Organic Cosolvents Research Articles

A Self-Assembling NHC-Pd-Loaded Calixarene as a Potent Catalyst for the Suzuki-Miyaura Cross-Coupling Reaction in Water.

Nanoformulated calix[8]arenes functionalized with N-heterocyclic carbene (NHC)-palladium complexes were found to be efficient nano-reactors for Suzuki-Miyaura cross-coupling reactions of water soluble iodo- and bromoaryl compounds with cyclic triol arylborates at low temperature in water without any organic co-solvent. Combined with an improved one-step synthesis of triol arylborates from boronic acid, this remarkably efficient new tool provided a variety of 4′-arylated phenylalanines and tyrosines in good yields at low catalyst loading with a wide functional group tolerance.

Impacts of water-organic solvents on polymerization of the sugars and furans in bio-oil

Polymerization is one major issue during acid-catalyzed conversion of sugars/furans to platform chemicals. Reaction medium is one of the main factors impacting the tendencies of sugars/furans towards polymerization. In this study, conversion of sugars (fructose/glucose/xylose/xylan) and furans (hydroxymethylfurfural (HMF)/furfural/furfuryl alcohol (FA)) over a solid acidic resin catalyst in various water-organic bi-solvents (toluene, chloroform, n-butanol, tetrahydrofuran (THF), dimethyl sulfoxide (DMSO) and ethyl acetate (EA)) were investigated. The results showed toluene/chloroform as the co-solvent did not suppress the polymerization of fructose, HMF, furfural and FA while diminished the formation of LA from fructose/HMF. The organic co-solvents remarkably affected properties of the coke formed. The presence of aprotic organic solvents tended to retain the CO group in the coke formed and affected its thermal stabilities and evolution of the functionalities. Additionally, polymerization tendency of the furans with the distinct structures showed very different sensitivity with the water in reaction medium.

DESign of Sustainable One-Pot Chemoenzymatic Organic Transformations in Deep Eutectic Solvents for the Synthesis of 1,2-Disubstituted Aromatic Olefins.

The self-assembly of styrene-type olefins into the corresponding stilbenes was conveniently performed in the Deep Eutectic Solvent (DES) mixture 1ChCl/2Gly under air and in the absence of hazardous organic co-solvents using a one-pot chemo-biocatalytic route. Here, an enzymatic decarboxylation of p-hydroxycinnamic acids sequentially followed by a ruthenium-catalyzed metathesis of olefins has been investigated in DES. Moreover, and to extend the design of chemoenzymatic processes in DESs, we also coupled the aforementioned enzymatic decarboxylation reaction to now concomitant Pd-catalyzed Heck-type C-C coupling to produce biaryl derivatives under environmentally friendly reaction conditions.

Learning about Enzyme Stability against Organic Cosolvents from Structural Insights by Ion Mobility Mass Spectrometry.

Ion mobility spectrometry (IMS) coupled with mass spectrometry (MS) enables the investigation of protein folding in solution. Herein, a proof‐of‐concept for obtaining structural information about the folding of a protein in dependency of the amount of an organic cosolvent in the aqueous medium by means of this IMS‐MS method is presented. By analyzing the protein with native nano‐electrospray ionization IMS‐MS, the impact of acetonitrile as a representative organic cosolvent and/or pH values on the folding of an enzyme was successfully evaluated in a fast and straightforward fashion, as exemplified for an ene reductase from Gluconobacter oxydans. The IMS‐MS results are in agreement with findings from the nicotinamide adenine dinucleotide phosphate (NADPH)‐based spectrophotometric enzyme activity tests under analogous conditions, and thus, also rationalizing these “wet” analytical data. For this ene reductase, a higher tolerance against CH3CN in the presence of a buffer was observed by both analytical methods. The results suggest that this IMS‐MS methodology could be a useful complementary tool to existing methods in process optimization and fine‐tuning of solvent conditions for biotransformations.

A water-soluble fluorescence sensor with high specificity for detecting hydrazine in river water detection and A549 cell imaging

Hydrazine is a serious hazard for humans; therefore, the detection of N2H4 is extremely important. In recent years, fluorescence sensing, which is a simple and efficient method, has attracted immense attention. Although sensors for hydrazine have been reported, only a few have successfully worked in almost pure water media, Therefore, organic cosolvents are required, however, they are known to interfere with the analysis of the real sample. Furthermore, a few currently known hydrazine sensors have emission wavelengths smaller than the size of the organism itself, thereby making it difficult to eliminate the inherent bioluminescence interference at short wavelengths. In order to solve these problems, we have developed a new type of water-soluble(LogP (Oct/buff) = 1.68, LogD7.4=-1.97), fluorescent, colorimetric sensor. This sensor is based on the ICT mechanism to specifically detect N2H4 in colorimetric and proportional modes (measurement scope is 0.28–120 μM, LOD = 1.22 ppb). In addition, it was successfully used to image A549 cells and detect hydrazine in river water samples and water vapor.

