 | |||
| |||
 A sample of dimethyl sulfoxide | |||
| Names | |||
|---|---|---|---|
| Preferred IUPAC name (Methanesulfinyl)methane | |||
| Systematic IUPAC name (Methanesulfinyl)methane(substitutive) Dimethyl(oxido)sulfur(additive) | |||
| Other names Methylsulfinylmethane Methyl sulfoxide (2:1), Dermasorb[1] | |||
| Identifiers | |||
| |||
3D model (JSmol) | |||
| Abbreviations | DMSO, Me2SO | ||
| 506008 | |||
| ChEBI | |||
| ChEMBL | |||
| ChemSpider |
| ||
| DrugBank |
| ||
| ECHA InfoCard | 100.000.604 | ||
| EC Number |
| ||
| 1556 | |||
| KEGG |
| ||
| MeSH | Dimethyl+sulfoxide | ||
| RTECS number |
| ||
| UNII | |||
| |||
| |||
| Properties | |||
| (CH3)2SO | |||
| 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 inDiethyl ether | Not soluble | ||
| Vapor pressure | 0.556 millibars or 0.0556 kPa at 20 °C[2] | ||
| Acidity (pKa) | 35[3] | ||
Refractive index (nD) | 1.479 εr = 48 | ||
| Viscosity | 1.996 cP at 20 °C | ||
| Structure | |||
| Cs | |||
| Trigonal pyramidal | |||
| 3.96 D | |||
| Pharmacology | |||
| G04BX13 (WHO) M02AX03 (WHO) | |||
| Hazards | |||
| Occupational safety and health (OHS/OSH): | |||
Main hazards | Irritant | ||
| NFPA 704 (fire diamond) | |||
| Flash point | 89 °C (192 °F; 362 K) | ||
| Safety data sheet (SDS) | Sigma-Aldrich SDS | ||
| Related compounds | |||
Relatedsulfoxides | Diethyl sulfoxide | ||
Related compounds | |||
| Supplementary data page | |||
| Dimethyl sulfoxide (data page) | |||
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |||
Dimethyl sulfoxide (DMSO) is anorganosulfur compound with theformula(CH3)2S=O. This colorless liquid is thesulfoxide most widely used commercially. It is an importantpolaraprotic solvent that dissolves bothpolar and nonpolar compounds and ismiscible in a wide range of organic solvents as well as water. It has a relatively high boiling point. DMSO is metabolised to compounds that leave agarlic-like taste in the mouth after DMSO is absorbed by skin.[5]
In terms of chemical structure, the molecule has idealizedCssymmetry. It has atrigonal pyramidal molecular geometry consistent with other three-coordinate S(IV) compounds,[6] with anonbonded electron pair on the approximatelytetrahedral sulfur atom.
Dimethyl sulfoxide was first synthesized in 1866 by the Russian scientistAlexander Zaytsev, who reported his findings in 1867.[7] Its modern use as an industrial solvent began through popularization by Thor Smedslund at the Stepan Chemical Company.[8] Dimethyl sulfoxide is produced industrially fromdimethyl sulfide, a by-product of thekraft process, by oxidation with oxygen ornitrogen dioxide.[9]
The sulfur center in DMSO isnucleophilic toward softelectrophiles and the oxygen is nucleophilic toward hard electrophiles. Withmethyl iodide it formstrimethylsulfoxonium iodide,[(CH3)3SO]+I−:
This salt can bedeprotonated withsodium hydride to form thesulfurylide:
The methyl groups of DMSO are only weakly acidic, with apKa = 35. For this reason, the basicities of many weakly basic organic compounds have been examined in this solvent.[10]
Deprotonation of DMSO requires strong bases likelithium diisopropylamide andsodium hydride. Stabilization of the resultantcarbanion is provided by the S(O)R group. The sodium derivative of DMSO formed in this way is referred to asdimsyl sodium. It is a base, e.g., for the deprotonation ofketones to form sodiumenolates,phosphonium salts to formWittig reagents, andformamidinium salts to formdiaminocarbenes. The dimsyl anion is a potent nucleophile.[11]
Inorganic synthesis, DMSO is used as a mild oxidant.[12] It forms the basis of several selectivesulfonium-based oxidation reactions including thePfitzner–Moffatt oxidation,Corey–Kim oxidation and theSwern oxidation.[13] TheKornblum oxidation is conceptually similar. These methods all involve formation of an intermediatesulfonium species (R2S+OX) where X is a heteroatom attached to oxygen).[14]
Related to its ability to dissolve many salts, DMSO is a commonligand incoordination chemistry. Illustrative is the complexdichlorotetrakis(dimethyl sulfoxide)ruthenium(II) (RuCl2(dmso)4). In this complex, three DMSO ligands are bonded toruthenium through sulfur. The fourth DMSO is bonded through oxygen. In general, the oxygen-bonded mode is more common.[15]
In carbon tetrachloride solutions DMSO functions as a Lewis base with a variety of Lewis acids such asI2,phenols,trimethyltin chloride, metalloporphyrins, and the dimerRh2Cl2(CO)4. The donor properties are discussed in theECW model. The relative donor strength of DMSO toward a series of acids, versus other Lewis bases, can be illustrated byC-B plots.[16][17]
DMSO is apolar aprotic solvent and is less toxic than other members of this class, such asdimethylformamide,dimethylacetamide,N-methyl-2-pyrrolidone, andhexamethylphosphoramide (HMPA). DMSO is frequently used as asolvent for chemical reactions involving salts, most notablyFinkelstein reactions and othernucleophilic substitutions. It is also extensively used as an extractant in biochemistry and cell biology. Because DMSO is only weakly acidic, it tolerates relatively strong bases and as such has been extensively used in the study ofcarbanions. A set of non-aqueouspKa values (C-H, O-H, S-H and N-H acidities) for thousands of organic compounds have been determined in DMSO solution.[18][10]
Because of its high boiling point, 189 °C (372 °F), DMSO evaporates slowly at normal atmospheric pressure. Samples dissolved in DMSO cannot as easily be recovered compared to other solvents, as it is very difficult to remove all traces of DMSO by conventionalrotary evaporation. One technique to fully recover samples is removal of the organic solvent by evaporation followed by addition of water (to dissolve DMSO) andcryodesiccation 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.
