyl sulfate exhibits 2D layered structure where both sulfate-ions and molecules of quinaldic acid function as linkers. Determination of stability constants for 1:1 complexes has shown that the complexation of U(VI) and Np(VI) with quinaldic acid in solution likely occurs via coordination of the carboxylic group. Prevalence of the zwitterionic form and the coordination via carboxylic group both in solution and solid-state is unexpected taking into account similarity in structures of quinaldic and picolinic acids.

Ion migration suppression mechanism via 4-sulfobenzoic acid monopotassium salt for 22.7% stable perovskite solar cells

The deep-level traps at grain boundaries (GBs) and halide ion migration are quite challenging for further enhancement of the stability and efficiency of perovskite solar cells (PSCs) as well as for the elimination of notorious hysteresis. Herein, we report a large-sized strongly coordinated organic anion GB anchoring strategy for suppressing ion migration and passivating defects in planar PSCs. The practical implementation of this strategy involves the incorporation of potassium salts containing a large-sized organic counter anion (4-sulfobenzoic acid monopotassium salt, SAMS) into the perovskite precursor. It has been found that anions within SAMS can be firmly anchored at GBs due to the strong coordination interaction between C=O and/or S=O at both ends of bulky anion and undercoordinated Pb2+ and/or halide vacancies, along with the hydrogen bond between −OH and formamidinium. SAMS can not only passivate shallow-level defects but also cause more effective passivation of the deep-level defects. The GB manipulation strategy results in a reduced defect density, an increased carrier lifetime as well as suppressed ion migration, which in turn contributed to enhanced efficiency and stability of PSCs together with a thorough elimination of hysteresis. As a result, the SAMS-modified device with an outstanding fill factor of 0.84 delivers a significant improvement in efficiency (22.7%) in comparison with the control device (20.3%). The unencapsulated modified device demonstrates only little degradation after 1320 h at 60°C.

Electro-responsive electrorheological effect and dielectric spectra analysis of topological self-crosslinked poly(ionic liquid)s

By changing the amount of vinylimidazole grafted on phenyl ring, we designed and prepared a series of topological self-crosslinked poly(ionic liquid)s (TS-PILs) with different number of spacer arms by free radical polymerization. The influences of the number of spacer arms on the electrorheological (ER) effect of TS-PILs in insulating carrier liquid were studied by rheological test under electric stimulus and the influence mechanism was analyzed by broadband dielectric spectroscopy. It was found that the ER effect of TS-PILs containing organic counterion bis(trifluoromethane sulfonylimide) (TFSI-) increased with the increase of the number of spacer arms. Broadband dielectric spectra analysis showed that the increased ER effect with the number of spacer arms was attributed to the increase of interfacial polarization strength and the decrease of electrode polarization with the number of spacer arms. Activation energy analysis indicated that increasing the number of spacer arms could promote ion pair dissociation and ion number density but inhibit long-range movement of ions, which was responsible for the increase of interfacial polarization strength and the decrease of electrode polarization. The results provided a guidance insight for the design and preparation of high-performance crosslinked PIL-based ER materials.

Caging Polycations: Effect of Increasing Confinement on the Modes of Interaction of Spermidine3+ With DNA Double Helices.

Polyamines have important roles in the modulation of the cellular function and are ubiquitous in cells. The polyamines putrescine2+, spermidine3+, and spermine4+ represent the most abundant organic counterions of the negatively charged DNA in the cellular nucleus. These polyamines are known to stabilize the DNA structure and, depending on their concentration and additional salt composition, to induce DNA aggregation, which is often referred to as condensation. However, the modes of interactions of these elongated polycations with DNA and how they promote condensation are still not clear. In the present work, atomistic molecular dynamics (MD) computer simulations of two DNA fragments surrounded by spermidine3+ (Spd3+) cations were performed to study the structuring of Spd3+ “caged” between DNA molecules. Microsecond time scale simulations, in which the parallel DNA fragments were constrained at three different separations, but allowed to rotate axially and move naturally, provided information on the conformations and relative orientations of surrounding Spm3+ cations as a function of DNA-DNA separation. Novel geometric criteria allowed for the classification of DNA-Spd3+ interaction modes, with special attention given to Spd3+ conformational changes in the space between the two DNA molecules (caged Spd3+). This work shows how changes in the accessible space, or confinement, around DNA affect DNA-Spd3+ interactions, information fundamental to understanding the interactions between DNA and its counterions in environments where DNA is compacted, e.g. in the cellular nucleus.

