Dimethyl sulfoxide

Dimethyl sulfoxide

Dimethyl sulfoxide
Stereo structural formula of dimethyl sulfoxide with an explicit electron pair and assorted dimensions
Spacefill model of dimethyl sulfoxide

A sample of dimethyl sulfoxide
Names
IUPAC name
Dimethyl sulfoxide
Systematic IUPAC name
Methanesulfinylmethane (substitutive)
Dimethyl(oxido)sulfur (additive)
Other names
Methylsulfinylmethane
Methyl sulfoxide
Identifiers
 Y
Abbreviations DMSO, Me2SO
ATC code G04
M02
506008
ChEBI  Y
ChEMBL  Y
ChemSpider  Y
DrugBank  Y
EC number 200-664-3
1556
Jmol-3D images Image
Image
KEGG  Y
MeSH
PubChem
RTECS number PV6210000
UNII  Y
Properties
C2H6OS
Molar mass 78.13 g·mol−1
Appearance Colourless liquid
Density 1.1004 g cm−3
Melting point 19 °C (66 °F; 292 K)
Boiling point 189 °C (372 °F; 462 K)
Miscible
Solubility in diethyl ether very soluble
Acidity (pKa) 35[1]
1.479
εr = 48
Viscosity 1.996 cP at 20 °C
Structure
Cs
trigonal pyramidal
3.96 D
Hazards
Main hazards Irritant and flammable
Safety data sheet See: data page
Oxford MSDS
R-phrases R36/37/38
S-phrases S26, S37/39
NFPA 704
2
1
0
Flash point 89 °C
Related compounds
Related sulfoxides
diethyl sulfoxide
Related compounds
sodium methylsulfinylmethylide,
dimethyl sulfide,
dimethyl sulfone,
acetone
Supplementary data page
Refractive index (n),
Dielectric constantr), etc.
Thermodynamic
data
Phase behaviour
solid–liquid–gas
UV, IR, NMR, MS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
 Y  (: Y/N?)

Dimethyl sulfoxide (DMSO) is an garlic-like taste in the mouth after contact with the skin.[2]

In terms of chemical structure, the molecule has idealized Cs symmetry. It has a trigonal pyramidal molecular geometry consistent with other three-coordinate S(IV) compounds,[3] with a nonbonded electron pair on the approximately tetrahedral sulfur atom.

Contents

  • Synthesis and production 1
  • Reactions 2
    • Reactions with electrophiles 2.1
    • Acidity 2.2
    • Oxidant 2.3
    • Ligand 2.4
  • Applications 3
    • Solvent 3.1
    • Biology 3.2
    • Medicine 3.3
    • Alternative medicine 3.4
    • Veterinary medicine 3.5
    • Taste 3.6
  • Safety 4
    • Toxicity 4.1
    • Explosions 4.2
  • See also 5
  • References 6
  • External links 7

Synthesis and production

It was first synthesized in 1866 by the Russian scientist Alexander Zaytsev, who reported his findings in 1867.[4] Dimethyl sulfoxide is produced from dimethyl sulfide, a by-product of kraft pulping. It is industrially produced by oxidation of dimethyl sulfide with oxygen or nitrogen dioxide.[5]

Reactions

Reactions with electrophiles

The sulfur center in DMSO is nucleophilic toward soft electrophiles and the oxygen is nucleophilic toward hard electrophiles. With methyl iodide it forms trimethylsulfoxonium iodide, [(CH3)3SO]I:

(CH3)2SO + CH3I → [(CH3)3SO]I

This salt can be deprotonated with sodium hydride to form the sulfur ylide:

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

Acidity

The methyl groups of DMSO are only weakly acidic, with a pKa=35. For this reason, the basicities of many weakly basic organic compounds have been examined in this solvent.

Deprotonation of DMSO requires strong bases like lithium diisopropylamide and sodium hydride. Stabilization of the resultant carbanion is provided by the S(O)R group. The sodium derivative of DMSO formed in this way is referred to as "dimsyl sodium". It is a base, e.g., for the deprotonation of ketones to form sodium enolates, phosphonium salts to form Wittig reagents, and formamidinium salts to form diaminocarbenes. It is also a potent nucleophile.

