Water-miscible Cosolvents Research Articles

Assessing Peroxygenase-Mediated Oxidations in the Presence of High Concentrations of Water-Miscible Co-Solvents

The use of water-miscible organic co-solvents in biocatalysis is a simple procedure for obtaining higher enzymatic activities toward hydrophobic substrates. However, effects on activity and stability have to be carefully evaluated, also with regard to the type and concentration of the respective co-solvent. In this contribution, we investigated and evaluated the effect of some common water-miscible co-solvents on the biocatalytic performance of the recombinant unspecific peroxygenase rAaeUPO from Agrocybe aegerita. rAaeUPO showed promising activities in the presence of high concentrations of the best co-solvent acetonitrile, which enabled to use higher substrate concentrations (≥100 mM). Employing high acetonitrile concentrations for UPO-mediated oxidation of ethylbenzene to (R)-1-phenylethanol was demonstrated under preparative scale conditions and led to product accumulation rates of 31 mM h−1.

Poloxamer 407 Based Gel Formulations for Transungual Delivery of Hydrophobic Drugs: Selection and Optimization of Potential Additives.

The current study aimed to develop poloxamer 407 (P407) gel for transungual delivery of antifungal hydrophobic drugs with sufficient gel strength and drug loading. Gel strength and drug loading of P407 gel was improved by use of functional additives. Hydration enhancement effect was used to select optimum nail penetration enhancer. Face-centered central composite design (FCCCD) was used to observe the effect of the selected penetration enhancer (thioglycolic acid (TGA)) and cosolvent (ethanol) on gelation behavior to develop formulation with enough loading of hydrophobic drug, i.e., terbinafine HCl (TBN), and its permeation across the nail plate without compromising on gel strength. It was observed that increasing concentration of P407 and TGA significantly reduced gelation temperature and enhanced the gel strength of P407 gel and can be used to improve P407 gel strength. Under the scanning electron microscope, the significant effect of TGA as an ungual penetration enhancer was observed on the morphology of the nail plate. Optimized P407 gel prepared with modified cold method showed a gelation temperature of 8.7 ± 0.16 °C, gel strength of 122 ± 7.5 s and drug loading of 1.2% w/w, which was four times more than the drug loading in the gels prepared with conventional cold method. Rheological behavior was pseudoplastic with 47.75 ± 3.48% of gel erosion after 12 washings and 67.21 ± 2.16% of drug release after 12 h. A cumulative amount of TBN permeated from P407 gel with and without PE after 24 h was 27.30 ± 4.18 and 16.69 ± 2.31 µg/cm2, respectively. Thioglycolic acid can be used as a nail penetration enhancer without the chemical modification or addition of extra additives while retaining the gel strength. Water miscible cosolvents with moderate evaporability such as ethanol, can be incorporated to P407 gel by minor modification in method of preparation to load the required dose of hydrophobic drugs. Developed P407 gel formulation with sufficient gel strength and drug loading will be a promising carrier for transungual delivery of hydrophobic antifungal agents.

Regioselectivity of Cobalamin-Dependent Methyltransferase Can Be Tuned by Reaction Conditions and Substrate.

Regioselective reactions represent a significant challenge for organic chemistry. Here the regioselective methylation of a single hydroxy group of 4‐substituted catechols was investigated employing the cobalamin‐dependent methyltransferase from Desulfitobacterium hafniense. Catechols substituted in position four were methylated either in meta‐ or para‐position to the substituent depending whether the substituent was polar or apolar. While the biocatalytic cobalamin dependent methylation was meta‐selective with 4‐substituted catechols bearing hydrophilic groups, it was para‐selective for hydrophobic substituents. Furthermore, the presence of water miscible co‐solvents had a clear improving influence, whereby THF turned out to enable the formation of a single regioisomer in selected cases. Finally, it was found that also the pH led to an enhancement of regioselectivity for the cases investigated.

Enthalpic incompatibility between two steric stabilizer blocks provides control over the vesicle size distribution during polymerization-induced self-assembly in aqueous media.

