Asymmetric syntheses of analogs of kainic acid

Kainic acid has been used for nearly 50 years as a tool in neuroscience due to its pronounced neuroexcitatory properties. However, the significant price increase of kainic acid resulting from the disruption in the supply from its natural source, the alga Digenea Simplex, as well as inefficient synthesis of kainic acid, call for the exploration of functional mimics of kainic acid that can be synthesized in a simpler way. Aza kainoids analog could be one of them. The unsubstituted aza analog of kainoids has demonstrates its ability as an ionotropic glutamate receptor agonist and showed affinity in the chloride dependent glutamate (GluCl) binding site. This opened a question of the importance of the presence of one nitrogen or both nitrogens in the aza kainoid analogs for binding to glutamate receptors. Therefore, two different pyrrolidine analogs of kainic acid, trans -4-(carboxymethyl)pyrrolidine-3-carboxylic acid and trans -2-carboxy-3-pyrrolidineacetic acid, were synthesized through multi-step sequences. The lack of the affinity of both pyrrolidine analogs in GluCl binding site indicated that both nitrogens in aza kainoid analogs are involved in hydrogen bonding with receptors, significantly enhancing their affinity in GluCl binding site. Another potential functional mimic of kainic acid is isoxazolidine analogs of kainoids whose skeleton can be constituted directly via a 1, 3 dipolar cycloaddition as the key step. The difficulty in synthesizing N-unsubstituted isoxazolidines when applying such common protecting groups as alkyl, phenyl and benzyl groups, and the requirement of a desired enantioselectivity due to the three chiral ceneters in kainic acid, pose great challenges. Hence, several different protected nitrones were studied to establish that diphenylmethine nitrone may be a good candidate as the dipole in that the generated isoxazolidines can be deprotected in mild conditions with high yields. Our investigations also indicated that the exo/endo selectivity of the 1, 3 dipolar cycloaddition can be controlled by Lewis acids, and that the application of a directing group in dipolarophiles can accomplish a satisfied enantioselectivity. Those results demonstrated the synthesis of isoxazoldines analogs of kainic acid is very promising.

Pressure induced structural changes and gas diffusion pathways in monomeric fluorescent proteins

Fluorescent proteins (FPs) are extremely valuable biochemical markers which have found a wide range of applications in cellular and molecular biology research. The monomeric variants of red fluorescent proteins (RFPs), known as mFruits, have been especially valuable for in vivo applications in mammalian cell imaging. Fluorescent proteins consist of a chromophore caged in the beta-barrel protein scaffold. The photophysical properties of an FP is determined by its chromophore structure and its interactions with the protein barrel. Application of hydrostatic pressure on FPs results in the modification of the chromophore environment which allows a systematic study of the role of the protein-chromophore interactions on photophysical properties of FPs. Using Molecular Dynamics (MD) computer simulations, I investigated the pressure induced structural changes in the monomeric variants mCherry, mStrawberry, and Citrine. The results explain the molecular basis for experimentally observed pressure responses among FP variants. It is found that the barrel flexibility, hydrogen bonding interactions and chromophore planarity of the FPs can be correlated to their contrasting photophysical properties at vaious pressures. I also investigated the oxygen diffusion pathways in mOrange and mOrange2 which exhibit marked differences in oxygen sensitivities as well as photostability. Such computational identifications of structural changes and oxygen diffusion pathways are important in guiding mutagenesis efforts to design fluorescent proteins with improved photophysical properties.

