Sulfur Analogues Research Articles

Biosignature Detection at an Arctic Analog to Europa

The compelling evidence for an ocean beneath the ice shell of Europa makes it a high priority for astrobiological investigations. Future missions to the icy surface of this moon will query the plausibly sulfur-rich materials for potential indications of the presence of life carried to the surface by mobile ice or partial melt. However, the potential for generation and preservation of biosignatures under cold, sulfur-rich conditions has not previously been investigated, as there have not been suitable environments on Earth to study. Here, we describe the characterization of a range of biosignatures within potentially analogous sulfur deposits from the surface of an Arctic glacier at Borup Fiord Pass to evaluate whether evidence for microbial activities is produced and preserved within these deposits. Optical and electron microscopy revealed microorganisms and extracellular materials. Elemental sulfur (S⁰), the dominant mineralogy within field samples, is present as rhombic and needle-shaped mineral grains and spherical mineral aggregates, commonly observed in association with extracellular polymeric substances. Orthorhombic α-sulfur represents the stable form of S⁰, whereas the monoclinic (needle-shaped) γ-sulfur form rosickyite is metastable and has previously been associated with sulfide-oxidizing microbial communities. Scanning transmission electron microscopy showed mineral deposition on cellular and extracellular materials in the form of submicron-sized, needle-shaped crystals. X-ray diffraction measurements supply supporting evidence for the presence of a minor component of rosickyite. Infrared spectroscopy revealed parts-per-million level organics in the Borup sulfur deposits and organic functional groups diagnostic of biomolecules such as proteins and fatty acids. Organic components are below the detection limit for Raman spectra, which were dominated by sulfur peaks. These combined investigations indicate that sulfur mineral deposits may contain identifiable biosignatures that can be stabilized and preserved under low-temperature conditions. Borup Fiord Pass represents a useful testing ground for instruments and techniques relevant to future astrobiological exploration at Europa.

Bifunctionalized linked bis-spiro[furo[2,3-d]pyrimidine-6,5'- pyrimidine]2,2',4,4',6'(3H,3'H,5H)-pentaones derived from one-pot reaction of (thio)barbituric acids with aromatic dialdehydes and BrCN in the presence of Et_3N

Reaction of pyrimidine-(1H,3H,5H)-2,4,6-trione (barbituric acid), 1,3-dimethyl pyrimidine-(1H,3H,5H)-2,4,6-trione (1,3-dimethyl barbituric acid), and 1,3-diethyl-2-thioxodihydropyrimidine-4,6(1H,5H)- dione (1,3-diethyl thiobarbituric acid) with cyanogen bromide and aromatic dialdehydes in the presence of triethylamine leads to the selective and efficient formation of a novel class of bifunctionalized stable heterocyclic bis-spiro[furo[2,3-d]pyrimidine-6,5'-pyrimidine] 2,2',4,4',6'(3H,3'H,5H)pentaones and their sulfur analogues, which are dimeric forms of barbiturate linked by a phenyl ring. A proposed mechanism was suggested for the formation of the products. The reaction of phthalaldehyde with BrCN and (thio)barbituric acids resulted in only monofunctionalized spiro[furo[2,3-d]pyrimidine-6,5'- pyrimidine]2,2',4,4',6'(3H,3'H,5H)pentaones, while isophthalaldehyde and terphthalaldehyde resulted in the bifunctionalized form.

Computational Design of Thiourea-based Cyclophane Sensors for Small Anions

The host–guest binding properties of a tri-thiourea cyclophane receptor (1) with several common anions have been investigated using density functional theory (DFT) and molecular dynamics calculations. Receptor 1 is predicted to be an effective receptor for binding small halogen and Y-shaped (NO3– and AcO–) anions in the gas phase, cyclohexane and chloroform. The calculated order of anion binding affinity for the receptor 1 in chloroform is F– > Cl– > AcO– > NO3– >Br– > H2PO4– > HSO4–. The binding free energies are strongly influenced by a dielectric solvent medium. The structures of the receptor–anion complexes are characterized by multiple (typically 6) hydrogen bonds in all cases. The overall binding affinity of various anions is determined by the basicity of anion, size and shape of the binding site, and solvent medium. Explicit chloroform solvent molecular dynamics simulations of selected receptor–anion complexes reveal that the anions are strongly bound within the binding pocket via hydrogen-bonding interactions to all the receptor protons throughout the simulation. A sulfur analogue of receptor 1 (2), with a larger central cavity, is shown to be a more effective sensor than 1 for small anions. Two different approaches to develop the thiourea-based cyclophane receptor into a chromogenic sensor were examined.

