DMSO activators General

Further information has appeared concerning the oxidation of primary, secondary, and benzylic alcohols (including hindered and bicyclic cases) using dimethyl sulphoxide (DMSO) activated by various electrophiles. Among previously unreported activators for this system, oxalyl chloride is generally effective. Primary and secondary alcohols activated by the pyridinium salt (1)... 

This chapter is written for a medicinal chemistry audience. The focus is on the importance of drug solubility in water and in dimethylsulfoxide (DMSO) in the types of activities likely to be of interest to medicinal chemists. The emphasis is on the discovery stage as opposed to the development stage. The reader will find numerous generalizations and rules of thumb relating to solubility in a drug discovery setting. 

In general the rate of false negatives are by definition difficult to ascertain. There are two general approaches to get a handle on false negatives. The first approach is based on what is known about the aqueous solubility of screening compounds since truly active compounds out of solution are the most common cause of false negatives. One can infer that perhaps 15% of true positives will be missed in an HTS. This inference comes from an analysis of the concordance or lack of concordance between nominal concentrations in DMSO stocks and nominal... 

Acetonitrile, methanol and DMSO had no apparent effect on umbelliferone glucuronidation in human hepatocytes at concentration up to 2% [32]. With HLMs or expressed UGTs, inhibitory effects of organic solvents on glucuronidation of 7-hydroxy-4-trifluoromethyl-coumarin (7-HFC) and estradiol generally followed the order acetonitrile > ethanol > methonal > DMSO [33], DMSO did not inhibit estradiol-3-glucuronidation activity at a concentration up... 

Weigh out 2 mg of sulfo-SMCC and add it to the above solution. Mix gently to dissolve. To aid in measuring the exact quantity of crosslinker, a concentrated stock solution may be made in water (or DMSO) and an aliquot equal to 2 mg transferred to the reaction solution. If a stock solution is made, it should be dissolved rapidly and used immediately to prevent extensive hydrolysis of the active ester. As a general guideline of addition for a particular protein activation, the use of a 40- to 80-fold molar excess of crosslinker over the amount of protein present usually results in good activation levels. 

Oxidation of alcohols.1 This phosphate is apparently as efficient as oxalyl chloride for activation of DMSO for oxidation, and the derived reagent is less prone to give chlorine-containing byproducts. The reactions are rapid at 20° or below, and yields are generally 75-95%. 

Temperature and pressure effects on rate constants for [Fe(phen)3] +/[Fe(phen)3] + electron transfer in water and in acetonitrile have yielded activation parameters AF was discussed in relation to possible nonadiabaticity and solvation contributions. Solvation effects on AF° for [Fe(diimine)3] " " " " half-cells, related diimine/cyanide ternary systems (diimine = phen, bipy), and also [Fe(CN)6] and Fe aq/Fe aq, have been assessed. Initial state-transition state analyses for base hydrolysis and for peroxodisulfate oxidation for [Fe(diimine)3] +, [Fe(tsb)2] ", [Fe(cage)] " " in DMSO-water mixtures suggest that base hydrolysis is generally controlled by hydroxide (de)hydration, but that in peroxodisulfate oxidation solvation changes for both reactants are significant in determining the overall reactivity pattern. ... 

Derived reagents. Mancuso and Swern2 have reviewed activated dimethyl sulfoxide reagents (100 references). Activation of DMSO with cither trifhioroacelic anhydride (7, 136) or oxalyl chloride (8, 200) provides the most generally useful... 

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