Mechanisms of Arsenic Detoxification and Resistance

Arsenic is a ubiquitous environmental toxic substance. As a consequence of continual exposure to arsenic, nearly every organism, from Escherichia coli to humans have evolved arsenic detoxification pathways. One of the pathways is extrusion of arsenic from inside the cells, thereby conferring resistance. The R773 arsRDABC operon in E. coli encodes an ArsAB efflux pump that confers resistance to arsenite. ArsA is the catalytic subunit of the pump, while ArsB forms the oxyanion conducting pathway. ArsD is an arsenite metallochaperone that binds arsenite and transfers it to ArsA. The interaction of ArsA and ArsD allows for resistance to As(III) at environmental concentrations. The interaction between ArsA ATPase and ArsD metallochaperone was examined. A quadruple mutant in the arsD gene encoding a K2A/K37A/K62A/K104A ArsD is unable to interact with ArsA. An error-prone mutagenesis approach was used to generate random mutations in the arsA gene that restored interaction with the quadruple arsD mutant in yeast two-hybrid assays. Three such mutants encoding Q56R, F120I and D137V ArsA were able to restore interaction with the quadruple ArsD mutant. Structural models generated by in silico docking suggest that an electrostatic interface favors reversible interaction between ArsA and ArsD. Mutations in ArsA that propagate changes in hydrogen bonding and salt bridges to the ArsA-ArsD interface also affect their interactions. The second objective was to examine the mechanism of arsenite resistance through methylation and subsequent volatilization. Microbial ArsM (As(III) S-adenosylmethyltransferase) catalyzes the formation of trimethylarsine as the volatile end product. The net result is loss of arsenic from cells. The gene for CrArsM from the eukaryotic green alga Chlamydomonas reinhardtii was chemically synthesized and expressed in E. coli. The purified protein catalyzed the methylation of arsenite into methyl-, dimethyl- and trimethyl products. Synthetic purified CrArsM was crystallized in an unliganded form. Biochemical and biophysical studies conducted on CrArsM sheds new light on the pathways of biomethylation. While in microbes ArsM detoxifies arsenic, the human homolog, hAS3MT, converts inorganic arsenic into more toxic and carcinogenic forms. An understanding of the enzymatic mechanism of ArsM will be critical in deciphering its parallel roles in arsenic detoxification and carcinogenesis.

Catalisadores bifuncionais à base de silicoaluminofosfato e fosfatos de nióbio para emprego em reações de hidroisomerização e hidrocraqueamento do n-hexadecano

Lubricants and cutting middle distillates typically have large amounts of n-paraffins to increase its freezing point and fluidity. Accordingly, the removal of n-paraffins of long chain lubricants oils and diesel is essential to get a product with good cold flow properties. The development of new catalysts, which exhibit thermal stability and catalytic activity for the hydroisomerization reaction is still a challenge. Thus, silicoaluminophosphates (SAPO) were synthesized by different routes. Have been used also post-synthesis treatment for obtaining hybrid structures and others synthesis have been carried out with mesoporous template (soft and hard-template). Therefore, SAPO have been impregnated with H2PtCl6 solution by the incipient wetness method. Then assessments of catalytic activities in hydroisomerization and hydrocracking reactions of hexadecane have been held. Besides SAPO, niobium phosphate - NbP - were also impregnated with platinum and evaluated in the same reaction. After impregnation, these catalysts have been characterized by X-ray diffraction (XRD), nitrogen adsorption, infrared spectroscopy with adsorbed pyridine (IV-PY), scanning electron microscopy (SEM) and resonance nuclear magnetic 29Si (29Si-NMR). The characterization results by XRD have shown that it has been possible to obtain mesoporous SAPOs. However, for the syntheses with soft template there was collapse of the structure after removal of the organic template. Even so, these catalysts have been actives. It was possible to obtain hybrid materials through the synthesis of SAPO-11 made with hard templates and by means of post-synthesis treatments samples of SAPO-11. Moreover, NbP has shown characteristic XRD of amorphous materials, with high acidity and were active in the conversion of hexadecane.

Catalisadores bifuncionais à base de silicoaluminofosfato e fosfatos de nióbio para emprego em reações de hidroisomerização e hidrocraqueamento do n-hexadecano