Regorafenib-loaded poly (lactide-co-glycolide) microspheres designed to improve transarterial chemoembolization therapy for hepatocellular carcinoma

Transarterial chemoembolization (TACE) has been widely introduced to treat hepatocellular carcinoma (HCC) especially for unresectable patients for decades. However, TACE evokes an angiogenic response due to the secretion of vascular endothelial growth factor (VEGF), resulting in the formation of new blood vessels and eventually tumor recurrence. Thus, we aimed to develop regorafenib (REGO)-loaded poly (lactide-co-glycolide) (PLGA) microspheres that enabled localized and sustained drug delivery to limit proangiogenic responses following TACE in HCC treatment. REGO-loaded PLGA microspheres were prepared using the emulsion-solvent evaporation/extraction method, in which DMF was selected as an organic phase co-solvent. Accordingly, we optimized the proportion of DMF, which the optimal ratio to DCM was 1:9 (v/v). After preparation, the microspheres provided high drug loading capacity of 28.6%, high loading efficiency of 91.5%, and the average particle size of 149 µm for TACE. IR spectra and XRD were applied to confirming sufficient REGO entrapment. The in vitro release profiles demonstrated sustained drug release of microspheres for more than 30 d To confirm the role of REGO-loaded microspheres in TACE, the cell cytotoxic activity on HepG2 cells and anti-angiogenic effects in HUVECs Tube-formation assay were studied in combination with miriplatin. Moreover, the microspheres indicated the potential of antagonizing miriplatin resistance of HepG2 cells in vitro. Pharmacokinetics preliminary studies exhibited that REGO could be sustainably released from microspheres for more than 30 d after TACE in vivo. In vivo anti-tumor efficacy was further determined in HepG2 xenograft tumor mouse model, demonstrating that REGO microspheres could improve the antitumor efficacy of miriplatin remarkably compared with miriplatin monotherapy. In conclusion, the obtained REGO microspheres demonstrated promising therapeutic effects against HCC when combined with TACE.

Temperature-Induced Formation of Uniform Polymer Nanocubes Directly in Water.

Conventional self-assembly methods of block copolymers in cosolvents (i.e., usually water and organic solvents) has yet to produce a pure and monodisperse population of nanocubes. The requirement to assemble a nanocube is for the second block to have a high molecular weight. However, such high molecular weight block copolymers usually result in the formation of kinetically trapped nanostructures even with the addition of organic cosolvents. Here, we demonstrate the rapid production of well-defined polymer nanocubes directly in water by utilizing the thermoresponsive nature of the second block (with 263 monomer units), in which the block copolymer was fully water-soluble below its lower critical solution temperature (LCST) and would produce a pure population of nanocubes when heated above this temperature. Incorporating a pH-responsive monomer in the second block allowed us to control the size of the nanocubes in water with pH and the LCST of the block copolymer. We then used the temperature and pH responsiveness to create an adaptive system that changes morphology when using a unique fuel. This fuel (H2O2 + MnO2) is highly exothermic, and the solution pH increases with the consumption of H2O2. Initially, a nonequilibrium spherical nanostructure formed, which transformed over time into nanocubes, and by controlling the exotherm of the reaction, we controlled the time for this transformation. This block copolymer and the water-only method of self-assembly have provided some insights into designing biomimetic systems that can readily adapt to the environmental conditions.

Time optimal control operation of bulk lyophilisation of materials on trays reduces the exergy losses and increases the efficiency of energy utilisation

Exergy represents a measure of quality of energy and because exergy is destroyed due to process irreversibilities within a system to produce entropy, the exergy expressions and analysis developed in this work could be used to operate the intrinsically unsteady-state lyophilisation processes more efficiently. It is shown that the time optimal control operation of a freeze dryer with respect to heat input to the trays and total pressure in the drying chamber, reduces the duration times of the primary and secondary drying stages by 42.43% and 41.17%, respectively, and this leads to a reduction of 38.19% in the magnitude of the total exergy losses of the lyophilisation system studied in this work. Also, the potential for reducing further the exergy losses when organic co-solvents and water forming non-ideal mixtures of solvents with positive deviations from Raoult's law are used in a lyophilisation system operated under time optimal control, is discussed.