Novel pharmaceutical salts of cephalexin with organic counterions: structural analysis and properties.

Three novel pharmaceutical salts of cephalexin (CPX) with 2,6-dihydroxybenzoic acid (DHBA), 5-chlorosalicylic acid (CSA) and 5-sulfosalicylic acid (SSA), which were obtained and thoroughly explored by various analytical techniques, were found to be crystallized invariably in hydrated forms. It is the proton transfer from carboxylic or sulfonic counterions to the CPX molecules that results in the salt formation. Crystal structure analyses reveal that the N-H⋯O and O-H⋯O hydrogen bonding interactions among the CPX, acidic guest molecules and water molecules play a crucial role in the packing motifs of crystal stabilization. All the salts exhibit higher solubility compared with the parent drug. These salts offer an alternative way of increasing the number of solid forms for CPX, which facilitates selection of a suitable form in the context of drug formulation development for further repurposing investigations.

Counterions determine uptake and effects of aluminum in human intestinal and liver cells

Aluminum (Al) is highly abundant in the biosphere and can occur in different physico-chemical states. It is present in human food and undergoes transitions between dissolved and particulate species during the passage of the gastrointestinal tract. Moreover, in a complex matrix such as food different inorganic and organic counterions can affect the chemical behavior of Al following oral uptake.In this work, the effects of different counterions, namely chloride, citrate, sulfate, lactate and acetylacetonate, on Al uptake and toxicity in the human intestine are studied. The respective Al salts showed different dissolution behavior in biological media and formed nanoscaled particles correlating in reverse with the amount of their dissolved fraction. The passage through the intestinal barrier was studied using a Caco-2 Transwell® system, showing counterion-dependent variance in cellular uptake and transport. In addition, Al toxicity was investigated using Al species (Al3+, metallic Al0 and oxidic γAl2O3 nanoparticles) and counterions individually or in mixtures on Caco-2 and HepG2 cells. The strongest toxicity was observed using a combination of Al species, depending on solubility, and the lipophilic counterion acetylacetonate. Notably, only the combination of both led to toxicity, while both substances individually did not show toxic effects. A toxification of previously non-toxic Al-species by the presence of acetylacetonate is shown here for the first time. The dependency on the concentration of free Al ions was demonstrated using sodium hydrogen phosphate, which was able to counteract the toxic effects by complexing free Al ions.These findings, using Al salts as an example for a common food contaminant, underline the importance of a consideration of the chemical properties of human nutrition, especially dissolution and hydrophobicity, which can significantly influence the cellular uptake and effects of xenobiotic substances.

Effects of cationic counterions and surfactant on viscosity of an amino acid-based surfactant system

Many sulfate-free and amino acid-based surfactant systems for personal care formulations do not respond to thickening with salt and/or amphoteric cosurfactants as readily as traditional sulfate-based formulations. Although this phenomenon is generally understood to be associated with large headgroups, the mechanistic basis for the difference is poorly understood. To address this question we have combined an empirical approach involving traditional determination of low shear viscoelasticity with a state-of-the-art mesoscopic analysis of micelle dynamics enabled by high frequency rheological measurements obtained optically (Zou and Larson, Journal of Rheology 2014, 58 (3), 681-721) We studied the impact of various organic and inorganic counterions as well as a cationic surfactant as alternative thickening agents for a model formulation of sodium lauroyl sarcosinate (SLSar) and cocamidopropyl hydroxysultaine (CAHS). These additives include lithium chloride (LiCl), sodium chloride (NaCl), L-arginine (Arg), triethanolamine (TEA), trimethylphenylammonium chloride (TMPAC), and cetyltrimethylammonium chloride (CTAC). The zero-shear viscosity for all systems studied was obtained using steady-state rheology at varying concentration and pH. The viscoelastic properties of systems containing an effective thickener (CTAC 1%) and an ineffective one (LiCl 1%) were obtained over a frequency range of 1–105 rad/s and subjected to the Zou and Larson analysis. The analysis showed that the high viscosity in the CTAC 1% system was associated with the combination of a high plateau modulus and a long relaxation time. The low viscosity in LiCl 1% system was attributable to the fast breakage time and high breakage rate constant. The latter result was consistent with findings from a previous study comparing the SLSar/CAHS system to a sodium lauryl ether sulfate/cocamidopropyl betaine (SLES/CAPB) formulation.