Lubricants and cutting middle distillates typically have large amounts of n-paraffins to increase its freezing point and fluidity. Accordingly, the removal of n-paraffins of long chain lubricants oils and diesel is essential to get a product with good cold flow properties. The development of new catalysts, which exhibit thermal stability and catalytic activity for the hydroisomerization reaction is still a challenge. Thus, silicoaluminophosphates (SAPO) were synthesized by different routes. Have been used also post-synthesis treatment for obtaining hybrid structures and others synthesis have been carried out with mesoporous template (soft and hard-template). Therefore, SAPO have been impregnated with H2PtCl6 solution by the incipient wetness method. Then assessments of catalytic activities in hydroisomerization and hydrocracking reactions of hexadecane have been held. Besides SAPO, niobium phosphate - NbP - were also impregnated with platinum and evaluated in the same reaction. After impregnation, these catalysts have been characterized by X-ray diffraction (XRD), nitrogen adsorption, infrared spectroscopy with adsorbed pyridine (IV-PY), scanning electron microscopy (SEM) and resonance nuclear magnetic 29Si (29Si-NMR). The characterization results by XRD have shown that it has been possible to obtain mesoporous SAPOs. However, for the syntheses with soft template there was collapse of the structure after removal of the organic template. Even so, these catalysts have been actives. It was possible to obtain hybrid materials through the synthesis of SAPO-11 made with hard templates and by means of post-synthesis treatments samples of SAPO-11. Moreover, NbP has shown characteristic XRD of amorphous materials, with high acidity and were active in the conversion of hexadecane.

Cocrystallisation involving the thioamide, amide and imide functional groups

The work presented in this dissertation focused on the development and characterisation of novel cocrystals that incorporated the thioamide, amide and imide functional groups. A particular emphasis was placed on the characterisation of these cocrystals by single crystal X-ray diffraction methods. In Chapter One a summary of the intermolecular interactions utilised in this work and a short review of the solid state and multicomponent systems is provided. A brief introduction to the ways in which different multicomponent systems can be distinguished, crystal engineering strategies and a number of cocrystal applications highlights the importance the understanding of intermolecular interactions can have on the physical and chemical properties of crystalline materials. Chapter Two is the first Results and Discussion chapter and includes an introduction that is specific to the chapter. The main body of this work focuses on the primary aromatic thioamide functional group and its propensity to cocrystallise with a number of sulfoxides. Unlike the amide functional group, thioamides are not commonly employed in cocrystallisation studies. This chapter presents the first direct comparison between the cocrystallisation abilities of these two functional groups and the intermolecular hydrogen bonding interactions present in the cocrystal structures are examined. Chapter Three describes the crystal landscape of a short series of secondary aromatic amides and their analogous thioamides. Building on the results obtained in Chapter Two, a cocrystal screen of the secondary thioamides with the sulfoxide functional group was carried out in order to determine the effect removing a hydrogen bond had on the supramolecular synthons observed in the cocrystals. These secondary thioamides are also utilised in Chapter Four, which examines their halogen bonding capabilities with two organoiodine coformers: 1,2- and 1,4-diiodotetrafluorobenzene. Chapter Five explores the cocrystallisation abilities of three related cyclic imides as coformers for cocrystallisation with a range of commonly used coformers. Chapter Six is an overall conclusions chapter that highlights the findings of the results presented in Chapters Two to Five. Chapter Seven details the instrument and experimental data for the compounds and cocrystals discussed in the Results and Discussion Chapters. The accompanying CD contains all of the crystallographic data in .cif format for the novel single crystal structures characterised in this work.

Study of the relation between the shape of lacosamide crystals and the composition of crystallization medium

Crystallization is the critical process used by pharmaceutical industries to achieve the desired size, size distribution, shape and polymorphism of a product material. Control of these properties presents a major challenge since they influence considerably downstream processing factors. Experimental work aimed at finding ways to control the crystal shape of Lacosamide, an active pharmaceutical ingredient developed by UCB Pharma, during crystallization was carried out. It was found that the crystal lattice displayed a very strong unidirectional double hydrogen bonding, which was at the origin of the needle shape of the Lacosamide crystals. Two main strategies were followed to hinder the hydrogen bonding and compete with the addition of a Lacosamide molecule along the crystal length axis: changing the crystallization medium or weakening the hydrogen bonding. Various solvents were tested to check whether the solvent used to crystallize Lacosamide had an influence on the final crystal shape. Solvent molecules seemed to slow down the growth in the length axis by hindering the unidirectional hydrogen bonding of Lacosamide crystals, but not enough to promote the crystal growth in the width axis. Additives were also tested. Certain additives have shown to compete in a more efficient way than solvent molecules with the hydrogen bonding of Lacosamide. The additive effect has also shown to be compatible with the solvent effect. In parallel, hydrogen atoms in Lacosamide were changed into deuterium atoms in order to weaken the hydrogen bonds strength. Weakening the hydrogen bonds of Lacosamide allowed to let the crystal grow in the width axis. Deuteration was found to be combinable with solvent effect while being in competition with the additive effect. The Lacosamide molecule was eventually deemed an absolute needle by the terms of Lovette and Doherty. The results of this dissertation are aimed at contributing to this classification.

