Ion-pair Method Research Articles

FORMULATION OF SELF-NANO EMULSIFYING SYSTEM (SNES) CONTAINING SNAKEHEAD FISH EXTRACT PROTEIN INCORPORATED INTO CORN OIL BY HYDROPHOBIC ION PAIRING METHOD

Objective: The purpose of this study was to determine whether the protein complexation of snakehead fish extract using the hydrophobic ion pairing method with Sodium Dodecyl Sulfate (SDS) as a complexing ligand could be loaded into the corn oil component of the SNES and to explore the ratio of oil, surfactant, and cosurfactant in the Self-Nanoemulsifying System (SNES) formula that can produce good SNES characteristics. Methods: Snakehead fish proteins were extracted using pressurized hot water and then complexed with SDS at acidic pH. The SDS-protein complex was loaded into the oil component of the SNES and then combined with the surfactant component (Tween 80) and cosurfactant (propylene glycol) in a ratio of 1:9:1, which, based on the preliminary miscibility screening, has the best miscibility among other screening results. Results: The results of the study were as follows. The binding efficiency of the SDS-protein-complex was 31.74% and the loading efficiency into SNES was 83.17%. The nanoemulsion formed had visible light transmittance of 100.4%, particle size 72.7 nm, zeta potential-53.03 mV, and emulsification time 71.67 seconds. The nanoemulsion was stable at storage and 100 and 1000 times dilution challenges using aqueous media, Simulated Gastric Fluid (SGF), and Simulated Intestinal Fluid (SIF). Conclusion: The hydrophobic ion-pair complexation of snakehead fish protein extract with SDS as the complexing ligand was able to load the protein into the oil component of SNES and the ratio of oil, surfactant, and cosurfactant in the SNES formula that produce good SNES characteristics was corn oil, Tween 80, and propylene glycol at a ratio of 1:9:1

Spectrophotometric Determination of Remdesivir Using the Ion Pair Complex Method Using through Alizarin Red S Dye

The research included the development of a simple and practical spectroscopic method for the estimation of remdesivir (RDV) by the ion-pair method, which is based on the interaction of RDV with Alizarin Red S (ARS) at laboratory temperature. Using water as a medium for the reaction, a product Red in color was formed, with a linear relation ranging from 1 to 25 ?g/ml. It gave the highest absorption at wavelength 524 nm, and the complex completed its reaction after an hour, as the value of the sample was a relative standard deviation of no more than 1%, the recovery rate is 100.2429%, and high sensitivity to low concentrations, where she was the values of limit of detection, limit of quantitation were 0.0198, 0.0602 ?g/ml, respectively, detection limit of 0.0139 ?g/mL, and a quantitation limit of 0.0422 ?g/mL. The molar absorptivity is 51340.668 L/mol/cm, and Sandell?s sensitivity value is 0.0117 ?g.cm-2. The recovery values ranged from 99.3088% to 100.5184%, with a relative standard deviation not exceeding 0.7886% for RDV. The method was successfully applied for the estimation of pharmaceutical preparations using both direct and standard addition methods.. KEYWORDS :Alizarin red S, Ion pair, Remdesivir, Spectrophotometric estimation.

Determination of Lansoprazole and Simvastatin via area under curve and ion pair methods

A two simple, sensitive, and economic methods were developed for the determination of lansoprazole and simvastatin in their pure and pharmaceutical dosages forms . first method based on measurement of area under curve (AUC) for zero order spectrum and the second method based on formation of ion pair complex between each of both drugs and Bromo phenol blue dye. Beer's law obeyed in concentrations ranges of (4-70 μg.ml-1) and (4-50 μg.ml-1) in the first method and (1-70 μg.ml-1) and (1-60 μg.ml-1) in the second method for lansoprazole (LNZ) and simvastatin (SMV) respectively . Average recovery percentage were (99.43%) and (99.36%) in the first method , and (99.71%) and (100.18%) in the second method for LNZ and SMV respectively. The RSD% values were (0.0044-0.0172%) and (0.1041-0.4129%) for LNZ in first and second methods, and (0.0097-0.0311%) and (0.1358-0.5165%) for SMV in the two methods mentioned above. Limit of detection of LNZ in the first method were (0.185×10-3 μg.ml-1) and (0.268×10-3 μg.ml-1) in the second method . While limit of quantification were (0.227×10-3 μg.ml-1) and (0.204×10-3 μg.ml-1) in the first method and (0.894×10-3 μg.ml-1) and (0.68×10-3 μg.ml-1) in the second method for LNZ and SMV respectively. The two methods were successfully applied for the determination of both drugs in pure and pharmaceutical dosages forms .

