A sulfoxide is an organic compound built around a sulfur atom bonded to an oxygen atom and two carbon-containing groups, giving it the general formula R₁R₂S=O. You have almost certainly encountered one without knowing it: dimethyl sulfoxide (DMSO) is among the most widely used solvents in chemistry and biology, garlic owes much of its chemistry to a sulfoxide called alliin, and the heartburn drugs omeprazole and its relatives are sulfoxides that only become active once they reach your stomach acid. The group is more versatile than its simple structure might suggest, showing up across atmospheric science, materials engineering, and the cellular machinery that repairs oxidative damage to proteins.
What the Sulfur-Oxygen Bond Actually Looks Like
Textbooks often draw the sulfur-oxygen linkage in sulfoxides as a double bond, but the reality is more nuanced. Computational analyses have shown that this bond is better described as a strongly polarized single bond in which sulfur donates electron density toward oxygen, creating a coordinate covalent link rather than a true double bond. The resulting S–O bond is still short and strong, partly because oxygen’s lone pairs feed electron density back toward sulfur, reinforcing the connection.
A separate study focused on DMSO and the related sulfone (dimethyl sulfone) reached a similar conclusion: natural bond order analyses indicate the sulfur-oxygen linkages are coordinate covalent S(+)→O(−) single bonds, not the double bonds that structural formulas traditionally depict.1PubMed. Why are dimethyl sulfoxide and dimethyl sulfone such good solvents? That built-in charge separation gives sulfoxides a large molecular dipole, which is a big part of why DMSO dissolves such a wide range of substances. The bonding picture for sulfoxides parallels what is seen in phosphoryl (P=O) compounds, where a similar pattern of polarization and backbonding creates unexpectedly strong single bonds.2PubMed. Nature of bonding in the sulfuryl group
Sulfoxides Have a Left Hand and a Right Hand
One feature that sets sulfoxides apart from many other functional groups is chirality. Because sulfur sits at the center of a pyramid with the oxygen, two different carbon groups, and a lone pair of electrons at the four corners, a sulfoxide whose two carbon groups differ from each other exists as two non-superimposable mirror images, much like left and right hands. This is not just a geometric curiosity. In drug design and asymmetric synthesis, which mirror image you use can determine whether a molecule works as intended or does nothing at all.
The handedness is stable because flipping the pyramid inside-out requires a lot of energy. Computational work on a series of simple sulfoxides found that the energy barrier for pyramidal inversion falls in the range of roughly 39 to 47 kcal/mol, values high enough that ordinary temperatures cannot scramble the two mirror-image forms.3PubMed. Pyramidal inversion mechanism of simple chiral and achiral sulfoxides: a theoretical study That stability means chemists can prepare a single-handed sulfoxide and trust it to stay that way through multiple reaction steps.
There are exceptions. Certain ring systems with the right electronic features can lower the inversion barrier substantially. A study of substituted benzodithiazole 1-oxides showed that electron-donating effects from the ring stabilized the transition state relative to the pyramidal ground state, making the barrier low enough that the two mirror-image forms interconverted on a practical timescale.4Chirality. Inversion barriers in sulfoxide functions studied by enantioselective liquid chromatography and chiroptical methods These low-barrier cases are useful for studying the inversion process itself, but they are the exception rather than the rule.
DMSO, the Sulfoxide You Probably Already Know
Dimethyl sulfoxide is the most commercially important sulfoxide by a wide margin. It is a clear, nearly odorless liquid that mixes with water in any proportion and dissolves an enormous range of organic and inorganic compounds. Labs use it as a reaction solvent, cell biologists use it as a cryoprotectant, and you may have seen it in liniments or topical creams.
Its role in cell freezing is especially interesting. The traditional explanation is that DMSO suppresses ice crystal formation, which would otherwise puncture and kill cells during freezing. A more recent investigation proposed an alternative: much of DMSO’s protective effect comes from blocking the crystallization of sodium chloride at very low temperatures. When salt in the freezing solution crystallizes into a eutectic solid, it damages cells. DMSO inhibits that eutectic NaCl crystallization, and researchers found a direct correlation between the loss of cell viability and the appearance of crystalline salt.5PubMed. Cryoprotective Mechanism of DMSO Induced by the Inhibitory Effect on Eutectic NaCl Crystallization The picture may well involve both mechanisms working together.
