Analytical Eco-Scale for Assessing the Greenness of a Developed Potentiometric Method for Lomefloxacin Hydrochloride Determination in its Different Dosage Forms, Plasma, and Dissolution Medium.

Background: Traditional methods for Lomefloxacin hydrochloride (LOM) determination involve pretreatment steps, which extend analysis time and use hazardous chemicals. Objective: The ability to provide a rapid route without sample pretreatment for quantitative determination of compounds via a low-cost instrument is a challenging task. In this work, a simple potentiometric method was developed to determine the antibacterial LOM via in-house fabricated ion selective electrodes. Methods: Different sensors were fabricated using a poly vinyl chloride-based membrane, potassium tetrakis(4-chlorophenyl) borate as a cation exchanger, and 2-Nitrophenyl octyl ether as a plasticizer (sensor 1). To increase the selectivity of sensor 1, a selective molecular recognition component 2-hydroxypropyl-ß-cyclodextrin was used as ionophore (sensor 2). Results: The proposed method was validated according to International Union of Pure and Applied Chemistry recommendations, in which the proposed sensors show a linear dynamic range from 1 × 10-5 to 1 × 10-2 mol/L, with Nernstian slopes of 55.829 and 58.229 mV/decade for sensors 1 and 2, respectively. It was applied to determine LOM in bulk powder, in different dosage forms, and in plasma with no sample pretreatment. Also, the suggested method can be used as a green, in-line bench top real-time analyzer for in-process monitoring of LOM release from its tablets, under U.S. Food and Drug Administration dissolution regulations, with clear discrimination from common excipients. Results obtained by the proposed potentiometric method were compared with those obtained by a reported HPLC method. Conclusions: The proposed method is considered as a perfect alternative to traditional reported methods for LOM determination.

Organic nanoparticles of malachite green with enhanced far-red emission: size-dependence of particle rigidity.

In tracing the biological processes using fluorescent probes, it is desirable to shift the excitation/emission energy to a far-red/near-infrared (FR/NIR) region. In this study, we successfully synthesize FR fluorescent organic nanoparticles via ion-association between the malachite green (MG) cations and tetrakis(4-fluorophenyl)borate (TFPB) anions in the presence of a neutral stabilizing polymer. Binding of MG with TFPB results in the prominent appearance of an absorption band that can be assigned to an H-aggregate of MG. The fluorescence intensity as well as the fluorescence lifetime shows a significant increase with a decrease in the nanoparticle size. Since the MG dye is known as a local viscosity or environmental rigidity probe showing a rotational friction dependence of the excited state lifetime, we find that the rigidity of the organic nanoparticle is strongly size-dependent; that is, the smaller the size of the nanoparticle, the greater the rigidity of the nanoparticle. We also reveal that surface regions of the ion-based organic nanoparticles are more rigid than inner regions. The presence of H-aggregates that are almost non-fluorescent is the major origin of aggregation-caused quenching (ACQ) and still avoids the enhancement of the fluorescence quantum yield of the MG nanoparticles, so we develop a new approach to prevent H-aggregation inside the nanoparticle by incorporating photochemically inert, bulky phosphonium cations, which results in a 430-fold enhancement of its fluorescence yield. We believe that such a methodology will open up an avenue in the development of new types of fluorescent nanomaterials for many applications.

A simple approach for fabricating solid-contact ion-selective electrodes using nanomaterials as transducers.

A simple and robust approach for the development of solid-state ion-selective electrodes (ISEs) using nanomaterials as solid contacts is described. The electrodes are fabricated by using the mixture of an ionic liquid (IL) and a nanomaterial as intermediate layer, formed by melting the IL. Tetradodecylammonium tetrakis(4-chlorophenyl)borate (ETH 500) is chosen as an model of IL to provide strong adhesion between the inner glassy carbon electrode and the intermediate layer. Nanomaterials including single-walled carbon nanotubes (SWCNTs) and graphene were used as active ion-to-electron transducers between the glassy carbon electrode and the ionophore-doped ISE membrane. By using the proposed approach, the solid-contact Cu(2+)- and Pb(2+)-selective electrodes based on ETH 500/SWCNTs and ETH 500/graphene as transducers, respectively, have been fabricated. The proposed electrodes show detection limits in the nanomolar range and exhibit a good response time and excellent stability.

