Bifunctional inducers

Figure 1 Transcriptional regulation of the rat GSTA2 and NQOl genes by bifunctional and mono functional inducers. The bifunctional inducers and the dioxin TCDD bind to and activate the AhR, which then translocates into the nucleus and associates with ARNT to activate transcription through the XRE. The bifunctional inducers can also activate transcription through the ARE via a separate pathway following their biotransformation into reactive metabolites that have characteristics of the monofunctional inducers. The monofunctional inducers can only act through the ARE-mediatedpathway. 3-MC, 3-methylcholanthrene B(a)P, benzo(a)pyrene TCDD, 2,3,7,8-tetrachlorodibenzo-/>-dioxin.

Monofunctional inducers share certain common chemical properties. They are electrophilic compounds that are capable of reacting with sulfhydryl groups in addition, certain compounds can also undergo oxidation-reduction reactions (28). The bifunctional inducers acquire these properties following oxidative metabolism. Compounds such as the isothiocyanates and diethyl maleate do not require metabolism and can directly react with sulfhydryl groups, oxidizing cysteine... 

Yannai S, Day AJ, Williamson G, Rhodes MJ. 1998. Characterization offlavonoids as monofunctional or bifunctional inducers of quinone reductase in murine hepatoma cell lines. Food Chem. Toxicol. 36 623-30... 

It is shown that these new supports induce an enhancement of the NO reduction which cannot be explained by a modification of the Pd electronic properties. A bifunctional mechanism is proposed and discussed in addition to the intrinsic roles of the metal and of the... 

For Ti02 and Z1O2, it is well known that sulfation induces a strong increase of acidity [17] and the participation of an add mechanism could then account for this promotion of activity. This mechamsm can be described as a bifunctional process oxidation of NO to NO on Cu sites, and nitration of a product of the oxidation of decane on the acid fiinction(8). The preparation of the catalyst must have a great influence on the activity. This has been shown by the comparison of three Cu/TiC catalysts prepared in different conditions one in which titania is first treated with sulfuric acid, then by Cu acetate (denominated Cu 04/Ti02, containing 0.S wt% Cu, 0.6 wt% S), one in which Cu is... 

Waluk J (2003) Hydrogen-bonding-induced phenomena in bifunctional heteroazaaromatics. Acc Chem Res 36 832-838... 

The above observations strongly indicate that O-protonation is an important step in this particular reaction for the reduction of coordinated CO. Recent studies in our laboratory provide other examples of proton induced reduction in metal cluster systems, and an example of proton induced CO reduction has recently been reported by Atwood (44). It thus appears that protons as well as Lewis acids are effective in the bifunctional activation of coordinated CO. 

For reactions of bifunctional chains X—Y, two different types of solvent interactions are considered, i.e. (i) solvation of the non-reacting part of the molecule affecting the ease of cyclisation through solvent-induced conformational changes, and (ii) solvation of the reacting ends affecting the inherent reactivity of the ends themselves. 

Several reports indicate the involvement of superoxide in the mediation of tolerance [67-69]. Based on these reports, a bifunctional superoxide dismutase-mimic NO donor was designed by Haj-Yehia s group [70]. The nitrate ester was incorporated into a nitroxide such as 3-hydroxymethyl-2,2,5,5-tetramethyl-l-pyrroHdinyloxy (HMP) by its conversion into 3-nitratomethyl-PROXYL (NMP) (Scheme 1.7). HMP is a stable, metal-independent, low-molecular weight SOD-mimic with excellent cell-permeability. So NMP is the first compound that can simultaneously generate NO and destroy superoxide. This may lead to novel nontolerance-inducing nitrovasodila-tors. 

Scheme 6.141 Mechanistic proposal for the 121-catalyzed asymmetric intramolecular Michael addition exemplified for the model substrates ( )-4-hydroxy-l-phenyl-2-buten-l-one (n = 0) and ( )-5-hydroxy-l-phenyl-2-buten-l-one (n = 1) 121 functions as push/pull-type bifunctional catalyst inducing the cyclization of boronic acid hemiester (1) to form intermediate (2) release ofdiol product (3) by oxidation.

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