Development and Validation of an Ion-Pair HPLC-UV Method for the Quantitation of Quinoline and Indoloquinoline Alkaloids in Herbal and Pharmaceutical Antimalarial Formulations

Quinine- and cryptolepine-based antimalarials serve as valuable alternatives to artemisinin-based combination therapies (ACTs) in Ghana. Their use, however, is associated with adulteration and substandard quality challenges. An HPLC method targeting quinoline and indoloquinoline antimalarial alkaloids was developed, validated, and applied to evaluate herbal and pharmaceutical antimalarial formulations (HPAFs) and starting materials (APIs). The separation/quantitation of the alkaloids (including quinine, quinidine, cinchonine, cinchonidine, dihydroquinine, dihydroquinidine, and cryptolepine) was achieved on a Zorbax SB-CN column (250 mm × 4.6 mm, 5 μm), with an isocratic elution system of methanol: trifluoroacetic acid (0.1%, v/v) (15 : 85, v/v) at 1.5 mL/min and 223 nm. Method validation was according to ICH Q2(R1) guidelines. It was then used to assess the quality of APIs (n = 3) and HPAFs (n = 44) including quinine-based pharmaceutical antimalarial formulations (QBPAFs) (n = 23) and herbal antimalarial products (HAMPs). The method was found to be specific, selective, accurate, precise, and robust toward the alkaloids with linearity achieved within specified concentration ranges (r2 > 0.995 for all analytes). Analyte stability ranged between 6 and 12 hours. All the APIs contained quinine <99.0%–101.0%, with dihydroquinine and cinchonidine at levels compliant with the established acceptance criteria. The QBPAFs had quinine content ranging between 50.2% and 151.2%, with 43.5% (n = 10/23) of them complying with the acceptance criteria. The related alkaloids observed in the QBPAFs included quinidine (56.5%, n = 13/23), dihydroquinine (100%, n = 23/23), dihydroquinidine (21.7%, n = 5/23), cinchonine (17.4%, n = 4/23), and cinchonidine (95.7%, n = 22/23). For the HAMPs, 81.0% (n = 17/21) were adulterated with quinine (0.59 ± 0.04 mg/10 mL–86.03 ± 0.02 mg/10 mL). Cryptolepine was identified in 19% (n = 4/21) of the HAMPs with concentration ranging between 43.99 ± 0.43 μg/mL and 747.86 ± 0.34 μg/mL. In conclusion, the application of the ion-pair HPLC method targeting quinoline and indoloquinoline antimalarials has demonstrated the presence of quality and poor-quality HPAFs on the Ghanaian market.

Comparison of Microflow and Analytical Flow Liquid Chromatography Coupled to Mass Spectrometry Global Metabolomics Methods Using a Urea Cycle Disorder Mouse Model.

Microscale-based separations are increasingly being applied in the field of metabolomics for the analysis of small-molecule metabolites. These methods have the potential to provide improved sensitivity, less solvent waste, and reduced sample-size requirements. Ion-pair free microflow-based global metabolomics methods, which we recently reported, were further compared to analytical flow ion-pairing reagent containing methods using a sample set from a urea cycle disorder (UCD) mouse model. Mouse urine and brain homogenate samples representing healthy, diseased, and disease-treated animals were analyzed by both methods. Data processing was performed using univariate and multivariate techniques followed by analyte trend analysis. The microflow methods performed comparably to the analytical flow ion-pairing methods with the ability to separate the three sample groups when analyzed by partial least-squares analysis. The number of detected metabolic features present after each data processing step was similar between the microflow-based methods and the ion-pairing methods in the negative ionization mode. The observed analyte trend and coverage of known UCD biomarkers were the same for both evaluated approaches. The 12.5-fold reduction in sample injection volume required for the microflow-based separations highlights the potential of this method to support studies with sample-size limitations.