Pharmaceutical Salts of Fenbendazole with Organic Counterions: Structural Analysis and Solubility Performance

Pharmaceutical Salts of Fenbendazole with Organic Counterions: Structural Analysis and Solubility Performance

Ion Pairs for Transdermal and Dermal Drug Delivery: A Review.

Ion pairing is a strategy used to increase the permeation of topically applied ionised drugs. Formation occurs when the electrostatic energy of attraction between oppositely charged ions exceeds their mean thermal energy, making it possible for them to draw together and attain a critical distance. These ions then behave as a neutral species, allowing them to partition more readily into a lipid environment. Partition coefficient studies may be used to determine the potential of ions to pair and partition into an organic phase but cannot be relied upon to predict flux. Early researchers indicated that temperature, size of ions and dielectric constant of the solvent system all contributed to the formation of ion pairs. While size is important, this may be outweighed by improved lipophilicity of the counter ion due to increased length of the carbon chain. Organic counter ions are more effective than inorganic moieties in forming ion pairs. In addition to being used to increase permeation, ion pairs have been used to control and even prevent permeation of the active ingredient. They have also been used to stabilise solid lipid nanoparticle formulations. Ion pairs have been used in conjunction with permeation enhancers, and permeation enhancers have been used as counter ions in ion pairing. This review attempts to show the various ways in which ion pairs have been used in drug delivery via the skin. It also endeavours to extract and consolidate common approaches in order to inform future formulations for topical and transdermal delivery.

Binding behaviour of hydrophobic drug tetracaine hydrochloride used as organic counterion on ionic surfactants

Many excipients have been used in the formulation of medications to improve drug properties during the drug delivery process. Current research may show that hydrophobic drugs can be used as organic counterions that improve the excipients properties of the medicine formulation. We have used the anesthetic cationic drug tetracaine hydrochloride (TC) as an organic counterion and anionic surfactant, sodium bis(2-ethylhexyl) sulfosuccinate (AOT) and sodium dodecyl sulfate (SDS) for this system. In aqueous media, TC significantly reduced the critical micelle concentration (CMC) of AOT and SDS. The counterion binding (B) and binding constant (Kb) values revealed that AOT micelles had a stronger interaction with TC than SDS micelles. Therefore, TC as an organic counterion could improve the micellization of surfactants. The UV spectroscopy experiment has also been used to estimate the TC mean ion occupancy (i0) per AOT/SDS micelles. We found that i0 values were 113.6 and 23.27 for AOT and SDS, respectively. These results indicated the i0 values were controlled by electrostatic interaction between drug and surfactants. Dynamic light scattering (DLS) and Transmission electron microscopy (TEM) measurement provided that the catanionic vesicle was formed with increased TC concentration. Finally, we concluded that the above formulation could be used to enhance interaction properties between the medicine and excipients in the pharmaceutical application.

Double Free: A Promising Route toward Moisture-Stable Hypotoxic Hybrid Perovskites

Double Free: A Promising Route toward Moisture-Stable Hypotoxic Hybrid Perovskites

Role of Surfactants Based on Fatty Acids in the Wetting Behavior of Solid-Oil-Aqueous Solution Systems.

