Dimethyl sulfoxide

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Dimethyl sulfoxide (DMSO) is the chemical compound with the formula (CH₃)₂SO. It was first synthesized in 1866 by the Russian scientist Alexander Saytzeff, who reported his findings in a German chemistry journal in 1867.. This colorless liquid is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is miscible in a wide range of organic solvents as well as water. It has a distinctive property of penetrating the skin very readily, so that one can taste it soon after it comes into contact with the skin. Its taste has been described as oyster- or garlic-like.

Production

Dimethyl sulfoxide is a by-product of wood pulping. A supplier of DMSO is the Gaylord Chemical Corporation in the USA.

Applications

Solvent

DMSO is an important polar aprotic solvent. It is less toxic than other members of this class such as dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, HMPA. Because of its excellent solvating power, DMSO is frequently used as solvent for chemical reactions involving salts, most notably Finkelstein reactions and other nucleophilic substitutions. Because DMSO is only weakly acidic, it tolerates relatively strong bases, and as such has been extensively used in the study and chemistry of carbanions. The work of the Bordwell group has provided a valuable set of non-aqueous pKa values (C-H, O-H, S-H and N-H acidities) for hundreds of organic compounds in DMSO.

A practical problem with DMSO as a solvent is its high boiling point, thus its solutions are not typically evaporated. Instead, reactions conducted in DMSO are often diluted with water to precipitate or phase separate organic products. DMSO is an effective paint stripper, being safer than many of the others such as nitromethane and dichloromethane. The relatively high freezing point of DMSO means that at, or just below, room temperature it is a solid, which can limit its utility in some chemical processes (e.g. crystallization with cooling).

In its deuterated form, i.e. DMSO-d₆, it is a useful but expensive solvent for NMR spectroscopy, again due to its ability to dissolve a wide range of analytes, its own simple spectrum, and its suitability for high-temperature NMR spectroscopic studies. Disadvantages to the use of DMSO-d₆ are its high viscosity, which broadens signals, and high boiling point, which interferes with sample recovery from the NMR solvent. Often it is mixed with CDCl₃ or CD₂Cl₂ for lower viscosity and melting points.

Reactions

The sulfur center in DMSO is nucleophilic toward soft electrophiles and the oxygen is nucleophilic toward hard electrophiles. The methyl groups of DMSO are somewhat acidic in character (pK_a=35) due to the stabilization of the resultant carbanion by the S(O)R group, and so are deprotonated with strong bases like lithium diisopropylamide and sodium hydride. The sodium salt of DMSO formed in this way (sometimes referred to as "dimsyl sodium") is a useful base, e.g. it is often used for the deprotonation of ketones to form sodium enolates, phosphonium salts to form Wittig reagents, and formamidinium salts to form diaminocarbenes.

DMSO reacts with methyl iodide to form a sulfoxonium salt [(CH₃)₃SO]I, which can be deprotonated with sodium hydride to form the sulfur ylide:

(CH₃)₂SO + CH₃I → [(CH₃)₃SO]I

[(CH₃)₃SO]I + NaH → [(CH₃)₂CH₂SO + NaI + H₂

In organic synthesis, DMSO is used as a mild oxidant, such as the Pfitzner-Moffatt oxidation and the Swern oxidation.

Products of ozonolysis, trioxolanes, are quenched with dimethyl sulfide to produce aldehydes and DMSO.

Biology

DMSO is used in PCR to inhibit secondary structures in the DNA template or the DNA primers. It is added to the PCR mix before reacting, where it interferes with the self-complementarity of the DNA, preventing the occurrence of interfering reactions. However, use of DMSO in PCR increases the mutation rate.

DMSO also sees use as a cryoprotectant, added to cell media in order to prevent the cells dying as they are frozen. Approximately 10% may be used with a slow-freeze method, and the cells may be frozen at -20°C or stored in liquid nitrogen safely.

