Dimethyl sulfoxide

Dimethyl sulfoxide
IUPAC name Dimethyl sulfoxide
Systematic name Methanesulfinylmethane (substitutive) Dimethyl(oxido)sulfur (additive)
Other names Methylsulfinylmethane Methyl sulfoxide
Identifiers
Abbreviations	DMSO
CAS number	67-68-5 Y
PubChem	679
ChemSpider	659 Y
UNII	YOW8V9698H Y
EC number	200-664-3
DrugBank	DB01093
KEGG	D01043 Y
MeSH	Dimethyl+sulfoxide
ChEBI	CHEBI:28262 Y
ChEMBL	CHEMBL504 Y
RTECS number	PV6210000
ATC code	G04BX13,M02AX03
Beilstein Reference	506008
Gmelin Reference	1556
Jmol-3D images	Image 1 Image 2
SMILES CS(=O)C CS(C)=O
InChI InChI=1S/C2H6OS/c1-4(2)3/h1-2H3 Y Key: IAZDPXIOMUYVGZ-UHFFFAOYSA-N Y InChI=1/C2H6OS/c1-4(2)3/h1-2H3 Key: IAZDPXIOMUYVGZ-UHFFFAOYAR
Properties
Molecular formula	C2H6OS
Molar mass	78.13 g mol−1
Exact mass	78.013935504 g mol-1
Appearance	Colourless liquid
Density	1.1004 g cm-3
Melting point	19 °C, 292 K, 66 °F
Boiling point	189 °C, 462 K, 372 °F
Solubility in water	Miscible
Acidity (pKa)	35[1]
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
Main hazards	Irritant (Xi), Flammable (F)
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 sulfoxide (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula (CH₃)₂SO. 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 penetrates the skin very readily, giving it the unusual property for many individuals of being secreted onto the surface of the tongue after contact with the skin and causing a garlic-like taste in the mouth.^[2]

Synthesis and production

It was first synthesized in 1866 by the Russian scientist Alexander Zaytsev, who reported his findings in 1867. Dimethyl sulfoxide is a by-product of kraft pulping. Oxidation of dimethyl sulfide with oxygen or nitrogen dioxide gives DMSO.^[3]

Applications

Solvent

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

DMSO is a polar aprotic solvent and is less toxic than other members of this class, such as dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, and HMPA. 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 as an extractant in biochemistry and cell biology.^[4] Because DMSO is only weakly acidic, it tolerates relatively strong bases and as such has been extensively used in the study of carbanions. A 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.^[5][6]

Because of its high boiling point (189 °C; 372.2 °F 462 K), DMSO evaporates slowly at normal atmospheric pressure. Samples dissolved in DMSO cannot be as easily recovered compared to other solvents, as it is very difficult to remove all traces of DMSO by conventional rotary evaporation. Reactions conducted in DMSO are often diluted with water to precipitate or phase-separate products. The relatively high freezing point (18.5 °C; 65.3 °F; 292 K) 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.^[7] 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 biopreservation especially stem cell banking. DMSO is an effective paint stripper, being safer than many of the others such as nitromethane and dichloromethane.

Because of its ability to dissolve many kinds of compounds, DMSO plays a role in sample management and high-throughput screening operations in drug design.^[8]

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 trimethylsulfoxonium iodide, [(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,^[9] as illustrated by the Pfitzner-Moffatt oxidation and the Swern oxidation.^[10]

DMSO is a common ligand in coordination chemistry. The complex dichlorotetrakis(dimethyl sulfoxide)ruthenium(II), RuCl₂(dmso)₄, features DMSO bonded to ruthenium 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.^[11]

DMSO may also be used as a cryoprotectant, added to cell media to prevent cell death during the freezing process.^[12] 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

Use of DMSO in medicine dates from around 1963, when an Oregon Health & Science University 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 medicine, DMSO is predominantly used as a topical analgesic, a vehicle for topical application of pharmaceuticals, as an anti-inflammatory, and an antioxidant.^[13] 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.

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% 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, Media and 30% fetal bovine serum. In the cryogenic freezing of heteroploid cell lines (MDCK, VERO, 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.

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.^[14] 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.

DMSO has been examined for the treatment of numerous conditions and ailments, but the U.S. Food and Drug Administration (FDA) has approved its use only for the symptomatic relief of patients with interstitial cystitis.

In interventional radiology, DMSO is used as a solvent for Ethylene Vinyl Alcohol in the Onyx liquid embolic agent, which is used in embolisation, the therapeutic occlusion of blood vessels.

Veterinary medicine

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.

Safety

DMSO by itself has low toxicity.^[15]

On September 9, 1965, the Wall Street Journal reported that a manufacturer of the chemical warned that the death of an Irish woman after undergoing DMSO treatment for a sprained wrist may have been due to the treatment, although no autopsy was done, nor was a causal relationship established.^[16] 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.^[17] 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 U.S. FDA granted "fast track" designation on clinical studies of DMSO's use in reducing brain tissue swelling following traumatic brain injury.^[17]

DMSO exposure to developing mouse brains can produce brain degeneration.^[18] 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.

