Ion-pair Complex Research Articles

Capture and displacement-based release of the bicarbonate anion by calix[4]pyrroles with small rigid straps.

Two-phenoxy walled calix[4]pyrroles 1 and 2 strapped with small rigid linkers containing pyridine and benzene, respectively, have been synthesized. 1H NMR spectroscopic analyses carried out in CDCl3 revealed that both of receptors 1 and 2 recognize only F− and HCO3− among various test anions with high preference for HCO3− (as the tetraethylammonium, TEA+ salt) relative to F− (as the TBA+ salt). The bound HCO3− anion was completely released out of the receptors upon the addition of F− (as the tetrabutylammonium, TBA+ salt) as a result of significantly enhanced affinities and selectivities of the receptors for F− once converted to the TEAHCO3 complexes. Consequently, relatively stable TEAF complexes of receptors 1 and 2 were formed via anion metathesis occurring within the receptor cavities. By contrast, the direct addition of TEAF to receptors 1 and 2 produces different complexation products initially, although eventually the same TEAF complexes are produced as via sequential TEAHCO3 and TBAF addition. These findings are rationalized in terms of the formation of different ion pair complexes involving interactions both inside and outside of the core receptor framework.

Ultrafast photoinduced electron transfer in conjugated polyelectrolyte–acceptor ion pair complexes

Conjugated polyelectrolytes (CPEs) are a promising class of materials for photovoltaic and sensing applications due to their ability to undergo efficient photoinduced electron transfer (ET).

Development of simple spectrophotometry method to determinate pitavastatin calcium in bulk and pharmaceutical preparations

An accurate, precise, sensitive and direct extraction-free simple spectrophotometry method has been developed and applied to determine Pitavastatin calcium (PTV) in raw material and tablets preparations. This Spectrophotometry method is based on the formation of yellow colored ion-pair complex in chloroform by Bromocresol Green (BCG). The complex has maximum absorptivity at 416 nm. The variable factors affecting the reaction such as solvents, time, and temperature and reagent concentration were studied and optimized to achieve the best results. Beer's law is obeyed over concentration ranges (2–24) μg/mL. Regression analysis showed a good correlation coefficient R2 = 0.9994. The limit of detection (LOD) and limit of quantification (LOQ) were to be 0.19μg/mL and 0.59μg/mL respectively and the molar absorptivity coefficient 61706 L/mole/cm. The average percent recovery was calculated and it was in range 98.59–101.97% for Pitavastatin calcium. All studied samples showed that the drug levels were confirmed due to Japanese pharmacopeia legislation.

Determination of Atenolol in Tablet Formulation by Analytical Spectrophotometry

Simple and rapid spectrophotometric method has been developed for the determination of Atenolol in bulk and tables formulation. The method is based on the formation of yellow ion-pair complex between Atenolol and Bromocresol green in 1, 2-dichloroethane medium. The maximum absorption of the complex was found to be 414nm. Different parameters affecting the reaction were optimized such as: effect of solvents, time, reagent concentration, correlation ratio, etc. The formed complex was quantified spectrophotometrically at maximum absorption. Linearity range was 2.66–26.63μg/mL. Regression analysis showed a good correlation coefficient R2 = 0.9999. The limit of detection (LOD) and limit of quantification (LOQ) were to be 0.22μg/mL and 0.66 μg/mL. The average percent recovery was found to be (97.23–101.53)% for Atenolol. The method was successfully applied for the determination of Atenolol in pharmaceutical tablets formulation in six Syrian pharmaceutical trademarks: (Tenormin MPI 100, Tenormin MPI 50, Hypoten UNIPHARMA 100, Hypoten UNIPHARMA 50, Normoten BARAKAT 100 and Normoten BARAKAT 50). The proposed method is simple, direct, sensitive and do not require any extraction process. Thus, this method could be readily applicable for the quality control and routine analysis.

