Evaluation of solubility and partition properties of ampicillin-based ionic liquids

In order to overcome the problems associated with low water solubility, and consequently low bioavailability of active pharmaceutical ingredients (APIs), herein we explore a modular ionic liquid synthetic strategy for improved APIs. Ionic liquids containing l-ampicillin as active pharmaceutical ingredient anion were prepared using the methodology developed in our previous work, using organic cations selected from substituted ammonium, phosphonium, pyridinium and methylimidazolium salts, with the intent of enhancing the solubility and bioavailability of l-ampicillin forms. In order to evaluate important properties of the synthesized API-ILs, the water solubility at 25 °C and 37 °C (body temperature) as well as octanol–water partition coefficients (Kow's) and HDPC micelles partition at 25 °C were measured. Critical micelle concentrations (CMC's) in water at 25 °C and 37 °C of the pharmaceutical ionic liquids bearing cations with surfactant properties were also determined from ionic conductivity measurements.

Shear-induced lamellar phase of an ionic liquid crystal at room temperature

The phase behaviour of a number of N-alkylimidazolium salts was studied using polarizing optical microscopy, differential scanning calorimetry and X-ray diffraction. Two of these compounds exhibit lamellar mesophases at temperatures above 50 degrees C. In these systems, the liquid crystalline behaviour may be induced at room temperature by shear. Sheared films of these materials, observed between crossed polarisers, have a morphology that is typical of (wet) liquid foams: they partition into dark domains separated by brighter (birefringent) walls, which are approximately arcs of circle and meet at "Plateau borders" with three or more sides. Where walls meet three at a time, they do so at approximately 120 degrees angles. These patterns coarsen with time and both T1 and T2 processes have been observed, as in foams. The time evolution of domains is also consistent with von Neumann's law. We conjecture that the bright walls are regions of high concentration of defects produced by shear, and that the system is dominated by the interfacial tension between these walls and the uniform domains. The control of self-organised monodomains, as observed in these systems, is expected to play an important role in potential applications.

How foam-like is the shear-induced lamellar phase of an ionic liquid crystal?

Philosophical Magazine Letters Volume 88, Issue 9-10, 2008 Special Issue: Solid and Liquid Foams. In commemoration of Manuel Amaral Fortes

Study on solubility of pharmaceutical compounds in ionic liquids

Dissertation to obtain the degree of master in Chemical and Biochemical Engineering

Interaction of cationic water-soluble meso-tetrakis(4-N-methylpyridiniumyl)porphyrin (TMPyP) with ionic and nonionic micelles: aggregation and binding

The equilibrium of meso-tetrakis(4-N-methylpyridiniumyl)porphyrin (TMPyP) in aqueous solution in the presence of surfactants was studied by optical spectroscopic techniques and SAXS (small angle X-ray scattering). Anionic SDS (sodium dodecyl sulfate), zwitterionic HPS (N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate) and nonionic TRITON X-100 (t-octyl-phenoxypolyethoxyethanol), surfactants were used. TMPyP is characterized by a protonation equilibrium with a pK(a) around 1.0, associated with the diacid-free base transition, and a second pK(a) around 12.0 related with the transition between the free base and the monoanion form. Three independent species were observed for TMPyP at pH 6.0 as a function of SDS concentration: free TMPyP, TMPyP-SDS aggregates and porphyrin monomer bound to micelles. For HPS and TRITON X-100, the equilibrium of TMPyP as a function of pH is quite similar to that obtained in pure aqueous solution: no aggregation was observed, suggesting that electrostatic contribution is the major factor in the interaction between TMPyP and surfactants. SAXS data analysis demonstrated a prolate ellipsoidal shape for SDS micelles; no significant changes in shape and size were observed for SDS-TMPyP co-micelles. Moreover, the ionization coefficient, alpha, decreases with the increase of the porphyrin concentration, suggesting the ""screening"" of the anionic charge of SDS by the cationic porphyrin. These results are consistent with optical absorption, fluorescence and RLS (resonance light scattering) spectroscopies data, allowing to conclude that neutral surfactants present a smaller interaction with the cationic porphyrin as compared with an ionic surfactant. Therefore, the interaction of TMPyP with the ionic and nonionic surfactants is predominantly due to the electrostatic contribution. Copyright (c) 2008 Society of Porphyrins & Phthalocyanines.