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.^[19] 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]} 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

• Varying oxidation of sulfur
  • Dimethyl sulfide (DMS), the corresponding sulfide, also produced by marine phytoplankton and emitted to the oceanic atmosphere where it is oxidized to DMSO, SO₂ and sulfate
  • Methylsulfonylmethane (MSM), a related chemical often marketed as a dietary supplement
• Related compounds with methyl on oxygen
  • Dimethyl sulfite, the corresponding sulfite
  • Dimethyl sulfate (also DMS), the corresponding sulfate: a mutagenic alkylating compound
  • Methyl methanesulfonate, another methylating agent

References

1. ^ Matthews, W.S., Bares, J.E., Bartmess, J.E., Bordwell, F.G., Cornforth, F.J., Drucker, G.E., Margolin, Z., McCallum, R.J., McCollum, G.J., Vanier, N.R., J. Am. Chem. Soc., 1975, 97, 7006.
2. ^ Novak, K. M., ed (2002). Drug Facts and Comparisons (56th ed.). St. Louis, Missouri: Wolters Kluwer Health.. p. 619. ISBN 1574391100 .
3. ^ Kathrin-Maria Roy “Sulfones and Sulfoxides” Ullmann's Encyclopedia of Industrial Chemistry 2002, Wiley-VCH, Weinheim. doi:10.1002/14356007.a25_487
4. ^ "DMSO". exactantigen.com. http://www.exactantigen.com/review/DMSO.html. Retrieved 2009-10-02. 
5. ^ Bordwell FG (1988). "Equilibrium acidities in dimethyl sulfoxide solution". Accounts of Chemical Research 21 (12): 456–463. doi:10.1021/ar00156a004. 
6. ^ Bordwell pKa Table in DMSO
7. ^ Kvakovszky G, McKim AS, Moore J. (2007). "A Review of Microelectronic Manufacturing Applications Using DMSO-Based Chemistries". ECS Transactions 11 (2): 227–234. doi:10.1149/1.2779383. 
8. ^ Balakin KV, Savchuk NP, Tetko IV. (2006). "In Silico Approaches to Prediction of Aqueous and DMSO Solubility of Drug-Like Compounds: Trends, Problems and Solutions". Current Medicinal Chemistry 13 (2): 223–241. doi:10.2174/092986706775197917. PMID 16472214. 
9. ^ Epstein WW, Sweat FW (March 1967). "Dimethyl Sulfoxide Oxidations". Chemical Reviews 67 (3): 247–260. doi:10.1021/cr60247a001. PMID 6042131. 
10. ^ Tidwell TT. (1990). "Oxidation of Alcohols by Activated Dimethyl Sulfoxide and Related Reactions: An Update". Synthesis 1990 (10): 857–870. doi:10.1055/s-1990-27036. 
11. ^ Chakrabarti R, Schutt CE. (August 2001). "The enhancement of PCR amplification by low molecular-weight sulfones". Gene 274 (1–2): 293–298. doi:10.1016/S0378-1119(01)00621-7. PMID 11675022. 
12. ^ Pegg, DE. (2007). Day JG, Stacey GN. ed. "Principles of Cryopreservation". Cryopreservation and Freeze-Drying Protocols, Second Edition. Methods in Molecular Biology (Humana Press) 368: 39–57. doi:10.1007/978-1-59745-362-2_3. ISSN 1064-3745. PMID 18080461. 
13. ^ Johannes Geiss (2001). The century of space science. Kluwer Academic. p. 20. ISBN 0-7923-7195-X. http://books.google.com/books?id=22FJysl__WcC&pg=PA20#v=onepage&q&f=false. Retrieved 2011 Aug 7. 
14. ^ Shirley SW, Stewart BH, Mirelman S. (March 1978). "Dimethyl Sulfoxide in Treatment of Inflammatory Genitourinary Disorders". Urology 11 (3): 215–220. doi:10.1016/0090-4295(78)90118-8. PMID 636125. http://www.dmso.org/articles/bladder/bladder1.htm. 
15. ^ Vignes, Robert (August 20–24, 2000). "Dimethyl Sulfoxide (DMSO) - A “New” Clean, Unique, Superior Solvent." (PDF). American Chemical Society Annual Meeting. http://www.gaylordchemical.com/bulletins/vignes-acs.pdf. Retrieved 2010-04-12. 
16. ^ Carley W. (September 9, 1965). "DMSO May Have Caused Death of Woman, Makers of 'Wonder' Drug Warn Doctors". Wall Street Journal (New York City). 
17. ^ ^{a b} http://www.fda.gov/ForIndustry/ImportProgram/ImportAlerts/ucm162294.htm^{[dead link]}
18. ^ Hanslick JL, Lau K, Noguchi KK, Olney JW, Zorumski CF, Mennerick S, Farber NB. (April 2009). "Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system". Neurobiology of Disease 34 (1): 1–10. doi:10.1016/j.nbd.2008.11.006. PMC 2682536. PMID 19100327. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2682536. 
19. ^ "Chemical Hygiene Plan" (PDF). Cornell University. October 1999. http://people.ccmr.cornell.edu/~cober/complete.chemical.hygiene.plan.2000.pdf. Retrieved 2010-04-12. 
20. ^ Glindemann D, Novak J, Witherspoon J. (January 2006). "Dimethyl Sulfoxide (DMSO) Waste Residues and Municipal Waste Water Odor by Dimethyl Sulfide (DMS): the North-East WPCP Plant of Philadelphia". Environmental Science and Technology 40 (1): 202–207. doi:10.1021/es051312a. PMID 16433352. 

External links

• International Chemical Safety Card 0459