Surfactants based on fatty acids have attracted extensive attention thanks to their eco-friendly and pH-responsive features. Here, we studied two fatty acid-based surfactants that were paired with the same organic counterion but distinguished by their aliphatic chain lengths (monoethanolamine-oleic acid (MEA-OA) and monoethanolamine-lauric acid (MEA-LA)). Both surfactants exhibited the ability to lower the oil-water interfacial tension but lost their interfacial activity in a low-pH environment. We experimentally investigated their influence on the receding and spreading of oil droplets on solid surfaces. It was found that the interfacial tension reduction could decrease the static contact angle of the aqueous phase and hindered displacement dynamics during the oil droplet receding. Meanwhile, the interfacial activity was more likely to suppress the initiation of the oil droplet spreading due to the more stable thin-film forming prior to the spreading process. Nevertheless, the experimental results also exhibited that MEA-OA was more effective than MEA-LA in suppressing the receding dynamics and the spreading initiation even when they were characterized by similar interfacial tension values. Such an interesting observation could be attributed to the more considerable Marangoni flow in the solution of MEA-OA whose molecules have longer aliphatic chains. The insight from this study is expected to improve the knowledge on the molecular design for more efficient applications of fatty acid-based surfactants.

Poly(Pyridinium Salt)s Containing 2,7-Diamino-9,9'-Dioctylfluorene Moieties with Various Organic Counterions Exhibiting Both Lyotropic Liquid-Crystalline and Light-Emitting Properties.

A series of poly(pyridinium salt)s-fluorene main-chain ionic polymers with various organic counterions were synthesized by using ring-transmutation polymerization and metathesis reactions. Their chemical structures were characterized by Fourier Transform Infrared (FTIR), proton (1H), and fluorine 19 (19F) nuclear magnetic resonance (NMR) spectrometers. These polymers showed a number-average molecular weight (Mns) between 96.5 and 107.8 kg/mol and polydispersity index (PDI) in the range of 1.12–1.88. They exhibited fully-grown lyotropic phases in polar protic and aprotic solvents at different critical concentrations. Small-angle X-ray scattering for one polymer example indicates lyotropic structure formation for 60–80% solvent fraction. A lyotropic smectic phase contains 10 nm polymer platelets connected by tie molecules. The structure also incorporates a square packing motif within platelets. Thermal properties of polymers were affected by the size of counterions as determined by differential scanning calorimetry and thermogravimetric analysis measurements. Their ultraviolet-visible (UV-Vis) absorption spectra in different organic solvents were essentially identical, indicating that the closely spaced π-π* transitions occurred in their conjugated polymer structures. In contrast, the emission spectra of polymers exhibited a positive solvatochromism on changing the polarity of solvents. They emitted green lights in both polar and nonpolar organic solvents and showed blue light in the film-states, but their λem peaks were dependent on the size of the counterions. They formed aggregates in polar aprotic and protic solvents with the addition of water (v/v, 0–90%), and their λem peaks were blue shifted.

Comment on the article The Cambridge Structural Database in chemical education: analysis of hydrogen-bonded networks in salts of hexaaqua metal ions with organic counter-ions

Comment on the article <i>The Cambridge Structural Database in chemical education: analysis of hydrogen-bonded networks in salts of hexaaqua metal ions with organic counter-ions</i>

Investigation the effect of sodium carboxymethylcellulose as polycounterion on cetirizine hydrochloride–sodium dodecyl sulphate mixed micelle