Selenoglucosinolates and their metabolites produced in Brassica spp. fertilised with sodium selenate

Glucosinolates are sulphur-containing glycosides found in many Brassica spp. that are important because their aglycone hydrolysis products protect the plant from herbivores and exhibit anti-cancer properties in humans. Recently, synthetically produced selenium analogues have been shown to be more effective at suppressing cancers than their sulphur counterparts. Although selenium is incorporated into a number of Brassica amino acids and peptides, firm evidence has yet to be presented for the presence of selenium in the glucosinolates and their aglycones in planta. In this study broccoli and cauliflower florets, and roots of forage rape, all obtained from plants treated with sodium selenate, were analysed for the presence of organoselenides. GC–MS analysis of pentane/ether extracts identified six organoselenium compounds including selenium analogues of known myrosinase-derived Brassica volatiles: 4-(methylseleno)butanenitrile, 5-(methylseleno)pentanenitrile, 3-(methylseleno)propylisothiocyanate, 4-(methylseleno)butylisothiocyanate, and 5-(methylseleno)pentylisothiocyanate. LC–MS analysis of ethanolic extracts identified three selenoglucosinolates: 3-(methylseleno)propylglucosinolate (glucoselenoiberverin), 4-(methylseleno)butylglucosinolate (glucoselenoerucin), and 5-(methylseleno)pentylglucosinolate (glucoselenoberteroin). LC–MS/MS analysis was used to locate the position of the selenium atom in the selenoglucosinolate and indicates preferential incorporation of selenium via selenomethionine into the methylselenyl moiety rather than into the sulphate or β-thioglucose groups. In forage rape, selenoglucosinolates and their aglycones (mainly isothiocyanates), occurred at concentrations up to 10% and 70%, respectively, of their sulphur analogues. In broccoli, concentrations of the selenoglucosinolates and their aglycones (mainly nitriles) were up to 60% and 1300%, respectively of their sulphur analogues. These findings indicate the potential for the incorporation of high levels of selenium into Brassica glucosinolates.

Synthesis of Branched Dithiotrisaccharides via Ring-Opening Reaction of Sugar Thiiranes

Satisfactory procedures are described for the synthesis of 5,6- and 3,4-thiirane derivatives from the respective hexofuranose or hexopyranose epoxide precursors. The controlled ring-opening reaction of thiiranes by 1-thioaldoses was successfully accomplished to afford, regio- and stereoselectively, β-S-(1→4)-3,4-dithiodisaccharides. For instance, the regioselective attack of per-O-acetyl-1-thioglucose (16) to C-4 of 2-propyl 2,6-di-O-acetyl-3,4-epithio-α-D-galactopyranoside (14) gave the derivative of Glcp-β-S-(1→4)-3,4-dithioGlcp-O-iPr (17). This thiodisaccharide was accompanied by the (1→3)-disulfide 18, formed between 16 and 17, and the symmetric (3→3)-disulfide 19, which resulted from the oxidative dimerization of 17. However, the S-acetyl derivative of 17 could be obtained in good yield (62%) by LiAlH(4) reduction of the crude mixture 17-19, followed by acetylation. The same sequence of reactions starting from 14 and the 1-thiolate of Galp afforded the per-O,S-acetyl derivative of Galp-β-S-(1→4)-3,4-dithio-α-D-Glcp-O-iPr (23), which was selectively S-deacetylated to give 25. The dithiosaccharides 17 and 25 are 3,4-di-S-analogues of derivatives of the natural disaccharides cellobiose and lactose, respectively. The ring-opening reaction of 5,6-epithiohexofuranoses of D-galacto (8) or L-altro (11) configuration with 1-thioaldoses was also regio- and stereoselective to give the respective β-S-(1→6)-linked 5,6-dithiodisaccharides 26 or 29 in excellent yields. Glycosylation of the free thiol group of 17, 25, or 26, using trichloroacetimidates as glycosyl donors, led to the corresponding branched dithiotrisaccharides. Some of them are sulfur analogues of derivatives of branched trisaccharides found in natural polysaccharides.

