Organic Cosolvents Research Articles

Stability Constants of Nickel(II) Complexes with [2.2.2]Cryptand in Aqueous Ethanol Solutions

The stability constants of nickel(II) complexes with [2.2.2]cryptand in aqueous ethanol solutions with a variable concentration of the organic co-solvent were determined by potentiometry at Т = 298 K and µ → 0. It was found that mononuclear, binuclear, and protonated nickel(II) cryptates can form in solution, whose stability increases with the ethanol content. The Gibbs energies of nickel(II) ion transfer from water to the aqueous ethanol solvent were calculated using published data. The contributions of resolvation of reagents in water–ethanol mixtures to the change in the stability of nickel(II) complexes with [2.2.2]cryptand were evaluated.

Heterocyclic Hemipiperazines: Water-Compatible Peptide-Derived Photoswitches.

Hemipiperazines are a recently discovered class of peptide-derived molecular photoswitches with high biocompatibility and therapeutic potential. Here, for the first time we describe photochromism of heterocyclic hemipiperazines. They demonstrate long thermal lifetimes, and enlarged band separation between photoisomers. Efficient photoisomerization occurs under aqueous conditions, although with a need for organic co-solvent. Bidirectional switching with visible light is observed for an extended aromatic system.

Anomalous Properties of Cyclodextrins and Their Complexes in Aqueous Solutions

Cyclodextrins (CDs) are cyclic oligosaccharides that emerged as industrial excipients in the early 1970s and are currently found in at least 130 marketed pharmaceutical products, in addition to numerous other consumer products. Although CDs have been the subject of close to 100,000 publications since their discovery, and although their structure and properties appear to be trivial, CDs are constantly surprising investigators by their unique physicochemical properties. In aqueous solutions, CDs are solubilizing complexing agents of poorly soluble drugs while they can also act as organic cosolvents like ethanol. CDs and their complexes self-assemble in aqueous solutions to form both nano- and microparticles. The nanoparticles have diameters that are well below the wavelength of visible light; thus, the solutions appear to be clear. However, the nanoparticles can result in erroneous conclusions and misinterpretations of experimental results. CDs can act as penetration enhancers, increasing drug permeation through lipophilic membranes, but they do so without affecting the membrane barrier. This review is an account of some of the unexpected results the authors have encountered during their studies of CDs as pharmaceutical excipients.

Obtaining a Water-soluble Form of Hydrophobic Indolelocarbazole Derivative Using Solubilizer Complex

Introduction. LHS-1269 is an indolocarbazole derivative with high antitumor activity. Due to the hydrophobic properties of the active substance, the use of organic co-solvents – dimethyl sulfoxide (DMSO) and ethanol – is required to obtain an injectable dosage form (DP). However, the inclusion of organic solvents in the composition of the DF carries a potential risk of side effects as a result of the use of the drug.Aim. Selection of auxiliary substances for obtaining an aqueous solution of hydrophobic indolecarbazole derivative, which allows minimizing the concentration of organic solvents in the composition of DF.Materials and methods. The object of the study is the active substance LHS-1269 series 010320, produced in the Chemical Synthesis Laboratory of the N. N. Blokhin National Medical Research Center of Oncology. The following auxiliary substances were used to obtain model compositions: Kollidon® 17 PF, Kollisolv® PEG-400, Kolliphor® P 188, Montanox™ 20, DMSO (p.a.), ethanol 95 % (standardized according to pharmacopoeia quality standard ФС.2.2.0019.18 of The State Pharmacopoeia of the Russian Federation). Analytical scales OHAUS Analytical Plus AP 100S and laboratory scales AND DL-120 were used for weighing LHS-1269 and auxiliary substances. The dissolution and mixing of the components was carried out on an IKA® C-MAG HS 4 magnetic stirrer.Results and discussion. In the course of the study, 2 groups of model compositions were obtained and estimated, comprising a complex of two or more auxiliary substances as a solubilizer. The first group of formulations contained DMSO at a concentration of 5 % and ethanol at concentrations from 0 to 15 %. The compositions of the second group included DMSO from 0 to 4 %. As a result, it was found that the addition of 5 % Kolliphor® P 188 to the composition of the solution reduces the content of ethanol to 5 %. In this case, with further decrease in ethanol, turbidity of the solution and precipitation are observed. Reducing the concentration of DMSO in the DF to 2 % was achieved by using a combination of 20 % ethanol and solubilizer complex – Kollidon® 17 (20 %), Kollisolv® PEG-400 (20 %) and Kolliphor® P 188 (5 %). In this case, the total dissolution of the active substance without DMSO was observed when compensating for the organic solvent by introducing additional auxiliary substances – Montanox™ 20 (5 %) and benzene (2 %).Conclusion. As a result of the research, the compositions of the auxiliary substances of solubilizers are selected, allowing to obtain an aqueous solution of the hydrophobic compound LHS-1269 with a minimum concentration of organic solvents.