DMSO is also famous for crossing the skin. If you spill it on your hand, you will taste garlic or oyster-like flavors in your mouth within seconds. Molecular dynamics simulations have shown that DMSO molecules wedge themselves into the lipid layers of the skin’s outermost barrier, weakening the lateral forces between lipid molecules. At high enough concentrations, the lipid structure transitions from a tightly packed gel phase to a more fluid liquid-crystalline phase that is far more permeable to dissolved substances.6PubMed Central. The permeability enhancing mechanism of DMSO in ceramide bilayers simulated by molecular dynamics This permeability boost is why DMSO shows up in some topical drug formulations.
That said, the concentration matters. Experimental work on model skin lipid systems found that at pharmaceutically relevant concentrations of around 10% and 30%, DMSO showed no measurable disruption of lipid packing, no extra water uptake in the headgroup region, and only a very slight leakage from test vesicles. The researchers suggested that at these lower concentrations, DMSO’s skin-penetrating effect likely works through the protein-rich cells themselves rather than through the lipid matrix between them.7PubMed. The effect of hydrophilic penetration/diffusion enhancer on stratum corneum lipid models: Part II*: DMSO So the skin-fluidizing mechanism that simulations predict at high concentrations does not simply scale down to the concentrations people actually use in creams and gels.
That garlic taste you notice after skin contact happens because the body converts some DMSO into dimethyl sulfide, a volatile sulfur compound. Early work in cats confirmed this: after DMSO was administered, gas chromatography and mass spectrometry identified dimethyl sulfide in the animals’ exhaled breath as the source of the characteristic sweet odor. The same metabolic reduction occurs in humans, which is why a distinctly garlicky breath can appear within minutes of skin exposure to DMSO.
Beyond biology, DMSO has found a role in materials science. In organic solar cells, the conductive polymer PEDOT:PSS is a standard electrode material, and adding a small amount of DMSO dramatically improves its conductivity. A structural study found that films doped with about 5% DMSO developed the most extended and well-organized polymer domains, yielding electrical conductivity as high as 1,230 S/cm.8Applied Surface Science. Near 5% DMSO is the best: A structural investigation of PEDOT: PSS thin films with strong emphasis on surface and interface for hybrid solar cell The solvent essentially reorganizes the polymer chains into a more ordered arrangement before evaporating, leaving behind a better-conducting film.
How Chemists Make Sulfoxides
The most straightforward route to a sulfoxide is to take a sulfide (a compound with two carbon groups on sulfur but no oxygen) and add exactly one oxygen atom. The challenge is stopping at one. Add too much oxidant and you get a sulfone, which has two oxygens on sulfur. Getting clean, selective oxidation to the sulfoxide stage has been a persistent problem in organic chemistry, and several practical solutions have emerged.
One approach uses o-iodoxybenzoic acid (IBX) with a tetraethylammonium bromide catalyst. The method is mild, fast, tolerant of many other functional groups on the molecule, and produces no over-oxidation to the sulfone.9PubMed. A mild, chemoselective oxidation of sulfides to sulfoxides using o-iodoxybenzoic acid and tetraethylammonium bromide as catalyst Another strategy relies on plain hydrogen peroxide, one of the cheapest and greenest oxidants available. A titanium-containing zeolite catalyst allows this reaction to run at room temperature with good selectivity for the sulfoxide, especially when the zeolite has an expanded interlayer structure.10Tetrahedron. Selective hydrogen peroxide oxidation of sulfides to sulfoxides or sulfones with MWW-type titanosilicate zeolite catalyst under organic solvent-free conditions And for labs that want something even simpler, hydrogen peroxide in glacial acetic acid with no metal catalyst at all can deliver sulfoxides in yields of 90–99%.11PubMed Central. Effective oxidation of sulfides to sulfoxides with hydrogen peroxide under transition-metal-free conditions
The growing emphasis on green chemistry has pushed the field toward metal-free, solvent-free, and aqueous-compatible methods. Hydrogen peroxide is attractive because its only byproduct is water, and removing heavy metals from the reaction avoids contamination of the product, something especially important in pharmaceutical manufacturing.