Interfacial processes studied by coupling electrochemistry at the polarised liquid-liquid interface with in situ confocal Raman spectroscopy.

Interfacial processes controlled by ion transfer voltammetry at the interface between two immiscible electrolyte solutions were studied by in situ Raman spectroscopy. Raman spectra of the interface between a 5 mM NaCl aqueous solution and 10 mM bis(triphenyl-phosphoranydieneammonium) tetrakis(4-chlorophenyl)borate in 1,2-dichloroethane were recorded at open circuit potential and at various interfacial potential differences. At open-circuit potential, Raman peaks assigned to vibrational modes of 1,2-dichloroethane are clearly visible and peaks of weak intensity are measured for the organic electrolyte ions. When a negative interfacial potential difference is applied, the intensity of the peaks of the cation of the organic electrolyte increases, confirming its transfer induced by the interfacial potential difference applied. The electrochemically assisted generation of mesoporous silica deposits was then followed by in situ confocal Raman spectroscopy. The condensation of mesoporous silica was controlled by the transfer of cetyltrimethylammonium (CTA(+)) ions to an aqueous phase containing hydrolysed silanes. The transfer of CTA(+) at the interface was monitored in situ by confocal Raman spectroscopy, and formation of silica was observed.

Reduction of thrombogenicity of PVC-based sodium selective membrane electrodes using heparin-modified chitosan.

Heparin-modified chitosan (H-chitosan) membrane was utilized to enhance biocompatibility of sodium selective membrane electrode based on the highly thrombogenic polyvinyl chloride (PVC). Sodium ion sensing film was prepared using PVC, sodium ionophore-X, potassium tetrakis(chlorophenyl)-borate, and o-nitrophenyloctylether. The PVC-based sensing film was sandwiched to chitosan or H-chitosan to prevent platelet adhesion on the surface of PVC. Potentiometric response characteristics of PVC-chitosan and PVC-H-chitosan membrane electrodes were found to be comparable to that of a control PVC based sodium-selective electrode. This indicates that chitosan and H-chitosan layers do not alter the response behaviour of the PVC-based sensing film. Biocompatibility of H-chitosan was confirmed by in vitro platelet adhesion study. The platelet adhesion investigations indicated that H-chitosan film is less thrombogenic compared to PVC, which could result in enhancement of biocompatibility of sodium selective membrane electrodes based on PVC, while maintaining the overall electrochemical performance of the PVC-based sensing film.

Halogen-free ionic liquid as an additive in zinc(II)-selective electrode: surface analyses as correlated to the membrane activity.

Two conventional Zn(II) polyvinyl chloride (PVC) membrane electrodes have been prepared and characterized. They were based on dibenzo-24-crown-8 (DBC) as a neutral carrier, dioctyl phthalate (DOP) as a plasticizer, and potassium tetrakis (p-chlorophenyl) borate, KTpClPB or the halogen-free ionic liquid, tetraoctylammonium dodecylbenzene sulfonate [TOA][DBS] as an additive. The use of ionic liquid has been found to enhance the selectivity of the sensor. For each electrode, the surfaces of two membranes were investigated using X-ray photoelectron, ion-scattering spectroscopy and atomic force microscopy. One of the two membranes was conditioned by soaking it for 24 h in a 1.0×10(-3) M Zn(NO(3))(2) solution and the second was soaked in bi-distilled water for the same interval (24 h). Comparing the two surfaces indicated the following: (a) the high selectivity in case of using [TOA][DBS] as an additive is due to the extra mediation caused by the ionic liquid and (b) the working mechanism of the electrode is based on phase equilibrium at the surface of the membrane associated with ion transport through the bulk of the membrane.