Pyrazolium-sulfonates. Mesomeric betaines possessing iminium-sulfonate partial structures

Pyrazolium-3-sulfonates and pyrazolium-4-sulfonates possessing the iminiomethanesulfonate and the 3-iminio-pro-1-ene-2-sulfonate partial structure are prepared. Formally, they represent sulfur analogs of cross-conjugated (CCMB) and pseudo-cross-conjugated heterocyclic mesomeric betaines (PCCMB) and sulfur trioxide adducts of abnormal N-heterocyclic carbenes (aNHC) and N-heterocyclic carbenes (NHC), respectively. The theoretical as well as experimental vibrational spectra of these two classes are compared. Results of calculations of HOMO/LUMO profiles and an X-ray single crystal structure analysis are presented.

Synthesis of optically active homotryptophan and its oxygen and sulfur analogues

d-Homotryptophan and its sulfur analogue have been synthesized by Sonogashira coupling between 3-iodoheteroarenes and ethynyloxazolidine followed by reduction of triple bond and oxidation of alcohol to acid. l-Homotryptophan and its oxygen analogue have been synthesized from silylated internal alkyne using Larock’s heteroannulation as the key reaction. The alkynyloxazolidines were synthesized from l-serine and l-glutamic acid, respectively.

OH···X (X = O, S) hydrogen bonding in thetrahydrofuran and tetrahydrothiophene

In this article, hydrogen bonding interaction between p-cresol (p-CR) and cyclic ether, tetrahydrofuran (THF) and thioether, tetrahydrothiophene (THT) has been investigated. Two-color resonantly enhanced two-photon ionization in conjunction with the fluorescence detected IR (FDIR) spectroscopy was used to record the changes in the OH stretching frequency in these complexes. The FDIR spectra showed existence of a single conformer of the p-CR·THF and two conformers of the p-CR·THT complex. With the help of computed IR spectra and atoms-in-molecules analysis, the two conformers of p-CR·THT were assigned as the complex of p-CR with THT (C(2))/THT (C(S)). The redshift of OH stretching frequency for the p-CR·THF complex was greater compared to those for the conformers of the p-CR·THT complex. The binding energies of the p-CR·THF and p-CR·THT complexes were computed to be 7.42 and 6.15 kcal/mole. These were of the same order as those for the acyclic analogs, diethylether (DEE), and diethylsulfide (DES), of the solvent molecules under investigation. Although the DEE and THF consist of same number of carbon atoms, the dispersion energy contribution was much higher (43%) for DEE than that for THF (30%). In the case of sulfur analogs, however, it was similar (~50%) in the case of both DES well as THT complexes. All the computed H-bond indicators for these two complexes nicely correlate with the observed redshift of the O-H stretch.

Catalytic activity of selenomethionine in removing amino acid, peptide, and protein hydroperoxides

Selenium is a critical trace element, with deficiency associated with numerous diseases including cardiovascular disease, diabetes, and cancer. Selenomethionine (SeMet; a selenium analogue of the amino acid methionine, Met) is a major form of organic selenium and an important dietary source of selenium for selenoprotein synthesis in vivo. As selenium compounds can be readily oxidized and reduced, and selenocysteine residues play a critical role in the catalytic activity of the key protective enzymes glutathione peroxidase and thioredoxin reductase, we investigated the ability of SeMet (and its sulfur analogue, Met) to scavenge hydroperoxides present on amino acids, peptides, and proteins, which are key intermediates in protein oxidation. We show that SeMet, but not Met, can remove these species both stoichiometrically and catalytically in the presence of glutathione (GSH) or a thioredoxin reductase (TrxR)/thioredoxin (Trx)/NADPH system. Reaction of the hydroperoxide with SeMet results in selenoxide formation as detected by HPLC. Recycling of the selenoxide back to SeMet occurs rapidly with GSH, TrxR/NADPH, or a complete TrxR/Trx/NADPH reducing system, with this resulting in an enhanced rate of peroxide removal. In the complete TrxR/Trx/NADPH system loss of peroxide is essentially stoichiometric with NADPH consumption, indicative of a highly efficient system. Similar reactions do not occur with Met under these conditions. Studies using murine macrophage-like J774A.1 cells demonstrate a greater peroxide-removing capacity in cells supplemented with SeMet, compared to nonsupplemented controls. Overall, these findings demonstrate that SeMet may play an important role in the catalytic removal of damaging peptide and protein oxidation products.