Oxidant

In

  • International Chemical Safety Card 0459
  • Dimethyl Sulfoxide Information Center

External links

  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.; Bares; Bartmess; Bordwell; Cornforth; Drucker; Margolin; McCallum; McCollum; Vanier (1975). "Equilibrium acidities of carbon acids. VI. Establishment of an absolute scale of acidities in dimethyl sulfoxide solution". J. Am. Chem. Soc. 97 (24): 7006.  
  2. ^ Novak, K. M., ed. (2002). Drug Facts and Comparisons (56th ed.). St. Louis, Missouri: Wolters Kluwer Health. p. 619.  
  3. ^ R. Thomas, C. B. Shoemaker and K. Eriks "The molecular and crystal structure of dimethyl sulfoxide, (H3C)2SO" Acta Cryst. 1966. vol. 21, pp. 12-20. doi:10.1107/S0365110X66002263
  4. ^ A. Saytzeff (1867) "Ueber die Einwirkung von Saltpetersäure auf Schwefelmethyl und Schwefeläthyl" (On the effect of nitric acid on methyl sulfide and ethyl sulfide) Annalen der Chemie und Pharmacie, 144: 148–156; see page 150, where dimethyl sulfoxide is called "Dimethylschwefeloxyd".
  5. ^ Kathrin-Maria Roy "Sulfones and Sulfoxides" in Ullmann's Encyclopedia of Industrial Chemistry, 2002, Wiley-VCH, Weinheim. doi:10.1002/14356007.a25_487
  6. ^ Epstein WW, Sweat FW; Epstein (March 1967). "Dimethyl Sulfoxide Oxidations".  
  7. ^ Tidwell TT. (1990). "Oxidation of Alcohols by Activated Dimethyl Sulfoxide and Related Reactions: An Update".  
  8. ^ Calligaris, Mario (2004). "Structure and bonding in metal sulfoxide complexes: An update". Coordination Chemistry Reviews 248 (3–4): 351.  
  9. ^ "DMSO". exactantigen.com. Retrieved 2009-10-02. 
  10. ^ Bordwell FG (1988). "Equilibrium acidities in dimethyl sulfoxide solution".  
  11. ^ Bordwell pKa Table in DMSO
  12. ^ Kvakovszky G, McKim AS, Moore J.; McKim; Moore (2007). "A Review of Microelectronic Manufacturing Applications Using DMSO-Based Chemistries".  
  13. ^ Balakin KV, Savchuk NP, Tetko IV.; Savchuk; Tetko (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.  
  14. ^ Chakrabarti R, Schutt CE.; Schutt (August 2001). "The enhancement of PCR amplification by low molecular-weight sulfones".  
  15. ^ "Guidelines for PCR Optimization with Phusion High-Fidelity DNA Polymerase". 
  16. ^ 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.  
  17. ^ Cai WJ, Huang JH, Zhang SQ, Wu B, Kapahi P, Zhang XM, Shen ZY; Huang; Zhang; Wu; Kapahi; Zhang; Shen (2011). Blagosklonny, Mikhail V, ed. "Icariin and its derivative icariside II extend healthspan via insulin/IGF-1 pathway in C. elegans".  
  18. ^ Johannes Geiss (2001). The century of space science. Kluwer Academic. p. 20.  
  19. ^ Shirley SW, Stewart BH, Mirelman S.; Stewart; Mirelman (March 1978). "Dimethyl Sulfoxide in Treatment of Inflammatory Genitourinary Disorders".  
  20. ^ J Michael. Kurzzeitbehandlung von Sportverletzungen. DMSO 1985, pp 58-60
  21. ^ Kelava T, Cavar I (Nov 2011). actions of drug solvents) "Biological actions of drug solvents" . Periodicum Biologorum 113 (3): 311–320. 
  22. ^ Kelava T, Cavar I; Cavar; Culo (Oct 2010). "Influence of small doses of various drug vehicles on acetaminophen-induced liver injury". Can J Physiol Pharmacol 88 (10): 980–87.  
  23. ^ a b c >DMSO, National Council Against Health Fraud
  24. ^ 187 fake cancer "cures" to avoid, FDA
  25. ^ Hall, M. D.; Telma, K. A.; Chang, K.-E.; Lee, T. D.; Madigan, J. P.; Lloyd, J. R.; Goldlust, I. S.; Hoeschele, J. D.; Gottesman, M. M. (8 May 2014). "Say No to DMSO: Dimethylsulfoxide Inactivates Cisplatin, Carboplatin and Other Platinum Complexes". Cancer Research 74 (14): 3913–22.  
  26. ^ a b DMSO information from American Cancer Society
  27. ^ DMSO at WebMD
  28. ^ Lã¼Bbert, Matthias; Kyereme, Jessica; Schã¶Bel, Nicole; Beltrã¡n, Leopoldo; Wetzel, Christian Horst; Hatt, Hanns (October 21, 2013). "Transient Receptor Potential Channels Encode Volatile Chemicals Sensed by Rat Trigeminal Ganglion Neurons". PLOS One 8 (10): e77998.  
  29. ^ [3], Material Safety Data Sheet DMSO
  30. ^ [4], Material Safety Data Sheet Ethanol
  31. ^ Hanslick, JL; Lau, K; Noguchi, KK; Olney, JW; Zorumski, CF; Mennerick, S; Farber, NB (2009). "Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system". Neurobiology of disease 34 (1): 1–10.  
  32. ^ Brisbane drug company convicted of counterfeiting, Therapeutic Goods Agency
  33. ^ Rubber Chemical Resistance Chart
  34. ^ "Chemical hygiene plan" (PDF).  
  35. ^ Carley W. (September 9, 1965). "DMSO may have caused death of woman, makers of 'Wonder' drug warn doctors". Wall Street Journal (New York City). 
  36. ^ a b http://www.fda.gov/ForIndustry/ImportProgram/ImportAlerts/ucm162294.htm
  37. ^ Hanslick JL, Lau K, Noguchi KK, Olney JW, Zorumski CF, Mennerick S, Farber NB.; Lau; Noguchi; Olney; Zorumski; Mennerick; Farber (April 2009). "Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system". Neurobiology of Disease 34 (1): 1–10.  
  38. ^ Glindemann D, Novak J, Witherspoon J.; Novak; Witherspoon (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.  
  39. ^ George Kvakovszky, et. al., "Process for preparing low malodorous dimethyl sulfoxide", US patent application number 20090005601 (2009).
  40. ^ a b c Roth/Weller: Gefährliche Chemische Reaktionen, ecomed Sicherheit, Verlagsgruppe Hüthig Jehle Rehm, Landsberg/Lech, 31. Ergänzungslieferung 8/2000.
  41. ^ Thieme Römpp Online

