Sorbate-nitrite interactions: acetonitrile oxide as an alkylating agent.
Because chemical species with DNA-damaging and mutagenic activity are formed in sorbate-nitrite mixtures and because sorbic acid sometimes coexists with nitrite occurring naturally or incorporated as a food additive, the study of sorbate-nitrite interactions is important. Here, the alkylating potential of the products resulting from such interactions was investigated. Drawn were the following conclusions: (i) Acetonitrile oxide (ACNO) is the compound responsible for the alkylating capacity of sorbate-nitrite mixtures; (ii) ACNO alkylates 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to those of DNA bases, forming an adduct (AD; epsilon = 1.4 x 10(4) M(-1) cm(-1); lambda = 519 nm); (iii) the NBP alkylation reaction complies with the rate equation, r = d[AD]/dt = k(alk)(ACNO)[ACNO][NBP]-k(hyd)(AD)[AD], k(alk)(ACNO) being the NBP alkylation rate constant for ACNO and k(hyd)(AD) the rate constant for the adduct hydrolysis reaction; (iv) the small fraction of ACNO forming the adduct with NBP, as well as the small magnitude of the quotient (k(alk) (ACNO)/k(hyd)(ACNO)) as compared with those reported for other alkylating agents, such as some lactones and N-alkyl-N-nitrosoureas, reveals the ACNO effective alkylating capacity to be less significant; (v) the low value of the NBP-ACNO adduct life (defined as the total amount of adduct present along the progression of the NBP alkylation per unit of alkylating agent concentration) points to the high instability of this adduct; and (vi) the obtained results are in accordance with the low carcinogenicity of ACNO.
Pérez-Prior
M Teresa
MT
Departamento de Quimica Fisica, Universidad de Salamanca, E-37008 Salamanca, Spain.
Gómez-Bombarelli
Rafael
R
González-Pérez
Marina
M
Manso
José A
JA
García-Santos
M Pilar
MP
Calle
Emilio
E
Casado
Julio
J
D000097:Acetonitriles / Q000737:chemistry* / Q000633:toxicity; D000477:Alkylating Agents / Q000737:chemistry* / Q000633:toxicity; D004249:DNA Damage; D007700:Kinetics; D009573:Nitrites / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry; D013011:Sorbic Acid / Q000737:chemistry*
D000097:Acetonitriles; D000477:Alkylating Agents; D009573:Nitrites; D011725:Pyridines; C544154:acetonitrile oxide; C008633:4-(4-nitrobenzyl)pyridine; D013011:Sorbic Acid; C032159:acetonitrile