Thiolation, oxidative

Fluid, natural cell membranes are based on phospholipids which contain fatty acid esters of various chain lengths. Such lipids formed random mixtures, separated into domains or produced a mixture of both, e.g. phospholipid dimers AA and BB, in which two amphiphiles are connected by disulfide bridges. Equilibration via reduction (thiolate) - oxidation (disulfide) cycles... 

Very few reports have been made using this approach to synthesize anti-body-liposome conjugates. Early work (38) showed that simple acyl hydra-zides in liposomes could be used to conjugate periodate-oxidized IgM in good yield. More recently, a lipid-PEG-hydrazide derivative has been reported that was used to couple oxidized IgG to liposomes (34), albeit in low yield. Subsequent work has reported optimized conditions that resolve these problems and minimize liposome-liposome crosslinking (10). We have recently reported a variation of these procedures in which a protected thiol-hydrazide crosslinker was used to thiolate oxidized IgG and subsequently to effect coupling to maleimide derivatized liposomes (36). 

The structural constraints on the cysteine in TICu have also been proposed to prevent adventitious chemistry such as thiolate oxidation reactions. In the study of... 

The influence of pH and other factors on the reductive desorption and oxidative reformation of a hexadecanethiol SAM on a gold electrode was studied by reflection-absorption infrared spectroscopy (RAIRS) and cyclic voltammetry. At low pH the lack of solubility of desorbed molecules was problematic however, after three adsorption-desorption cycles the process was reproducible301. The reductive desorption in alkaline solution of an alkanethiol SAM on a single-crystal Au(l 11) electrode involves a one-electron process to yield a thiolate. Oxidative removal is a complicated process, involving up to eleven electrons per alkanethiol molecule302. 

As shown in Table III, the high-spin complex 1 and the low-spin nitrosyl complex 3 display charge transfer bands at 631 nm (15,800 cm ) and 650 nm (15,400 cm ), respectively. This is a difference of only 400 cm even though Ae spin-states are different and the reduction potentials differ by -300 mV. The similarities result from nearly identical potential differences between thiolate oxidation and metal reduction, 1.24 and 1.19 V, respectively. Conversely, the... 

Mekhalif et al. [160-162] studied the formation and structure of alkanethiol SAMs on nickel, comparing cleaned/polished substrates with others that underwent additional electrochemical pretreatment to remove surface oxide. Polycrystalline Ni disks were mechanically polished with diamond paste and rinsed with acetone and ethanol. The additional electrochemical pretreatment consisted of 20 min reduction in 1 M HCIO4 at 0.7 V versus SCE. Exposure time to the atmosphere prior to self-assembly was less than 3 s. Samples that were not electrochemically treated produced poor quality SAMs, with considerable part of the thiolates oxidized to sulfonates and sulfinates [160, 162]. 

Phosphate triesters (18) are iatermediates ia both the phosphotriester and phosphoramidite methods, and under appropriate conditions for deprotection of the bases and cleavage of the support, can be obtained directiy by usiag these approaches. The ethyl and isopropyl esters have been obtained directiy by usiag the phosphoramidite method because these are stable duting the normal deprotection procedure (62). By changing the oxidizing agent to Sg, both amidate and triester thiolates can be obtained. 

Chemisorption of alkanethiols as well as of di- -alkyl disulfides on clean gold gives indistinguishable monolayers (251) probably forming the Au(l) thiolate species. A simple oxidative addition of the S—S bond to the gold surface is possibly the mechanism in the formation of SAMs from disulfides ... 

The fdr studies reveal that the alkyl chains in SAMs of thiolates on Au(lll) usually are tilted 26-28° from the surface normal, and display 52-55° rotation about the molecular axis. This tilt is a result of the chains reestabUshing VDW contact in an assembly with - 0.5 nm S—S distance, larger than the distance of - 0.46 nm, usually quoted for perpendicular alkyl chains in a close-packed layer. On the other hand, thiolate monolayers on Ag(lll) are more densely packed owing to the shorter S—S distance. There were a number of different reports on chain tilt in SAMs on Ag(lll), probably owing to different amounts of oxide, formed on the clean metallic surface (229,230,296,297). In carefully prepared SAMs of alkanethiolates on a clean Ag(lll) surface, the alkyl chains are practically perpendicular to the surface. 

In choosing a SAM system for surface engineering, there are several options. Silane monolayers on hydroxylated surfaces are an option where transparent or nonconductive systems are needed. However, trichlorosilane compounds are moisture-sensitive and polymeri2e in solution. The resulting polymers contaminate the monolayer surface, which occasionally has to be cleaned mechanically. CarboxyUc acids adsorb on metal oxide, eg, AI2O2, AgO through acid—base interactions. These are not specific therefore, it would be impossible to adsorb a carboxyUc acid selectively in the presence of, for example, a terminal phosphonic acid group. In many studies SAMs of thiolates on Au(lll) are the system of choice. 

Thiirane 1-oxide undergoes acid-catalyzed ring opening by ethanethiol to give ethyl 2-ethylthioethyl disulfide. Treatment of thiirane 1,1-dioxide with thiolate anions, sodium sulfide or thiourea gives /3-mercaptosulfinic acid derivatives (75S55). Thiiranium ions are attacked at carbon by most sulfur nucleophiles (79ACR282), but see Section 5.06.3.4.3 for exceptions. 

The final step in the /3-oxidation cycle is the cleavage of the /3-ketoacyI-CoA. This reaction, catalyzed by thiolase (also known as j8-ketothiolase), involves the attack of a cysteine thiolate from the enzyme on the /3-carbonyI carbon, followed by cleavage to give the etiolate of acetyl-CoA and an enzyme-thioester intermediate (Figure 24.17). Subsequent attack by the thiol group of a second CoA and departure of the cysteine thiolate yields a new (shorter) acyl-CoA. If the reaction in Figure 24.17 is read in reverse, it is easy to see that it is a Claisen condensation—an attack of the etiolate anion of acetyl-CoA on a thioester. Despite the formation of a second thioester, this reaction has a very favorable A).q, and it drives the three previous reactions of /3-oxidation. 

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

Thiols, the sulfur analogs of alcohols, are usually prepared by Sjv 2 reaction of an alkyl halide with thiourea. Mild oxidation of a thiol yields a disulfide, and mild reduction of a disulfide gives back the thiol. Sulfides, the sulfur analogs of ethers, are prepared by an Sk2 reaction between a thiolate anion and a primary or secondary alkyl halide. Sulfides are much more nucleophilic than ethers and can be oxidized to sulfoxides and to sulfones. Sulfides can also be alkylated by reaction with a primary alkyl halide to yield sulfonium ions. 

The conversion of a thiolactone to a cyclic ether can also be used as a key step in the synthesis of functionalized, stereochemically complex oxacycles (see 64—>66, Scheme 13). Nucleophilic addition of the indicated higher order cuprate reagent to the C-S double bond in thiolactone 64 furnishes a tetrahedral thiolate ion which undergoes smooth conversion to didehydrooxepane 65 upon treatment with 1,4-diiodobutane and the non-nucleophilic base 1,2,2,6,6-pentamethylpiperidine (pempidine).27 Regio- and diastereoselective hydroboration of 65 then gives alcohol 66 in 89 % yield after oxidative workup. Versatile vinylstannanes can also be accessed from thiolactones.28 For example, treatment of bis(thiolactone) 67 with... 

They doubtless owe their stability to the bulk of the aryl thiolate ligand they have tbp structures with equatorial nitrile that can be displaced by CO to give rare carbonyls of a metal in the +4 oxidation state. 

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