Interfacial complexes between a protein and lipophilic ions at an oil-water interface.

The interaction between an intact protein and two lipophilic ions at an oil-water interface has been investigated using cyclic voltammetry, impedance based techniques and a newly developed method in which the biphasic oil-water system is analyzed by biphasic electrospray ionization mass spectrometry (BESI-MS), using a dual-channel electrospray emitter. It is found that the protein forms interfacial complexes with the lipophilic ions and that it specifically requires the presence of the oil-water interface to be formed under the experimental conditions. Furthermore, impedance based techniques and BESI-MS with a common ion to polarize the interface indicated that the Galvani potential difference across the oil-water interface significantly influences the interfacial complexation degree. The ability to investigate protein-ligand complexes formed at polarized liquid-liquid interfaces is thus a new analytical method for assessing potential dependent interfacial complexation using a structure elucidating detection principle.

4-[2-(3-Methoxyphenyl)ethenyl]-N-methylpyridinium tetraphenylborate.

In the title compound, C(15)H(16)NO(+).C(24)H(20)B(-), the pyridinium ring of the cation makes a dihedral angle of 4.3 (2) degrees with the benzene ring. Each is rotated in the same direction with respect to the central C-CH=CH-C linkage, by 10.0 (2) and 7.8 (2) degrees , respectively. The anions have a slightly distorted tetrahedral geometry. The most interesting feature of the structure is that the anions form a honeycomb-like hexagonal structure down the b axis through C-H...pi interactions. The hexagon is constructed from six BPh(4)(-) anions. The cations interact in a head-to-tail fashion along [010], forming chains, and pack antiparallel inside the above honeycomb-like structure through C-H...pi interactions.

Amodiaquine polymeric membrane electrode.

The construction and electrochemical response characteristics of two types of poly(vinyl chloride) (PVC) membrane sensors for the determination of amodiaquine hydrochloride (ADQ.2HCl) are described. The sensing membrane comprised an ion-pair formed between the cationic drug and sodium tetraphenyl borate (NaTPB) or potassium tetrakis(4-chlorophenyl) borate (KTCPB) in a plasticized PVC matrix. Eight PVC membrane ion-selective electrodes were fabricated and studied. Several plasticizers were studied namely, dioctyl phthalate (DOP), 2-nitrophenyl octyl ether (NPOE), dioctyl phenylphosphonate (DOPP) and bis(2-ethylhexyl)adipate (EHA). The sensors display a fast, stable and near-Nernstian response over a relative wide ADQ concentration range (3.2 x 10(-6) to 2.0 x 10(-2) M), with slopes comprised between 28.5 and 31.4 mV dec(-1) in a pH range comprised between pH 3.7 and 5.5. The assay of amodiaquine hydrochloride in pharmaceutical dosage forms using one of the proposed sensors gave average recoveries of 104.3 and 99.9 with R.S.D. of 0.3 and 0.6% for tablets (Malaritab) and a reconstituted powder containing ADQ.2HCl, respectively. The sensor was also used for dissolution profile studies of two drug formulations. The sensor proved to have a good selectivity for ADQ.2HCl over some inorganic and organic compounds, however, berberine chloride interfered significantly. The results were validated by comparison with a spectrophotometric assay according to the USP pharmacopoeia.

Organic cation transport by Malpighian tubules of Drosophila melanogaster: application of two novel electrophysiological methods.

