Cosolvent DMSO

Kegiospecific synthesis of Manmch bases. Hooz and Bridson have described a new rcgiospecific synthesis of certain Mannich bases which involves first reaction of a trialkylborane with an a-diazoketone in THF to form an cnol borinate (1) after evolution of nitrogen ceases, dimcthyl(methylene)ammonium iodide (2) in DMSO is added. The Mannich base (3) is obtained in 85 100% yield after hydrolytic workup. Cosolvent DMSO is crucial for high yields. 

Acidity constants for ionization of weak carbon acids in water caimot be determined by direct measurement when the strongly basic carbanion is too unstable to exist in detectable concentrations in this acidic solvent. Substituting dimethyl-sulfoxide (DMSO) for water causes a large decrease in the solvent acidity because, in contrast with water, the aprotic cosolvent DMSO does not provide hydrogenbonding stabilization of hydroxide ion, the conjugate base of water. This allows the determination of the pfC s of a wide range of weak carbon acids in mixed DMSO/water solvents by direct measurement of the relative concentrations of the carbon acid and the carbanion at chemical equilibrium [3, 4]. The pfC s determined for weak carbon acids in this mixed solvent can be used to estimate pfC s in water. 

The maximum activity of the isolated enzyme was observed at 30 °C and pH 6.5 in a buffer system with 5% (v/v) DMSO as a cosolvent. The enzyme was very stable at pH 7.5 and retained full activity after incubation at 40 °G for 6 h. Interestingly, when the cosolvent DMSO was replaced by an emulsifier (Tween-80, 0.5% w/v) as an alternative modulator to disperse the water-in-soluble substrate, the apparent activity of the epoxide hydrolase significantly increased by 1.8-fold, while the optimum temperature shifted from 30 to 40 °C and the half-life of the enzyme at 50 °C increased by 2.5 times (Figure 2.5). The enzymatic hydrolysis of rac-PGE was highly enantioselective, with an B-value (enantiomeric ratio) of 69.3 in the Tween-80 emulsion system, which is obviously superior than that (41.2) observed in the DMSO-modulated system. ... 

It is noteworthy that the cosolvent DMSO also turned out to be beneficial when using other enzymes, for example, P450-monooxygenases [41], The use of short-chain alcohols as water-miscible solvents in biotransformations has been reported widely in the field of esterase-catalyzed reactions, for example, in PLE-catalyzed asymmetric syntheses [42],... 

Pesticide Solvent. The majority of organic fungicides, insecticides, and herbicides (qv) are soluble in DMSO, including such difficult-to-solvate materials as the substituted ureas and carbamates (see Fungicides, agricultural Insect control technology Pesticides). Dimethyl sulfoxide forms cosolvent systems of enhanced solubiUty properties with many solvents (109). 

Moreover, with a change of solvent, a new tautomeric form can arise owing to formation of intermolecular hydrogen bonds in place of the previously existent intramolecular hydrogen bonds. This situation is characteristic, for example, for pyrimidine derivatives 49, for which the use of polar (DMSO, DMF, MeOH, HMPT) solvents or specifically solvating cosolvents (S) (e.g., a small amount of water or A-methylpyrrolidinone) leads to the appearance of ylidene tautomer 49b with the p-quinonoid disposition of the double bonds (Scheme 18) [88KGS521 90UK457]. 

Hydrolysis of substrates is performed in water, buffered aqueous solutions or biphasic mixtures of water and an organic solvent. Hydrolases tolerate low levels of polar organic solvents such as DMSO, DMF, and acetone in aqueous media. These cosolvents help to dissolve hydrophobic substrates. Although most hydrolases require soluble substrates, lipases display weak activity on soluble compounds in aqueous solutions. Their activity markedly increases when the substrate reaches the critical micellar concentration where it forms a second phase. This interfacial activation at the lipid-water interface has been explained by the presence of a... 

Soluble organic solvents have often been used as cosolvents to solubilize miscible organic substrates. Since organic compounds including solvents are possibly incorporated inside of the enzyme, they may affect the stereoselectivity of enzymatic reactions. For example, dimethyl sulfoxide (DMSO) (10%) enhance not only chemical yield but also enantioselectivity of yeast reduction. Thus, the poor yield of 23% with 80% ee was increased to 65% yield with >99% ee (Figure 8.20) [17]. 

Furthermore, pH electrode calibration can be performed in situ by the new method [48], concurrently with the pKj determination. This is a substantial improvement in comparison to the traditional procedure of first doing a blank titration to determine the four Avdeef-Bucher parameters [24]. The traditional cosolvent methods used with sparingly soluble molecules can be considerably limited in the pH<4 region when DMSO-water solutions are used. This is no longer a serious problem, and routine blank titrations are now rarely needed in the new in situ procedure. 

Mixed-solvent solutions of various cosolvent-water proportions are titrated and psKa (the apparent pKa) is measured in each mixture. The aqueous pKa is deduced by extrapolation of the psKa values to zero cosolvent. This technique was first used by Mizutani in 1925 [181-183]. Many examples may be cited of pKa estimated by extrapolation in mixtures of methanol [119,161,162,191,192,196,200], ethanol [184,188-190,193], propanol [209], DMSO [212,215], dimethylformamide [222], acetone [221], and dioxane [216]. Plots of psKa versus weight percent organic solvent, Rw = 0 — 60 wt%, at times show either a hockey-stick or a bow shape [119]. For Rw > 60 wt%, S-shaped curves are sometimes observed. (Generally, psKa values from titrations with Rw > 60 wt% are not suitable for extrapolation to zero cosolvent because KC1 and other ion pairing interferes significantly in the reduced dielectric medium [223].)... 