The Improved Cargo Loading and Physical Stability of Ibuprofen Orodispersible Film: Molecular Mechanism of Ion-Pair Complexes on Drug-Polymer Miscibility

High drug cargo loading in polymer and physical stability was essential for the development of orodispersible films (ODFs) because of the small amount of excipients used in a thin film. The present study aimed to investigate the mechanism of ion-pair strategy in improving drug cargo loading and physical stability of drug in ODFs. The results showed that the ion pair, especially ibuprofen-ethanolamine, improved the drug solubility in polymer up to 60% (w/w) and physical stability by 30% than the pure ibuprofen film. In addition, drug dissolution rate was increased over 2 times. The high drug cargo loading, physical stability and drug dissolution rate was derived from the improved the drug-polymer miscibility introduced by the formation of ion-pair complex. Investigations from the standpoint of physicochemical properties, intermolecular interaction, and polymer mobility indicated the modulation mechanism of ion-pair complexes in the ODFs at molecular level. The amino group and −OH of counter ion exhibited strong hydrogen bond forming ability, which increased the bilateral interaction with both drug and polymer, delayed the onset temperature of sublimation and decreased the polymer mobility. Therefore, ion-pair technology is a promising strategy for high drug loading ODFs in improving the drug-excipient miscibility and stability.

The Green Box: An Electronically Versatile Perylene Diimide Macrocyclic Host for Fullerenes.

The powerful electron accepting ability of fullerenes makes them ubiquitous components in biomimetic donor-acceptor systems that model the intermolecular electron transfer processes of Nature's photosynthetic center. Exploiting perylene diimides (PDIs) as components in cyclic host systems for the noncovalent recognition of fullerenes is unprecedented, in part because archetypal PDIs are also electron deficient, making dyad assembly formation electronically unfavorable. To address this, we report the strategic design and synthesis of a novel large, macrocyclic receptor composed of two covalently strapped electron-rich bis-pyrrolidine PDI panels, nicknamed the "Green Box" due to its color. Through the principle of electronic complementarity, the Green Box exhibits strong recognition of pristine fullerenes (C60/70), with the noncovalent ground and excited state interactions that occur upon fullerene guest encapsulation characterized by a range of techniques including electronic absorption, fluorescence emission, NMR and time-resolved EPR spectroscopies, cyclic voltammetry, mass spectrometry, and DFT calculations. While relatively low polarity solvents result in partial charge transfer in the host donor-guest acceptor complex, increasing the polarity of the solvent medium facilitates rare, thermally allowed full electron transfer from the Green Box to fullerene in the ground state. The ensuing charge separated radical ion paired complex is spectroscopically characterized, with thermodynamic reversibility and kinetic stability also demonstrated. Importantly, the Green Box represents a seminal type of C60/70 host where electron-rich PDI motifs are utilized as recognition motifs for fullerenes, facilitating novel intermolecular, solvent tunable ground state electronic communication with these guests. The ability to switch between extremes of the charge transfer energy continuum is without precedent in synthetic fullerene-based dyads.

8-Hydroxyquinoline Anchoring 3-D Networking Silica Gel Utilizing Its HOMO as a Metal Trapping Center for Selective Sample Cleanup of Cu(II), Cr(III), and Co(II) and Chemical Speciation of Sorbed Species

8-Hydroxyquinoline has been chemically anchored on three-dimensional networking silica gel (SG) for selective sample cleanup of Co(II), Cr(III), and Cu(II) amidst several other naturally occurring ions as matrix. The extractor, utilizing its frontier orbital makes a 1:1 “ion-pair complexation” with different aqua species of Co(II), Cr(III), and Cu(II), identified as {Co2(OH)(H2O)4}3+, {Cr3(OH)4(H2O)10}5+, and {Cu2(OH)2(H2O)3}2+, through first-order sorption kinetics. The chemically stable (4 M HNO3) reusable material (820 cycles) attains an appreciable breakthrough capacity (BTC) of 557, 835, and 552 μmol·g–1, respectively, for Co(II), Cr(III), and Cu(II). The process is endothermic and spontaneous and becomes more ordered upon an eventual consequence of sorption. After sorption, exploiting the differences in the stripping behavior, the analytes were sequentially resolved and retrieved with selective eluents (Co(II): 0.01 M HNO3, Cr(III): 0.05 M H2SO4 and Cu(II): 0.1 M HCl) of minimum volume (4 mL) to att...

