DMSO, solubility issues

Several strategies can be applied to overcome solubility issues in DMSO. These are listed in Table 2 and are discussed below. 

Non-DMSO Storage Approach Overcome stability and solubility issues High initial investment Not suitable for all assays... 

The Wacker-type oxidation of the olefins is one of the oldest homogeneous transition metal-catalyzed reactions. The mechanism of the oxidation of ethylene to acetaldehyde by a PdCl2/CuCl2/02 system is shown in Figure 23. Interestingly, the selectivity of the oxidation of olefins with longer alkyl chains is dependent on their solubility in water. Furthermore, the production of chlorinated side-products and isomerized olefins has also occurred for olefins with low water solubility. In order to avoid the solubility issues, co-solvents such as DMSO, acetone, THF, dioxane, acetonitrile, DMF, and ethanol were used and DMF seemed to be the best. ... 

For biological studies CO-RM-2 typically requires pre-dissolution in DMSO or another polar solvent due to solubility issues. However, this compound can exhibit various beneficial effects within a biological system. Chen and co-workers have shown that mice unable to produce HO-1... 

Precipitation of compound from a DMSO stock is an issue of compound solubility in DMSO [14]. However, operationally, most organizations dissolving compounds in DMSO do not encounter problems in the solubilization process. This apparent paradox is explained by the issue of amorphous compounds. The vast majority of compounds solubilized into DMSO stocks are amorphous and inherently more soluble in DMSO (as previously discussed). The vast majority of the same compounds precipitating from DMSO are crystalline and much less soluble in DMSO (as previously discussed). The problem of compounds precipitating from DMSO occurs because so many compounds entering into screening libraries are amorphous. The precipitation of compounds from DMSO would be far less of a problem if screening compounds were entirely crystalline as they were 20 years ago. Quite simply DMSO insoluble crystalline compounds would never have been successfully dissolved in DMSO in the first place. 

This section focuses on compound precipitation from compound in DMSO stock solutions. This is an issue of compound solubility in DMSO as well as wet DMSO. 

Caco-2 model is easily affected by commonly used organic solvents or co-solvents [e.g., methanol, ethanol, polyethylene glycol (PEG), dimethyl sulfoxide (DMSO)] at relatively low concentrations (<1% v/v). Therefore, NCEs with poor aqueous solubility may not be adequately evaluated by this model. It has become a common practice in the pharmaceutical industry to test solubility of compounds before performing any other in vitro screens and eliminate NCEs with poor aqueous solubility, thus preventing false negatives due to this issue. 

Lipinski, C.A. 2004. Solubility in water and DMSO issues and potential solutions. In Borchardt, RT. et al., Eds. Pharmaceutical Profiling in Drug Discovery for Lead Selection Biotechnology. Arlington AAPS Press, pp. 93-125. 

Typically, nonstabilized ylides are utilized for the synthesis of (Z)-alkenes. In 1986, Schlosser published a paper summarizing the factors that enhance (Z)-selectivity. Salt effects have historically been defined as the response to the presence of soluble lithium salts. Any soluble salt will compromise the (Z)-selectivity of the reaction, and typically this issue has been resolved by the use of sodium amide or sodium or potassium hexamethyldisilazane (NaHMDS or KHMDS) as the base. Solvent effects are also vital to the stereoselectivity. In general, ethereal solvents such as THF, diethyl ether, DME and t-butyl methyl ether are the solvents of choice." In cases where competitive enolate fomnation is problematic, toluene may be utilized. Protic solvents, such as alcohols, as well as DMSO, should be avoided in attempts to maximize (Z)-selectivity. Finally, the dropwise addition of the carbonyl to the ylide should be carried out at low temperature (-78 C). Recent applications of phosphonium ylides in natural product synthesis have been extensively reviewed by Maryanoff and Reitz. 

Catalytic inhibition, Cl, of polymerization was discovered almost simultaneously with CCT.13 In searching for the best CCT catalyst, the solubility of the catalyst is one of the important issues. Cobalt chelates with large planar ligands are poorly soluble in the desired monomers and common organic solvents such as acetone and dichloroethane. The solubility can be improved by incorporating more substituents into the equatorial ligands of the complexes, but this approach requires substantial synthetic effort. The easier approach is to use amides and DMSO as solvents because these solvents will dissolve most of the complexes both as their electroneutral forms and as salts. 

Storage of compounds in DMSO and having them readily available greatly facilitates HTS and different screening assays. However, because of solubility and stability issues associated with compounds stored as DMSO solution, several non-DMSO storage concepts have been developed. 

Lipinski CA. Solubility in Water and DMSO Issues and Potential Solutions. 

HMF synthesis has classically involved either water or polar aprotic organic solvents such as DMSO as the reaction medium, since the sugar feedstocks are soluble in these media. Of all the technical issues that have confronted the industrialization of HMF production, first and foremost has been the high solubility of HMF in these solvents, which complicates product isolation. This problem has been mitigated to some extent by the recent development of biphasic reaction systems that involve continuous extraction of HMF into lower boiling solvents [5]. Salting out strategies can also increase the efficiency of this approach. 

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