Isopropanol accelerated crystallization of AlPO-18 membranes for CO2/CH4 and N2/CH4 separations

The aluminophosphate (AlPO-n) materials are the potential candidates for the gas separations. And the characters of zeolite crystals on membrane commonly affected its separation properties. In this work, a co-solvent strategy was used to tune the crystal growth behaviors on the synthesis of AlPO-18 membrane. Isopropanol (IPA), served as the organic co-solvent, was adopted to prepare the AlPO-18 membrane. The effects of the IPA/DIPEA ratio and the synthesis time on the AlPO-18 membranes preparation were investigated. The crystallization of AlPO-18 membrane was accelerated when adding the extra isopropanol into the initial synthetic gel. A similar acceleration effect also occurred with the addition of methanol or ethanol into the initial gel. Under the same reaction condition, the morphology of the AlPO-18 crystals on membranes tends to develop from flake-like to bulk-like after the addition of the extra IPA, the size of AlPO-18 crystals increased with the increase of IPA/DIPEA molar ratio. Compared with the case of water as sole solvent, the synthetic time for the AlPO-18 membrane with good gas permeation properties was reduced to 12 h, where less template N-Ethyldiisopropylamine (DIPEA) was used. The optimized AlPO-18 membrane exhibited a CO2 and N2 permeance of (9.1, 0.79) × 10−7 mol/(m2∙s∙Pa) with the CO2/CH4 (50/50) and N2/CH4 (50/50) mixture selectivity of 91 and 5.0 at 298 K, 0.2 MPa. Those results may provide a strategy to prepare the AlPO-18 molecular sieve with reduced synthesis times.

Features of l-Tryptophan Solvation in Some Water–Organic Mixtures at T = 298.15 K

The effect of changes in the composition of some water–organic mixtures on the thermodynamic parameters of dissolution and solvation of l-tryptophan was studied by the method of calorimetry of dissolution at T = 298.15 K. To explain the experimental results, the enthalpic coefficients of pairwise interactions between l-tryptophan and organic cosolvent molecules and the energy contributions of the side chain to the energy of intermolecular interactions are calculated, and the influence of some properties of organic solvents on these interactions is estimated. All the data obtained were compared with those for l-phenylalanine to reveal the influence of the side chain structure on the energy of intermolecular interactions of aromatic amino acids with organic solvent molecules in aqueous solutions.

Fast Triacylglycerol Fingerprinting in Edible Oils by Subcritical Solvent Chromatography

Supercritical fluid chromatography (SFC) has witnessed a resurge of interest in the last decade, motivated by substantial progress in hardware capabilities and the development of specifically tailored packing materials. Meanwhile, the technique has been transitioning to the use of mobile phases in which an organic co-solvent is mixed to carbon dioxide under subcritical conditions (subFC). The use of a mobile phase modifier will also affect the selectivity, and extend the range of SFC-amenable compounds, including lipids. In this research, a subFC method was developed for the separation of triacylglycerols (TAGs) in edible oils of vegetable origin, namely borage, corn, hazelnut, olive, palm, peanut, and soybean oil. For all the samples investigated, elution of the TAG species was achieved within 8 min, the only exception being borage oil (14 min run), characterized by TAGs spanning in a wide range of partition number (PN 36–56), as constituted by fatty acids differing for alkyl chain lengths (CN 14–24), and degree of unsaturation (DB 0–9). The coupling to mass spectrometry (MS) detection allowed for the average parameters of fatty acid composition to be derived in the oil TAG constituents. A total of 121 TAGs were identified by subFC-MS, with reduced analysis time and solvent consumption (1.5 mL per analysis) compared to common chromatographic approaches. Key features of the method developed hereby are low toxicity, costs, and environmental impact. Notably, the achieved separations were conducted at room temperature, which is beneficial in terms of column life.