Design and Synthesis of Acridine-Based Macrocyclic G-Quadruplex DNA Ligands

DNA sequences that are rich in the guanine nucleic base possess the ability to fold into higher order structures called G-quadruplexes. These higher level structures are formed as a result of two sets of four guanine bases hydrogen-bonding together in a planar arrangement called a guanine quartet. Guanine quartets subsequently stack upon each other to form quadruplexes. G-quadruplexes are mainly localized in telomeres as well as in oncogene promoters. One unique and promising therapeutic approach against cancer involves targeting and stabilizing G-quadruplexes with small molecules, generally in order to suppress oncogene expression and telomerase enzyme activity; the latter has been found to contribute to “out-of control” cell growth in ca. 80-85% of all cancer cells and primary tumours while being absent in normal somatic cells. In this work, we present efforts towards designing and synthesizing acridine-based macrocycles (Mh) and (Mb) with the purpose of providing potential G4 ligands that are suited for selective binding to G4 vs. duplex DNA, and stabilize G-quadruplex structures. Two ligands described in this study include an acridine core which provides an aromatic surface capable of π-π interactions with the surface of G-quadruplexes. The successful synthesis of 4,5-diaminoacridine is described in chapter 2, as an essential fragment of the macrocycles (Mh) and (Mb). In order to investigate the synthetic method for macrocyclization, model compounds composing almost half of the designed macrocycles were explored. As discussed in chapter 3, the synthesis of the model compound for (Mb) turned out to be challenging. However, as a step towards the synthesis of (Mh), the synthesis of the hydrogen-containing model compound, which is almost half of the desired macrocycle (Mh) was achieved in our group and proved to be promising.

The use of binary polymeric networks in stabilising polyethylene oxide solid dispersions

The objective of this study was to determine if a high Tg polymer (Eudragit® S100) could be used to stabilize amorphous domains of polyethylene oxide (PEO) and hence improve the stability of binary polymer systems containing celecoxib (CX). We propose a novel method of stabilizing the amorphous PEO solid dispersion through inclusion of a miscible, high Tg polymer, namely, that can form strong inter-polymer interactions. The effects of inter-polymer interactions and miscibility between PEO and Eudragit S100 are considered. Polymer blends were first manufactured via hot-melt extrusion at different PEO/S100 ratios (70/30, 50/50, and 30/70 wt/wt). Differential scanning calorimetry and dynamic mechanical thermal analysis data suggested a good miscibility between PEO and S100 polymer blends, particularly at the 50/50 ratio. To further evaluate the system, CX/PEO/S100 ternary mixtures were extruded. Immediately after hot-melt extrusion, a single Tg that increased with increasing S100 content (anti-plasticization) was observed in all ternary systems. The absence of powder X-ray diffractometry crystalline Bragg’s peaks also suggested amorphization of CX. Upon storage (40°C/75% relative humidity), the formulation containing PEO/S100 at a ratio of 50:50 was shown to be most stable. Fourier transform infrared studies confirmed the presence of hydrogen bonding between Eudragit S100 and PEO suggesting this was the principle reason for stabilization of the amorphous CX/PEO solid dispersion system.