Over the past two decades, block copolymer vesicles have been widely used by many research groups to encapsulate small molecule drugs, genetic material, nanoparticles or enzymes. They have also been used to design examples of autonomous self-propelled nanoparticles. Traditionally, such vesicles are prepared via post-polymerization processing using a water-miscible co-solvent such as DMF or THF. However, such protocols are invariably conducted in dilute solution, which is a significant disadvantage. In addition, the vesicle size distribution is often quite broad, whereas aqueous dispersions of relatively small vesicles with narrow size distributions are highly desirable for potential biomedical applications. Alternatively, concentrated dispersions of block copolymer vesicles can be directly prepared via polymerization-induced self-assembly (PISA). Moreover, using a binary mixture of a relatively long and a relatively short steric stabilizer block enables the convenient PISA synthesis of relatively small vesicles with reasonably narrow size distributions in alcoholic media (C. Gonzato et al., JACS, 2014, 136, 11100-11106). Unfortunately, this approach has not yet been demonstrated for aqueous media, which would be much more attractive for commercial applications. Herein we show that this important technical objective can be achieved by judicious use of two chemically distinct, enthalpically incompatible steric stabilizer blocks, which ensures the desired microphase separation across the vesicle membrane. This leads to the formation of well-defined vesicles of around 200 nm diameter (size polydispersity = 13-16%) in aqueous media at 10% w/w solids as judged by transmission electron microscopy, dynamic light scattering and small-angle X-ray scattering.

Kinetically controlled acylation of 6-APA catalyzed by penicillin acylase from Streptomyces lavendulae: effect of reaction conditions in the enzymatic synthesis of penicillin V

Enzymatic synthesis of penicillin V (penV) by acylation of 6-aminopenicillanic acid (6-APA) was carried out using methyl phenoxyacetate (MPOA) as activated acyl donor and soluble penicillin acylase from Streptomyces lavendulae (SlPVA) as biocatalyst. The effect of different reaction conditions on penV synthesis was investigated, such as enzyme concentration, pH, molar ratio of 6-APA to MPOA, as well as presence of DMSO as water-miscible co-solvent at different concentrations. Time-course profiles of all reactions followed the typical pattern of kinetically controlled synthesis (KCS) of β-lactam antibiotics: penV concentration reached a maximum (highest yield or Ymax) and then decreased gradually. Such maximum was higher at pH 7.0, observing that final penV concentration was abruptly reduced when basic pH values were employed in the reaction. Under the selected conditions (100 mM Tris/HCl buffer pH 7.0, 30 °C, 2.7% (v/v) DMSO, 20 mM MPOA, 0.3 UI/ml of SlPVA), Ymax was enhanced by increasing the substrate molar ratio (6-APA to MPOA) up to 5, reaching a maximum of 94.5% and a S/H value of 16.4 (ratio of synthetic activity to hydrolytic activity). As a consequence, the use of an excess of 6-APA as nucleophile has allowed us to obtain some of the highest Ymax and S/H values among those reported in literature for KCS of β-lactam antibiotics. Although many penicillin G acylases (PGAs) have been described in kinetically controlled acylations, SlPVA should be considered as a different enzyme in the biocatalytic tool-box for novel potential synthetic processes, mainly due to its different substrate specificity compared to PGAs.

NanoDSF as screening tool for enzyme libraries and biotechnology development.