Host-guest complexation of phthalimide-derived strigolactone mimics with cyclodextrins. Application in agriculture against parasitic weeds.

Parasitic weeds are noxious plants that damage crops of economic relevance, especially in Mediterranean and African countries. The strategy of suicidal germination was proposed to deal with this plague by using seed germination inducers that work as a pre-emergence herbicide and reduce the parasitic seed load before sowing. N-Substituted phthalimides with a furanone ring were found to be efficient in inducing the germination of Phelipanche ramosa and Orobanche cumana, two of the most problematic parasitic weeds of crops. However, the solubility of these compounds in water is low. A strategy for enhancing their aqueous solubility is the synthesis of host-guest complexes with cyclodextrins. Three bioactive phthalimide-lactones (PL01, PL04, and PL07) were selected and studied to form complexes of increased water solubility with α-, β-, HP-β-, and γ-cyclodextrin. The complexes obtained by the coprecipitation method, with increased aqueous solubility (up to 3.8 times), were studied for their bioactivity and they showed similar or slightly higher bioactivity than free phthalimide-lactones, even without the addition of organic solvents. A theoretical study using semiempirical calculations of molecular models including a solvation system confirmed the physicochemical empirical results. These results demonstrated that cyclodextrins can be used to improve the physicochemical and biological properties of parasitic seed germination inducers.

Removal of PFAS from groundwater using weak‐base anion exchange resins

AbstractThis research provides new insights on the application of weak‐base (WB) anion exchange resins (AERs) for groundwater treatment of six perfluoroalkyl acids (PFAAs) with different properties. Continuous‐flow column adsorption and regeneration experiments involving WB, polyacrylic, and WB, polystyrene resins were conducted considering salt‐only regeneration solutions and two representative strong‐base (SB)‐AERs of analogous polymer composition and a third solution of methanol/salt used as baseline for comparison. The WB, polyacrylic resin was regenerated using salt‐only solutions of NaOH due to deprotonation of the tertiary amine functional group at alkaline pH. However, organic cosolvent was required to weaken the hydrophobic interactions between PFAAs and the nonpolar WB, polystyrene resin. Removal was predominantly influenced by polymer composition with free‐base WB‐AERs exhibiting similar selectivity and higher capacity as SB resin counterparts. This work highlights WB‐AER selection based on PFAA‐selective removal and more sustainable regeneration strategies.

Effects of Water Miscible Organic Co-solvents on Enzyme Kinetic Parameters of Drug Metabolizing Enzymes in Rat Liver Microsomes

We have investigated the effects of methanol, acetonitrile, dimethyl sulphoxide or dioxane on enzyme kinetic parameters (Km and Vmax) of p-nitrophenol hydroxylation, phenacetin deethylation and metoprolol metabolism in rat liver microsomes, at different solvent concentrations. In the case of p-nitrophenol hydroxylation, methanol (0.1 %-0.75 % v/v) and dimethyl sulphoxide (0.01 %-0.075 % v/v) showed 1.3 and 2.5-fold increase respectively, in the Km with a less marked effect on the Vmax. In contrast, dimethyl sulphoxide (0.1 %-0.75% v/v) showed a 1.96-fold decrease in the Vmax. Unlike, methanol and dimethyl sulphoxide, acetonitrile showed activation of the p-nitrophenol hydroxylation activity as indicated by a 0.7-fold decrease in the Km. In the case of metoprolol metabolism, dioxane resulted in a 1.5 to 3.1-fold increase in the Km of all the three metabolite formation pathways in concentration dependent manner, with less marked effect on Vmax of the reaction. Interestingly, while acetonitrile did not affect the Km for metabolite 1 and 2 formation, the Km of metabolite 3 formation was decreased in a concentration dependent manner again with little effect on all the three Vmax values. Further, methanol had little to no effect on the Vmax of metabolite 1 and 2 formation while metabolite 3 formation was increased by 2-fold. The Km of all three metabolite formations was found to be decreased in presence of methanol. The phenacetin deethylation activity in rat liver microsomes followed atypical kinetics. Methanol and dimethyl sulphoxide did not affect the auto activation kinetics at concentration range studied. Dimethyl sulphoxide and dioxane appeared to be unsuitable for characterizing the Cytochrome450 mediated reactions because they showed a very significant effect on the Vmax/Km ratio, starting at concentrations of 0.025 % v/v and 0.25 % v/v, respectively. Methanol and acetonitrile at concentration <0.5 % v/v appeared to be acceptable solvents for solubilization of substrates metabolized by Cytochrome450s.