Transport of the prototypical organic cation tetraethylammonium (TEA) by the Malpighian tubules, ureters and gut of Drosophila melanogaster was studied using two novel electrophysiological techniques. Both techniques exploited the high selectivity of the cation exchanger potassium tetra-p-chlorophenylborate for tetraalkylammonium compounds relative to inorganic cations such as K(+). In the first technique, TEA fluxes were measured using a non-invasive self-referencing TEA-selective microelectrode positioned in the unstirred layer near the surface of each tissue. TEA fluxes from bath to lumen as large as 6 pmol cm(-2) s(-1) were measured across the lower (reabsorptive) segment of the Malpighian tubule and the ureter bathed in saline containing 0.1 mmol l(-1) TEA. Corresponding bath-to-lumen fluxes across the secretory main segment of the Malpighian tubule and the posterior midgut were approximately 1 pmol cm(-2) s(-1). TEA transport by the lower Malpighian tubule was enhanced by hyperpolarization of the basolateral membrane potential and was inhibited by cimetidine, quinidine, vinblastine and verapamil. In the second technique, TEA concentration was measured using a TEA-selective microelectrode positioned in droplets of fluid secreted by Malpighian tubules set up in saline droplets under oil in a Ramsay assay. Results from the Ramsay assay confirmed the dominant role of the lower Malpighian tubule in net transepithelial secretion of TEA and inhibition of TEA transport by cimetidine. Kinetic parameters (J(max) and K(t)) were determined using both approaches.

A novel potentiometric approach for detection of beta-adrenergics and beta-adrenolytics in high-performance liquid chromatography.

Potentiometric approach enabling sensitive and reliable detection for a series of 20 autonomic beta-adrenergic ligands with the use of poly(vinyl chloride) (PVC) based liquid membrane electrode coatings in the normal-bore cation exchange HPLC and narrow-bore reversed phase HPLC system is presented. It was found that in both kinds of HPLC modes with a contemporary hybrid polymer-silica packings an application of electrodes containing a tetrakis(p-chlorophenyl)borate (TCPB) gives limits of detection below to 8.0x10(-7) mol l(-1) (injected concentrations). In case of highly hydrophobic beta-adrenergic drugs the use of binary aqueous mobile phases with high concentrations of acetonitrile (up to 25% v/v) shifting an observable detection limits (DL) down to 2.0x10(-8) mol l(-1), especially for electrodes with addition of trioctylated alpha-cyclodextrin. The characteristics of developed potentiometric detectors was established by proposed a quantitative structure-potentiometric response relationships (QSPRRs) for a series of diversified beta-adrenergic compounds and for a set of the PVC based electrodes using TCPB alone as well as in combination with trioctylated alpha-cyclodextrin, dibenzo-18-crown-6, or calix[6]arene hexaethylester as the neutral macrocycle ionophore. A highly significant QSPRRs equations were obtained leading to reasonable prediction of the DL of specified electrodes in terms of the computationally derived set of molecular descriptors of beta-adrenergics and beta-blocking agents and similar amino alcohol type xenobiotics.

A chronoamperometric method to estimate changes in the membrane composition of ion-selective membranes.

A new chronoamperometric method is used to estimate changes in the membrane composition of mobile-site, ionophore-based membranes. The characteristic features of the chronoamperometric curves (initial current, slope, break time) of valinomycin-based, potassium-selective membranes loaded with potassium tetrakis(4-chlorophenyl)borate are correlated with the mobile-site and free ionophore concentration in the membrane. limiting cases for strong and negligible ion pair formation are distinguished. Replicate measurements indicate a relative standard deviation in the calculated values less than 10%. The practical applicability of the method was tested with membranes incorporated into conventional ion-selective electrode bodies or cast onto microfabricated planar sensor structures.

Fentanyl-selective polymeric membrane electrode.

A poly (vinyl chloride) membrane electrode with dibutyl phthalate as plasticizer based on a fentanyl-tetrakis(4-chlorophenyl)borate ion-pair complex for the determination of fentanyl citrate in injections is described. A linear response over the range 1 x 10(-5) mol.dm-3 to 1 x 10(-2) mol.dm-3 drug with a slope of 59.3 +/- 0.6 mV/decade was established. The optimum pH range was 1 to 6. The lower detection limit was 8 x 10(-6) mol.dm-3 fentanyl citrate (2.7 micrograms cm-3 fentanyl). There were negligible interferences from a number of inorganic cations, structural analogues, and some common drug additives used in injections. The electrode proposed has been successfully applied to determine fentanyl citrate in injections. The results correlated well with those obtained by the United States Pharmacopoeia standard procedure.