Measurements of activity coefficients at infinite dilution of organic solutes and water on polar imidazolium-based ionic liquids

The activity coefficients at infinite dilution, gamma(infinity)(13), of 55 organic solutes and water in three ionic liquids with the common cation 1-butyl-3-methylimidazolium and the polar anions Cl--,Cl- [CH3SO3](-) and [(CH3)(2)PO4](-), were determined by (gas + liquid) chromatography at four temperatures in the range (358.15 to 388.15) K for alcohols and water, and T = (398.15 to 428.15) K for the other organic solutes including alkanes, cycloalkanes, alkenes, cycloalkenes, alkynes, ketones, ethers, cyclic ethers, aromatic hydrocarbons, esters, butyraldehyde, acetonitrile, pyridine, 1-nitropropane and thiophene. From the experimental gamma(infinity)(13) values, the partial molar excess Gibbs free energy, (G) over bar (E infinity)(m), enthalpy (H) over bar (E infinity)(m), and entropy (S) over bar (E infinity)(m), at infinite dilution, were estimated in order to provide more information about the interactions between the solutes and the ILs. Moreover, densities were measured and (gas + liquid) partition coefficients (KL) calculated. Selectivities at infinite dilution for some separation problems such as octane/benzene, cyclohexane/benzene and cyclohexane/thiophene were calculated using the measured gamma(infinity)(13), and compared with literature values for N-methyl-2-pyrrolidinone (NMP), sulfolane, and other ionic liquids with a common cation or anion of the ILs here studied. From the obtained infinite dilution selectivities and capacities, it can be concluded that the ILs studied may replace conventional entrainers applied for the separation processes of aliphatic/aromatic hydrocarbons.

Selection of ionic liquids to be used as separation agents for terpenes and terpenoids

In this work, ionic liquids are evaluated for the first time as solvents for extraction and entrainers in separation processes involving terpenes and terpenoids. For that purpose, activity coefficients at infinite dilution, γ13 ∞, of terpenes and terpenoids, in the ionic liquids [C4mim]Cl, [C4mim][CH3SO3], [C4mim][(CH3)2PO4] and [C4mim][CF3SO3] were determined by gas−liquid chromatography at six temperatures in the range 398.15 to 448.15 K. On the basis of the experimental values, a correlation of γ13 ∞ with an increase of the solubility parameters is proposed. The infinite dilution thermodynamic functions were calculated showing the entropic effect is dominant over the enthalpic. Gas−liquid partition coefficients give indications about the recovery and purification of terpenes and terpenoids from ionic liquid solutions. Presenting a strong innovative character, COSMO-RS was evaluated for the description of the selectivities and capacities, showing to be a useful tool for the screening of ionic liquids in order to find suitable candidates for terpenes and terpenoids extraction, and separation. COSMO-RS predictions show that in order to achieve the maximum separation efficiency, polar anions should be used such as bis(2,4,4-trimethylpentyl)phosphinate or acetate, whereas high capacities require nonpolar cations such as phosphonium.

IONIC LIQUID EXTRACTION UNVEILS PREVIOUSLY OCCLUDED HUMICBOUND IRON IN PEAT POREWATER

Extracellular iron reduction has been suggested as a candidate metabolic pathway that may explain a large proportion of carbon respiration in temperate peatlands. However, the o-phenanthroline colorimetric method commonly employed to quantitate iron and partition between redox species is known to be unreliable in the presence of humic and fulvic acids, both of which represent a considerable proportion of peatland dissolved organic matter. We propose ionic liquid extraction as a more accurate iron quantitation and redox speciation method in humic-rich peat porewater. We evaluated both o-phenanthroline and ionic liquid extraction in four distinct peatland systems spanning a gradient of physico-chemical conditions to compare total iron recovery and Fe2+:Fe3+ ratios determined by each method. Ionic liquid extraction was found to provide more accurate iron quantitation and speciation in the presence of dissolved organic matter. A multivariate approach utilizing fluorescence- and UV-Vis spectroscopy was used to identify dissolved organic matter characteristics in peat porewater that lead to poor performance of the o-phenanthroline method. Where these interferences are present, we offer an empirical correction factor for total iron quantitation by o-phenanthroline, as verified by ionic liquid extraction. The written work presented in this thesis is in preparation for submission to Soil Biology and Biochemisrty by T.J. Veverica, E.S. Kane, A.M. Marcarelli, and S.A. Green.

Chemical Immobilization Of Crosslinked Polymeric Ionic Liquids On Nitinol Wires Produces Highly Robust Sorbent Coatings For Solid-phase Microextraction.