The multifaceted effects of DMSO and high hydrostatic pressure on the kinetic constants of hydrolysis reactions catalyzed by α-chymotrypsin.

The use of cosolvents and high hydrostatic pressure (HHP) has been described as an efficient means to modulate the stability of enzymes and their catalytic activity. Cosolvents and pressure can lead to increased reaction rates without affecting the stability of the enzyme. Here, we studied the combined effects of one of the most used organic cosolvents, dimethyl sulfoxide (DMSO), and HHP to reveal their combined effect on the kinetic constants of an α-chymotrypsin-catalyzed peptide hydrolysis reaction. The Michaelis constant and the turnover number of the reaction respond differently to the two variables, and we observed an opposite effect of hydrostatic pressure and the dipolar cosolvent DMSO on the kinetic parameters. The results could be rationalized by determining the volume diagram of the reaction at the different solution conditions. In our case, the use of high hydrostatic pressure in concert with DMSO does not lead to an improvement of the enzymatic activity. However, the advantages of DMSO and HHP to increase the temperature stability of the enzyme and to increase the solubility of more hydrophobic substrates could still be useful.

Time optimal control operation of bulk lyophilisation of materials on trays reduces the exergy losses and increases the efficiency of energy utilisation

Exergy represents a measure of quality of energy and because exergy is destroyed due to process irreversibilities within a system to produce entropy, the exergy expressions and analysis developed in this work could be used to operate the intrinsically unsteady-state lyophilisation processes more efficiently. It is shown that the time optimal control operation of a freeze dryer with respect to heat input to the trays and total pressure in the drying chamber, reduces the duration times of the primary and secondary drying stages by 42.43% and 41.17%, respectively, and this leads to a reduction of 38.19% in the magnitude of the total exergy losses of the lyophilisation system studied in this work. Also, the potential for reducing further the exergy losses when organic co-solvents and water forming non-ideal mixtures of solvents with positive deviations from Raoult's law are used in a lyophilisation system operated under time optimal control, is discussed.

Efficient laccase/TEMPO oxidation of alkyl glycosides: Effects of carbohydrate group and alkyl chain length

Alkyl glycosides with long hydrophobic chains have attractive surfactant properties, but their wider application is hampered by their low solubility in water. Here, a route to increased solubility by introduction of carboxyl groups via laccase/TEMPO oxidation is presented. The oxidation pathways for dodecyl β-maltoside and hexadecyl β-maltoside were studied in detail. Close to full conversion was achieved for both substrates and conditions were found under which the diacid products dominated, with only minor amounts of under-oxidized and over-oxidized products. Dodecyl β-maltoside oxidation was improved to give a yield of 85 % of the diacid derivative. Interestingly, in spite of low substrate solubility the oxidation of hexadecyl β-maltoside was very efficient in aqueous medium, due to the higher solubility of the products. Addition of organic cosolvents did not provide additional advantages. The method is promising for producing soluble anionic derivatives of alkyl glycosides in an environmentally friendly and efficient way.

Optimization of Ring-Opening Metathesis Polymerization (ROMP) under Physiologically Relevant Conditions.

Ring opening metathesis polymerization (ROMP) is widely considered an excellent living polymerization technique that proceeds rapidly under ambient conditions and is highly functional group tolerant when performed in organic solvents. However, achieving the same level of success in aqueous media has proved to be challenging, often requiring an organic co-solvent or a very low pH to obtain fast initiation and high monomer conversion. The ability to efficiently conduct ROMP under neutral pH aqueous conditions would mark an important step towards utilizing aqueous ROMP with acid-sensitive functional groups or within a biological setting. Herein we describe our efforts to optimize ROMP in an aqueous environment under neutral pH conditions. Specifically, we found that the presence of excess chloride in solution as well as relatively small changes in pH near physiological conditions have a profound effect on molecular weight control, polymerization rate and overall monomer conversion. Additionally, we have applied our optimized conditions to polymerize a broad scope of water-soluble monomers and used this methodology to produce nanostructures via ring opening metathesis polymerization induced self-assembly (ROMPISA) under neutral pH aqueous conditions.

Polymer principles behind solubilizing lignin with organic cosolvents for bioenergy

Polymer theory, developed for simple homopolymers, is applicable to the interaction of lignin with aprotic organic pretreatment solvents.

