Comparison of the alkylation of nicotinamide and 4-(p-nitrobenzyl)pyridine for the determination of aliphatic epoxides

Abstract

The alkylation of nicotinamide by a series of ten propylene oxides with subsequent formation of a chromophore In a new procedure Is compared to the conventional 4-(p-nltrobenzyl)pyrldlne (NBP) test. Both reactions exhibited similar rates of alkylation, competing rates of solvolysis and correlation of the extent of alkylation to the Taft * values of substituent groups. The nicotinamide procedure has the advantage that the Initial alkylation can be run under more physiological conditions and that there Is an Increase In the stability of the final chromophore.

Reactivity of propylene oxides towards deoxycytidine and identification of reaction products

“…However, although differences in reactivity are present, it was total reactivity (represented by the ratio of remaining unreacted material, peak 2, to internal standard) that correlated to Taft o*-electron withdrawing values [ 7] for the substituents. The correlation of total reactivity to Taft o*-values was excellent (r = 0.9999) and is comparable to our previous correlation [28] with nicotinamide (r = 0.9438) and p-nitrobenzyl pyridine (r = 0.9474) reactivities. Deoxycytidine alkylation may be interesting to pursue in other alkylation studies since O2-ethylcytosine has been found to persist in alkylated DNA in vivo [29,30], and the more extensively studied formation and persistence of O6-alkylguanine has not always correlated with toxicity [31--35].…”

Characterization and quantitation of 3-alkylthymidines from reactions of mutagenic propylene oxides with thymidine

“…Taft u* electron withdrawing values [9] for the substituents on the epoxides were used for a prediction of epoxide reactivity and correlated well with either 3-alkylthymidine formation or thymidine remaining after the reaction (r = 0.99). The correlation of epoxide reactivity with thymidine to Taft values was comparable to previous correlations obtained with the analytically useful model nucleophiles, 4-(p-nitrobenzyl)pyridine and nicotinamide [30]. There was also a good correlation of published Ames Assay TAlOO mutagenicity values [lo] to 3-alkylthymidine formation In general, our studies were run in methanol in order to facilitate the semi-preparative isolation and characterization of the reaction products of epoxides with thymidine.…”

Quantitative structure-activity relationships for the mutagenicity of propylene oxides with Salmonella

“…The rates of alkylation were compared by reaction of the epoxides at equimolar concentrations at 37°C for 20 min as previously described with NBP (Nelis et al, 1982) and with nicotinamide (Calbiochem, Los Angeles, CA) by the procedure of Nelis et al (1981).…”

“…We have previously reported, for a series of propylene oxides (Nelis et al, 1982), on the correlation between alkylating ability and Taft or* values, which measure the electron-withdrawing strength of substituent groups in aliphatic systems. Subsequent studies on propylene oxide and three derivatives demonstrated a correlation between Taft or* values and reactivity to the deoxynucleosides in DNA (Djuric et al, 1986).…”