Enzymes are attractive tools for synthetic applications. To be viable for industrial use, enzymes need sufficient stability towards the desired reaction conditions such as high substrate and cosolvent concentration, non‐neutral pH and elevated temperatures. Thermal stability is an attractive feature not only because it allows for protein purification by thermal treatment and higher process temperatures but also due to the associated higher stability against other destabilising factors. Therefore, high‐throughput screening (HTS) methods are desirable for the identification of thermostable biocatalysts by discovery from nature or by protein engineering but current methods have low throughput and require time‐demanding purification of protein samples. We found that nanoscale differential scanning fluorimetry (nanoDSF) is a valuable tool to rapidly and reliably determine melting points of native proteins. To avoid intrinsic problems posed by crude protein extracts, hypotonic extraction of overexpressed protein from bacterial host cells resulted in higher sample quality and accurate manual determination of several hundred melting temperatures per day. We have probed the use of nanoDSF for HTS of a phylogenetically diverse aldolase library to identify novel thermostable enzymes from metagenomic sources and for the rapid measurements of variants from saturation mutagenesis. The feasibility of nanoDSF for the screening of synthetic reaction conditions was proved by studies of cosolvent tolerance, which showed protein melting temperature to decrease linearly with increasing cosolvent concentration for all combinations of six enzymes and eight water‐miscible cosolvents investigated, and of substrate affinity, which showed stabilisation of hexokinase by sugars in the absence of ATP cofactor.EnzymesAlcohol dehydrogenase (NADP+) (EC 1.1.1.2), transketolase (EC 2.2.1.1), hexokinase (EC 2.7.1.1), 2‐deoxyribose‐5‐phosphate aldolase (EC 4.1.2.4), fructose‐6‐phosphate aldolase (EC 4.1.2.n).

Mining the Genome of Streptomyces leeuwenhoekii: Two New Type I Baeyer-Villiger Monooxygenases From Atacama Desert.

Actinobacteria are an important source of commercial (bio)compounds for the biotechnological and pharmaceutical industry. They have also been successfully exploited in the search of novel biocatalysts. We set out to explore a recently identified actinomycete, Streptomyces leeuwenhoekii C34, isolated from a hyper-arid region, the Atacama desert, for Baeyer–Villiger monooxygenases (BVMOs). Such oxidative enzymes are known for their broad applicability as biocatalysts by being able to perform various chemical reactions with high chemo-, regio-, and/or enantioselectivity. By choosing this specific Actinobacterium, which comes from an extreme environment, the respective enzymes are also expected to display attractive features by tolerating harsh conditions. In this work, we identified two genes in the genome of S. leeuwenhoekii (sle_13190 and sle_62070) that were predicted to encode for Type I BVMOs, the respective flavoproteins share 49% sequence identity. The two genes were cloned, overexpressed in E. coli with phosphite dehydrogenase (PTDH) as fusion partner and successfully purified. Both flavin-containing proteins showed NADPH-dependent Baeyer–Villiger oxidation activity for various ketones and sulfoxidation activity with some sulfides. Gratifyingly, both enzymes were found to be rather robust by displaying a relatively high apparent melting temperature (45°C) and tolerating water-miscible cosolvents. Specifically, Sle_62070 was found to be highly active with cyclic ketones and displayed a high regioselectivity by producing only one lactone from 2-phenylcyclohexanone, and high enantioselectivity by producing only normal (-)-1S,5R and abnormal (-)-1R,5S lactones (ee > 99%) from bicyclo[3.2.0]hept-2-en-6-one. These two newly discovered BVMOs add two new potent biocatalysts to the known collection of BVMOs.

Characterization of an atypical, thermostable, organic solvent- and acid-tolerant 2'-deoxyribosyltransferase from Chroococcidiopsis thermalis.

In our search for thermophilic and acid-tolerant nucleoside 2'-deoxyribosyltransferases (NDTs), we found a good candidate in an enzyme encoded by Chroococcidiopsis thermalis PCC 7203 (CtNDT). Biophysical and biochemical characterization revealed CtNDT as a homotetramer endowed with good activity and stability at both high temperatures (50-100°C) and a wide range of pH values (from 3 to 7). CtNDT recognizes purine bases and their corresponding 2'-deoxynucleosides but is also proficient using cytosine and 2'-deoxycytidine as substrates. These unusual features preclude the strict classification of CtNDT as either a type I or a type II NDT and further suggest that this simple subdivision may need to be updated in the future. Our findings also hint at a possible link between oligomeric state and NDT's substrate specificity. Interestingly from a practical perspective, CtNDT displays high activity (80-100%) in the presence of several water-miscible co-solvents in a proportion of up to 20% and was successfully employed in the enzymatic production of several therapeutic nucleosides such as didanosine, vidarabine, and cytarabine.