Aldol reaction of enol esters catalyzed by cationic species paired with tetrakis(pentafluorophenyl)borate.

The crossed aldol reaction of enol esters, which are weak carbon nucleophiles, with aldehydes was effectively carried out under mild conditions by using a catalytic amount of several cationic species paired with tetrakis(pentafluorophenyl)borate.

In vivo antileishmanial action of Ir-(COD)-pentamidine tetraphenylborate on Leishmania donovani and Leishmania major mouse models.

Ir-(COD)-pentamidine tetraphenylborate which has previously been studied on promastigote forms of Leishmania, was investigated for its antileishmanial properties compared with pentamidine used as reference compound. In vitro, the iridium complex had the same IC50 value on intracellular forms of Leishmania as pentamidine (15 microM). In vivo, the compound could not be injected intravenously due to the DMSO excipient so that the treatments were performed intraperitoneally or subcutaneously. On the L. donovani LV9/Balb/C mouse model, the iridium complex was not toxic after intraperitoneal treatment at 232 mg/kg/day x 5 or 147 mumoles/kg/day x 5, whereas all the mice died within five days when treated at the same dose with pentamidine isethionate. However, only 23% of parasite suppression was observed with the iridium complex. On a L. major MON 74/Balb/C mouse model, susceptible to intravenously administered pentamidine at 6.7 mumoles/kg/day x 5 (54% of parasite suppression), the iridium complex exhibited 32% of parasite suppression after a treatment at 76 mumoles/kg/day x 5 administered subcutaneously. This slight activity is of interest since pentamidine isethionate is not active under these conditions. Transmission electron microscopy of amastigotes from infected and treated mice show aggregation of ribosomal material, distension of the nuclear membrane and kDNA depolymerization. The mechanism of action therefore involves several targets: membranes, ribosomes and kDNA. According to our results, the Iridium complex is a suitable candidate to be encapsulated in drug carriers such as liposomes or nanoparticles.

Uptake into leishmania donovani promastigotes and antileishmanial action of an organometallic complex derived from pentamidine.

Iridium (Ir)-(COD)-pentamidine tetraphenylborate (CAS 225-75-4) was selected from a primary screening to be evaluated in vitro on three Leishmania (L.) strains comparatively to pentamidine used as reference compound. The IC50 values obtained from in vitro evaluation on promastigotes of L. major CRE 26, L. donovani DD8 and L. donovani LV9 were 3.9, 23.5, and 3.3 mumol/l for Ir-(COD)-pentamidine tetraphenylborate and 1.6, 7.7, and 3.9 mumol/l for pentamidine isethionate, respectively. Cytotoxicity on mouse peritoneal macrophages led to determine a chemotherapeutic index of 1.7 for Ir-(COD)-pentamidine tetraphenylborate and 4 for pentamidine. Considering L. donovani DD8, the uptake of iridium complex by the promastigotes was shown to be saturable with a Km value of 17.4 mumol/l and Vmax of 1.3 nmol/mg protein/2 h. After 2 and 4 h incubation of treated promastigotes in drug free medium the absence of Ir-complex efflux is in favour of intracellular drug binding. As a matter of fact iridium complex was shown to bind ribosomal subunits in vitro, with no effect on macromolecular biosynthesis.

Structure of tBuCO-Gly-Gly psi [CH2-N+H2]NHEt.BPh4-.

