Iodoacetates

Methylene iodide [75-11-6], CH2I2, also known as diio dome thane, mol wt 267.87, 94.76% I, mp 6.0°C, and bp 181°C, is a very heavy colorless Hquid. It has a density of 3.325 g/mL at 20°C and a refractive index of 1.7538 at 4°C. It darkens in contact with air, moisture, and light. Its solubiHty in water is 1.42 g/100 g H2O at 20°C it is soluble in alcohol, chloroform, ben2ene, and ether. Methylene iodide is prepared by reaction of sodium arsenite and iodoform with sodium hydroxide reaction of iodine, sodium ethoxide, and hydroiodic acid on iodoform the oxidation of iodoacetic acid with potassium persulfate and by reaction of potassium iodide and methylene chloride (124,125). Diiodoform is used for determining the density and refractive index of minerals. It is also used as a starting material in the manufacture of x-ray contrast media and other synthetic pharmaceuticals (qv). 

For deterrnination of tryptophan, 4 M methanesulfonic acid hydrolysis is employed (18). For cystine, the protein is reduced with 2-mercaptoethanol, the resultant cysteine residue is carboxymethylated with iodoacetic acid, and then the protein sample is hydroly2ed. Also, a one-pot method with mercaptoethanesulfonic acid has been developed for tryptophan and cystine (19). 

How might iodoacetic acid affect the glyceraldehyde-3-phosphate dehydrogenase reaction in glycolysis Justify your answer. 

The different configurations of the salts obtained by var3dng the sequence of alkylation are well illustrated by the reaction of pseudo-tropine (14) with ethyl iodoacetate to give 15, while the opposite order... 

Problem 26.10 1 Show the structure of the product you would expect to obtain by SN2 reaction of a cysteine residue with iodoacetic acid. 

Aqueous solutions of aequorin also emit light upon the addition of various thiol-modification reagents, such as p-quinone, Br2, I2, N-bromosuccinimide, N-ethylmaleimide, iodoacetic acid, and p-hydroxymercuribenzoate (Shimomura et al., 1974b). The luminescence is weak and long-lasting ( 1 hour). The quantum yield varies with the conditions, but seldom exceeds 0.02 at 23-25°C. The luminescence is presumably due to destabilization of the functional moiety caused by the modification of thiol and other groups on the aequorin molecule. 

The action of a peptidase can be neutralized by an inhibitor. Some inhibitors are very broad in their action and are capable of inhibiting many different peptidases, including peptidases of different catalytic types. Some inhibitors are assumed to be specific for a particular catalytic type, but can inhibit peptidases of different types. Leupeptin, for example, is widely used as an inhibitor of serine peptidases from family SI, but it is also known to inhibit cysteine peptidases from family Cl. Cysteine pqrtidase inhibitors such as iodoacetic acid interact with the thiol of the catalytic cysteine. However, this reduction can occur on any thiol group and can affect other, predominantly intracellular, peptidases with a thiol dependency. One example is thimet oligopepti-dase. Metal chelators such as EDTA can inhibit meta-llopeptidases, but can also affect peptidases that have a requirement for metal ions that is indq>endent of their catalytic activity, such as the calcium-dependent cysteine endopqrtidase calpain 1. 

Ribosomal protein L12 was oxidized with 0.3 M H202 at 30°C for 1 h. After dialysis, the protein was incubated in the presence of 0.8 M 2-mercaptoethanol for 48 min at 37 °C and dialyzed. The amount of methionine residues was quantitated by exhaustive alkylation of the protein with [14C]iodoacetic acid. 

Figure 17-3. Mechanism of oxidation of giyceraldehyde 3-phosphate. (Enz, glycer-aldehyde-3-phosphate dehydrogenase.) The enzyme is inhibited by the— 5H poison iodoacetate, which is thus abie to inhibit glycolysis. The NADH produced on the enzyme is not as firmly bound to the enzyme as is NAD. Consequently, NADH is easily displaced by another molecule of NAD". ...

Cemeli E, ED Wagner, D Anderson, SD Richardson, MI Plewa (2006) Modulation of the cytoxicity and geno-toxicity of the drinking water disinfection byproduct iodoacetic acid by suppressors of oxidative stress. Environ Sci Technol 40 1878-1883. 

Radical addition to alkenes has been used in cyclizations in aqueous media. Oshima and co-worker studied triethylborane-induced atom-transfer radical cyclization of iodoacetals and iodoacetates in water.121 Radical cyclization of the iodoacetal proceeded smoothly both in aqueous methanol and in water. Atom-transfer radical cyclization of allyl iodoacetate is much more efficient in water than in benzene or hexane. For instance, treatment of allyl iodoacetate with triethylborane in benzene or hexane at room temperature did not yield the desired lactone. In contrast, the compound cyclized much more smoothly in water and yielded the corresponding y-lactone in high yield (Eq. 3.31). 

An affinity label is a molecule that contains a functionality that is chemically reactive and will therefore form a covalent bond with other molecules containing a complementary functionality. Generally, affinity labels contain electrophilic functionalities that form covalent bonds with protein nucleophiles, leading to protein alkylation or protein acylation. In some cases affinity labels interact selectively with specific amino acid side chains, and this feature of the molecule can make them useful reagents for defining the importance of certain amino acid types in enzyme function. For example, iodoacetate and A-ethyl maleimide are two compounds that selectively modify the sulfur atom of cysteine side chains. These compounds can therefore be used to test the functional importance of cysteine residues for an enzyme s activity. This topic is covered in more detail below in Section 8.4. 

ND = Not determined DTNB 2,2 -Dithiobis(5-nitropyridine) DTNP 2,2 -Dithiobis(5-nitrobenzoate) DEDC Diethyldithiocarbamate IA Iodoacetate NEM N-ethylmaleimide PCMB p-chloromercuribenzoate 1, 10-PT 1, 10-phenanthroline 8-Q 8-Quinolinol 2, 2 -BP 2, 2 -Bipyridyl. 

Asymmetric additions of Reformatsky-type reagents to nitrones 258a and 258b have also been reported (Scheme 139). The reagents were prepared in situ from ZnEt2 and the corresponding iodoacetic acid ester. Diisopropyl (R,R)-tartrate 262 was employed as a chiral inductor. Enantioselectivities varied significantly the best results were obtained at 0 °C when a nitrone was added to the reaction mixture over a 2 h period. 

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