References

See also

DMSO can decompose at the boiling temperature of 189 °C at normal pressure,[40] possibly leading to an explosion. The decomposition is catalyzed by acids and bases and therefore can be relevant at even lower temperatures.[40] A strong to explosive reaction also takes place in combination with halogen compounds, metal nitrides, metal perchlorates, sodium hydride, periodic acid and fluorinating agents.[40][41]

Dimethyl sulfoxide can produce an explosive reaction when exposed to acyl chlorides; at a low temperature, this reaction produces the oxidant for Swern oxidation.

Explosions

DMSO disposed into sulfide) and C-S-H (mercaptan) linkages. Deodorization of DMSO is achieved by removing the odorous impurities it contains.[39]

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.[35] Clinical research using DMSO was halted and did not begin again until the National Academy of Sciences (NAS) published findings in favor of DMSO in 1972.[36] In 1978, the US FDA approved DMSO for treating interstitial cystitis. In 1980, the US Congress held hearings on claims that the FDA was slow in approving DMSO for other medical uses. In 2007, the US FDA granted "fast track" designation on clinical studies of DMSO's use in reducing brain tissue swelling following traumatic brain injury.[36] DMSO exposure to developing mouse brains can produce brain degeneration. This neurotoxicity could be detected at doses as low as 0.3 mL/kg, a level exceeded in children exposed to DMSO during bone marrow transplant.[37]

Because DMSO easily penetrates the skin, substances dissolved in DMSO may be quickly absorbed. Glove selection is important when working with DMSO. Butyl rubber, fluoroelastomer, neoprene, or thick (15 mil) latex gloves are recommended.[33] Nitrile gloves, which are very commonly used in chemical laboratories, may protect from brief contact but have been found to degrade rapidly with exposure to DMSO.[34]

Early clinical trials with DMSO were stopped because of questions about its safety, especially its ability to harm the eye. The most commonly reported side effects include headaches and burning and itching on contact with the skin. Strong allergic reactions have been reported. DMSO can cause contaminants, toxins, and medicines to be absorbed through the skin, which may cause unexpected effects. DMSO is thought to increase the effects of blood thinners, steroids, heart medicines, sedatives, and other drugs. In some cases this could be harmful or dangerous.[26] It is a developmental neurotoxin.[31] In Australia it is listed as a schedule 4 poison, and a company has been prosecuted for adding it to products as a preservative.[32]

DMSO is a non-toxic solvent with a median lethal dose higher than ethanol (DMSO: LD50 Oral-Rat-14,500 mg/kg,[29] Ethanol: LD50 Oral-Rat-7,060 mg/kg [30]).

Toxicity

Safety

The perceived garlic taste upon skin contact with DMSO may be due to nonolfactory activation of TRPA1 receptors in trigeminal ganglia.[28] Unlike dimethyl and diallyl disulfide (also with odors resembling garlic), the mono- and tri- sulfides (typically with disgusting odors), and other similar structures, the pure chemical DMSO is odorless.

Taste

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.