Studies of Protein-Protein and Protein-Water Interactions by Small Angle X-Ray Scattering, Terahertz Spectroscopy, ASMOS, And Computer Simulation

The protein folding problem has been one of the most challenging subjects in biological physics due to its complexity. Energy landscape theory based on statistical mechanics provides a thermodynamic interpretation of the protein folding process. We have been working to answer fundamental questions about protein-protein and protein-water interactions, which are very important for describing the energy landscape surface of proteins correctly. At first, we present a new method for computing protein-protein interaction potentials of solvated proteins directly from SAXS data. An ensemble of proteins was modeled by Metropolis Monte Carlo and Molecular Dynamics simulations, and the global X-ray scattering of the whole model ensemble was computed at each snapshot of the simulation. The interaction potential model was optimized and iterated by a Levenberg-Marquardt algorithm. Secondly, we report that terahertz spectroscopy directly probes hydration dynamics around proteins and determines the size of the dynamical hydration shell. We also present the sequence and pH-dependence of the hydration shell and the effect of the hydrophobicity. On the other hand, kinetic terahertz absorption (KITA) spectroscopy is introduced to study the refolding kinetics of ubiquitin and its mutants. KITA results are compared to small angle X-ray scattering, tryptophan fluorescence, and circular dichroism results. We propose that KITA monitors the rearrangement of hydrogen bonding during secondary structure formation. Finally, we present development of the automated single molecule operating system (ASMOS) for a high throughput single molecule detector, which levitates a single protein molecule in a 10 µm diameter droplet by the laser guidance. I also have performed supporting calculations and simulations with my own program codes.

L'orientation et la propriété de mémoire de forme des polymères cristallins liquides à chaînes latérales covalents et supramoléculaires

