Diethylenetriamine NO

NO mediates zinc release from the zinc-storage protein metallothionein via S-nitrosation and subsequent formation of disulphides (Kroncke et al. 1994). Culture of rat islet cells for 24 h in the presence of nontoxic concentrations (0.5 mM) of the slow-releasing NO donor diethylenetriamine/NO resulted in a significantly reduced Zn -dependent Zinquin (25 [iM) fluorescence (Tartler et al. 2000). 

The source of nitric oxide was diethylenetriamine/nitric oxide, DETA/ NO (Scheme 20.4) a compound that has been used in studies of the cytostatic, vasodilatory and other pharmacological properties of NO [65-67]. DETA/NO is a 1-substituted diazen-l-ium-l,2-diolate containing the [N(0)N0] functional group that has been proved to be useful for the reliable generation of nitric oxide in homogenous solutions [68]. When dissolved in blood, cell culture medium or buffer this compound dissociates to generate NO leaving the nucleophilic structure as a by-product. 

Mixed y-Ga203-Al203 oxides of different stoichiometry were prepared by the solvothermal method from Ga(acac)3 and Al(OPr-i)3 as starting materials and were used as catalysts for selective reduction of NO with methane. The initial formation of gallium oxide nuclei controls the crystal structure of the mixed gallium-aluminum oxides. It is found that the acid density per surface area is independent of the Al Ga feed ratio but depends on the reaction medium (diethylenetriamine, 2-methylaminoethanol, toluene, 1,5-pentanediol etc.), whereby in diethylenetriamine the catalyst had lower densities of acid sites and showed a higher methane efficiency. 

Such experiments show that oxalate, tartrate, and citrate give fairly strong complexes, and indeed these mixtures do not suffer quite such rapid oxidation as the other systems (57, 70). Stability constants for the complexing of U(III) by acetate, 2-hydroxy-2-methylpropionate, nitriloacetate, trans-cyclohexyl-1,2-diaminotetraacetate, ethylenedi-amine tetraacetate, and diethylenetriamine pentaacetate have been reported, but no pure compounds have been isolated (71). Thiocyanate also accelerates oxidation of the uranium, but the blue complex that is formed can be extracted with triethyl phosphate, tributyl phosphate, or better, trioctyl phosphine oxide the organic extract decomposes only slowly (45, 72). 

Imidazolinium salts are also derived from diethylenetriamine. The diami-doamine that results from the esterification of this molecule is dehydrated into an imidazoline, then quaternized with dimethylsulfate, as shown in Figure 12.4 [51]. The resulting molecule is no longer susceptible to hydrolysis. Despite the low price of the material from which they derive, imidazolinium salts are expensive because of their manufacturing cost. This is due to the costly conditions necessary to convert the diamidoamine into imidazoline [3], Details of the synthesis may be found in Egan [37] or Billenstein and Blaschke [38],... 

The derivatives of a new condensed triazabicyclo-[5.3.0]dec-4-ene system with a nodal nitrogen atom (7-trifluoromethyl-5-phenyl-l,4,8-triazabicyclo[5.3.0]dec-4-ene 72) are obtained in reactions of aminoenones 71 with diethylenetriamine (room temperature, no solvent, 4-7 days) (yield 64-74% for the trifluoromethyl substituent and 23-33% for tetrafluoroethyl) (99IZV1410) (Scheme 76). 

FIGURE 3 Structures of candidate antirestenosis agents used in the series of experiments described herein. DEA, Diethylamine NO, nitric oxide DETA, diethylenetriamine MAHMA, methylaminohexylmethylamine. 

With this series of compounds, an easy solution was available in the form of DETA/NO (synthesized from diethylenetriamine and NO), whose half-life under these culture conditions is 20 hr. Its structure (3) is also shown in Fig. 3. In contrast to DEA/NO, DETA/NO was potently antiproliferative in this system (Mooradian et al., 1995). From the data summarized in Fig. 4B, the initial concentration of DETA/NO capable of inhibiting DNA synthesis by 50% was calculated to be 40 /x,M. Apparently, the cytostatic effect of a given molar quantity of NO is greatest when administered continu-... 

FIGURE 4 Effects of candidate cytostatic agents on DNA synthesis by rat aorta smooth muscle cells in culture. (A) The diethylamine/nitric oxide adduct (DEA/NO), whose half-life for NO release is 2.1 min under the conditions used (B) The diethylenetriamine/nitric oxide adduct (DETA/NO), with a half-life of 20 hr. Cells were incubated at 37°C for 22 hr after addition of the given drug at the indicated concentrations, whereupon [ H]thymidine was added. After an additional 2-hr incubation DNA was isolated from the cells and subjected to scintillation counting to provide a quantitative measure of DNA synthesis by these cells. [Adapted from Mooradian et al. (1995) with permission.]... 

FIGURE 5 Antiproliferative effect of the diethylenetriamine/nitric oxide adduct (DETA/ NO) on rat aorta smooth muscle cells in culture over a 7-day observation period. Cells were allowed to attach in a serum-free medium for 24 hr, then cultured in a medium containing 10% fetal bovine serum. On days 1, 3, 5, and 7, cells were counted with a hemocytometer the medium was replaced on each of these days with a fresh medium containing 500 /uAl DETA/NO on days 1, 3, and 5 (V) on days 1 and 3 only (V) on day 1 only ( ) or not at all (O). [Reprinted from Mooradian et al. (1995) with permission.]... 

Precaution If mixed with water, methanol will form (vapors are toxic and flamm.) reaction with water is rapid and exothermic Hazardous Ingredients Diethylenetriamine (< 2%), methanol (< 2%) Hazardous Decomp. Prods. Burning CO NO, SiO,... 

Amylose 2-Butanol Butoxydiglycol Candelilla (Euphorbia cerifera) wax N-Cyclohexyl-p-toluenesulfonamide Decyl acrylate homopolymer Di-t-butyIhydroquinone Diethylenetriamine DItrldecyl sodium sulfosuccinate Erucamide Ethoxydiglycol Ethylene/acrylic acid/vinyl acetate copolymer FD C Blue No. 1 Aluminum Lake Glyceryl caprate Hexylene glycol... 

The most frequently registered allergens in hardeners were benzyl alcohol, tri(dimethylaminomethyl)phenol and several amines (triethylenetetramine, isophoronediamine, diethylenetriamine, tetraethylenepentamine). No specific changes in the registration were observed. 

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