Elucidating the Anomalous Binding Enhancement of Isoquinoline Boronic Acid for Sialic Acid Under Acidic Conditions: Expanding Biorecognition Beyond Vicinal Diols.

A zwitterionic heterocyclic boronic acid based on 4-isoquinolineboronic acid (IQBA) exhibits the highest reported binding affinity for sialic acid or N-acetylneuraminic acid (Neu5Ac, K=5390±190 m-1 ) through the formation of a cyclic boronate ester complex under acidic conditions (pH 3). This anomalous pH-dependent binding enhancement does not occur with common neutral saccharides (e.g., glucose, fructose, sorbitiol), because it is mediated via selective complexation to a α-hydroxycarboxylate moiety forming a stable ion pair and ternary complex with Neu5Ac in phosphate buffer. IQBA expands biorecognition beyond classical vicinal diols under neutral or alkaline buffer conditions, which enables the direct analysis of Neu5Ac by native fluorescence with sub-micromolar detection limits.

Cloud point extraction for separation, preconcentration and determination zinc (ii) in different pharmaceutical samples

Joining solvent extraction with cloud point extraction methods obtained a susceptible method for separation, pre-concentration, extraction and categorization of Zn (II), after forming an ion-pair association complex between Zn+2 and 4-(3-methyl phenyl azo)-4,5- diphenyl imidazole (MPADPI) with wavelength for maximum absorbance λmax.=496 Nm. This study shows optimum conditions for the formation and exaction ion-pair association complex under pH=9 and 0.5 mL Tritonx-100, 1×10-4 M (MPADPI) and heating at 80 Co for 20 minutes so that this study involved the effect of electrolyte and interferences along with the spectrophotometric determination of Zinc (II) in diverse samples.

Development of a Novel Simple Gel Formulation Containing an Ion-Pair Complex of Diclofenac and Phenylephrine

Background and Aim: Since the pharmacological effects of diclofenac (DF) are short-lived because of its short half-life, prolongation of the pharmacological effect in a topical formulation is needed for more appropriate clinical use. For the enhancement of dermal accumulation and prolongation of the pharmacological effect of drugs, the aim of this study was to develop a simple gel formulation containing an ion-pair complex of DF and phenylephrine (PHE), which induce constriction of the vascular smooth muscles. Materials and Methods: The ion-pair complex was prepared by mixing sodium DF and an ethanolic solution of PHE. The formed complex was characterized by powder X-ray diffraction (PXRD) and Fourier-transform infrared (FT-IR) spectroscopy. The ion-pair complex for the gel formulation was prepared by mixing an equimolar concentration of 50% 1,3-butylene glycol and distilled aqueous solution of 2% xanthan gum, which was characterized by proton nuclear magnetic resonance (¹H-NMR). Skin permeation and accumulation of DF and PHE were evaluated by in vitro and in vivo studies. Results: From the results of PXRD and FT-IR, it was suggested that new crystalline peaks formed by the ion-pair complex and their complex interacted with the carboxyl group in DF and the amino group in PHE. In the gel formulation, the ion-pair complexes were detected by ¹H-NMR. The ion-pair complex enhanced the accumulation of DF in the skin in the in vitro study. On the other hand, PHE accumulation in the dermis increased with the ion-pair complex, as exhibited by the in vivo study. Conclusion: A new gel formulation containing the ion-pair complex of DF and PHE was developed, which improved the accumulation of DF in skin.

