Selenium is an essential micronutrient in humans due to the important roles of the selenocysteine-containing selenoproteins. Organoselenium metabolites are generally found to be substrates for the biochemical pathways of their sulfur analogs, and the redox chemistry of selenomethionine and some other metabolites have been previously reported. We now report the first synthesis and characterization of -adenosylselenohomocysteine selenoxide (SeAHO) prepared via hydrogen peroxide oxidation of -adenosylselenohomocysteine (SeAH). The selenoxide SeAHO, in contrast to its corresponding sulfoxide -adenosylhomocysteine (SAHO), can form hydrate, has an electrostatic interaction between the α-amino acid moiety and the highly polar selenoxide functional group, and readily oxidizes glutathione (GSH) and cysteine thiols.

A variety of reactions of singlet oxygen with metal-bound thiolates are described, and contrasted with the photooxidation of organic sulfides. Superficially, these two processes appear to involve similar mechanisms, but there are important differences: unlike the photooxidation of organic sulfides, the rate of the initial reaction of metal-thiolates with singlet oxygen (k(t)) appears to be affected by protic solvents and acids. The nucleophilicity of the thiolate moiety is reduced by addition of acids or in protic solvents, leading to significantly lower k(t) values. The primary intermediate in the photooxidation of organic sulfides is a nucleophilic persulfoxide, which can be stabilized by protic solvents or by addition of acid. However, the primary intermediate in the photooxidation of metal thiolates cannot be trapped with phosphite, suggesting that it may be less nucleophilic than its organic counterpart. Support for this hypothesis is also derived from the rather modest (compared with organic sulfides) acceleration of the rate of product formation by addition of acid.

Novel photolabile amphiphiles containing thioxanthone-based fluorogenic caging groups are developed. Photoinduced fragmentation in dithiane-thioxanthone adducts was demonstrated to occur with 100% quantum efficiency at λ ~ 320 nm and more than 50% at λ ~ 360 nm. A plausible mechanism involves homolytic fission of a carbon-carbon single bond in the excited thioxanthone followed by disproportionation via hydrogen transfer. The critical feature of the system is that fluorescence of a substituted thioxanthone is recovered as a result of photofragmentation, making dithiane-thioxanthone adducts efficient fluorogenic caging groups. Photolabile amphiphiles containing these fluorogens are synthesized and their photoinduced disassembly is probed while following the fluorescence recovery. This methodology allows for destabilizing supramolecular assemblies of amphiphiles and at the same time offers a feedback mechanism for monitoring the process by fluorescence.

A short synthetic route to β,d-arabinofuranosyl 1-C-sulfonic acid (), a possible biomimetic for the arabinofuranosyl anomeric phosphate, is described. The furanosyl 1--sulfonate was prepared by buffered DMDO oxidation of an -acetyl-1-thio-β-arabinofuranose derivative. Deprotection under mild conditions allowed isolation of the free sulfonic acid without desulfonylation.

A carbon-sulfur molecule has been designed as a mimic of peptides. Density functional theory calculations showed that the oxidation of 10 moles of methanedithiol led to a polydisulfide oligomer, HS(CHSS)CHSH. The polydisulfide can adopt an α-helix type of secondary structure, where the chain is coiled. Unlike proteins, the S-S bonds in the polydisulfide function as secondary rather than tertiary structural elements. The helix contains 8 non-hydrogen atoms per turn, 2.7 Å methylenes per turn, a pitch distance of 8.6 Å, and a radius of 1.00 Å. The methylene sites could carry R group residues similar to amino acids.

4--Alkyl/aryl--ribosylhomocysteine (SRH) analogues were prepared by coupling of homocysteine with 4-substituted ribofuranose derivatives. The diastereoselective incorporation of the methyl substituent into the 4 position of the ribose ring was accomplished by addition of methylmagnesium bromide to the protected ribitol-4-ulose yielding the 4--methylribitol in 85% yield as single 4 diastereomer. The 4- hexyl, octyl, vinyl, and aryl ribitols were prepared analogously. Chelation controlled addition of a carbanion to ketones from the (-face) was responsible for the observed stereochemical outcome. Oxidation of the primary alcohol of the 4- ribitols with the catalytic amount of tetrapropylammonium perruthenate in the presence of -methylmorpholine -oxide produced 4--alkylribono-1,4-lactones in high yields. Mesylation of the latter compounds at the 5-hydroxyl position and treatment with a protected homocysteine thiolate afforded protected 4--alkyl/aryl-SRH analogues as the lactones. Reduction with lithium triethylborohydride and successive global deprotections with TFA afforded 4--alkyl/aryl SRH analogues. These analogues might impede the -ribosylhomocysteinase(LuxS)-catalyzed reaction by preventing β-elimination of a homocysteine molecule, and thus depleting the production of quorum sensing signaling molecule AI-2.