Mechanisms of sulfur mustard analog 2-chloroethyl ethyl sulfide-induced DNA damage in skin epidermal cells and fibroblasts

Employing mouse skin epidermal JB6 cells and dermal fibroblasts, here we examined the mechanisms of DNA damage by 2-chloroethyl ethyl sulfide (CEES), a monofunctional analog of sulfur mustard (SM). CEES exposure caused H2A.X and p53 phosphorylation as well as p53 accumulation in both cell types, starting at 1h, that was sustained for 24h, indicating a DNA-damaging effect of CEES, which was also confirmed and quantified by alkaline comet assay. CEES exposure also induced oxidative stress and oxidative DNA damage in both cell types, measured by an increase in mitochondrial and cellular reactive oxygen species and 8-hydroxydeoxyguanosine levels, respectively. In the studies distinguishing between oxidative and direct DNA damage, 1h pretreatment with glutathione (GSH) or the antioxidant Trolox showed a decrease in CEES-induced oxidative stress and oxidative DNA damage. However, only GSH pretreatment decreased CEES-induced total DNA damage measured by comet assay, H2A.X and p53 phosphorylation, and total p53 levels. This was possibly due to the formation of GSH–CEES conjugates detected by LC-MS analysis. Together, our results show that CEES causes both direct and oxidative DNA damage, suggesting that to rescue SM-caused skin injuries, pleiotropic agents (or cocktails) are needed that could target multiple pathways of mustard skin toxicities.

Experimental and Theoretical Evidence of Aromatic Behavior in Heterobenzene-Like Molecules with Metal-Metal Multiple Bonds

Binding two quadruply bonded dimolybdenum units [Mo(2)(DAniF)(3)](+) (DAniF=N,N'-di-p-anisylformamidinate) with two chalcogen atoms generated two molecules with a central core composed of a cyclic six-membered [Mo(2)](2)(μ-EH)(2) species (E=S in 1 and O in 3, and [Mo(2)] is a quadruple-bonded [Mo(2)(formamidinate)(3)] unit). Aerobic oxidation of 1 and 3 followed by concomitant deprotonation gave rise to the corresponding [Mo(2)](2)(μ-E)(2) compounds 2 and 4. The latter show a striking coplanarity and near-bond equalization of the Mo/E cluster. The oxidized species 2 and 4 are diamagnetic in the measured temperature range of 5 to 300 K, which is somewhat unexpected for molecules that have dimetal units with a σ(2)π(4)δ(1) electronic configuration. This suggests there are strong interactions between the dimolybdenum units through the E atoms. The large electronic delocalization of the δ electrons over the entire Mo/E core is supported by the exceptionally large potential separation for the two successive one-electron reductions of the linked Mo(2)(5+) units from the oxidized species (ΔE(½)=1.7 V for the sulfur analogue). This large electronic delocalization has an important effect on the NMR spectroscopic signals for the two sets of methine (N-(CH)-N) protons from the DAniF ligands. Those essentially parallel to the core, H(∥), and those essentially perpendicular to the core, H(⊥), exhibit downfield and upfield chemical shifts, respectively, that are separated by δ=1.32 ppm. The structural, electronic, magnetic, and chemical behaviors for 2 and 4 are consistent with aromaticity, with the [Mo(2)E(2)Mo(2)] cores that resemble the prototypical benzene molecule. Theoretical studies, including DFT calculations, natural bond orbital (NBO) analyses, and gauge-independent atomic orbital (GIAO) NMR spectroscopic calculations, are also consistent with the aromaticity of the [Mo(2)](2)(μ-E)(2) units being promoted by d(δ)(Mo(2))-p(π)(E) π conjugation. The cyclic π conjugation of the central moiety in 2 and 4 involves a total of six electrons with 2e from δ(Mo(2)) and 4e from p(π)(E) orbitals, thereby conforming to Hückel's rule when electrons in the MOs with δ character are considered part of the delocalized system.