SPECTROPHOTOMETRIC DETERMINATION OF ATORVASTATIN CALCIUM AND PITAVASTATIN CALCIUM THROUGH ION-PAIR COMPLEX FORMATION USING ACID DYES IN PHARMACEUTICAL FORMULATIONS AND HUMAN URINE SAMPLES

Objective: The main objective was to develop simple, cost-effective, rapid and selective spectrophotometric methods for the determination of atorvastatin calcium and pitavastatin calcium in pure and pharmaceutical formulations using acid dyes like bromothymol blue, bromocresol purple and bromocresol green and also in human urine samples.
 Methods: The developed methods were based on the formation of ion-pair complexes between statin drugs and acid dyes after studying the optimization conditions. The association constants of the developed ion-pair complexes were evaluated using Benesi–Hildebrand equation. The methods were validated according to ICH guidelines.
 Results: The formed ion-pair complexes showed maximum absorbance which was measured at 637 nm for both methods A and D, 601 nm, 606 nm for methods B and E and 631 nm for both methods C and F respectively with correlation coefficients 0.999. The analytical parameters and their effects in the developed methods were investigated. The ion-pair complexes were stable up to 24 h and showed good linearity. The molar absorptivity, Sandell sensitivity, detection, and quantification limits were also calculated. The stoichiometry ratio in all the cases was 1:2 by using Job’s method of continuous variation. The recovery studies again showed good results because co-formulated substances did not interfere for the determination of ATC and PTC in the developed methods.
 Conclusion: The developed methods were applicable for routine quality control analysis of ATC and PTC in pure and pharmaceutical dosage forms. Good results were obtained when the developed methods were applied in healthy human urine samples.

Targeted live-cell nuclear delivery of the DNA 'light-switching' Ru(II) complex via ion-pairing with chlorophenolate counter-anions: the critical role of binding stability and lipophilicity of the ion-pairing complexes.

We have found recently that nuclear uptake of the cell-impermeable DNA light-switching Ru(II)-polypyridyl cationic complexes such as [Ru(bpy)2(dppz)]Cl2 was remarkably enhanced by pentachlorophenol (PCP), by forming ion-pairing complexes via a passive diffusion mechanism. However, it is not clear whether the enhanced nuclear uptake of [Ru(bpy)2(dppz)]2+ is only limited to PCP, or it is a general phenomenon for other highly chlorinated phenols (HCPs); and if so, what are the major physicochemical factors in determining nuclear uptake? Here, we found that the nuclear uptake of [Ru(bpy)2(dppz)]2+ can also be facilitated by other two groups of HCPs including three tetrachlorophenol (TeCP) and six trichlorophenol (TCP) isomers. Interestingly and unexpectedly, 2,3,4,5-TeCP was found to be the most effective one for nuclear delivery of [Ru(bpy)2(dppz)]2+, which is even better than the most-highly chlorinated PCP, and much better than its two other TeCP isomers. Further studies showed that the nuclear uptake of [Ru(bpy)2(dppz)]2+ was positively correlated with the binding stability, but to our surprise, inversely correlated with the lipophilicity of the ion-pairing complexes formed between [Ru(bpy)2(dppz)]Cl2 and HCPs. These findings should provide new perspectives for future investigations on using ion-pairing as an effective method for delivering other bio-active metal complexes into their intended cellular targets.

Correction to "Ion-Pair Complexes of Pyrylium and Tetraarylborate as New Host-Guest Dyes: Photoinduced Electron Transfer Promoting Radical Polymerization".

Ultrafast transient absorption spectroscopy, NOESY-NMR, and EPR spectroscopy shed light on how π–π stacking interactions combined with electrostatic interactions can be used to form stable ion-pair...

Extractive Spectrophotometric Method for the Determination of Glibenclamide by Ion-Pair Complex in Pure Form and Pharmaceutical Formulation

Simple, rapid and sensitive extractive spectrophotometric method is presented for the determination of glibenclamide (Glb) based on the formation of ion-pair complex between the Glb and anionic dye, methyl orange (MO) at pH 4. The yellow colored complex formed was quantitatively extracted into dichloromethane and measured at 426 nm. The colored product obeyed Beer’s law in the concentration range of (0.5-40) μg.ml-1. The value of molar absorptivity obtained from Beer’s data was found to be 31122 L.mol-1.cm-1, Sandell’s sensitivity value was calculated to be 0.0159 μg.cm-2, while the limits of detection (LOD) and quantification (LOQ) were found to be 0.1086 and 0.3292 μg.ml-1, respectively. The stoichiometry of the complex created between the Glb and MO was 1:1 as determined via Job’s method of continuous variation and mole ratio method. The method was successfully applied for the analysis of pharmaceutical formulation.