The aim of this research was to investigate the binding properties of sodium carboxymethylcellulose (NaCMCu) as polycounterions on mixed micelles of drug surfactants. Mixed micellization behavior of cetirizine hydrochloride (CTZ) and sodium dodecyl sulphate (SDS) was investigated in the absence and presence of NaCMCu using electrical conductivity, surface tension, fluorescence measurements, dynamic light scattering and UV measurements. The critical micelle concentration (CMC) in the aqueous and NaCMCu medium of CTZ + SDS mixed micelle was lower than the single micelle of CTZ and SDS. The presence of electrostatic interaction between NaCMCu and CTZ + SDS could increase the stability of mixed micelle from αSDS 1.0–0.0. The results showed that CTZ + SDS monomers could bind to the NaCMCu chains and form free mixed micelles in the solution, whereas no SDS / NaCMCu micelle-like complexes were found due to repulsive interaction. NaCMCu significantly decreased the CMC of CTZ. The values of counterion binding (B) from Corrin–Harkins approach and binding constant (Kb) indicated that the CTZ micelles bound to electrostatic interaction by –COO¯ ions of NaCMCu. UV absorbance data given a significant parameter, mean ion occupancy per micelle (i0) which estimated the occupancy per micelle of polycounterions for αSDS 1.0–0.0. However, the turbidity data and micellar size showed that the amount of NaCMCu increased, and the mixed micellar size also increased. Eventually, this system demonstrated that polyelectrolyte was used as an organic counterion to improve the micellar properties of amphiphilic drugs for the formulation of pharmaceutical medicinal products.

The Cambridge Structural Database in chemical education: analysis of hydrogen-bonded networks in salts of hexaaqua metal ions with organic counter-ions

This paper describes a laboratory course that introduces basic crystallographic data analysis to chemistry students encountering for the first time the world of crystals and crystal structures. The aim of the course is to provide students with direct contact with crystal structures and hands-on experience in structure analysis. To this end, a set of appropriately simple inorganic molecular structures was selected, consisting of salts of hexaaqua metal ions with organic counter-ions. By exploiting the crystallographic tools available in the Cambridge Structural Database program Mercury, students learn how to visualize and analyse a set of atomic coordinates. In this way they learn how to extract bonding and structural information concerning intramolecular interactions in both salt components. Intermolecular interactions are next analysed by looking closely at supramolecular motifs and packing patterns generated by hydrogen bonds. This pragmatic approach turned out to be effective and extremely useful for summarizing many chemical concepts learned by students during a bachelor degree course in chemistry. The experience provides at the same time some basic capabilities for properly managing crystal structure analysis.

1,2,3-Triazole based poly(ionic liquids) as solid dielectric materials

1,2,3-triazole based polyionic liquids (PIL) are an emerging field among polymeric dielectrics in organic electronics. 1,2,3-triazole based PILs can be obtained from poly(4-vinylbenzylchloride) by copper-catalyzed azide-alkyne cycloaddition (CuAAC) ‘click’ reaction. The polymer architecture and the charge of the PILs can be manipulated by choosing a suitable alkyne, azide containing moiety, and by the alkylation of the 1,2,3-triazole group. Thus, we were able to prepare PILs carrying either inorganic (Na+ or Cl−) or the organic counterions 1-butyl-3-methyl-imidazolium (C4mim+) or 1-butyl-3-methyl-imidazolium (TFSI−). Metal-insulator-metal capacitors were fabricated and the dielectric properties were characterized through electrochemical impedance spectroscopy. The PILs demonstrated an increase in capacitance density with decreasing frequency, characteristic for the polarization of the polymer layer and electrical double layer formation. Substitution of inorganic counterions with organic counterions improved the transition frequency of the capacitors and the conductivity of the polymers. This was due to increased ion mobility and decreased glass transition temperatures.

Role of the organic counterions on the protonation of Strandberg-type phosphomolybdates

Strandberg-type phosphomolybdate anions are metal-oxide clusters with general formula [HnP2Mo5O23](6−n)− (n = 0, 1, 2). The protonation/deprotonation of this anion affects its redox properties. Herein, we explain how to select the organic counterions to direct the synthesis towards the non-protonated or protonated anion. The method is illustrated with the synthesis of two new compounds (C5H16N2)3[P2Mo5O23]·4H2O (1) and (CH6N)4[H2P2Mo5O23].CH5N·4H2O (2). The two compounds were characterized by UV–Visible absorption, IR spectroscopy and single crystal X-ray diffraction. Their thermal stabilities and redox properties were also investigated.