Evaluation of the urinary iodine concentration (UIC) in pregnant women using ion-pair HPLC-UV method

Evaluation of the urinary iodine concentration (UIC) in pregnant women using ion-pair HPLC-UV method

The cell-impermeable Ru(II) polypyridyl complex as a potent intracellular photosensitizer under visible light irradiation via ion-pairing with suitable lipophilic counter-anions

Developing the cell-impermeable Ru(II) polypyridyl cationic complexes as effective photosensitizers (PS) which have high cellular uptake and photo-toxicity, but low dark toxicity, is quite challenging. Here we found that the highly reactive singlet oxygen (1O2) can be generated by the irradiation of a typical Ru(II) polypyridyl complex Ru(II)tris(tetramethylphenanthroline) ([Ru(TMP)3]2+) under visible light irradiation by ESR with TEMPO (2,2,6,6-tetramethyl-4-piperidone-N-oxyl) as 1O2 probe. Effective cellular and nuclear delivery of cationic [Ru(TMP)3]2+ was achieved through our recently developed ion-pairing method, and 2,3,4,5-tetrachlorophenol (2,3,4,5-TeCP) was found to be the most effective among all chlorophenols tested. The accelerated cellular, especially nuclear uptake of [Ru(TMP)3]2+ results in the formation of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and DNA strand breaks, caspase 3/7 activation and cell apoptosis in HeLa cells upon light irradiation. More importantly, compared with other traditional photosensitizers, [Ru(TMP)3]2+ showed significant photo-toxicity but low dark toxicity. Similar effects were observed when 2,3,4,5-TeCP was substituted by the currently clinically used anti-inflammatory drug flufenamic acid. This represents the first report that the cell-impermeable Ru(II) polypyridyl complex ion-paired with suitable lipophilic counter-anions functions as potent intracellular photosensitizer under visible light irradiation mainly via a 1O2-mediated mechanism. These findings should provide new perspectives for future investigations on other metal complexes with similar characteristics as promising photosensitizers for potential photodynamic therapy.

A Novel Approach for Development of Intraocular Biodegradable Ranibizumab Implant: A Solution for Stability of Protein Activity.

Purpose: Ranibizumab is a monoclonal antibody fragment, targeting all isoforms of vascular endothelial growth factor A (VEGF-A), a protein involved in angiogenesis. It is used to treat age-related macular degeneration (AMD), retinal vein occlusion (RVO), and diabetic macular edema (DME), which are associated with blindness worldwide. However, proper treatment can decrease the loss of vision in about 90% of patients. Because of poor drug uptake in topical therapy and several adverse side effects of systemic irregularities and intravitreal injections, sustained-release drug delivery systems are more suitable for treatment. However, there are many challenges in the development of these systems due to the loss of protein activities. Methods: After drug complexation by the ion pairing method and preparation of a polymeric implant, containing the drug, the characteristics of the complexes were examined by Fourier-transform infrared spectroscopy and circular dichroism spectroscopy. The stability of antibody activity and biocompatibility of the released drug from the implant were assessed by bioassays and MTT assay, respectively. Finally, the release kinetics were investigated. Results: The bioassays showed the higher activity of the drug complex, compared to the free form, besides good biocompatibility in vitro. Also, the release data confirmed sustained and controlled release characteristics for the prepared implant. Conclusion: In this study, for the first time, we proposed a method for developing a sustained-release intraocular implant, consisting of ranibizumab by the heating method. This method allows for the industrial production of ranibizumab by extrusion and eliminates the complications related to reservoir systems.