Prediction of solid solute solubility in supercritical carbon dioxide with and without organic cosolvents from PSRK EOS

Solid solute solubility in supercritical carbon dioxide (ScCO2) with and without organic cosolvents provides important information for design and optimization of processes involving ScCO2 in industry. The accuracy of PSRK EOS in predicting solid solute solubility in ScCO2 with and without organic cosolvents is systematically investigated in this study. The first-principles thermodynamic model PR + COSMOSAC EOS and four well-known group contribution models are used to estimate critical properties and acentric factors for all solid solutes to overcome the lack of experimental critical properties for most investigated solid solutes. The results show that combining PSRK EOS with pure substance properties from a certain group contribution model provides the lowest overall deviations, but those from the first-principles thermodynamic model give greater accuracy for solutes with complicated molecular structures. In general, the PSRK EOS is able to provide useful solubility information, especially when no experimental data is available.

Cell uptake and anti-tumor effect of liposomes containing encapsulated paclitaxel-bound albumin against breast cancer cells in 2D and 3D cultured models

Paclitaxel (PTX), a water insoluble anticancer drug, was incorporated into the inner aqueous core of a liposome without the aid of an organic co-solvent, via non-covalent binding with bovine serum albumin (BSA) to form a PTX-BSA liposome. In the present study, PTX-BSA-liposomes are shown to have potent effects on human-derived breast cancer cell lines, MCF-7 cells and MDA-MB-231 cells, in 2D monolayer cultured cells and 3D multicellular tumor spheroids. The results of cellular uptake studies in 2D monolayer cultured cells clearly showed that the fluorescence derived from dansyl-l-asparagine (DNSA), a model encapsulated drug, and Cy5-cholesterol (a model membrane) of DNSA-BSA-liposome were observed inside the cells. Along with cell uptake, the PTX-BSA-liposomes exhibited a concentration-dependent cytotoxicity against MCF-7 and MDA-MB-231 cells but the IC50 value of the PTX-BSA-liposomes was higher than that of free PTX and nab-PTX (albumin-bound PTX nanoparticle). On the other hand, PTX-BSA-liposome, as in the cases of free PTX and nab-PTX, inhibited cell growth in both 3D MCF-7 and MDA-MB-231 tumor spheroids, indicating that PTX-BSA-liposomes penetrated into the tumor spheroid. These results suggest that PTX-BSA-liposomes are an organic solvent free PTX formulation that would have potent anti-proliferative effects against breast cancer.

Supercritical fluid-assisted crystallization of CH3NH3PbI3 perovskite films

Crystallization of CH3NH3PbI3 perovskite films was performed in supercritical carbon dioxide with and without organic cosolvents. Post deposition crystallization of the films was performed in a binary, single phase supercritical fluid at constant conditions (45℃, 1200 psi) but with varying cosolvent volume fractions up to 2 %. Organic cosolvents with varying polarity, propensity for hydrogen bonding and strength of solvation were used and the resulting perovskite film morphology, crystal structure and optical absorption spectra were measured. It was determined that the cosolvents can provide selective interactions with one or both of the perovskite precursor compounds resulting in different film morphologies ranging from uniform films containing large grains to films exhibiting large cubic or hexagonal crystals or preferential crystallographic orientations. The use of supercritical fluids to enhance or tune crystallization in solid-state thin films could have broad applications toward the realization of high efficiency photovoltaic devices.

1,3‐Adamantanedicarboxylate and 1,3‐Adamantanediacetate as Uranyl Ion Linkers: Effect of Counterions, Solvents and Differences in Flexibility

Seven homo‐ or heterometallic uranyl ion complexes with 1,3‐adamantanedicarboxylic acid (H2ADC) or 1,3‐adamantanediacetic acid (H2ADA) have been synthesized under solvo‐hydrothermal conditions in the presence of different counterions and organic cosolvents, and characterized by their crystal structure and uranyl emission spectrum. [PPh3Me][UO2(ADC)(NO3)] (1) crystallizes as a simple monoperiodic chain, but [PPh4]2[(UO2)2(ADC)3]·2H2O (2) and [PPh4]2[(UO2)2(ADA)3] (3) display trough‐like monoperiodic polymers (assembled in pairs in 3) in the cavity of which the counterions are located. A similar arrangement is found in [Ni(cyclen)(H2O)][(UO2)2(ADC)3]·H2O (4). Diaxial bonding of NiII in [(UO2)2(ADC)2Ni(R,S‐Me6cyclam)(HCOO)2]·CH3CN (5) and [UO2(ADA)2Ni(R,S‐Me6cyclam)] (6) results in bridging monoperiodic uranyl‐containing subunits into neutral, diperiodic networks. [UO2(ADA)(DMPU)] (7), containing coordinated N,N′‐dimethylpropyleneurea, is also a diperiodic assembly with the common fes topological type. Except complex 6 which is non‐luminescent, all complexes give solid‐state emission spectra displaying the usual vibronic fine structure, albeit with low photoluminescence quantum yields.