Medicine

In cryobiology DMSO has been used as a cryoprotectant and is still an important constituent of cryoprotectant vitrification mixtures used to preserve organs, tissues, and cell suspensions. Without it, up to 90 percent of frozen cells will become inactive. It is particularly important in the freezing and long-term storage of embryonic stem cells and hematopoietic stem cells, which are often frozen in a mixture of 10% DMSO and 90% fetal bovine serum. As part of an autologous bone marrow transplant the DMSO is re-infused along with the patient's own hematopoietic stem cells.

Use of DMSO in medicine dates from around 1963, when a University of Oregon Medical School team, headed by Stanley Jacob, discovered it could penetrate the skin and other membranes without damaging them and could carry other compounds into a biological system.

In a 1978 study at the Cleveland Clinic Foundation in Cleveland, Ohio, researchers concluded that DMSO brought significant relief to the majority of the 213 patients with inflammatory genitourinary disorders that were studied. They recommended DMSO for all inflammatory conditions not caused by infection or tumor in which symptoms were severe or patients failed to respond to conventional therapy.

Some people report an onion- or garlic-like taste after touching DMSO. (Onion and garlic also derive their stinginess from sulfoxides syn-propanethial-S-oxide and allicin.) In the medical field DMSO is predominantly used as a topical analgesic, a vehicle for topical application of pharmaceuticals, as an anti-inflammatory and an antioxidant. It has been examined for the treatment of numerous conditions and ailments. The Food and Drug Administration (FDA) has approved DMSO usage only for the palliative treatment of interstitial cystitis. Medicinal-grade DMSO for this purpose is manufactured by Insource, Inc. under the name RIMSO.

Because DMSO increases the rate of absorption of some compounds through organic tissues including skin, it can be used as a drug delivery system.

Dimethyl sulfoxide dissolves a variety of organic substances, including carbohydrates, polymers, peptides, as well as many inorganic salts and gases. Loading levels of 50-60 wt.% are often observed vs 10-20 wt.% with typical solvents. For this reason DMSO plays a role in sample management and high-throughput screening operations in drug design.

DMSO is commonly used in veterinary medicine as a liniment for horses, alone or in combination with other ingredients. In the latter case, often, the intended function of the DMSO is as a solvent, to carry the other ingredients across the skin. Also in horses, DMSO is used intravenously, again alone or in combination with other drugs. It is used alone for the treatment of increased intracranial pressure and/or cerebral edema in horses.

History

On September 9, 1965, the Wall Street Journal reported the death of an Irish woman after undergoing DMSO treatment for a sprained wrist. Clinical research using DMSO halted and did not begin again until the National Academy of Sciences (NAS) published findings in favor of DMSO in 1972. In 1978, the FDA approved DMSO for treating interstitial cystitis. In 1980, Congress held hearings on claims that the FDA was slow in approving DMSO for other medical uses. In 2007, the FDA granted "fast track" designation on clinical studies of DMSO's use in reducing brain tissue swelling following traumatic brain injury.

Safety

Glove selection is important when working with DMSO. Thick rubber gloves are recommended. Nitrile gloves, which are very commonly used in chemical laboratories, have been found to dissolve rapidly with exposure to DMSO. Because DMSO easily penetrates the skin, substances dissolved in DMSO may be quickly absorbed. For instance, a solution of sodium cyanide in DMSO can cause cyanide poisoning through skin contact. DMSO by itself has low toxicity. Dimethyl sulfoxide can produce an explosive reaction when exposed to acid chlorides; at a low temperature, this reaction produces the oxidant for Swern oxidation.

Recently, it was found that DMSO waste disposal into sewers can cause environmental odor problems in cities: Waste water bacteria transform DMSO under hypoxic (anoxic) conditions into dimethyl sulfide (DMS) that is slightly toxic and has a strong disagreeable odor, similar to rotten cabbage.

See also

• Dimethyl sulfide (DMS), the corresponding sulfide
• Dimethyl sulfate (also DMS), the corresponding sulfate: a mutagenic alkylating compound
• Methylsulfonylmethane (MSM), a related chemical often used as a dietary supplement

References