Protection of Protein Drugs by Self-Emulsified Nanoemulsion Against Proteolysis

The present study aimed to develop a self-emulsified nanoemulsion for salmon calcitonin (sCT) for non-invasive delivery. Hydrophobic ion pairing method was used to form hydrophobic complex of sCT with 4 counter ions (oleate, deoxycholate, docusate and tripolyphosphate). The partition coefficient and dissociation of the complexes in water of various pH were investigated. The complex-loaded nanoemulsions were characterized for droplet size, leakage of sCT from the droplets, and protection of sCT from enzymatic degradation. The results show that all the counter ions could form complexes with sCT with a complexation efficiency about 95% at pH 8.0. The complexes significantly increased the partition coefficient of sCT. The dissociation of the complexes in water was pH-dependent. At pH 6.8 and 7.4, the dissociation was negligible. At pH 1.0, the dissociation was 71%, 8%, 37% and 50% for sCT-polyphosphate, sCT-docusate, sCT-oleate and sCT-deoxycholate, respectively. The developed nanoemulsions had a size in the range of 27–62 nm. The leakage of sCT from the nanodroplets into the aqueous phase depended on the lipophilicity of the counter ions: 60%, 56%, and 24% leakage for sCT-docusate, sCT-oleate and sCT-deoxycholate, respectively. The nanoemulsion protected sCT from enzyme degradation when loaded inside the droplets, but not the leaked sCT.

Enhancement of exfoliating efficacy of L-carnitine with ion-pair method monitored by nuclear magnetic resonance spectroscopy

Carnitine (CAR), an amino acid derivative, has great potential as a facial exfoliating agent owing to its calcium chelating property under weakly acidic or neutral conditions. However, its application is limited by its poor transdermal penetration. To optimise its exfoliation efficacy with minimal concentration, we propose the ion-pair method. The ionic interaction between CAR and a zwitterionic substance was successfully monitored by measuring conductivity. The alterations of penetration and exfoliation efficacy for CAR addition to different types of counter ions were investigated in vitro and in vivo. We found that hydrogenated soya phosphatidylcholine (HSC), an amphiphilic counter ion, significantly increases the stratum corneum penetration and exfoliation efficacy of CAR. The changes of the CAR-HSC ionic interaction in the presence of calcium ions were also investigated by 1H nuclear magnetic resonance (NMR) spectroscopy. The NMR spectra for amino groups of CAR first decreased with HSC and then gradually recovered and shifted as calcium ions were added. From the results, a noble exfoliating complex of CAR with high exfoliation efficacy could be proposed. Moreover, the results demonstrate that NMR spectroscopy is useful to obtain direct experimental evidence of the molecular dynamics simulations of the alteration of an exfoliating complex as it penetrates.

LC-MS/MS measurements of urinary guanidinoacetic acid and creatine: Method optimization by deleting derivatization step

BackgroundCerebral Creatine deficiency syndromes (CCDS) include three hereditary diseases affecting the metabolism of creatine (Cr): arginine glycine amidinotransferase deficiency, guanidinoacetate methyltransferase deficiency and disorders of creatine transporter. These pathologies cause a brain creatine deficiency responsible of non-specific neurological impairments with mental retardation. LC-MS/MS measurements of guanidinoacetic acid (GAA) and creatine in urine and plasma are an important screening test to identify the deficit. Analysis of this polar and basic molecules not hold on standard column requires a derivatization step to butyl-esters. To overcome this long and fastidious derivatization, an ion pairing (IP) method was chosen in this study. MethodIP method was validated using Comité francais d'accréditation (COFRAC) recommendations. Then, urine GAA and creatine of 15 patients with a CDS deficiency suspected were tested y LC-MS/MS using IP technique, and performances were assessed with reference laboratory method (butylation method). Moreover, references values were suggested y the study of 100 urines samples of healthy patients. ResultsThe method developed provided a good accuracy and precision with intra and inter-day coefficients of variation (CVs) <15%. The curve was linear for the biological and pathological concentrations. The comparison with the reference method did not reveal any significant difference for analytical performances but showed a simplification of the preparation of samples. ConclusionThe use of IP technique that we have developed demonstrated a good correlation with the butylation method. Moreover, this new method not only allows a simplification of the technique, but also decreases in run time.

