Dimethyl sulfoxide

Dimethyl sulfoxide is an organosulfur compound with the formula. This colorless liquid is the sulfoxide most widely used commercially. It 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 relatively high boiling point. DMSO is metabolised to compounds that leave a garlic-like taste in the mouth after DMSO is absorbed by skin.
In terms of chemical structure, the molecule has idealized C_s symmetry. It has a trigonal pyramidal molecular geometry consistent with other three-coordinate S compounds, with a nonbonded electron pair on the approximately tetrahedral sulfur atom.

Synthesis and production

Dimethyl sulfoxide was first synthesized in 1866 by the Russian scientist Alexander Zaytsev, who reported his findings in 1867. Its modern use as an industrial solvent began through popularization by Thor Smedslund at the Stepan Chemical Company. Dimethyl sulfoxide is produced industrially from dimethyl sulfide, a by-product of the kraft process, by oxidation with oxygen or nitrogen dioxide.

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

Acidity

The methyl groups of DMSO are only weakly acidic, with a. 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 SR 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. The dimsyl anion is a potent nucleophile.

Oxidant

In organic synthesis, DMSO is used as a mild oxidant. It forms the basis of several selective sulfonium-based oxidation reactions including the Pfitzner–Moffatt oxidation, Corey–Kim oxidation and the Swern oxidation. The Kornblum oxidation is conceptually similar. These methods all involve formation of an intermediate sulfonium species where X is a heteroatom attached to oxygen).

Ligand and Lewis base

Related to its ability to dissolve many salts, DMSO is a common ligand in coordination chemistry. Illustrative is the complex dichlorotetrakisruthenium. 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.
In carbon tetrachloride solutions DMSO functions as a Lewis base with a variety of Lewis acids such as iodine|, phenols, trimethyltin chloride, metalloporphyrins, and the dimer Rhodium carbonyl chloride|. The donor properties are discussed in the ECW model. The relative donor strength of DMSO toward a series of acids, versus other Lewis bases, can be illustrated by C-B plots.

Applications

Solvent

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 hexamethylphosphoramide. 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. 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 pK_a values for thousands of organic compounds have been determined in DMSO solution.
Because of its high boiling point,, 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 conventional rotary evaporation. One technique to fully recover samples is removal of the organic solvent by evaporation followed by addition of water and cryodesiccation 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,, means that at, or just below, room temperature it is a solid.
In its deuterated form, 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 can be mixed with CDCl₃ or CD₂Cl₂ for lower viscosity and melting points.
DMSO is used to dissolve test compounds in in vitro drug discovery and drug design screening programs, including high-throughput screening programs. This is because it is able to dissolve both polar and nonpolar compounds, can be used to maintain stock solutions of test compounds, is readily miscible with water and cell culture media, and has a high boiling point. One limitation with DMSO is that it can affect cell line growth and viability, with low DMSO concentrations sometimes stimulating cell growth, and high DMSO concentrations sometimes inhibiting or killing cells.
DMSO is used as a vehicle in in vivo studies of test compounds. It has, for example, been employed as a co-solvent to assist absorption of the flavonol glycoside icariin in the nematode worm Caenorhabditis elegans. As with its use in in vitro studies, DMSO has some limitations in animal models. Pleiotropic effects can occur and, if DMSO control groups are not carefully planned, then solvent effects can falsely be attributed to the prospective drug. For example, even a very low dose of DMSO has a powerful protective effect against paracetamol -induced liver injury in mice.
DMSO finds some use in manufacturing processes to produce microelectronic devices. It is widely used to strip photoresist in TFT-LCD 'flat panel' displays and advanced packaging applications.
DMSO is also an excellent swelling agent for cellulosic fibres, and occasionally is utilised as solvent in some laboratory analyses respecting wood or fibre related quality control.

Biology

DMSO is used in the polymerase chain reaction 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.
DMSO in a PCR is applicable for supercoiled plasmids or DNA templates with high GC-content. For example, 10% final concentration of DMSO in the PCR mixture with Phusion decreases primer annealing temperature by.
It is well known as a reversible cell cycle arrester at phase G1 of human lymphoid cells.
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. Approximately 10% may be used with a slow-freeze method, and the cells may be frozen at or stored in liquid nitrogen safely.
In cell culture, DMSO is used to induce differentiation of P19 embryonic carcinoma cells into cardiomyocytes and skeletal muscle cells.

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. Because DMSO increases the rate of absorption of some compounds through biological 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.
DMSO has been examined for the treatment of numerous conditions and ailments, but the U.S. Food and Drug Administration 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.
In 2009, the first to obtain FDA approval for topical DMSO usage was PENNSAID, which contains diclofenac in a carrier with 45.5% DMSO

Each 1 mL of TDiclo contains 16.05 mg diclofenac sodium. TDiclo solution also contains 45.5% dimethyl sulfoxide 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, followed by contact dermatitis

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.
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, a freezing medium, and 30% fetal bovine serum. In the cryogenic freezing of heteroploid cell lines a mixture of 10% DMSO with 90% EMEM is used. As part of an autologous bone marrow transplant the DMSO is re-infused along with the patient's own hematopoietic stem cells.
DMSO is metabolized by disproportionation 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.