Dimethyl sulfoxide

Dimethyl sulfoxide
IUPAC name	Dimethyl sulfoxide
Other names	Methyl sulfoxide methylsulfinylmethane DMSO
Identifiers
CAS number	67-68-5 Y
PubChem	679
RTECS number	PV6210000
SMILES	CS(C)=O
ChemSpider ID	659
Properties
Molecular formula	C2H6OS
Molar mass	78.13 g/mol
Appearance	Clear, colorless liquid
Density	1.1004 g/cm3, liquid
Melting point	18.5 °C (292 K)
Boiling point	189 °C (462 K)
Solubility in water	Miscible
Acidity (pKa)	35
Refractive index (nD)	1.479 εr = 48
Viscosity	1.996 cP at 20 °C
Structure
Dipole moment	3.96 D
Hazards
MSDS	External MSDS
R-phrases	R36/37/38
S-phrases	S26, S37/39
NFPA 704	1 1 0
Flash point	89 °C
Related compounds
Related sulfoxides	diethyl sulfoxide
Related compounds	sodium methylsulfinylmethylide, dimethyl sulfide, dimethyl sulfone, acetone
Supplementary data page
Structure and properties	n, εr, etc.
Thermodynamic data	Phase behaviour Solid, liquid, gas
Spectral data	UV, IR, NMR, MS
Y (what is this?)  (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Dimethyl sulfoxide (DMSO) is the chemical compound with the formula (CH₃)₂SO. It was first synthesized in 1866 by the Russian scientist Alexander Zaytsev, who reported his findings in a German chemistry journal in 1867.^[1][2] 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. Other reported side effects include stomach upset, sensitivity to light, visual disturbances, and headache. Skin irritation can develop at the site where DMSO is applied topically.

Production

Dimethyl sulfoxide is a by-product of kraft pulping. The sulfide used as a nucleophile also attacks the methoxy groups of lignin, producing methanethiol and dimethyl sulfide, which is oxidized to DMSO. Suppliers of DMSO are Arkema, Toray and the Gaylord Chemical Corporation.

Applications

Solvent

Distillation of DMSO requires a partial vacuum to achieve a lower boiling point.

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 a solvent for chemical reactions involving salts, most notably Finkelstein reactions and other nucleophilic substitutions. It is also extensively used to dissolve chemicals in biochemical or cell biology experiments.^[3] Because DMSO is only weakly acidic, it tolerates relatively strong bases and as such has been extensively used in the study of carbanions. A valuable set of non-aqueous pKa values (C-H, O-H, S-H and N-H acidities) for thousands of organic compounds have been determined in DMSO solution.^[4]

Because of its high boiling point, DMSO evaporates slowly at normal atmospheric pressures. Reactions conducted in DMSO are often diluted with water to precipitate or phase-separate 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 (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 its hygroscopicity, which leads to an overwhelming H₂O resonance in the ¹H NMR spectrum. It is often mixed with CDCl₃ or CD₂Cl₂ for lower viscosity and melting points.

DMSO is finding increased use in manufacturing processes to produce microelectronic devices.^[5] It is widely used to strip photoresist in TFT-LCD 'flat panel' displays and advanced packaging applications (such as wafer-level packaging / solder bump patterning).It also used in biopresevation especvially stem cell banking.

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,^[6] as illustrated by the Pfitzner-Moffatt oxidation and the Swern oxidation.^[7]

DMSO is a common ligand in coordination chemistry. The complex dichlorotetrakis(dimethyl sulfoxide) ruthenium(II), RuCl₂(dmso)₄, features DMSO bonded to Ru through sulfur and through oxygen.

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, minimizing interfering reactions.^[8] However, use of DMSO in PCR increases the mutation rate.^{[citation needed]}

DMSO also sees use as a cryoprotectant, added to cell media in order to prevent the cells dying as they are frozen.^[9] Approximately 10% may be used with a slow-freeze method, and the cells may be frozen at -80°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. In the cryogenic freezing of heteroploid cell lines (MDCK, VIRO, etc) a mixture of 10% DMSO with 90% EMEM (70% EMEM + 30% fetal bovine serum + antibiotic mixture) is used. 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.^[10] 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.

In the medical field DMSO is predominantly used as a topical analgesic,^[11] a vehicle for topical application of pharmaceuticals, as an anti-inflammatory^[12] and an antioxidant^{[citation needed]}. Because DMSO increases the rate of absorption of some compounds through organic tissues including skin, it can be used as a drug delivery system. It is frequently compounded with antifungal medications, enabling them to penetrate not just skin but also toe and fingernails.

DMSO has been examined for the treatment of numerous conditions and ailments, but the Food and Drug Administration (FDA) has approved its use only for the palliative treatment of interstitial cystitis. Some people report an onion- or garlic-like taste after touching DMSO. (Onion and garlic also derive their odor from sulfoxides syn-propanethial-S-oxide and allicin.)

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.^[13]

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.

Side-effects

Taking DMSO internally is reported to cause a fish- or oyster-like taste or odor in the mouth, likely due to the sulfoxide metabolites of DMSO.^[14]

Safety

On September 9, 1965, the Wall Street Journal reported the death of an Irish woman after undergoing DMSO treatment for a sprained wrist although no autopsy was done nor was a causal relationship established.^[15] 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.^[16] In 1978, the U.S. FDA approved DMSO for treating interstitial cystitis. In 1980, the U.S. 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.^[16]

New concerns were raised when research in mice revealed that DMSO exposure to the developing brain can produce brain degeneration within hours of exposure.^[17] This neurotoxicity could be detected at doses as low as 0.3 ml/kg, a level exceeded in children exposed to DMSO during certain medical treatments. As a result, special caution should be used when exposure to the developing brain is possible.

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.^[18] 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.^{[citation needed]} DMSO by itself has low toxicity.^[19] 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, DMSO disposed into sewers caused odor problems in cities: waste water bacteria transform DMSO under hypoxic (anoxic) conditions into dimethyl sulfide (DMS) that has a strong disagreeable odor, similar to rotten cabbage.^[20]

See also

Wikimedia Commons has media related to: dimethyl sulfoxide

• 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