SEPARATION AND ANALYSIS OF AMLODIPINE/BENAZEPRIL COMBINATION IN CAPSULES BY A NOVEL ION PAIR LIQUID CHROMATOGRAPHY

Objective: The objective of this study was to develop and validate a novel ion-pair liquid chromatography method, in order to separate and assay of amlodipine/benazepril combination in capsules. This method was a fast, practical and additional choice in quality control laboratories.Methods: The chromatographic conditions comprised of a classical C18-type stationary phase (250 × 4.6 mm, 5μ), with a mobile phase consisting of: 45% of 10-3 M of cetrimide and 55% acetonitrile. The flow rate was 1 ml/min; the detection wavelength was at 242 nm, under ambient temperature.Results: The method was validated for linearity with correlation coefficients very close to one, the accuracy with mean recovery values between 95.0-105.0%, precision with relative standard deviations of the calculated concentrations less than 5.0% and specificity in the presence of degradation products and excipients.Conclusion: The results presented in this paper showed that the developed method was fast and applicable, for the separation and determination of amlodipine/benazepril combination in capsules.

Isolation and identification of four major impurities in capreomycin sulfate

Capreomycin has good clinical utility to treat multidrug resistant tuberculosis, but it is only used as a second line drug due to its adverse reactions. Literature has demonstrated that the toxicity of capreomycin product is significantly influenced by the impurities in it. Unfortunately, so far, no one impurity in capreomycin has ever been isolated and definitely identified due to its extremely strong basic character and high polarity. An ion-pair method reported in literature can provide separation of capreomycin and its impurities, but it is hard to be used for the preparative purpose. In this study, this ion-pair method was further improved to detect more impurities in capreomycin sulfate substance. Besides the four main components (IA, IB, IIA and IIB), four impurities (impurity A–D) with their contents much higher than the identification threshold were observed. Furthermore, a two dimensional (2D) LC quadrupole-time of flight (Q-TOF) MS method was established to realize high resolution MS analysis of these impurities. For the purpose of preparative isolation, a hydrophilic interaction chromatography (HILIC) method was established. The four main components were well isolated, but unfortunately, the four impurities were co-eluted with each other or with IB by the HILIC method. Fortunately, the degradation experiments revealed that IA and IB could yield clean impurity A and B respectively in acidic medium, and can yield clean impurity D and C respectively in alkaline medium. Therefore, IA and IB were first isolated by the preparative HILIC method, then pure IA and IB underwent acid degradation and base degradation separately and followed by re-isolation by the HILIC method to obtain pure impurity A–D respectively. Based on Q-TOF MS and NMR analysis, the structures (including absolute configuration) of the four isolated impurities were definitely identified.

Pollution levels and risk assessment of perfluoroalkyl acids (PFAAs) in beef muscle and liver from southern Xinjiang

The presence of perfluoroalkyl acids (PFAAs) in animal foods is worldwide, and their fate and spatial distribution in Xinjiang are not well understood. In this study, beef muscle and liver collected from five major cities in southern Xinjiang were analyzed (n = 70) for 13 PFAAs using an ion-pairing method combined with HPLC-MS/MS. Overall, PFAA contamination was widespread, exceeding 50% of samples with concentrations ranged from below the limits of detection to 6.118ng/g. Perfluorooctane sulfonate, perfluorooctanoic acid, and perfluoroundecanoic acid were the predominant PFAAs of ten detected compounds, with maximum concentrations in Korla liver samples of 2.543, 0.856, and 1.386ng/g, respectively. When comparing the five cities, the highest levels and detection frequencies were observed in samples from Korla (muscle, 0.013ng/g; liver, 3.336ng/g), followed by Yanqi, Akesu, Kashgar, and Hotan. The different pollution patterns and distribution profiles of PFAAs among cities were significantly related to local economy and geographical conditions. In addition, the dietary intake assessments for PFAAs showed that samples originating from Korla had the greatest impact on human health, but the total hazard ratio was 0.814 × 10-3, which is far less than 1, indicating that consumption of beef muscle and liver poses no immediate harm to local residents.