Task-Specific Properties and Prospects of Ionic Liquids in Cross-Coupling Reactions.

Ionic liquids (ILs) are considered as highly useful materials for potential diverse uses such as greener and more convenient alternatives to volatile organic solvents, reagents, additives, ligands and co-solvents. Thermal stability, negligible vapor pressure and high polarity with ionic environments have possibly conferred some unique physico-chemical properties and a wider electrochemical window on ILs. More importantly, these properties are tuneable, depending on variations in alkyl chains and counter-anions. On the other hand, various transition-metal-catalyzed cross-coupling reactions constitute an important backbone of contemporary organic synthesis. A vast number of C-C and C-heteroatom cross-coupling reactions are reported in the presence of ILs, often showing better performance. The influence of IL on the action of a given catalyst or on the course of a reaction can be relatively complex, and is not understood well enough to be able to draw succinct conclusions. However, there are a few reports in the literature that help understand the role of actual and active catalytic species stabilized in an IL environment. Stabilization, which can be either helpful or detrimental to catalysis depends on specific circumstances. This review article is aimed primarily at summarizing the various applications of ILs during the past decade, focusing as far as possible on the task-specific properties of ILs in transition-metal-catalyzed C-C and C-heteroatom cross-coupling reactions. Several successful achievements and noteworthy progress in this field of research leads to the sensible conclusion that future prospects in this field of research are not only bright but promise new horizons.

The hulling effect on aroma composition of Ohadi variety pistachio

Sucrose phosphorylase (SPase) is capable of specifically catalysing transglucosylation reactions and can be employed in the enzymatic synthesis of α-D-glycosides. In the present study, a putative Thermobacillus SPase gene (TSPase) was synthesised with optimised codons and overexpressed in Escherichia coli. The 1467 bp gene encodes a 488-amino acid protein with a calculated molecular mass of 55.8 kDa. The specific activity of the recombinant TSPase (rTSPase) was 6.42 U/mg for sucrose, and the optimum temperature and pH were 65 °C and pH 7.0. The T1/2 value of the rTSPase was 212 h at 50 °C and 98 h at 60 °C. A stimulating effect on the activity of the rTSPase was observed in the presence of 5 mM Co2+. The rTSPase showed increased stability against DMSO as organic co-solvent at 50 °C. The Km and kcat of the rTSPase with sucrose were determined as 6.24 mM and 5.73 s−1 respectively. The rTSPase produced 2-O-α-D-Glucopyranosyl-L-ascorbic acid (AA-2 G) from ascorbic acid in both crude extract and whole-cell forms. A maximum yield of 19.7% (39.94 ± 0.17 g/L) was achieved after incubation of ascorbic acid sodium salt and sucrose (1:2) with 19.76 U/mL of the rTSPase at pH 7.0 and 50 °C for 24 h.

Preparation and application of PHA based nanofibers and nanoparticles as natural organic UV filtres with anti-inflammatory effect

Sucrose phosphorylase (SPase) is capable of specifically catalysing transglucosylation reactions and can be employed in the enzymatic synthesis of α-D-glycosides. In the present study, a putative Thermobacillus SPase gene (TSPase) was synthesised with optimised codons and overexpressed in Escherichia coli. The 1467 bp gene encodes a 488-amino acid protein with a calculated molecular mass of 55.8 kDa. The specific activity of the recombinant TSPase (rTSPase) was 6.42 U/mg for sucrose, and the optimum temperature and pH were 65 °C and pH 7.0. The T1/2 value of the rTSPase was 212 h at 50 °C and 98 h at 60 °C. A stimulating effect on the activity of the rTSPase was observed in the presence of 5 mM Co2+. The rTSPase showed increased stability against DMSO as organic co-solvent at 50 °C. The Km and kcat of the rTSPase with sucrose were determined as 6.24 mM and 5.73 s−1 respectively. The rTSPase produced 2-O-α-D-Glucopyranosyl-L-ascorbic acid (AA-2 G) from ascorbic acid in both crude extract and whole-cell forms. A maximum yield of 19.7% (39.94 ± 0.17 g/L) was achieved after incubation of ascorbic acid sodium salt and sucrose (1:2) with 19.76 U/mL of the rTSPase at pH 7.0 and 50 °C for 24 h.