Aurones: Small Molecule Visible Range Fluorescent Probes Suitable for Biomacromolecules

Aurones, derivatives of 2-benylidenebenzofuran-3(2H)-one, are natural products that serve as plant pigments. There have been reports that some of these substances fluoresce, but little information about their optical properties is in the literature. In this report, series of aurone derivatives were synthesized as possible fluorescent probes that can be excited by visible light. We found that an amine substituent shifted the lowest energy absorption band from the near-UV to the visible region of the electromagnetic spectrum. Four amine-substituted aurone derivatives were synthesized to explore the effect of this substituent on the absorption and emission properties of the aurone chromophore. The emission maxima and intensities of the molecules are strongly dependent on the nature of the substituent and the solvent polarity. Overall, the emission intensity increases and the maximum wavelength decreases in less polar solvents; thus, the aurones may be useful probes for hydrophobic sites on biological molecules. A limited investigation with model protein, nucleic acid and fixed cells supports this idea. It is known that the sulfur analog of aurone can undergo photo-induced E/Z isomerization. This possibility was investigated for one of the aminoaurones, which was observed to reversible photoisomerize. The two isomers have similar absorption spectra, but the emission properties are distinct. We conclude that appropriately substituted aurones are potentially useful as biological probes and photoswitches.

Synthetic Application and Structural Elucidation of Axially Chiral Dicarboxylic Acid: Asymmetric Mannich-type Reaction with Diazoacetate, (Diazomethyl)phosphonate, and (Diazomethyl)sulfone

The past decade has witnessed the burgeoning research fields of chiral Brønsted acid catalysis. However, carboxylic acids, arguably the most general acids in organic chemistry, have rarely been used as chiral Brønsted acid catalysts. In this context, we developed axially chiral dicarboxylic acid and evaluated its catalytic activity in asymmetric Mannich-type reaction of aromatic aldehyde-derived N-Boc imines and tert-butyl diazoacetate. To demonstrate the remarkable generality of this catalytic system, tert-butyl diazoacetate was replaced with its phosphorus and sulfur analogues, (diazomethyl)phosphonate and (diazomethyl)sulfone, by which synthetically valuable chiral β-amino phosphonates and β-amino sulfones could be obtained with high enantioselectivities under identical reaction conditions. X-ray crystallographic analysis of axially chiral dicarboxylic acid complexed with a pyridine derivative revealed its unique internal hydrogen bonding, a property that serves as a basis for its distinctive acidity and chiral scaffold.

The bacterial redox signaller pyocyanin as an antiplasmodial agent: comparisons with its thioanalog methylene blue

The quorum sensor and signalling molecule pyocyanin (PYO) contributes significantly to the pathophysiology of Pseudomonas aeruginosa infections. Comparison to phenothiazine drugs suggests that the antimalarial compound methylene blue (MB) can be regarded as a sulfur analog of PYO. This working hypothesis would explain why the synthetic drug MB behaves as a compound shaped in biological evolution. Here we report on redox-associated biological and biochemical properties of PYO in direct comparison to its synthetic analog MB. We quantitatively describe the reactivity of both compounds toward cellular reductants, the reactivity of their reduced leuco-forms towards O2, and their interactions with FAD-containing disulfide reductases. Furthermore, the interaction of PYO with human glutathione reductase was studied in structural detail by x-ray crystallography, showing that a single PYO molecule binds to the intersubunit cavity of the enzyme. Like MB, also PYO was also found to be active against blood schizonts of the malaria parasite P. falciparum in vitro. Furthermore, both compounds were active against the disease transmitting gametocyte forms of the parasites, which was systematically studied in vitro. As shown for mice, PYO is too toxic to be used as a drug. It may, however, have antimalarial activity in numerous human patients with concomitant Pseudomonas infections. MB, in contrast to PYO, is well tolerated and represents a promising agent for MB-based combination therapies against malaria. Current and future clinical studies can be guided by the comparisons between MB and PYO reported here. Additionally, it is of interest to study if and to what extent the protection from malaria in patients with cystic fibrosis or with severe wound infections is based on PYO produced by Pseudomonas species.

Molecular Structures and Vibrational Spectra of Roesky’s Ketone, its Isomers and their Novel Sulfur and Selenium Analogues: An Insight using Density Functional Theory

Molecular Structures and Vibrational Spectra of Roesky’s Ketone, its Isomers and their Novel Sulfur and Selenium Analogues: An Insight using Density Functional Theory

ChemInform Abstract: Unexpected Preparation of (Z)‐Chloromethyleneketals and Their Sulfur Analogues by a Novel Three‐Component Condensation.

AbstractThe obtained chlorovinyl adducts can be further functionalized by metal‐catalyzed cross‐coupling reactions [cf.