N-(tert-Butylcarbonylglycylaminoethyl)-N-(ethyl)ammonium tetraphenylborate, C11H24N3O+2.C24H20B-, Mr = 549.57, triclinic, P-1, a = 11.567 (2), b = 11.922 (2), c = 14.484 (3) A, alpha = 70.99 (2), beta = 74.83 (2), gamma = 59.33 (1) degrees, V = 1613.1 A3, Z = 2, D chi = 1.13 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu = 4.69 cm-1, mu Rmax much less than 1, F(000) = 592, T = 293 K, R = 0.058 for 3491 observed reflections. This pseudopeptide is folded by a short N(+)-H ... O = C hydrogen bond (N3 ... O1 = 2.81 A) which closes a ten-membered ring. This results in a beta-turn structure that can be classified as type II on the basis of the conformational angles for the N-terminal glycine. The conformational angles phi 1, psi 1, phi 2 and psi 2 are -53.4 (6), 139.7 (4), 91.5 (5) and -62.6 (6) degrees respectively.

Structure of hexakis(N-methylimidazole-N')iron(II) tetraphenylborate dichloromethane solvate.

[Fe(C4H6N2)6][B(C6H5)4]2.CH2Cl2, Mr = 1271.88, monoclinic, P2(1)/c, a = 20.5320 (6), b = 15.113 (3), c = 23.611 (7) A, beta = 109.01 (3) degrees, V = 6926.9 (1) A3, Z = 4, Dx = 1.23 g cm-3, mu(Mo K alpha) = 0.70966 A, graphite monochromator, mu = 3.37 cm-1, F(000) = 2680, T = 298 K, R = 0.057 for 2310 unique observed reflections. The asymmetric unit consists of a single [Fe(C4H6N2)6]2+ cation, two distinct BPh-4 anions, and one CH2Cl2. The Fe atom is octahedrally coordinated by six N-methylimidazole ligands. The six Fe-N bond distances per cation range from 2.174 (11) to 2.228 (10) A, the average being 2.207 (12) A. This average distance is within the range previously observed for high-spin ferrous complexes. The ring planes of N-methylimidazole ligands that lie trans to each other have interplane angles of 17.56, 18.48 and 157.56 degrees. These ring planes lie approximately either parallel or perpendicular to equatorial Fe-N bonds.

Structural requirement for the rapid movement of charged molecules across membranes. Experiments with tetraphenylborate analogues.

Charge-pulse experiments were performed in the presence of structural analogues of tetraphenylborate (TPB) on membranes made of dioleoyl phosphatidylethanolamine and dioleoyl phosphatidylcholine. The analysis of the experimental results using a previously proposed model allowed the calculation of the partition coefficient, beta, and of the translocation rate constant, kappa i. The temperature dependence of the partition coefficients was used to calculate the thermodynamics of the adsorption of the lipophilic ions to the membranes. The analysis of the translocation rate constants obtained at different temperatures yielded detailed information on the free energy of the TPB-analogues within artificial lipid bilayer membranes, and on the activation energy of the translocation rate constants. The adsorption of the different TPB-analogues to the membranes was only slightly affected by their structure, whereas a dramatic influence of the structure on the free energy of the lipophilic ions within the membranes was observed. The free energy of the ions in the membranes decreased from triphenylcyanoborate (TPCB) to tetrakis(3-trifluoromethylphenyl)borate (TTFPB) by more than 31 kJ/mol (7.4 kcal/mol). This could be concluded from the observed increase in the translocation rate constant by almost six orders of magnitude. The change of the free energy in the membrane was used for the estimation of an effective radius of the TPB-analogues with respect to TPB.

A liquid ion-exchanger alternative to KCl for filling intracellular reference microelectrodes.

We have developed a filling solution for silanised microelectrodes consisting of potassium tetrakis (p-chlorophenyl) borate in octanol. Microelectrodes filled with this reference liquid ion-exchanger (RLIE) have equal selectivities to Na and K, and give the same membrane potential as do KCl-filled microelectrodes. The RLIE microelectrodes are more stable, less damaging to the cell membrane and do not leak Cl- ions. Their high resistance, however, makes them unsuitable for recording rapid potential changes or for passing current.