Modified Extraction-Free Ion-Pair Methods for the Determination of Flunarizine Dihydrochloride in Bulk Drug, Tablets, and Human Urine

Two simple and sensitive extraction-free spectrophotometric methods are described for the determination of flunarizine dihydrochloride. The methods are based on the ion-pair complex formation between the nitrogenous compound flunarizine (FNZ), converted from flunarizine dihydrochloride (FNH), and the acidic dye phenol red (PR), in which experimental variables were circumvented. The first method (method A) is based on the formation of a yellow-colored ion-pair complex (1:1 drug:dye) between FNZ and PR in chloroform, which is measured at 415 nm. In the second method (method B), the formed drug-dye ion-pair complex is treated with ethanolic potassium hydroxide in an ethanolic medium, and the resulting base form of the dye is measured at 580 nm. The stoichiometry of the formed ion-pair complex between the drug and dye (1:1) is determined by Job's continuous variations method, and the stability constant of the complex is also calculated. These methods quantify FNZ over the concentration ranges 5.0–70.0 in method A and 0.5–7.0 μg/mL in method B. The calculated molar absorptivities are 6.17 × 103 and 5.5 × 104 L/mol·cm–1 for method A and method B, respectively, with corresponding Sandell sensitivity values of 0.0655 and 0.0074 μg/cm2. The methods are applied to the determination of FNZ in pure drug and human urine.

Oxygen scavenging polymer coating prepared by hydrophobic modification of glucose oxidase

Trace oxygen in packaged foods, beverages, and pharmaceuticals can promote a range of oxidative degradation reactions and support microbial growth, ultimately impacting product quality and shelf-life. Oxygen scavenging active packaging systems have therefore been explored to control headspace oxygen content. Herein, we report on a hydrophobic ion pairing method to render glucose oxidase hydrophobic, and thus soluble in organic solvents. Hydrophobic modified glucose oxidase was blended with ethylene vinyl acetate and cast on the interior of glass vials to demonstrate potential as a commercially translatable coating method for enzyme immobilization. The resulting oxygen scavenging polymer coatings were topographically uniform and presented 0.553 μg/cm2 enzyme at the coating interface. The coatings effectively reduced headspace oxygen by 2% in a closed-vial system filled 50 vol% with citrate buffer, pH 3.5. Less than 25% protein migrated from the coating over an 8-week leaching study, with no detectable protein leached in the first 4 weeks. Hydrophobic ion pairing of glucose oxidase enabled a facile, high-throughput enzyme immobilization technique without use of complicated, time-consuming surface modification chemistries and reagents. Such oxygen scavenging polymer coatings can support controlling headspace oxygen in packaged goods, and thus retaining stability of oxygen-sensitive components such as colors, flavors, and nutrients.

Multifunctional Composite Microcapsules for Oral Delivery of Insulin.

In this study, we designed and developed a new drug delivery system of multifunctional composite microcapsules for oral administration of insulin. Firstly, in order to enhance the encapsulation efficiency, insulin was complexed with functional sodium deoxycholate to form insulin-sodium deoxycholate complex using hydrophobic ion pairing method. Then the complex was encapsulated into poly(lactide-co-glycolide) (PLGA) nanoparticles by emulsion solvent diffusion method. The PLGA nanoparticles have a mean size of 168 nm and a zeta potential of −29.2 mV. The encapsulation efficiency was increased to 94.2% for the complex. In order to deliver insulin to specific gastrointestinal regions and reduce the burst release of insulin from PLGA nanoparticles, hence enhancing the bioavailability of insulin, enteric targeting multifunctional composite microcapsules were further prepared by encapsulating PLGA nanoparticles into pH-sensitive hydroxypropyl methyl cellulose phthalate (HP55) using organic spray-drying method. A pH-dependent insulin release profile was observed for this drug delivery system in vitro. All these strategies help to enhance the encapsulation efficiency, control the drug release, and protect insulin from degradation. In diabetic fasted rats, administration of the composite microcapsules produced a great enhancement in the relative bioavailability, which illustrated that this formulation was an effective candidate for oral insulin delivery.