Enantioselective synthesis of amines via reductive amination with a dehydrogenase mutant from Exigobacterium sibiricum: Substrate scope, co-solvent tolerance and biocatalyst immobilization

In recent years, the reductive amination of ketones in the presence of amine dehydrogenases emerged as an attractive synthetic strategy for the enantioselective preparation of amines starting from ketones, an ammonia source, a reducing reagent and a cofactor, which is recycled in situ by means of a second enzyme. Current challenges in this field consists of providing a broad synthetic platform as well as process development including enzyme immobilization. In this contribution these issues are addressed. Utilizing the amine dehydrogenase EsLeuDH-DM as a mutant of the leucine dehydrogenase from Exigobacterium sibiricum, a range of aryl-substituted ketones were tested as substrates revealing a broad substrate tolerance. Kinetics as well as inhibition effects were also studied and the suitability of this method for synthetic purpose was demonstrated with acetophenone as a model substrate. Even at an elevated substrate concentration of 50 mM, excellent conversion was achieved. In addition, the impact of water-miscible co-solvents was examined, and good activities were found when using DMSO of up to 30% (v/v). Furthermore, a successful immobilization of the EsLeuDH-DM was demonstrated utilizing a hydrophobic support and a support for covalent binding, respectively, as a carrier.

Excluded volume contribution to cosolvent-mediated modulation of macromolecular folding and binding reactions

Water-miscible cosolvents may stabilize or destabilize proteins, nucleic acids, and their complexes or may exert no influence. The mode of action of a specific cosolvent is determined by the interplay between the excluded volume effect and direct solute–cosolvent interactions. Excluded volume refers to the steric exclusion of water and cosolvent molecules from the space occupied by solute, an event accompanied by a decrease in translational entropy. In thermodynamic terms, the excluded volume effect is modeled by creating a cavity which is sufficiently large to accommodate the solute and which is inaccessible to surrounding molecules of water and cosolvent(s). An understanding of the relationship between the energetic contributions of cavity formation and direct solute–cosolvent interactions is required for elucidating the molecular origins of the stabilizing or destabilizing influence of specific cosolvents. In this work, we employed the concepts of scaled particle theory to compute changes in free energy of cavity formation, ∆∆GC, accompanying the ligand–protein binding, protein dimerization, protein folding, and DNA duplex formation events. The computations were performed as a function of the concentration of methanol, urea, ethanol, ethylene glycol, and glycine betaine. Resulting data were used in conjunction with a previously developed statistical thermodynamic algorithm to estimate the excluded volume contribution to changes in preferential hydration, ∆Γ21, and interaction, ∆Γ23, parameters and m-values associated with the reactions under study. The excluded volume contributions to ∆Γ21, ∆Γ23, and m-values are very significant ranging from 30 to 70% correlating with the size of the cosolvent molecule. Our results suggest that a pair of “fully excluded cosolvents” with negligible solute–solvent interactions may differ significantly with respect to their excluded volume contributions to ∆Γ21, ∆Γ23, and m-values thereby differently influencing the equilibrium of the reaction being sampled. This notion has implications for understanding the long-standing observation that, in osmotic stress studies, various osmolytes may produce significantly distinct estimates of hydration/dehydration for the same reaction.

Chemo-enzymatic synthesis route to poly(glucosyl-acrylates) using glucosidase from almonds