A modified hydrophobic ion-pairing complex strategy for long-term peptide delivery with high drug encapsulation and reduced burst release from PLGA microspheres

Poor encapsulation and high initial burst were two major obstacles for the water-soluble peptide drug loaded microspheres preparation using the industrial emulsification method. In the present study, we hypothesized that the hydrophobic ion-pairing (HIP) complex strategy with a further healing of the pores within the microspheres may improve drug encapsulation and initial burst release. DSS was chosen as the most suitable one among the three test ion-pairing agents (SDS, DSS and STC) due to its high binding efficiency with drug and reversible dissociation capacity in presence of counter ions. The formation of HIP complex between octreotide acetate and DSS successfully reversed the highly water-soluble nature of the drug. A specific S/O/W method was adopted to encapsulate such drug containing HIP complex. The encapsulation efficiency of the drug was greatly improved compared with the conventional W1/O/W2 method (from 44% to 90%). Under the optimal healing conditions (the healing time 6 h, temperature 40 °C and 4% DEP content), the pores within the microspheres were effectively healed. Initial burst amount of octreotide acetate in S/O/W microspheres decreased to 3.56%. The pore healing effect was further confirmed by the scanning electron microscopy and fluorescence microscopy results. In the process of testing the drug release performance of such new strategy in vitro and in vivo, a more satisfactory single phase release profile with sustained and steady drug release was observed. These results suggested that the modified HIP strategy could be a promising platform for water-soluble peptide encapsulation with high encapsulation efficiency, low initial burst and stable drug release mechanism.

Spectrofluorimetric method for determination of bupropion in pharmaceutical dosage forms

Bupropion is a noradrenaline and dopamine reuptake inhibitor which is used as an antidepressant drug. Few HPLC and spectrophotometric methods have been reported before for the determination of bupropion. Most of the previous methods reported for determination of bupropion in pharmaceutical dosage forms are somehow dangerous to health and environment because of using organic solvents. In the present method bupropion was determined in pharmaceutical dosage forms by spectrofluorimetry after ion-pair complex formation with eosin Y. The ion-pair complex formation was optimized for reagent amount, buffer pH and time. The developed method was linear over the range of 3-120μgmL-1 with an acceptable precision (CV<1.5%) and accuracy (Error<1%). The present method is applicable for determination of bupropion in pharmaceutical dosage forms for routine quality control analysis.

Disulfonimides versus Phosphoric Acids in Brønsted Acid Catalysis: The Effect of Weak Hydrogen Bonds and Multiple Acceptors on Complex Structures and Reactivity.

In Brønsted acid catalysis, hydrogen bonds play a crucial role for reactivity and selectivity. However, the contribution of weak hydrogen bonds or multiple acceptors has been unclear so far since it is extremely difficult to collect experimental evidence for weak hydrogen bonds. Here, our hydrogen bond and structural access to Brønsted acid/imine complexes was used to analyze BINOL-derived chiral disulfonimide (DSI)/imine complexes. 1H and 15N chemical shifts as well as 1JNH coupling constants revealed for DSI/imine complexes ion pairs with very weak hydrogen bonds. The high acidity of the DSIs leads to a significant weakening of the hydrogen bond as structural anchor. In addition, the five hydrogen bond acceptors of DSI allow an enormous mobility of the imine in the binary DSI complexes. Theoretical calculations predict the hydrogen bonds to oxygen to be energetically less favored; however, their considerable population is corroborated experimentally by NOE and exchange data. Furthermore, an N-alkylimine, which shows excellent reactivity and selectivity in reactions with DSI, reveals an enlarged structural space in complexes with the chiral phosphoric acid TRIP as potential explanation of its reduced reactivity and selectivity. Thus, considering factors such as flexibility and possible hydrogen bond sites is essential for catalyst development in Brønsted acid catalysis.