46 - Redirecting Ru(II)-Complex Into Live-Cell Nucleus for Enantioselective DNA-Imaging and Photosensitizing Via Simple Yin-Yang Ion-Pairing

Targeted delivery of diagnostic-probes and therapeutics into specific compartments inside a cell is of utmost importance in the improvement of disease detection and treatment. The molecular DNA “light-switch” Ru(II)-polypyridyl complex [Ru(DIP)2(dppz)]2+ has been shown to be accumulated only in the cytoplasm and membrane, but excluded from its intended nuclear DNA target. Here we show that chlorophenolate and flufenamate drugs can redirect [Ru(DIP)2(dppz)]2+ into live-cell nucleus while maintaining its original DNA recognition characteristics, where it acts as an unparalleled nuclear DNA imaging agent which is enantioselective, resistant to photo-bleaching, and suitable for both luminescent and transmission electron microscopy. The underlying molecular mechanism for the preferential nuclear uptake was found to be due to formating a neutral and relatively strong ion-pair between the Ru(II) cationic complex and chlorophenolate or flufenamate counter-anion, which may help the Ru(II) complex escape cytoplasmic traps, and cross the nuclear membrane via passive diffusion. More interestingly, enantioselective apoptosis was induced for cells pretreated with [Ru(DIP)2(dppz)]2+/chlorophenol (or flufenamic acid) upon prolonged visible-light irradiation. We suggest that this novel ion-pairing method and concept can be employed to deliver other similar cationic and bioactive metal complexes with promising theranostic potentials to their preferred intracellular targets.

Presence of Nitrate and Nitrite in Well Water in Mureș County

Abstract Objective: One of the most important sources of nitrite and nitrate anions, besides vegetables and meat products, is the drinking water. Presence of nitrite and nitrate in the water in higher concentrations than those set by EFSA (0.5 mg/l nitrite, 50 mg/l nitrate), may have toxicological significance. A quantitative determination of these ions in samples collected from several pleases from Mureș County was made. Methods: Ninety-seven well water samples were tested from 12 different places from Mureș County. We used a simple HPLC-UV ion pair method for the determination of nitrite and nitrate concentrations. Sensitivity of the method enables the quantification for concentrations far below the MCL value. Results: The highest amounts of nitrate and nitrite were measured in Sangeorgiu de Mureș and Cristești. Concentrations of nitrite and nitrate were exceeded in 4.12% and respectively 44.32% of the samples. Conclusions: The high amounts of nitrites and nitrates existing in well water go beyond the expected extent. This pollution can become a health risk since this water is used in human nutrition especially in child nourishment.

Delivering the cell-impermeable DNA 'light-switching' Ru(ii) complexes preferentially into live-cell nucleus via an unprecedented ion-pairing method.

The dipyridophenazine (dppz) based ruthenium polypyridyl complexes are known as molecular 'light-switches' for DNA. This property is poised to serve in diagnostic and therapeutic applications, but the poor cellular uptake restricts their use in live cells. Herein, we show that the cellular uptake, and more interestingly and surprisingly, the nuclear uptake of cell-impermeable Ru(ii)-polypyridyl cationic complexes such as [Ru(bpy)2(dppz)]2+ were remarkably enhanced by three structurally unrelated biochemical agents (pentachlorophenol, carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone and tolfenamic acid), by forming lipophilic and relatively stable ion-pair complexes, via a passive diffusion mechanism. Enantioselective imaging of live-cell nuclear DNA was observed between the two chiral forms of Ru(ii) complexes. This represents the first report of an unprecedented new method for delivering the DNA 'light-switching' Ru(ii) complexes into the nucleus of living cells via ion-pairing, which could serve as a promising general live-cell delivery method for other potentially bio-medically important but cell-impermeable metal complexes.