In itsdeuterated form (DMSO-d6), it is a useful solvent forNMR 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 itshygroscopicity, which leads to an overwhelming H2O resonance in the1H-NMR spectrum. It can be mixed withCDCl3 orCD2Cl2 for lower viscosity and melting points.
DMSO is used to dissolve test compounds inin vitrodrug discovery[19][20] anddrug design[21]screening programs, includinghigh-throughput screening programs.[20][21] This is because it is able to dissolve bothpolar andnonpolar compounds,[19][21] can be used to maintainstock solutions of test compounds (important when working with a largechemical library),[20] is readilymiscible with water andcell culture media, and has a high boiling point (this improves the accuracy of test compound concentrations by reducing room temperature evaporation).[19] One limitation with DMSO is that it can affectcell line growth and viability, with low DMSO concentrations sometimes stimulating cell growth, and high DMSO concentrations sometimes inhibiting or killing cells.[19]
DMSO is used as a vehicle inin vivo studies of test compounds. It has, for example, been employed as a co-solvent to assist absorption of theflavonol glycosideicariin in thenematode wormCaenorhabditis elegans.[22] As with its use inin vitro studies, DMSO has some limitations inanimal models.[23][24]Pleiotropic effects can occur and, if DMSO control groups are not carefully planned, then solvent effects can falsely be attributed to the prospective drug.[23] For example, even a very low dose of DMSO has a powerful protective effect againstparacetamol (acetaminophen)-induced liver injury in mice.[24]
DMSO finds some use in manufacturing processes to produce microelectronic devices.[25] 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).
DMSO is also an excellent swelling agent for cellulosic fibres,[26] and occasionally is utilised as solvent in some laboratory analyses respecting wood or fibre related quality control.
DMSO is used in thepolymerase chain reaction (PCR) to inhibitsecondary structures in theDNA template or theDNA primers. It is added to the PCR mix before reacting, where it interferes with the self-complementarity of the DNA, minimizing interfering reactions.[27]
DMSO in a PCR is applicable for supercoiled plasmids (to relax before amplification) or DNA templates with highGC-content (to decreasethermostability). 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).[28]
It is well known as a reversible cell cycle arrester at phase G1 of human lymphoid cells.[29]
DMSO may also be used as acryoprotectant, added to cell media to reduce ice formation and thereby prevent cell death during the freezing process.[30] Approximately 10% may be used with a slow-freeze method, and the cells may be frozen at −80 °C (−112 °F) or stored inliquid nitrogen safely.[citation needed]
In cell culture, DMSO is used to inducedifferentiation ofP19 embryonic carcinoma cells intocardiomyocytes andskeletal muscle cells.[citation needed]
Use of DMSO in medicine dates from around 1963, when anOregon Health & Science University Medical School team, headed byStanley 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 topicalanalgesic, a vehicle for topical application of pharmaceuticals, as ananti-inflammatory, and anantioxidant.[31] Because DMSO increases the rate of absorption of some compounds throughbiological tissues, includingskin, it is used in sometransdermaldrug delivery systems. Its effect may be enhanced with the addition ofEDTA. It is frequently compounded with antifungal medications, enabling them to penetrate not just skin but also toenails and fingernails.[32]
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 withinterstitial cystitis.[33] A 1978 study concluded that DMSO broughtsignificant relief to the majority of the 213 patients with inflammatorygenitourinary disorders that were studied.[34]
In 2009, the first to obtain FDA approval for topical DMSO usage was PENNSAID, which contains diclofenac in a carrier with 45.5% DMSO[35]
Each 1 mL of TDiclo contains 16.05 mg diclofenac sodium. TDiclo solution also contains 45.5% dimethyl sulfoxide (DMSO) vehicle, which can result in enhanced penetration of active drug through the skin.The most common adverse event reported was dry skin at the application site (25.3% of patients), followed by contact dermatitis (13.0%)[36]
Ininterventional radiology, DMSO is used as a solvent forethylene vinyl alcohol in theOnyx liquid embolic agent, which is used inembolization, the therapeutic occlusion of blood vessels.[citation needed]
Incryobiology DMSO has been used as acryoprotectant and is still an important constituent of cryoprotectantvitrification 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 ofembryonic stem cells andhematopoietic 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 anautologousbone marrow transplant the DMSO is re-infused along with the patient's ownhematopoietic stem cells.[citation needed]