Figure 6.10 High-throughput solubility-pH determination of chlorpromazine. The horizontal line indicates the set upper limit of solubility, where the compound completely dissolves and solubility cannot be specified. The points below the horizontal line are measured in the presence of precipitation and indicate solubility. The solubility pH curve was collected in the presence of 0.5 vol% DMSO, and is affected by the cosolvent (see text). [Avdeef, A., Cun Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

Yamashita et al. [82] tested the effect of PEG400, DMSO, and ethanol, with up to 10% added to solutions in Caco-2 assays. PEG400 caused a dramatic decrease (75%) in the permeability of dexamethasone at 10% cosolvent concentration DMSO caused a 50% decrease, but ethanol had only a slight decreasing effect. 

Under the experimental conditions dehalogenation proved to be extremely rapid and was complete within 1 min. This contrasts with the 90-270 min at 100 °C required for thermal debromination of 2-bromonapthalene. No dehalogenation takes place in the absence of the formate donor and when the deuterium is located in the cosolvent rather than the donor (i. e. HCOOK + D20) hardly any deuterium incorporation takes place. Another interesting observation was that the amount (%) deuterium incorporation was always lower when protic solvents such as alcohols were used than aprotic solvents such as dimethyl sulfoxide (DMSO). These are both interesting and useful findings which are valuable for proposed tritiation studies. 

DMF), /V,/V-dimethylacetamide (DMAc), DMSO, hexamethylphosphoric triamide (HMPA), and AT-methyl-2-pyrrolidone (NMP) may be used as cosolvents. 

In recent years, a great diversity of structurally well-defined functionalized fullerenes has been designed and synthesized for that purpose. Some of them exhibit pronounced solubility in water (vide infra). But even for compounds being virtually insoluble in water, stable aqueous phases can be obtained in plenty of cases by diluting stock solutions of the compounds in polar organic solvents with various amounts of water. Notably, dimethyl sulfoxide (DMSO) and tetrahydro-furan (THF) have turned out to be excellent surfactants for preparing stable aqueous fullerene solutions (Angelini et al., 2005 Cassell et al., 1999 Da Ros et al., 1996 Gun kin et al., 2006 Illescas et al., 2003). Also cosolvents such as dimethylforma-mide (DMF) and methanol can be used to promote water solubility. After subsequent dilution of a saturated solution of C60 in benzene with THF, acetone and finally water, actually stable aqueous suspensions of pristine fullerene can be obtained (Scrivens et al., 1994). 

An also frequently occurring problem may be the low solubility of test compounds in aqueous solvents. Organic cosolvents, such as DMSO or ethanol can be used however, due to limited cell viability, final concentrations above 1 % have to be avoided. 

Studies of medium effects on hexacyanoferrate(II) reductions have included those of dioxygen,iodate, peroxodisulfate, - [Co(NH3)5(DMSO)] +, and [Co(en)2Br2]+. Rate constants for reaction with dioxygen depended strongly on the electron-donor properties of the organic cosolvent. Rate constants for reduction of peroxodisulfate in several binary aqueous media were analyzed into their ion association and subsequent electron transfer components. Rate constants for reduction of [Co(en)2Br2] in methanol water and dioxan water mixtures were analyzed by a variety of correlatory equations (dielectric constant Grunwald-Winstein Swain Kamlet-Taft). 

At almost the same time as other polymer-supported phase transfer catalysts were first reported, polymer-supported solvents and cosolvents were found to be effective catalysts for phase transfer reactions 155-156>. Dipolar aprotic solvents such as hexa-methylphosphoramide (HMPA)157, dimethylsulfoxide (DMSO)158), and tertiary amides159,1601 are well known to coordinate strongly with alkali and alkaline earth metal cations, and hence promote nucleophilic displacement reactions of the anions161). Catalysts 44 155-162>163> and 45163),... 

Iodoxvbenzoic acid (IBX) is also a useful oxidizing reagent. Insoluble in most solvents (except DMSO) it can be used with other cosolvent mixtures. 

The cosolvents chosen for this study were urea (U), acetone (ACT), di-methylsulfoxide (DMSO), p-dioxane (D), piperidine (PD), morpholine (M), terf-butanol (TBA), and to a lesser extent acetamide (ACM). The study of the binary system was also extended to piperazine (PZ) and tetrahydropyran (THP). This choice of cosolvents is sufficiently varied to allow an examination of the various factors which influence the transfer functions. 

As a consequence of the model employed, values of Hb(H20) and N ought to be independent of the choice of the cosolvent as long as specific structural effects are absent. Therefore, we applied Equation 3 to the enthalpies of solution of n-Bu4NBr in DMSO-water mixtures (iO), since DMSO is a dipolar aprotic solvent like DMF. The best fit of the AHE values in this mixture yields Hb(H20) = —49.2 kj mol-1 and N/4 = 6.4, in excellent agreement with our values at 25°C given in Table III. 

In our work, we have used thermal analysis and have confirmed that the transition temperatures of NIPA gels are very close to the cloud points of aqueous solutions of NIPA polymers [5]. This can be seen in Figs. 2 and 3 which compare the phase transitions in the presence of an inorganic salt and in the presence of a cosolvent such as DMSO [5, 6]. Clearly, the transition temperature of the gel shows the same tendency as that of the polymer. 

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