Native lignin extraction from soft- and hardwood by green and benign sub/supercritical fluid extraction methodologies.

Lignin constitutes an impressive resource of high-value low molecular weight compounds. However, robust methods for isolation of the extractable fraction from lignocellulose are yet to be established. In this study, supercritical fluid extraction (SFE) and CO2-expanded liquid extraction (CXLE) were employed to extract lignin from softwood and hardwood chips. Ethanol, acetone, and ethyl lactate were investigated as green organic co-solvents in the extractions. Additionally, the effects of temperature, CO2 percentage and the water content of the co-solvent were investigated using a design of experiment approach employing full factorial designs. Ethyl lactate and acetone provided the highest gravimetric yields. The water content in the extraction mixture had the main impact on the amount of extractable lignin monomers (LMs) and lignin oligomers (LOs) while the type of organic solvent was of minor importance. The most effective extraction was achieved by using a combination of liquid CO2/acetone/water (10/72/18, v/v/v) at 60 °C, 350 bar, 30 min and 2 mL min-1 flow rate. The optimized method provided detection of 13 LMs and 6 lignin dimers (LDs) from the hardwood chips. The results demonstrate the potential of supercritical fluids and green solvents in the field of mild and bening lignin extraction from wood.

Engineered Myoglobin Catalysts for Asymmetric Intermolecular Cyclopropanation Reactions.

Biocatalysis has covered an increasingly important role in the synthesis and manufacturing of pharmaceuticals and other high value compounds. In the interest of expanding the range of synthetically useful reactions accessible via biocatalysts, our group has explored the potential and application of engineered myoglobins for 'abiological' carbene transfer catalysis. These transformations provide a direct route for the construction of new carbon-carbon and carbon-heteroatom bonds, including the synthesis of cyclopropane rings, which are key motifs and pharmacophores in many drugs and bioactive natural products. In this award article, we survey the progress made by our group toward the development of myoglobin-based catalysts for asymmetric intermolecular cyclopropanation reactions. The high stereoselectivity exhibited by these biocatalysts in these reactions, combined with their broad substrate scope, scalability, and robustness to high substrate loading and organic co-solvents, contribute to make these systems particularly useful for chemical synthesis and biocatalysis at the preparative scale. Extension of the scope of biocatalytic carbene transfer reactions to include different classes of carbene donor reagents has created new opportunities for the asymmetric synthesis of functionalized cyclopropanes. Furthermore, the integration of myoglobin-catalyzed stereoselective cyclopropanations with chemical diversification of the enzymatic products has furnished attractive chemoenzymatic strategies to access a diverse range of optically active cyclopropane scaffolds of high value for drug discovery, medicinal chemistry, and the synthesis of natural products.

Removal and destruction of perfluoroalkyl ether carboxylic acids (PFECAs) in an anion exchange resin and electrochemical oxidation treatment train

Perfluoroalkyl ether carboxylic acids (PFECAs) are a group of emerging recalcitrant contaminants that are being developed to replace legacy per- and polyfluoroalkyl substances (PFAS) in industrial applications and that are generated as by-products in fluoropolymer manufacturing. Here, we report on the removal and destruction of four structurally different PFECAs using an integrated anion exchange resin (AER) and electrochemical oxidation (ECO) treatment train. Results from this work illustrated that (1) flow-through columns packed with PFAS-selective AERs are highly effective for the removal of PFECAs and (2) PFECA affinity is strongly correlated with their hydrophobic features. Regeneration of the spent resin columns revealed that high percentage (e.g., 80%) of organic cosolvent is necessary for achieving 60-100% PFECA release, and regeneration efficiency was higher for a macroporous resin than a gel-type resin. Treatment of spent regenerants showed (1) >99.99% methanol removal was achieved by distillation, (2) >99.999% conversion of the four studied PFECAs was achieved during the ECO treatment of the still bottoms after 24 hours with an energy per order of magnitude of PFECA removal (EE/O) <1.03 kWh/m3 of total groundwater treated, and (3) >85% of the organic fluorine was recovered as inorganic fluoride. Trifluoroacetic acid (TFA), perfluoropropionic acid (PFPrA), and perfluoro-2-methoxyacetic acid (PFMOAA) were confirmed via high-resolution mass spectrometry as transformation products (TPs) in the treated still bottoms, and two distinctive degradation schemes and four reaction pathways are proposed for the four PFECAs. Lastly, dissolved organic matter (DOM) inhibited uptake, regeneration, and oxidation of PFECAs throughout the treatment train, suggesting pretreatment steps targeting DOM removal can enhance the system's treatment efficiency. Results from this work provide guidelines for developing effective separation-concentration-destruction treatment trains and meaningful insights for achieving PFECA destruction in impacted aquatic systems.