Reactions That Sulfoxides Undergo
Sulfoxides are not inert once formed. Two of their most important transformations are the Pummerer reaction and sulfoxide elimination, both of which exploit the S–O bond in different ways.
In the Pummerer reaction, a sulfoxide is treated with an activating agent such as acetic anhydride, which first acetylates the oxygen and then triggers loss of an acetate group, ultimately generating a carbon-sulfur bond at a new oxidation state. Computational studies of this mechanism found that the initial acetylation step is rate-determining, and that additives used in stereoselective versions of the reaction work by stabilizing the transition state of that first step.12PubMed. Mechanism of the Pummerer reaction: a computational study The Pummerer reaction has been adapted beyond traditional synthesis: researchers have repurposed it to detect oxidized methionine residues in proteins. By treating methionine sulfoxide with trimethylsilyl chloride and a thiol reagent, they generated a stable dithioacetal product that could be identified by mass spectrometry, providing a way to map which methionine residues in a peptide have been damaged by oxidation.13PubMed Central. Repurposing the Pummerer Rearrangement: Determination of Methionine Sulfoxides in Peptides
Sulfoxide elimination is a thermal process in which a sulfoxide with a hydrogen on the carbon next to sulfur breaks apart to release a sulfenic acid and an alkene (or, in some cases, an aldehyde or alkyne). Gas-phase measurements put the activation enthalpies for representative sulfoxide eliminations in the range of roughly 33 to 42 kcal/mol, consistent with the reaction requiring significant heating to proceed at useful rates.14ACS Publications (The Journal of Organic Chemistry). Thermolysis of alkyl sulfoxides and derivatives: a comparison of experiment and theory Sulfoxide elimination is a classic way to introduce a carbon-carbon double bond into a molecule under relatively mild conditions compared to other elimination methods.
Sulfoxides You Eat and Sulfoxides That Treat You
Garlic is one of the richest dietary sources of sulfoxides. Its signature compound, alliin (S-allyl-L-cysteine sulfoxide), sits quietly in intact garlic cloves. When you crush or chop garlic, an enzyme called alliinase converts alliin into allicin, the pungent, reactive thiosulfinate responsible for the smell. Chemical profiling of garlic extracts using chromatography and mass spectrometry has confirmed alliin’s presence alongside a roster of related sulfur amino acid derivatives.15PubMed Central. Chemical analysis of Alliin-Rich Allium sativum (Garlic) extract and its safety evaluation in Drosophila melanogaster Onions contain their own sulfoxide variants, which is why cutting onions triggers a different set of volatile sulfur products than crushing garlic. The sulfoxide functional group in these food compounds acts as a chemical trigger, waiting for enzymatic activation.
In medicine, some of the most widely prescribed drugs in the world are sulfoxides. Omeprazole, lansoprazole, and their relatives are proton pump inhibitors (PPIs), used to treat acid reflux and ulcers. They are prodrugs, meaning the sulfoxide form you swallow is inactive. Once it reaches the acidic environment of the stomach’s parietal cells, the sulfoxide is rearranged into a reactive sulfenic acid intermediate, which then forms a covalent disulfide bond with a cysteine residue on the proton pump, shutting it down.16PubMed Central. Pharmacokinetics and pharmacodynamics of the proton pump inhibitors 17PubMed. Hydrogen sulfide reduces omeprazole and is oxidized to polysulfides and elemental sulfur The acid-triggered activation is elegant: the drug is stable everywhere except the one place it needs to work.
The chirality of sulfoxides matters here too. Omeprazole is a mixture of its two mirror-image forms, but esomeprazole is the purified single-handed version. Because the body metabolizes the two forms at different rates, the single form can achieve higher blood levels and longer acid suppression. Chiral sulfoxides as drug building blocks and as auxiliaries for controlling handedness in other reactions remain an active area in medicinal and process chemistry.18PubMed Central. Modern Stereoselective Synthesis of Chiral Sulfinyl Compounds
Methionine Sulfoxide and Protein Repair
Sulfoxide chemistry plays out constantly inside your cells in a context that has nothing to do with solvents or medicines. The amino acid methionine, one of the building blocks of proteins, is particularly vulnerable to oxidation by reactive oxygen species. When its sulfur atom picks up an oxygen, it becomes methionine sulfoxide, a modification that can alter how the protein folds and functions. This is not a rare event; it happens routinely as a consequence of normal aerobic metabolism and ramps up under stress.