Density functional theory calculations of redox properties of iron–sulphur protein analogues

A central issue in understanding redox properties of iron–sulphur (Fe–S) proteins is determining the factors that tune the reduction potentials of the Fe–S clusters. Studies of redox site analogues play an important role, particularly because individual factors can be examined independently of the environment by combining calculations and experiments of carefully designed ligands for the analogues. For iron–sulphur analogues, our study has shown that broken-symmetry density functional theory gives good energetics when the geometry is optimised using B3LYP with a double-ζ basis set with polarisation functions, and the energies of these geometries are calculated using B3LYP with additional diffuse functions added to the sulphurs. A comparison of our calculated energies for redox site analogues in the gas phase against electron detachment energies measured by a combination of electrospray ionisation and photoelectron spectroscopy (EI–PES) by Wang and co-workers has been essential because the comparison is for exactly the same molecule with no approximation for the environment. Overall, the correlation of our B3LYP/ 6-31(++)SG**//B3LYP/6-31G** detachment energies with EI–PES experiments is excellent for a wide variety of analogues. Moreover, our calculations at this level have provided insight into a wide variety of properties of iron–sulphur proteins.

Efficient synthesis of 3-O-thia-cPA and preliminary analysis of its biological activity toward autotaxin

The efficient synthesis of 3-O-thia-cPAs (4a-d), sulfur analogues of cyclic phosphatidic acid (cPA), has been achieved. The key step of the synthesis is an intramolecular Arbuzov reaction to construct the cyclic thiophosphate moiety. The present synthetic route enables the synthesis of 4a-d in only four steps from the commercially available glycidol. Preliminary biological experiments showed that 4a-d exhibited a similar inhibitory effect on autotaxin (ATX) as original cPA.

Metal-Stabilized o-Quinone Methides, Thioquinones, and Selenoquinones: Trapping Important Reactive Intermediates and Beyond

Quinone methides (quinomethanes) act as important intermediates in organic syntheses, as well as in chemical and biological processes. However, examples of such isolated species are scarce owing to their high reactivity. Other important reactive intermediates are thio- and selenoquinones. However, unlike quinones, they are highly unstable and consequently do not exist in nature, hence their chemical and biological properties remain unknown. In this account, we describe the first isolation of the above important reactive intermediates, by π-coordination to a (pentamethylcyclopentadienyl)iridium (Cp*Ir) moiety, and their X-ray molecular structures. Further, the reactivity of such trapped intermediates is reported. For instance, the metalated o-quinone methide underwent an unusual cycloaddition reaction compared with the free o-quinone methide, while the metalated thioquinones were successfully used as organometallic linkers (OM-linkers) to construct luminescent coordination assemblies. The anticancer activity of the selenoquinone metalated complex was studied, together with related oxygen and sulfur analogues, and remarkably it was shown to be the only cytotoxic compound with a comparable activity to cisplatin.

Synthesis of sulfur containing analogues of the soluble guanylate cyclase inhibitor 8-bromo-4 H-[1,2,4]oxadiazolo[3,4- c][1,4]benzoxazin-1-one NS2028

Sulfur analogues of the soluble guanylate cyclase (sGC) inhibitor NS2028 1a are synthesized. Treating 8-bromo-2 H-benzo[ b][1,4]oxazin-3(4 H)-one oxime ( 6) with 1,1′-thiocarbonyldiimidazole (1.1 equiv) gave the carbamothioate 8-bromo-4 H-[1,2,4]oxadiazolo[3,4- c][1,4]benzoxazine-1-thione ( 3a) in 83% yield. Alternatively reacting NS2028 1a with P 2S 5 (0.5 equiv) affords the carbamothioate 3a in 80% yield. Similar treatment of 8-aryl substituted NS2028 analogues 1b– d with P 2S 5 gave the carbamothioates 3b– d in 64–91% yields. Although quite stable, the carbamothioates 3a– d could be thermally isomerized in the presence of Cu (10 mol %) to afford the thiocarbamates 4a– d in high yields. Interestingly, in the case of carbamothioate 3a Pd and In metals also facilitated the isomerization. Furthermore, treatment of the thiocarbamates 4a– d with P 2S 5 (0.5 equiv) affords the carbamodithioates 5a– d in 72–89% yields. All new compounds are fully characterized including single crystal X-ray data for carbamothioate 3a and thiocarbamate 4a. Finally, a mechanism is proposed for the carbamothioate to thiocarbamate isomerization.