The effect of natural deep eutectic solvents on laccase activity and oligomerization of rutin

Natural deep eutectic solvents (NADESs) were investigated for the activity and stability of the laccase enzyme. Laccase was found to be active only in a low amount of choline chloride containing NADESs while it maintained its activity both in high and low amounts of betaine containing NADESs. Rutin, as a flavonoid monomer shows high antioxidant, antibacterial, antiviral and anti-inflammatory properties and these properties are enhanced in the polymerised form. In this study, the organic co-solvent that is conventionally used in the oligomerization of rutin was replaced with two different green solvents, choline chloride-ethylene glycol (1:2 molar ratio) and betaine-mannose (5:2 molar ratio). LC-MS results revealed spontaneous derivatization of rutin as well as the oligomerization of the derivatives besides rutin. The final products were found to have enhanced superoxide radical activity. In this study, enzymatic oligomerization of rutin was investigated for the first time in the presence of eco-friendly green solvents presenting an alternative pathway without any toxic components.

Probing cellulose–solvent interactions with self-diffusion NMR: Onium hydroxide concentration and co-solvent effects

The molecular self-diffusion coefficients were accessed, for the first time, in solutions of microcrystalline cellulose, dissolved in 30 wt% and 55 wt% aqueous tetrabutylammonium hydroxide, TBAH (aq), and in mixtures of 40 wt% TBAH (aq) with an organic co-solvent, dimethylsulfoxide (DMSO), through pulsed field gradient stimulated echo NMR measurements. A two-state model was applied to estimate α (i.e., average number of ions that “bind” to each anhydroglucose unit) and Pb (i.e., fraction of “bound” molecules of DMSO, TBAH or H2O to cellulose) parameters. The α values suggest that TBA+ ions can bind to cellulose within 0.5 TBA+ to 2.3 TBA+/AGU. On the other hand, the Pb parameter increases when raising cellulose concentration for TBA+, DMSO and water in all solvent systems. Data suggests that TBAH interacts with the ionized OH groups from cellulose forming a sheath of bulky TBA+ counterions which consequently leads to steric hindrance between cellulose chains.

Asymmetric synthesis of sulfoxides by novel Baeyer-Villiger monooxygenase from Fusarium

In the chemical industry, the oxidation reaction is one of the essential reactions, although some oxidizing reagents are potentially explosive. Hence, the safe reaction catalyzed by monooxygenases, enzymes that can catalyze oxidation reactions using molecular oxygen in the air, becomes an attractive alternative as it promotes green and sustainable chemistry. Herein, sulfoxidation of alkyl aryl sulfides by a novel Baeyer-Villiger monooxygenase from a fungus, Fusarium sp. NBRC 109816 (FBVMO), was investigated. The effect of organic cosolvents was also examined using purified FBVMO, improving the activity by up to 247%. E. coli whole cell expressing FBVMO was used for the synthetic purpose, and various chiral sulfoxides were obtained successfully in up to 92% isolated yield and up to 99% ee (R).