Cells fight back with a dedicated repair system: the methionine sulfoxide reductases (MsrA and MsrB). These enzymes strip the oxygen back off, restoring functional methionine. The system has been linked to protection against oxidative stress, regulation of protein activity, and has attracted interest in aging research.19PubMed Central. The Oxidized Protein Repair Enzymes Methionine Sulfoxide Reductases and Their Roles in Protecting against Oxidative Stress, in Ageing and in Regulating Protein Function
Mice engineered to lack MsrA showed heightened sensitivity to chemical oxidative stress, confirming the enzyme’s protective role. Interestingly, though, those same mice did not have shortened lifespans under normal laboratory conditions, suggesting that MsrA’s importance may be more about handling acute oxidative insults than about setting the overall pace of aging.20PubMed Central. Lack of methionine sulfoxide reductase A in mice increases sensitivity to oxidative stress but does not diminish life span The reversible nature of the methionine-to-methionine-sulfoxide conversion has also led to the idea that some proteins use it as a deliberate signaling switch, toggling function on and off through controlled oxidation and enzymatic reduction.
Sulfoxides in the Atmosphere
Dimethyl sulfide (DMS), produced mainly by marine phytoplankton, is one of the largest natural sources of sulfur entering the atmosphere. Once airborne, DMS is oxidized through several pathways, and DMSO is a major intermediate in the process. Global modeling indicates that the reaction of DMS with the halogen radical BrO accounts for about 44% of atmospheric DMSO production, followed by the OH radical addition channel at about 41%, with smaller contributions from chlorine atoms and aqueous-phase ozone.21Atmospheric Chemistry and Physics. DMS oxidation and sulfur aerosol formation in the marine troposphere: a focus on reactive halogen and multiphase chemistry
This matters for climate because the further oxidation of DMSO leads to sulfur-containing aerosol particles that can seed cloud droplets. Chamber experiments studying DMSO’s reaction with OH radicals found rapid aerosol formation, with roughly 14–47% of the reacted sulfur ending up in the particle phase under varying conditions, without requiring the intermediate formation of sulfur dioxide.22PubMed Central. Chamber studies of OH + dimethyl sulfoxide and dimethyl disulfide: insights into the dimethyl sulfide oxidation mechanism The route from ocean biology to cloud formation, with sulfoxides as a waypoint, is one of the pathways through which living organisms influence regional weather and climate on a large scale.
Cleaning Up Fuel With Sulfoxide Chemistry
Petroleum fuels contain organosulfur compounds, mostly thiophenes, that produce sulfur dioxide when burned. Regulations worldwide have pushed sulfur limits in diesel and gasoline steadily lower, and oxidative desulfurization is one of the newer approaches to meeting those targets. The idea is simple: oxidize the stubborn thiophenic sulfur compounds into sulfoxides and then sulfones, which are far more polar and can be pulled out of the fuel by extraction or adsorption onto a solid. Ultrasound-assisted oxidative desulfurization selectively converts these sulfur species to sulfoxides and sulfones for removal, and has been demonstrated at industrial scale.23Ultrasonics Sonochemistry. Ultrasound-assisted oxidative desulfurization of liquid fuels and its industrial application The approach complements conventional hydrodesulfurization, which uses high-pressure hydrogen and expensive catalysts. Oxidative methods work under milder conditions and are especially effective against the compounds that resist traditional treatment.
Sulfoxides also coordinate with metal ions, and this ability has practical consequences in catalysis and materials chemistry. The sulfoxide group can bind to a metal through its oxygen or through its sulfur, depending on the metal’s electronic preferences. Softer, more electron-rich metal centers tend to bind through sulfur, while harder metals prefer the oxygen end. This switchable coordination, combined with the inherent chirality of unsymmetrical sulfoxides, makes metal-sulfoxide complexes useful as catalysts for reactions that need to produce a specific mirror-image product.