Super elastic nitinol (NiTi) wires were exploited as highly robust supports for three distinct crosslinked polymeric ionic liquid (PIL)-based coatings in solid-phase microextraction (SPME). The oxidation of NiTi wires in a boiling (30%w/w) H2O2 solution and subsequent derivatization in vinyltrimethoxysilane (VTMS) allowed for vinyl moieties to be appended to the surface of the support. UV-initiated on-fiber copolymerization of the vinyl-substituted NiTi support with monocationic ionic liquid (IL) monomers and dicationic IL crosslinkers produced a crosslinked PIL-based network that was covalently attached to the NiTi wire. This alteration alleviated receding of the coating from the support, which was observed for an analogous crosslinked PIL applied on unmodified NiTi wires. A series of demanding extraction conditions, including extreme pH, pre-exposure to pure organic solvents, and high temperatures, were applied to investigate the versatility and robustness of the fibers. Acceptable precision of the model analytes was obtained for all fibers under these conditions. Method validation by examining the relative recovery of a homologous group of phthalate esters (PAEs) was performed in drip-brewed coffee (maintained at 60 °C) by direct immersion SPME. Acceptable recoveries were obtained for most PAEs in the part-per-billion level, even in this exceedingly harsh and complex matrix.

Development Of Egg Pc/cholesterol/α-tocopherol Liposomes With Ionic Gradients To Deliver Ropivacaine.

Ropivacaine (RVC) is an aminoamide local anesthetic widely used in surgical procedures. Studies with RVC encapsulated in liposomes and complexed in cyclodextrins have shown good results, but in order to use RVC for lengthy procedures and during the postoperative period, a still more prolonged anesthetic effect is required. This study therefore aimed to provide extended RVC release and increased upload using modified liposomes. Three types of vesicles were studied: (i) large multilamellar vesicle (LMV), (ii) large multivesicular vesicle (LMVV) and (iii) large unilamellar vesicle (LUV), prepared with egg phosphatidylcholine/cholesterol/α-tocopherol (4:3:0.07 mol%) at pH 7.4. Ionic gradient liposomes (inside: pH 5.5, pH 5.5 + (NH4)2SO4 and pH 7.4 + (NH4)2SO4) were prepared and showed improved RVC loading, compared to conventional liposomes (inside: pH 7.4). An high-performance liquid chromatography analytical method was validated for RVC quantification. The liposomes were characterized in terms of their size, zeta potential, polydispersion, morphology, RVC encapsulation efficiency (EE(%)) and in vitro RVC release. LMVV liposomes provided better performance than LMV or LUV. The best formulations were prepared using pH 5.5 (LMVV 5.5in) or pH 7.4 with 250 mM (NH4)2SO4 in the inner aqueous core (LMVV 7.4in + ammonium sulfate), enabling encapsulation of as much as 2% RVC, with high uptake (EE(%) ∼70%) and sustained release (∼25 h). The encapsulation of RVC in ionic gradient liposomes significantly extended the duration of release of the anesthetic, showing that this strategy could be a viable means of promoting longer-term anesthesia during surgical procedures and during the postoperative period.

Visual demonstration of the ionic strength effect in the classroom: the Debye-Hückel limiting law

The effects of ionic strength on ions in aqueous solutions are quite relevant, especially for biochemical systems, in which proteins and amino acids are involved. The teaching of this topic and more specifically, the Debye-Hückel limiting law, is central in chemistry undergraduate courses. In this work, we present a description of an experimental procedure based on the color change of aqueous solutions of bromocresol green (BCG), driven by addition of electrolyte. The contribution of charge product (z+|z-|) to the Debye-Hückel limiting law is demonstrated when the effects of NaCl and Na2SO4 on the color of BCG solutions are compared.

Synthesis of diaryl selenides using electrophilic selenium species and nucleophilic boron reagents in ionic liquids

We described herein the use of imidazolium ionic liquids [bmim]PF(6) and [bmim]BF(4) in the selective, metal and catalyst-free synthesis of unsymmetrical diaryl selenides by electrophilic substitution in arylboron reagents with arylselenium halides (Cl and Br) at room temperature. This is a general substitution reaction and it was performed with arylboronic acids or potassium aryltrifluoroborates bearing electron-withdrawing or electron-donating groups, affording the corresponding diaryl selenides in good to excellent yields. The ionic liquid [bmim][PF(6)] was easily recovered and utilized for further substitution reactions.