DMSO is metabolized bydisproportionation todimethyl sulfide anddimethyl 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 bornehalitosis symptom.[citation needed]
DMSO's popularity as analternative medicine is stated to stem from a March 198060 Minutes documentary "The Riddle of DMSO"[37] and April 1980Time magazine article[38] covering the treatments of ardent DMSO advocate Dr. Stanley Jacob beginning in the 1960s.[39]
The use of DMSO as an alternative treatment for cancer is of particular concern, as it has been shown to interfere with a variety ofchemotherapy drugs, includingcisplatin,carboplatin, andoxaliplatin.[40] There is insufficient evidence to support the hypothesis that DMSO has any effect,[41] 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 theusual disclaimer. DMSO is an ingredient in some products listed by the U.S. FDA as fake cancer cures[42] and the FDA has had a running battle with distributors.[37] One such distributor is Mildred Miller, who promoted DMSO for a variety of disorders and was consequently convicted ofMedicare fraud.[37]
DMSO is commonly used in veterinary medicine as aliniment forhorses, 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.[43]
The perceived garlic taste upon skin contact with DMSO may be due tononolfactory activation ofTRPA1 receptors intrigeminal ganglia.[44] Unlikedimethyl anddiallyl disulfides (which have odors resembling garlic),mono- andtri- sulfides (which typically have foul odors), and similar odiferous sulfur compounds, the pure chemical DMSO is odorless.
DMSO is a non-toxic solvent with amedian lethal dose higher than ethanol (DMSO: LD50, oral, rat, 14,500 mg/kg;[45][46] ethanol: LD50, oral, rat, 7,060 mg/kg[47]).
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.[48]
Because DMSO easily penetrates theskin, substances dissolved in DMSO may quickly be absorbed.Glove selection is important when working with DMSO.Butyl rubber,fluoroelastomer,neoprene, or thick (15 mil / 0.4 mm)latex gloves are recommended.[49]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.[50]
Considering its wide use, especially for cryopreservation andin vitro assays, we evaluated biological effect of DMSO using these technological innovations. We exposed 3D cardiac and hepatic microtissues to medium with or without 0.1% DMSO and analyzed the transcriptome, proteome and DNA methylation profiles. In both tissue types, transcriptome analysis detected >2000 differentially expressed genes affecting similar biological processes, thereby indicating consistent cross-organ actions of DMSO.[35]
There aretranscriptional,translational andepigenetic changes caused by low concentration DMSO, despite the lack of acute toxicity.
This is more of a concern for molecular biology experiments, because human bodyreact transcriptionally to exogenic substances which can be totally normal and benign. For comparison, ethanol produces transcriptional changes that cause metabolic disorder.
In Australia, it is listed as aSchedule 4 (S4) Drug, and a company has been prosecuted for adding it to products as a preservative.[51]
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.[full citation needed]
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.[52]Clinical research using DMSO was halted and did not begin again until theNational Academy of Sciences (NAS) published findings in favor of DMSO in 1972.[53] In 1978, the US FDA approved DMSO for treatinginterstitial 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 followingtraumatic brain injury.[53]
DMSO exposure to developing mouse brains can produce brain degeneration. Thisneurotoxicity could be detected atdoses as low as 0.3 mL/kg, a level exceeded in children exposed to DMSO duringbone marrow transplant.[54]
DMSO disposed intosewers can cause odor problems in municipal effluents: waste waterbacteria transform DMSO underhypoxic (anoxic) conditions intodimethyl sulfide (DMS) that has a strong disagreeable odor, similar to rotten cabbage.[55] However, chemically pure DMSO is odorless because of the lack of C-S-C (sulfide) and C-S-H (mercaptan) linkages. Deodorization of DMSO is achieved by removing the odorous impurities it contains.[56]
Dimethyl sulfoxide can produce an explosive reaction when exposed toacyl chlorides; at a low temperature, this reaction produces theoxidant forSwern oxidation.[citation needed]
DMSO can decompose at the boiling temperature of 189 °C at normal pressure, possibly leading to an explosion. The decomposition is catalyzed by acids and bases and therefore can be relevant at even lower temperatures. A strong to explosive reaction also takes place in combination with halogen compounds, metal nitrides, metal perchlorates, sodium hydride, periodic acid and fluorinating agents.[57]
| International | |
|---|---|
| National | |
| Other | |
