Hydrolysis of genotoxic methyl-substituted oxiranes : Experimental kinetic and semiempirical studies

Kirkovsky, Leonid I, Lermontov, Sergei A, Zavorin, Sergei I, Sukhozhenko, Ivan I, Zavelsky, Vladamir I, Thier, Ricarda, & Bolt, Hermann M (1998) Hydrolysis of genotoxic methyl-substituted oxiranes : Experimental kinetic and semiempirical studies. Environmental Toxicology and Chemistry, 17(11), pp. 2141-2147.

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The kinetics of acid-catalyzed hydrolysis of seven methylated aliphatic epoxides - R1R2C(O)CR3R4 (A: R1=R2=R3=R4=H; B: R1=R2=R3=H, R4=Me; C: R1=R2=H, R3=R4=Me; D: R1=R3=H, R2=R4=Me(trans); E: R1=R3=H, R2=R4=Me(cis); F: R1=R3=R4=Me, R2=H; G: R1=R2=R3=R4=Me) - has been studied at 36 ± 1.5°C. Compounds with two methyl groups at the same carbon atom of the oxirane ring exhibit highest rate constants (k(eff) in reciprocal molar concentration per second: 11.0 ± 1.3 for C, 10.7 ± 2.1 for F, and 8.7 ± 0.7 for G as opposed to 0.124 ± 0.003 for B, 0.305 ± 0.003 for D, and 0.635 ± 0.036 for E). Ethylene oxide (A) displays the lowest rate of hydrolysis (0.027 M-1 s-1). The results are consistent with literature data available for compounds A, B, and C. To model the reactivities we have employed quantum chemical calculations (MNDO, AM1, PM3, and MINDO/3) of the main reaction species. There is a correlation of the logarithm k(eff) with the total energy of epoxide ring opening. The best correlation coefficients (r) were obtained using the AM1 and MNDO methods (0.966 and 0.957, respectively). However, unlike MNDO, AM1 predicts approximately zero energy barriers for the oxirane ring opening of compounds B, C, E and G, which is not consistent with published kinetic data. Thus, the MNDO method provides a preferential means of modeling the acidic hydrolysis of the series of methylated oxiranes. The general ranking of mutagenicity in vitro, A > B > C, is in line with the concept that this sequence also gradually leaves the expoxide reactivity optimal for genotoxicity toward reactivities leading to higher biological detoxifications.

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ID Code: 77464
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Epoxide reactivity, Epoxide stability, Ethylene oxide, Substituted oxiranes, ethylene oxide derivative, article, calculation, chemical reaction kinetics, correlation function, genotoxicity, hydrolysis, model, molecular dynamics, mutagenicity, priority journal
DOI: 10.1002/etc.5620171103
ISSN: 1552-8618
Divisions: Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: Copyright 1998 John Wiley & Sons, Inc.
Deposited On: 16 Oct 2014 23:41
Last Modified: 16 Oct 2014 23:41

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