Novel types of glucosyl-acrylate monomers are obtained by β-glucosidase from almond catalyzed glycosidation reaction. The saccharide-acrylate monomers were synthesized by reaction of D-glucose with hydroxyl functional acrylates: 2-hydroxyethyl acrylate (2-HEA), 2-hydroxyethyl methacrylate (2-HEMA) and 4-hydroxybutyl acrylate (4-HBA). The reaction products could be identified as 2-(β-glucosyloxy)-ethyl acrylate, 2-(β-glucosyloxy)-ethyl methacrylate and 4-(β-glucosyloxy)-ethyl acrylate respectively. The synthesis yield was optimized by variation of the 2-HEA–water ratio, the presence of water-miscible co-solvents and the reaction time. The optimal reaction mixture was found to contain 13 vol% water, 80 vol% 2-HEA and 7 vol%; 1.4-dioxane. The maximal yield under these conditions was 50 wt% based on D-glucose after 24 hours of reaction. The enzymatically synthesized glucosyl-acrylates were successfully polymerized by free radical polymerization in DMF and water. The glycosidic linkage of the glycosyl-acrylate monomers was retained during the polymerization process. The enzymatically synthesized glucosyl-acrylates could be successfully copolymerized with vinyl monomers 2-HEA, 2-HEMA, methacryl amide and N-vinyl imidazole.

Seeking effective dyes for a mediated glucose–air alkaline battery/fuel cell

A significant level of power generation from an abiotic, air breathing, mediated reducing sugar–air alkaline battery/fuel cell has been achieved in our laboratories at room temperature without complicated catalysis or membrane separation in the reaction chamber. Our prior studies suggested that mass transport limitation by the mediator is a limiting factor in power generation. New and effective mediators were sought here to improve charge transfer and power density. Forty-five redox dyes were studied to identify if any can facilitate mass transport in alkaline electrolyte solution; namely, by increasing the solubility and mobility of the dye, and the valence charge carried per molecule. Indigo dyes were studied more closely to understand the complexity involved in mass transport. The viability of water-miscible co-solvents was also explored to understand their effect on solubility and mass transport of the dyes. Using a 2.0 mL solution, 20% methanol by volume, with 100 mM indigo carmine, 1.0 M glucose and 2.5 M sodium hydroxide, the glucose–air alkaline battery/fuel cell attained 8 mA cm–2 at short-circuit and 800 μW cm–2 at the maximum power point. This work shall aid future optimization of mediated charge transfer mechanism in batteries or fuel cells.

One-step enzymatic synthesis of nucleosides from low water-soluble purine bases in non-conventional media

The effect of several water-miscible cosolvents on activity and stability of soluble and immobilized 2′-deoxyribosyltransferase from Lactobacillus reuteri on Sepabeads® has been studied in order to establish optimal conditions for enzymatic synthesis of nucleosides using purine bases with low solubility in aqueous buffer. As a rule of thumb, there was a general reduction of soluble enzyme activity when cosolvent content was gradually increased in reaction medium. In contrast, immobilized enzyme activity was enhanced 1.2–1.4-fold at 20% of methanol, ethanol, 2-propanol, diethylene glycol, and acetone; and at 10% and 30% acetonitrile. Likewise, highest increased activity (1.8-fold) was also obtained in presence of 20% acetonitrile. Immobilized enzyme was successfully used in the synthesis of 2′-deoxyxanthosine and 2′-deoxyguanosine using 2′-deoxyuridine as sugar donor and the corresponding poor water-soluble base in the presence of 30% of methanol, ethanol, 2-propanol, ethylene glycol, acetonitrile, and DMSO, giving high nucleoside yields at 4h.

Immunity by formulation design: Induction of high CD8 + T-cell responses by poly(I:C) incorporated into the CAF01 adjuvant via a double emulsion method