In many studies of the side-chain liquid crystalline polymers (SCLCPs) bearing azobenzene mesogens as pendant groups, obtaining the orientation of azobenzene mesogens at a macroscopic scale as well as its control is important, because it impacts many properties related to the cooperative motion characteristic of liquid crystals and the trans-cis photoisomerization of the azobenzene molecules. Various means can be used to align the mesogens in the polymers, including rubbed surface, mechanical stretching or shearing, and electric or magnetic field. In the case of azobenzene-containing SCLCPs, another method consists in using linearly polarized light (LPL) to induce orientation of azobenzene mesogens perpendicular to the polarization direction of the excitation light, and such photoinduced orientation has been the subject of numerous studies. In the first study realized in this thesis (Chapter 1), we carried out the first systematic investigation on the interplay of the mechanically and optically induced orientation of azobenzene mesogens as well as the effect of thermal annealing in a SCLCP and a diblock copolymer comprising two SCLCPs bearing azobenzene and biphenyl mesogens, respectively. Using a supporting-film approach previously developed by our group, a given polymer film can be first stretched in either the nematic or smectic phase to yield orientation of azobenzene mesogens either parallel or perpendicular to the strain direction, then exposed to unpolarized UV light to erase the mechanically induced orientation upon the trans–cis isomerization, followed by linearly polarized visible light for photoinduced reorientation as a result of the cis–trans backisomerization, and finally heated to different LC phases for thermal annealing. Using infrared dichroism to monitor the change in orientation degree, the results of this study have unveiled complex and different orientational behavior and coupling effects for the homopolymer of poly{6-[4-(4-methoxyphenylazo)phenoxy]hexyl methacrylate} (PAzMA) and the diblock copolymer of PAzMA-block- poly{6-[4-(4-cyanophenyl) phenoxy]hexyl methacrylate} (PAzMA-PBiPh). Most notably for the homopolymer, the stretching-induced orientation exerts no memory effect on the photoinduced reorientation, the direction of which is determined by the polarization of the visible light regardless of the mechanically induced orientation direction in the stretched film. Moreover, subsequent thermal annealing in the nematic phase leads to parallel orientation independently of the initial mechanically or photoinduced orientation direction. By contrast, the diblock copolymer displays a strong orientation memory effect. Regardless of the condition used, either for photoinduced reorientation or thermal annealing in the liquid crystalline phase, only the initial stretching-induced perpendicular orientation of azobenzene mesogens can be recovered. The reported findings provide new insight into the different orientation mechanisms, and help understand the important issue of orientation induction and control in azobenzene-containing SCLCPs. The second study presented in this thesis (Chapter 2) deals with supramolecular side-chain liquid crystalline polymers (S-SCLCPs), in which side-group mesogens are linked to the chain backbone through non-covalent interactions such as hydrogen bonding. Little is known about the mechanically induced orientation of mesogens in S-SCLCPs. In contrast to covalent SCLCPs, free-standing, solution-cast thin films of a S-SCLCP, built up with 4-(4’-heptylphenyl) azophenol (7PAP) H-bonded to poly(4-vinyl pyridine) (P4VP), display excellent stretchability. Taking advantage of this finding, we investigated the stretching-induced orientation and the viscoelastic behavior of this S-SCLCP, and the results revealed major differences between supramolecular and covalent SCLCPs. For covalent SCLCPs, the strong coupling between chain backbone and side-group mesogens means that the two constituents can mutually influence each other; the lack of chain entanglements is a manifestation of this coupling effect, which accounts for the difficulty in obtaining freestanding and mechanically stretchable films. Upon elongation of a covalent SCLCP film cast on a supporting film, the mechanical force acts on the coupled polymer backbone and mesogenic side groups, and the latter orients cooperatively and efficiently (high orientation degree), which, in turn, imposes an anisotropic conformation of the chain backbone (low orientation degree). In the case of the S-SCLCP of P4VP-7PAP, the coupling between the side-group mesogens and the chain backbone is much weakened owing to the dynamic dissociation/association of the H-bonds linking the two constituents. The consequence of this decoupling is readily observable from the viscoelastic behavior. The average molecular weight between entanglements is basically unchanged in both the smectic and isotropic phase, and is similar to non-liquid crystalline samples. As a result, the S-SCLCP can easily form freestanding and stretchable films. Furthermore, the stretching induced orientation behavior of P4VP-7PAP is totally different. Stretching in the smectic phase results in a very low degree of orientation of the side-group mesogens even at a large strain (500%), while the orientation of the main chain backbone develops steadily with increasing the strain, much the same way as amorphous polymers. The results imply that upon stretching, the mechanical force is mostly coupled to the polymer backbone and leads to its orientation, while the main chain orientation exerts little effect on orienting the H-bonded mesogenic side groups. This surprising finding is explained by the likelihood that during stretching in the smectic phase (at relatively higher temperatures) the dynamic dissociation of the H-bonds allow the side-group mesogens to be decoupled from the chain backbone and relax quickly. In the third project (Chapter 3), we investigated the shape memory properties of a S-SCLCP prepared by tethering two azobenzene mesogens, namely, 7PAP and 4-(4'-ethoxyphenyl) azophenol (2OPAP), to P4VP through H-bonding. The results revealed that, despite the dynamic nature of the linking H-bonds, the supramolecular SCLCP behaves similarly to covalent SCLCP by exhibiting a two-stage thermally triggered shape recovery process governed by both the glass transition and the LC-isotropic phase transition. The ability for the supramolecular SCLCP to store part of the strain energy above T[subscript g] in the LC phase enables the triple-shape memory property. Moreover, thanks to the azobenzene mesogens used, which can undergo trans-cis photoisomerization, exposure the supramolecular SCLCP to UV light can also trigger the shape recovery process, thus enabling the remote activation and the spatiotemporal control of the shape memory. By measuring the generated contractile force and its removal upon turning on and off the UV light, respectively, on an elongated film under constant strain, it seems that the optically triggered shape recovery stems from a combination of a photothermal effect and an effect of photoplasticization or of an order-disorder phase transition resulting from the trans-cis photoisomerization of azobenzene mesogens.

Investigations into the mechanism of orotidine 5'-monophosphate decarboxylase: Sources of substrate destabilization and transition state stabilization

