68758-86-1Relevant academic research and scientific papers
Specificity of DNA alkylation by 1-(2-chloroethyl)-3-alkyl-3- acyltriazenes depends on the structure of the acyl group: Kinetic and product studies
Smith,Schmidt,Czerwinski,Taneyhill,Snyder,Kline,Michejda,Smith Jr.
, p. 466 - 475 (2007/10/03)
The reactions of calf thymus DNA with ten 1-(2-chloroethyl)-3-alkyl-3- acyltriazenes of varying acyl side chain structure were studied alone, or in the presence of porcine liver esterase in pH 7.0 phosphate buffer. In several of the key triazenes, the acyl substituent contained a free carboxylic acid group. With esterase present in the reaction mixture, the resultant levels of DNA alkylation could be correlated with the kinetic rates of decomposition of the triazenes. Under these conditions, the predominant pathway of decomposition involved deacylation of the parent triazene and eventual production of an alkanediazonium ion. This intermediate subsequently alkylated DNA-guanine to give 7-alkylguanine as the principal reaction product. In the absence of esterase, the order of DNA alkylation for all of the acyltriazenes did not correlate with their respective rates of decomposition, leading to the conclusion that the triazenes did not decompose by the expected mode of uncatalyzed N(2)-N(3) heterolyic cleavage. The major DNA alkylation product from the N(3)-methyltriazenes was 7-methylguanine, instead of the expected 7-(chloroethyl)- and 7-(hydroxyethyl)guanine products, which suggested that the acyl group was being hydrolyzed. However, acyltriazenes with an N(3)-benzyl group rather than a methyl in this position produced very little 7-benzylguanine product, contrary to prediction. An alternative mechanism involving internally assisted hydrolysis of the side chain ester is proposed to explain these results. NMR product analysis and computational studies were carried out to lend support to the postulated mechanism.
Conformation-directing effects of a single intramolecular amide-amide hydrogen bond: Variable-temperature NMR and IR studies on a homologous diamide series
Gellman, Samuel H.,Dado, Gregory P.,Liang, Gui-Bai,Adams, Bruce R.
, p. 1164 - 1173 (2007/10/02)
We have studied intramolecular hydrogen bonding in a homologous series of diamides (compounds 1-6) in methylene chloride, 9:1 carbon tetrachloride/benzene, and acetonitrile. By correlating variable-temperature 1H NMR and IR measurements, we have shown that the temperature dependence of the amide proton NMR chemical shift (Δδ/ΔT) can provide qualitative (and in some cases quantitative) information on the thermodynamic relationship between the intramolecularly hydrogen bonded and non-hydrogen-bonded states of flexible molecules. Among the hydrogen-bonded ring sizes represented in the diamide series, the intramolecular interaction is particularly enthalpically favorable in the nine-membered hydrogen-bonded ring (compound 4). Variable-temperature IR and NMR data indicate that the internally hydrogen bonded state of diamide 4 is 1.4-1.6 kcal/mol more favorable enthalpically than the non-hydrogen-bonded state, in methylene chloride solution; the non-hydrogen-bonded state is 6.8-8.3 eu more favorable entropically in this solvent. In contrast, there appear to be much smaller enthalpy differences between the internally hydrogen bonded and non-hydrogen-bonded states of diamides 2 and 3. Our findings are important methodologically because the temperature dependences of amide proton chemical shifts are commonly used to elucidate peptide conformation in solution. Our results show that previous "rules" for the interpretation of such data are incomplete. In non-hydrogen-bonding solvents, small amide proton Δδ/ΔT values have been taken to mean that the proton is either entirely free of hydrogen bonding or completely locked in an intramolecular hydrogen bond over the temperature range studied. We demonstrate that an amide proton can be equilibrating between intramolecularly hydrogen bonded and non-hydrogen-bonded states and still manifest a small chemical shift temperature dependence (implying that the hydrogen-bonded and non-hydrogen-bonded states are of similar enthalpy).
KINETICS AND MECHANISM OF REVERSIBLE, BASE-CATALYSED RING CLOSURE OF 3-(METHOXYCARBONYL)PROPIONANILIDE AND O-(METHOXYCARBONYLMETHYL)-N-PHENYLCARBAMATE
Kavalek, Jaromir,Machacek, Vladimir,Svobodova, Gabriela,Sterba, Vojeslav
, p. 1005 - 1011 (2007/10/02)
The rate constants of reversible, base-catalysed ring closure of 3-(methoxycarbonyl)propionanilide (I) and O-(methoxycarbonylmethyl)-N-phenylcarbamate (II) to 1-phenyl-2,5-pyrrolidinedione (III) and 3-phenyl-2,4-oxazolidinedione (IV), respectively, and the rates of solvolyses of the cyclization products III and IV in water and methanol have been measured.In both cases, an equilibrium is established between the starting ester and the cyclization product in methoxide solutions which is strongly shifted in favour of the starting ester.In the case of ester II in methoxidesolutions, the cyclization is followed by a much slower splitting of the cyclization product to give glycolic acid anilide.The effects of the group X=NH, CH2, O, S in the esters RNHCOXCH2COOCH3 on the rates of the cyclization and solvolysis of the cyclization products is discussed.