Spectrophotometric Determination of Cinnarizine and Domperidone Maleate in Pharmaceutical Preparations by Ion Pair Complex Formation with Rose Bengal Dye

A simple, rapid and sensitive spectrophotometric method has been developed for the determination of cinnarizine (CIN) and domperidone maleate (DOM) in bulk and pharmaceutical formulations. The method is based on the formation of ion-pair complexes between the studied drugs and rose Bengal dye in buffer solution (pH5). The complexes give maximum absorbance at 571 nm. The method obeys Beer’s law in the range of 0.5-34 and 0.5-36 µg ml-1 with molar absorptivity of 2.55×104 and 2.42×104 l.mol-1.cm-1 for CIN and DOM respectively. The method has been successfully applied for the determination of studied drugs on pharmaceutical dosages with no interferences. The results have been compared with official method and standard procedure with a good agreement.

Selective and Preferential Separation of Rhodium (III) from Palladium (II) and Platinum (IV) Using a m-Phenylene Diamine-Containing Precipitant

Although Rh is an industrially important and the most expensive platinum group metal (PGM), the selective and preferential separation of Rh from PGM mixtures still remains as a big challenge. In this work, the separation of Rh (III) from Pd (II) and Pt (IV) in a hydrochloric acid (HCl) solution was studied using a m-phenylene diamine-containing precipitant (m-PDA). At high HCl concentrations (6.0–8.0 M), most of the Rh (III) (>90%) was precipitated, and Pd (II) and Pt (IV) were hardly precipitated (<5%). On the other hand, over 85% of Pd (II) and Pt (IV) precipitated along with small amount of Rh (III) (<25%) at low HCl concentrations (1.0–2.0 M). As a consequence, m-PDA enabled selective and preferential precipitation of Rh (III) at high HCl concentrations. XPS and TG analyses revealed that the Rh-containing precipitate is an ion-pair complex composed of one [RhCl6]3− anion and three m-PDA cations. The Rh desorption from the precipitate as well as the recovery of m-PDA was successfully achieved using an NH4OH solution. This method is a promising practical approach to Rh recovery.

Unique Anion-exchange Properties of 3,3'-Diaminobenzidine Resulting in High Selectivity for Rhodium(III) over Palladium(II) and Platinum(IV) in a Concentrated Hydrochloric Acid Solution.

The effective recovery of Rh(III) from mixtures also containing Pd(II) and Pt(IV) is one of the most difficult tasks in platinum group metal refining. Adding 3,3'-diaminobenzidine (DAB) to 7 and 10 M HCl aqueous solutions containing Rh(III), Pd(II), and Pt(IV) chlorido species affords the effective separation of Rh(III) from Pd(II) and Pt(IV) through a process where Rh(III) becomes sequestered into solid phases composed of DAB. The stoichiometry and inner coordination sphere of the metal in Rh-DAB complexes were determined by estimating the Rh(III), H+, and Cl- concentrations in the solid phase and X-ray absorption fine structure measurements to clarify the mechanism of DAB selectivity for Rh(III). These results indicate that the Rh-DAB reaction in a concentrated HCl solution occurs in two steps: (1) the precipitation of DAB trihydrochloride salts, where DAB's amino groups are protonated and (2) anion exchange of the trihydrochloride salts for chloride ions with [RhCl6]3-, which is the predominant species in a concentrated HCl solution. By contrast, ion-pair complexes with [PdCl4]2- and [PtCl6]2- were not observed in DAB phases. The significantly lower affinity of the DAB trihydro cation for [PtCl6]2- and [PdCl4]2- than for [RhCl6]3- in 7 and 10 M HCl solutions accounts for the effective separation of Rh(III) from Pd(II) and Pt(IV).