Orotidine 5′-monophosphate decarboxylase (OMPDC) achieves a rarely paralleled rate acceleration, yet the catalytic basis prompting this enhancement have yet to be fully elucidated. To accomplish decarboxylation, OMPDC must overcome the high energy barrier due to the localized anionic charge of the intermediate. Mechanistic studies employing enzyme mutagenesis and product or intermediate analogues were used to investigate possible transition state stabilization by a carbene resonance structure. Viability of the carbene structure depends upon a key hydrogen bond between O4 of the substrate and the amide backbone of a conserved serine or threonine. Substitution of the conserved residue with Pro resulted in a kcat/KM of 1 M-1s-1; deletion of the FUMP O4 resulted in a product analogue that does not undergo H6 exchange or inhibit decarboxylation. Hence, indirect evidence reveals the O4-backbone interaction plays an important role for binding and catalysis. OMPDC likely has honed multiple mechanisms to attain its remarkable catalysis. The successful crystallizations of OMPDC a decade ago sparked hypotheses that structure and sequence conserved residues induced productive strain on the substrate-enzyme complex. Here, we demonstrate a new source of stress: a hydrophobic pocket adjacent to the OMP carboxylate that exhibits kinetic parameters characteristic of substrate destabilization. Substitution of these residues with hydrophilic side-chains, by providing hydrogen-bonding partners, decreased kcat by 10 to 10^4–fold. The same substitutions display very little change in the rate of product H6 exchange, supporting that this hydrophobic pocket affects the substrate-enzyme complex before the transition state. We also provide evidence that hydrophilic residues can insert water molecules into the pocket with detrimental effects to catalysis.

Assessing the activity coefficients of water in cholinium-based ionic liquids: experimental measurements and COSMO-RS modeling

The vapor liquid-equilibrium of water + ionic liquids is relevant for a wide range of applications of these compounds. It is usually measured by ebulliometric techniques, but these are time consuming and expensive. In this work it is shown that the activity coefficients of water in a series of cholinium-based ionic liquids can be reliably and quickly estimated at 298.15K using a humidity meter instrument. The cholinium based ionic liquids were chosen to test this experimental methodology since data for water activities of quaternary ammonium salts are available in the literature allowing the validation of the proposed technique. The COSMO-RS method provides a reliable description of the data and was also used to understand the molecular interactions occurring on these binary systems. The estimated excess enthalpies indicate that hydrogen bonding between water and ionic liquid anion is the dominant interaction that governs the behavior of water and cholinium-based ionic liquids systems, while the electrostatic-misfit and van der Walls forces have a minor contribution to the total excess enthalpies.

Probing the interactions between ionic liquids and water: experimental and quantum chemical approach

For an adequate choice or design of ionic liquids, the knowledge of their interaction with other solutes and solvents is an essential feature for predicting the reactivity and selectivity of systems involving these compounds. In this work, the activity coefficient of water in several imidazolium-based ionic liquids with the common cation 1-butyl-3-methylimidazolium was measured at 298.2 K. To contribute to a deeper insight into the interaction between ionic liquids and water, COSMO-RS was used to predict the activity coefficient of water in the studied ionic liquids along with the excess enthalpies. The results showed good agreement between experimental and predicted activity coefficient of water in ionic liquids and that the interaction of water and ionic liquids was strongly influenced by the hydrogen bonding of the anion with water. Accordingly, the intensity of interaction of the anions with water can be ranked as the following: [CF3SO3](-) < [SCN](-) < [TFA](-) < Br(-) < [TOS](-) < Cl(-) < [CH3SO3](-) [DMP](-) < [Ac](-). In addition, fluorination and aromatization of anions are shown to reduce their interaction with water. The effect of temperature on the activity coefficient of water at infinite dilution was measured by inverse gas chromatography and predicted by COSMO-RS. Further analysis based on COSMO-RS provided information on the nature of hydrogen bonding between water and anion as well as the possibility of anion-water complex formation.

Effect of the cation on the interactions between alkyl methyl imidazolium chloride ionic liquids and water

A systematic study of the interactions between water and alkyl methyl imidazolium chloride ionic liquids at 298.2 K, based on activity coefficients estimated from water activity measurements in the entire solubility range, is presented. The results show that the activity coefficients of water in the studied ILs are controlled by the hydrophilicity of the cation and the cation-anion interaction. To achieve a deeper understanding on the interactions between water and the ILs, COSMO-RS and FTIR spectroscopy were also applied. COSMO-RS was used to predict the activity coefficient of water in the studied ionic liquids along with the excess enthalpies, suggesting the formation of complexes between three molecules of water and one IL molecule. On the basis of quantum-chemical calculations, it is found that cation-anion interaction plays an important role upon the ability of the IL anion to interact with water. The changes in the peak positions/band areas of OH vibrational modes of water as a function of IL concentration were investigated, and the impact of the cation on the hydrogen-bonding network of water is identified and discussed.