Crystal Contact Engineering for Enhanced Cross-Linking Efficiency of HheG Crystals

The generation of cross-linked enzyme crystals is a very attractive method for immobilization of enzymes displaying high crystalizability. However, the commonly used cross-linker glutaraldehyde is not always compatible with enzyme activity. Therefore, we previously reported the engineering of halohydrin dehalogenase HheG from Ilumatobacter coccineus to enable thiol-specific cross-linking during CLEC generation by insertion of cysteine residues in the crystal contact. To broaden the applicability of this approach, herein crystal contact engineering of HheG has been performed to incorporate additional lysine residues as defined cross-linking sites for CLEC generation. Using the primary amine-specific cross-linker dithiobis(succinimidyl propionate) (DSP), CLECs of HheG variant V46K were obtained that displayed a high gain in thermal stability compared to wild-type HheG, while using only a low cross-linker concentration. Moreover, respective V46K CLECs exhibited a 10 K higher reaction temperature optimum as well as significantly improved activity and stability at acidic pH and in the presence of organic co-solvents. Overall, our study demonstrates that lysine-specific cross-linkers can also be used as an alternative to glutaraldehyde for stable CLEC generation of halohydrin dehalogenases, and that cross-linking efficiency is significantly improved upon crystal contact engineering.

Self-assembled Ru(bda) Coordination Oligomers as Efficient Catalysts for Visible Light-Driven Water Oxidation in Pure Water.

Water-soluble multinuclear complexes based on ruthenium 2,2'-bipyridine-6,6'-dicarboxylate (bda) and ditopic bipyridine linker units are investigated in three-component visible light-driven water oxidation catalysis. Systematic studies revealed a strong enhancement of the catalytic efficiency in the absence of organic co-solvents and with increasing oligomer length. In-depth kinetic and morphological investigations suggest that the enhanced performance is induced by the self-assembly of linear Ru(bda) oligomers into aggregated superstructures. The obtained turnover frequencies (up to 14.9 s-1 ) and turnover numbers (more than 1000) per ruthenium center are the highest reported so far for Ru(bda)-based photocatalytic water oxidation systems.

Is the solvent activation strategy before heat treatment applicable to all reverse osmosis membranes?

In our previous work, it has been proved that regulated solvent activation by mechanical force before heat-treatment was an effective strategy to prepare high-permselectivity polyamide (PA) reverse osmosis (RO) membrane. However, the universality of the regulated solvent activation for the membranes prepared with different interfacial polymerization (IP) processes has not been explored. The influence of mechanical force-regulated solvent activation on structure and performance of RO membranes prepared with different additives was analyzed systematically in this work. Dimethyl carbonate (DMC) as an organic co-solvent which could produce a thicker and looser PA skin layer and 1-methylimidazole (1-MI) as an aqueous additive which could produce a denser and thinner PA skin layer were used to change the IP processes, respectively. When DMC was added to modify IP, the mechanical force-regulated solvent activation improved the rejection of DMC-modified membrane effectively while maintaining the excellent flux. It was concluded that mechanical force-regulated solvent activation was suitable for the co-solvent-optimized IP process. But the mechanical force-regulated solvent activation had no significant influence on structure and performance of 1-MI-modified membrane, which may be due to the high compactness of the PA skin layer prepared with 1-MI. This work provides the insight of the applicability of the regulated solvent activation for different membrane structures.

Life in Multi-Extreme Environments: Brines, Osmotic and Hydrostatic Pressure─A Physicochemical View.

Elucidating the details of the formation, stability, interactions, and reactivity of biomolecular systems under extreme environmental conditions, including high salt concentrations in brines and high osmotic and high hydrostatic pressures, is of fundamental biological, astrobiological, and biotechnological importance. Bacteria and archaea are able to survive in the deep ocean or subsurface of Earth, where pressures of up to 1 kbar are reached. The deep subsurface of Mars may host high concentrations of ions in brines, such as perchlorates, but we know little about how these conditions and the resulting osmotic stress conditions would affect the habitability of such environments for cellular life. We discuss the combined effects of osmotic (salts, organic cosolvents) and hydrostatic pressures on the structure, stability, and reactivity of biomolecular systems, including membranes, proteins, and nucleic acids. To this end, a variety of biophysical techniques have been applied, including calorimetry, UV/vis, FTIR and fluorescence spectroscopy, and neutron and X-ray scattering, in conjunction with high pressure techniques. Knowledge of these effects is essential to our understanding of life exposed to such harsh conditions, and of the physical limits of life in general. Finally, we discuss strategies that not only help us understand the adaptive mechanisms of organisms that thrive in such harsh geological settings but could also have important ramifications in biotechnological and pharmaceutical applications.