The combination of nucleic acid-based Toll-like receptor (TLR)-3 or TLR9 agonists and cationic liposomes constitutes an effective vaccine adjuvant approach for eliciting CD8 + T-cell responses. However, complexing cationic liposomes and oppositely charged oligonucleotides generally results in highly unstable and heterogeneous formulations with limited clinical applicability. The aim of this study was to design, formulate, and carefully characterize a stable CD8-inducing adjuvant based on the TLR3 ligand polyinosinic–polycytidylic acid [poly(I:C)] incorporated into a cationic adjuvant system (CAF01) composed of dimethyldioctadecylammonium (DDA) and trehalose 6,6′-dibehenate (TDB). For this purpose, a modified double emulsion solvent evaporation method was investigated for complexation of high amounts of anionic poly(I:C) to gel-state DDA/TDB liposomes. Addition of a volatile, water-miscible co-solvent (ethanol) to the outer water phase enabled preparation of colloidally stable liposomes, presumably by reducing the poly(I:C)-enhanced rigidity of the lipid bilayer. Cryo-transmission electron microscopy (TEM) revealed the formation of unilamellar as well as multilamellar liposomes, the latter suggesting that poly(I:C) is intercalated between the membrane bilayers in an onion-like structure. Finally, immunization of mice with the model antigen ovalbumin (OVA) and DDA/TDB/poly(I:C) liposomes induced a remarkably strong, antigen-specific CD8 + T-cell response, which was maintained for more than two months. Importantly, whereas injection of soluble poly(I:C) led to rapid production of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 in serum, administration of poly(I:C) in complex with the cationic DDA/TDB liposomes prevented this non-specific systemic pro-inflammatory response. These data emphasize the importance of improving the quality of the vaccine formulation to indeed overcome some of the major obstacles for using CD8-inducing agents such as poly(I:C) in future subunit vaccines.

Protease-Catalyzed Oligomerization of Hydrophobic Amino Acid Ethyl Esters in Homogeneous Reaction Media Using l-Phenylalanine as a Model System

Enzymatic synthesis of oligopeptides from l-phenylalanine ethyl ester hydrochloride (l-Phe-Et.HCl) and other l-form hydrophobic amino acid ester hydrochlorides in water miscible organic cosolvents was studied. Different proteases, water miscible cosolvents, and effect of different ratios of water miscible cosolvents for protease-catalyzed oligo-phenylalanine [oligo(l-Phe)] were compared. The importance of the use of water miscible cosolvents in transforming reactions from heterogeneous to homogeneous conditions as a potent medium engineering tool for protease-catalyzed oligopeptide synthesis is highlighted. For example, at 0.125 M l-Phe-Et.HCl, 20% (v/v) methanol, 18.6 mg/mL bromelain, in phosphate buffer (0.25M, pH 8), 40 degrees C, for 3 h, oligo(l-Phe) precipitated from the solution to yield 45 +/- 5%, in contrast, in the absence of cosolvent oligo(l-Phe) yield of 29 +/- 5% was obtained. The following reaction conditions were optimized for bromelain catalyzed oligo(l-Phe) synthesis: pH, temperature, substrate, enzyme, and cosolvent concentrations. DP(avg) and chain length distribution in the product peptides were investigated by (1)H NMR and MALDI-TOF.

Drug release from and sterilization of in situ cubic phase forming monoglyceride drug delivery systems

Since a monoglyceride-based cubic phase is too viscous to be injected parenterally, mixtures of monoglyceride, water and water-miscible cosolvents were investigated as low viscosity injectable in situ cubic phase-forming formulations. Upon contact with the release medium, a highly viscous cubic phase formed rapidly and served as an extended release matrix for the oligonucleotide drug. Extended drug release was obtained with all formulations. The drug release followed the square root of time relationship indicating a diffusion-controlled release mechanism. The release depended on the type of cosolvent and followed the order of ethanol > PEG 300 > 2-pyrrolidone > DMSO. Higher water or monoglycerides contents decreased the drug release because of an increased viscosity and increased swollen matrix thickness. The bioburden of different commercially available monoglycerides and of the prepared in situ cubic phase-forming formulations met USP XXIII requirements. Monoglycerides can be successfully sterilized by gamma irradiation or by autoclaving and the in situ cubic phase-forming formulations by autoclaving and aseptic filtration. The monoglycerides and in situ cubic phase-forming formulations retained their phase behaviour and release properties after sterilization.