Ionic and Histological Studies of Salivary Glands in Rats with Diabetes and Their Glycemic State After Laser Irradiation

Objectives: To evaluate the effect of laser irradiation (LI) on the glycemic state and the histological and ionic parameters of the parotid and submandibular glands in rats with diabetes. Methods: One hundred twenty female rats were divided into eight groups. Diabetes was induced by administration of streptozotocin and confirmed later according to results of glycemia testing. Twenty-nine days after the induction, the parotid and submandibular glands of the rats were irradiated with 5, 10, and 20 J/cm(2) using a laser diode (660nm/100mW) (without diabetes: C5, C10, and C20; with diabetes: D5, D10, and D20, respectively). On the following day, the rats were euthanized, and blood glucose determined. Histological and ionic analyses were performed. Results: Rats with diabetes without irradiation (D0) showed lipid droples accumulation in the parotid gland, but accumulation decreased after 5, 10, and 20 J/cm(2) of laser irradiation. A decrease in fasting glycemia level from 358.97 +/- 56.70 to 278.33 +/- 87.98mg/dL for D5 and from 409.50 +/- 124.41 to 231.80 +/- 120.18 mg/dL for D20 (p < 0.05) was also observed. Conclusion: LI should be explored as an auxiliary therapy for control of complications of diabetes because it can alter the carbohydrate and lipid metabolism of rats with diabetes.

Phase transitions and spatially ordered counterion association in ionic-lipid membranes: A statistical model

We propose a statistical model to account for the gel-fluid anomalous phase transitions in charged bilayer- or lamellae-forming ionic lipids. The model Hamiltonian comprises effective attractive interactions to describe neutral-lipid membranes as well as the effect of electrostatic repulsions of the discrete ionic charges on the lipid headgroups. The latter can be counterion dissociated (charged) or counterion associated (neutral), while the lipid acyl chains may be in gel (low-temperature or high-lateral-pressure) or fluid (high-temperature or low-lateral-pressure) states. The system is modeled as a lattice gas with two distinct particle types-each one associated, respectively, with the polar-headgroup and the acyl-chain states-which can be mapped onto an Ashkin-Teller model with the inclusion of cubic terms. The model displays a rich thermodynamic behavior in terms of the chemical potential of counterions (related to added salt concentration) and lateral pressure. In particular, we show the existence of semidissociated thermodynamic phases related to the onset of charge order in the system. This type of order stems from spatially ordered counterion association to the lipid headgroups, in which charged and neutral lipids alternate in a checkerboard-like order. Within the mean-field approximation, we predict that the acyl-chain order-disorder transition is discontinuous, with the first-order line ending at a critical point, as in the neutral case. Moreover, the charge order gives rise to continuous transitions, with the associated second-order lines joining the aforementioned first-order line at critical end points. We explore the thermodynamic behavior of some physical quantities, like the specific heat at constant lateral pressure and the degree of ionization, associated with the fraction of charged lipid headgroups.

Ionic liquids as recycling solvents for the synthesis of magnetic nanoparticles

This work describes an easy synthesis (one pot) of MFe(2)O(4) (M = Co, Fe, Mn, and Ni) magnetic nanoparticles MNPs by the thermal decomposition of Fe(Acac)(3)/M(Acac)(2) by using BMI center dot NTf(2) (1-n-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) or BMI center dot PF(6) (1-n-butyl-3-methylimidazolium hexafluorophosphate) ionic liquids (ILs) as recycling solvents and oleylamine as the reducing and surface modifier agent. The effects of reaction temperature and reaction time on the features of the magnetic nanomaterials (size and magnetic properties) were investigated. The growth of the MNPs is easily controlled in the IL by adjusting the reaction temperature and time, as inferred from Fe(3)O(4) MNPs obtained at 150 degrees C, 200 degrees C and 250 degrees C with mean diameters of 8, 10 and 15 nm, respectively. However, the thermal decomposition of Fe(Acac)(3) performed in a conventional high boiling point solvent (diphenyl ether, bp 259 degrees C), under a similar Fe to oleylamine molar ratio used in the IL synthesis, does not follow the same growth mechanism and rendered only smaller NPs of 5 nm mean diameter. All MNPs are covered by at least one monolayer of oleylamine making them readily dispersible in non-polar solvents. Besides the influence on the nanoparticles growth, which is important for the preparation of highly crystalline MNPs, the IL was easily recycled and has been used in at least 20 successive syntheses.