Veterinary medicine

The use of DMSO as an alternative treatment for cancer is of particular concern, as it has been shown to interfere with a variety of chemotherapy drugs, including cisplatin, carboplatin, and oxaliplatin.[25] The American Cancer Society lists DMSO as an ineffective alternative cancer cure.[26] There is insufficient evidence to support the hypothesis that DMSO has any effect,[27] and most sources agree that its history of side effects when tested warrants caution when using it as a dietary supplement, for which it is marketed heavily with the usual disclaimer.

DMSO is marketed as an alternative medicine. Its popularity as an alternative cure is stated to stem from a 60 Minutes documentary featuring an early proponent.[23] However, DMSO is listed by the U.S. FDA as a fake cancer cure[24] and the FDA has had a running battle with distributors.[23] One such distributor is Mildred Miller, who promoted DMSO for a variety of disorders and was consequently convicted of Medicare fraud.[23]

Alternative medicine

DMSO is metabolized to dimethyl sulfide and dimethyl sulfone. It is subject to renal and pulmonary excretion. A possible side effect of DMSO is therefore elevated blood dimethyl sulfide, which may cause a blood borne halitosis symptom.

In embryonic stem cells and hematopoietic stem cells, which are often frozen in a mixture of 10% DMSO, a freezing medium, 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 medical research, DMSO is often used as a drug vehicle in in vivo and in vitro experiments. However, when a researcher is unaware of its pleiotropic effects, or when the control groups are not carefully planned, a bias can occur; an effect of DMSO can be falsely attributed to the drug.[21] For example, even a very low dose of DMSO has a powerful protective effect against paracetamol (acetaminophen)-induced liver injury in mice.[22]

In interventional radiology, DMSO is used as a solvent for ethylene vinyl alcohol in the Onyx liquid embolic agent, which is used in embolization, the therapeutic occlusion of blood vessels.

Dolobene gel, containing DMSO, dexpanthenol, and heparin, is sold in Germany and eastern Europe for topical use in sprains, tendinitis, and local inflammation.[20]

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. A 1978 study concluded that DMSO brought significant relief to the majority of the 213 patients with inflammatory genitourinary disorders that were studied.[19] The authors recommended DMSO for genitourinary inflammatory conditions not caused by infection or tumor in which symptoms were severe or patients failed to respond to conventional therapy.

Use of DMSO in medicine dates from around 1963, when an tissues, including skin, it is used in some transdermal drug delivery systems. Its effect may be enhanced with the addition of EDTA. It is frequently compounded with antifungal medications, enabling them to penetrate not just skin but also toenails and fingernails.

Medicine

In cell culture, DMSO is used to induce differentiation of P19 embryonic carcinoma cells into cardiomyocytes and skeletal muscle cells.

DMSO has been used as a co-solvent to assist absorption of the flavonol glycoside Icariin into the C. elegans nematode worm.[17]

DMSO may also be used as a cryoprotectant, added to cell media to reduce ice formation and thereby prevent cell death during the freezing process.[16] Approximately 10% may be used with a slow-freeze method, and the cells may be frozen at −80 °C (−112 °F) or stored in liquid nitrogen safely.

DMSO is used in polymerase chain reaction (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.[14] DMSO in a PCR reaction is applicable for supercoiled plasmids (to relax before amplification) or DNA templates with high GC-content (to decrease thermostability). For example, 10% final concentration of DMSO in the PCR mixture with Phusion decreases primer annealing temperature (i.e. primer melting temperature) by 5.5–6.0 °C (9.9–10.8 °F).[15]

Biology

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.[13]

DMSO is finding increased use in manufacturing processes to produce microelectronic devices.[12] 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.

In its deuterated form (DMSO-d6), it is a useful solvent for NMR spectroscopy, again due to its ability to dissolve a wide range of analytes, the simplicity of its own 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.

Because of its high boiling point, 189 °C (372 °F), 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 lyophilisation to remove both DMSO and water. Reactions conducted in DMSO are often diluted with water to precipitate or phase-separate products. The relatively high freezing point of DMSO, 18.5 °C (65.3 °F), 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).

[11][10] DMSO is a

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

Solvent

Applications

Related to its ability to dissolve many salts, DMSO is a common ligand in coordination chemistry.[8] Illustrative is the complex dichlorotetrakis(dimethyl sulfoxide)ruthenium(II) (RuCl2(dmso)4). In this complex, three DMSO ligands are bonded to ruthenium through sulfur. The fourth DMSO is bonded through oxygen. In general, the oxygen-bonded mode is more common.

Ligand

[7].Swern oxidation and the Pfitzner–Moffatt oxidation as illustrated by the [6]