Influence of Organic Solvents on the Structure and Enzymatic Activity of Haloalkane Dehalogenase DhaA

Organisms with the ability to degrade anthropogenic chemicals are using for this purpose haloalkane dehalogenases. Hereby, a active site nucleophile attacks a carbon atom of the halogenated substrate, leading to cleavage of the carbon-halogen bond, displacement of a halide and formation of a covalent alkyl-enzyme intermediate that is subsequently hydrolyzed. The haloalkane dehalogenase DhaA from Rhodococcus rhodochrous NCIMB13064 is enzymatically active for a broad range of halogenated substrates including 1,2,3-trichloropropane (TCP) (2) and sulphur mustard (3), some of them with high hydrophobicity and low solubility in water. Improving the solubility by addition of water miscible co-solvents like dimethyl sulfoxide (DMSO) to the reaction mixture could be a way to enhance the range of potential applications for these enzymes. Therefore, in the present study we investigate effects of DMSO on structure and dynamics of DhaA using molecular dynamics (MD) simulations demonstrating that the DMSO molecules penetrate to the active site of protein and compete with the halogentaed substrate for the catalytic site histidine272. On the other hand, histidine 272 traps DMSO and thus prevents further progress of DMSO deeper into the active site. With respect to protein solubility, interactions of DMSO with the protein surface decrease the solvation energy of the protein compared to protein in pure water. However, the enzyme is clearly stable in up to 42% DMSO and we can conclude that the enzyme activity is expected to be less than in pure water, however retained.

Pd nanoparticles as catalysts for green and sustainable oxidation of functionalized alcohols in aqueous media

The previously described catalyst system for the aerobic oxidation of alcohols, comprising palladium(II) acetate in combination with neocuproine in a 1:1 mixture of water and a water-miscible cosolvent such as ethylene carbonate or dimethylsulfoxide, was shown to involve palladium nanoparticles as the active catalyst. The latter are formed in situ or can be preformed by reduction of the palladium–neocuproine complex with hydrogen and they are stabilized by both the neocuproine ligand and the cosolvent. This catalyst system was successfully used for the selective aerobic oxidation of the steroidal secondary alcohols, nandrolone and 5α-pregnan-3α-ol-20-one, to the corresponding ketones.

Solubility Screening on a Series of Structurally Related Compounds: Cosolvent-Induced Changes on the Activity Coefficient of Hydrophobic Solutes

A homologous series of solutes was chosen as a model for a group of structurally related compounds with different physicochemical properties, as is commonly the case during the screening of potential drug candidates. Thermal properties of the crystalline solutes and solubility determinations were used to quantify the two independent factors that determine the solubility of organic compounds: crystallinity and hydrophobicity. A solubility screening study was conducted on the series. By expressing the obtained solubility enhancement expressed as changes in the activity coefficient, it is possible to visually compare the effect of different cosolvents. The results show the importance of solute-solvent polarity match. Polarity match between water miscible cosolvents and hydrophobic compounds is not truly attainable, but comparison of the screening results points out the closest matches (optimal effect), facilitating the systematic evaluation of solubilization approaches.

Effects of Cosolvent and Temperature on the Desorption of Polynuclear Aromatic Hydrocarbons from Contaminated Sediments of Chien-Jen River, Taiwan

This study evaluated the effects of the water-miscible cosolvent and temperature on the sorption-desorption of polynuclear aromatic hydrocarbons (PAHs) from contaminated sediments in Chien-Jen River, Taiwan. Sediment samples from five sampling stations of downstream section were utilized in this study. Phenanthrene and anthracene were selected as target compounds. The cosolvent effect on sorption of phenanthrene and anthracene was examined by the addition of various volume fractions of methanol (i.e., 0.3, 0.5, 0.7, and 0.9, respectively) in the sediment/water systems. The utility of the log-linear cosolvency model for predicting PAH sorption from solvent mixtures was evaluated. An inverse relationship was observed for sorption coefficients of phenanthrene and anthracene as a function of increasing cosolvent. The effect of temperature on sorption of phenanthrene and anthracene was conducted at temperature from 10°C to 40°C. The use of elevated temperatures in desorption experiments increased the PAH release from sediments. It was observed that sorption of phenanthrene and anthracene onto sediments decreased when temperature increased. The decrease of sorption coefficient of phenanthrene was more sensitive than that of anthracene. The magnitude of decreased sorption was attributed by the increased desorption rate constant, solubility, and heterogeneities of sediments.