41263-73-4Relevant academic research and scientific papers
4-Substituted 1-chloro-2-nitrobenzenes: Structure-activity relationships and extension of the substrate model of rat glutathione S-transferase 4-4
Van Der Aar, Ellen M.,De Groot, Marcel J.,Bouwman, Tialda,Bijloo, Greetje J.,Commandeur, Jan N. M.,Vermeulen, Nico P. E.
, p. 439 - 449 (1997)
In the present study, eleven 4-substituted 1-chloro-2-nitrobenzenes were tested for their GSH conjugation capacity when catalyzed by base or rat glutathione S-transferase (GST) 4-4. Kinetic parameters (k(s) and K(m), k(cat), and k(cat)/K(m)) were determined and subsequently used for the description of structure-activity relationships (SAR's). For this purpose, eight physicochemical parameters (electronic, steric, and lipophilic) of the substituents and five computer-calculated parameters of the substrates (charge distributions and several energy values) were used in regression analyses with the kinetic parameters. The obtained SAR's are compared with corresponding SAR's for the GSH conjugation of 2-substituted 1-chloro-4- nitrobenzenes, previously determined [Van der Aar et al. (1996) Chem. Res. Toxicol. 9, 527-534]. The kinetic parameters of the 4-substituted 1-chloro- 2-nitrobenzenes correlated well with the Hammett σ(p)- constant; the Hammett σ(p) constant corrected for 'through resonance', while the corresponding kinetic parameters of the 2-substituted 1-chloro-4- nitrobenzenes did not. The base-and GST 4-4-catalyzed GSH conjugation reactions of 2-substituted 1-chloro-4-nitrobenzenes depend to a different extent on the electronic properties of the ortho substituents, suggesting the involvement of different rate-limiting transition states. The base- and GST 4-4-catalyzed conjugation of 4-substituted 1-chloro-2-nitrobenzenes, however, showed a similar dependence on the electronic properties of the para substituents, indicating that these substrates are conjugated to GSH via a similar transition state. Multiple regression analyses revealed that, besides electronic interactions, also steric and lipophilic restrictions appeared to play an important role in the GST 4-4-catalyzed GSH conjugation of 4- substituted 1-chloro-2-nitrobenzenes. Finally, the 4-substituted 1-chloro-2- nitrobenzenes were also used to extend the previously described substrate model for GST 4-4 [De Groot et al. (1995) Chem. Res. Toxicol. 8, 649-658], by which a specific steric restriction of substrates for GST 4-4 became clear.
Nucleophilic displacement at the benzoyl centre: A study of the change in geometry at the carbonyl carbon atom
Colthurst, Matthew J.,Williams, Andrew
, p. 1493 - 1497 (2007/10/03)
The second-order rate constants for the reaction between hydroxide ion and phenoxide ion with 4-nitrophenyl esters of substituted benzoic acids in 10% acetonitrile-water (v/v) solution obey Hammett σ correlations. The values of the Hammett ρ of 1.67 (κArO) and 2.14 (κOH) are consistent with a large change in hybridization at the central carbon by comparison with the ρ value for a standard reaction where a full sp2 to sp3 change occurs. The transition state for the concerted reaction thus has a substantially tetrahedral geometry. The observation of the anti-Hammond effect whereby the ρ value for the hydroxide ion exceeds that of the less reactive phenoxide ion is consistent with a concerted, ANDN, mechanism for these reactions. A stepwise mechanism, AN + DN, is unlikely to yield a measurable break in the Hammett correlation for a change in the benzoyl substituent if the partitioning of the putative tetrahedral intermediate involves forward and reverse reactions with Hammett correlations possessing similar ρ values.
