The levelling effect of solvational imbalances in the reactions of oximate alpha-nucleophiles with electrophilic phosphorus centers. Relevance to detoxification of organophosphorus esters.

A study of the reactions of oximate alpha-nucleophiles with diisopropylphosphorofluoridate (DFP) and two model phosphonates, has revealed either a levelling-off in reactivity or a bell-shaped behaviour in accordance with a critical decoupling of desolvation and bond formation (solvational imbalances); the relevance of these results to detoxification is emphasized.

Solvent effect on the alpha-effect for the reactions of aryl acetates with butane-2,3-dione monoximate and p-chlorophenoxide in MeCN-H2O mixtures.

Second-order rate constants have been measured spectrophotometrically for the nucleophilic reactions of three substituted phenyl acetates with butane-2,3-dione monoximate (Ox(-)) as an alpha-nucleophile and p-chlorophenoxide (ClPhO(-)) as corresponding normal nucleophile, in MeCN-H2O mixtures of varying compositions at 25.0 +/- 0.1 degrees C. The reactivity of Ox(-) toward the aryl acetates decreases upon addition of MeCN to the reaction medium up to ca. 30 mol % MeCN, followed by a gradual increase in rate upon further addition of MeCN. A similar result has been obtained for the reaction of ClPhO(-) with the aryl acetates. However, the decrease in rate is more significant for the less reactive ClPhO(-) than for the more reactive Ox(-). Thus, for all the aryl acetates studied, Ox(-) exhibits a sizable alpha-effect (k(Ox)-/k(ClPhO)-) whose magnitude increases as the mol % MeCN in the reaction medium increases. The relative basicities (DeltapK(a)) of Ox(-) and ClPhO(-) have been determined spectrophotometrically using piperazine as a reference base. The DeltapK(a) values increase on increasing the mol % MeCN in the medium for both Ox(-) and ClPhO(-). The difference in the relative basicities of these nucleophiles (DeltaDeltapK(a)) becomes larger with increasing mol % MeCN. The plots of log k(Ox)-/k(ClPhO)- vs DeltaDeltapK(a) for the three substrates are linear with near-unit slope, indicating that the difference in the relative basicity of the nucleophiles is largely responsible for the increasing alpha-effect with medium composition in this system.

Dual behavior of 4-aza-6-nitrobenzofuroxan. A powerful electrophile in hydration and sigma-complex formation and a potential dienophile or heterodiene in diels-alder type reactions

In investigating the reactivities of aza analogues of super-electrophile 4,6-dinitrobenzofuroxan (DNBF, 1), we have found that the nitro-substituted pyridofuroxan 2 gives a remarkably stable hydrate 3 in aqueous solution (as evidenced by the requirement of ca. 50% H(2)SO(4) (H(0) approximately -3) for complete recovery of 2). The equilibrium constant K(H)()2(O) for hydration of 2 is estimated to be >/= 100, being comparable only with the K(H)()2(O) values reported for hydration of highly activated neutral polyazaaromatics such as 2- and 6-hydroxypteridines or 7-azapteridine. Interestingly, the NH group of 3 undergoes ionization at rather low pH (p = 5.79), affording an anionic hydroxy sigma-adduct 4 which is thermodynamically 10(8) times more stable than the related sigma-adduct of pteridine. The experimental evidence is that 4 is slightly more stable than the hydroxy sigma-adduct of DNBF, indicating not only that 2 ranks among the most electrophilic heteroaromatics known to date but also than an aza group may in fact be as efficient as a nitro group in promoting sigma-complex formation. 2 is also found to be a versatile Diels-Alder reagent, as a result of the low aromatic character of its six-membered ring. Upon treatment of 2 with cyclopentadiene and 2,3-dimethylbutadiene, various reactivity patterns have been observed. These led to different cycloadducts arising from normal as well as inverse electron-demand condensations involving the pyridine ring as the dienophile or the heterodiene contributor. Altogether, the results reveal major differences between the reactivity of 2 and that of DNBF, with in particular a remarkable tendency of the pyridofuroxan adducts to undergo covalent hydration, resulting in the formation of stable carbinolamines. Also noteworthy is the characterization of a diadduct which results from a Diels-Alder trapping of the o-dinitroso intermediate involved in the exchange of the 1-oxide and 3-oxide tautomers of 2.

Metal ion effects in isotopic hydrogen exchange in biologically important heterocycles.

The binding of metal ions to heteroatomic centers of biomolecules has been utilized as a probe of metal ion effects in living systems. This article focuses on the effect of N-coordination by transition metals, especially Pt(II), Co(III), Cr(III), on isotopic C(2)-H or C(8)-H exchange of imidazoles, thiazoles, and purines. The usual reactivity trend, protonated >> metalated >> neutral substrate, is excepted for Cr(III)/1-methylimidazole, where Cr(III) activates stronger than H(+). An interplay of factors is considered, including metal-to-ligand back-bonding, electronic structure of metal ions, and differences in crystal field stabilization energy.

The origin of the alpha-effect: dissection of ground-state and transition-state contributions

The origin of the alpha-effect has been probed through a combination of calorimetric and kinetic studies involving butane-2,3-dione monoximate as alpha-nucleophile and p-chlorophenoxide as normal nucleophile in the reaction with p-nitrophenyl acetate in DMSO-H(2)O mixtures, which has been shown to exhibit a bell-shaped profile in the alpha-effect with solvent composition. The study, involving determination of enthalpies of solution and activation parameters, has allowed a dissection of contributions to the alpha-effect of ground-state destabilization and transition-state stabilization in these DMSO-H(2)O solvent media. It has been found that over the solvent composition 0-50 mol % DMSO desolvation of the alpha-nucleophile is the main driving factor to the increasing alpha-effect. However, in solvent mixtures covering 50-90 mol % DMSO the thermodynamic activation parameters suggest an interplay of factors that result in the bell-shaped alpha-effect profile. Discussion is presented that includes possible medium-dependent nonsynchronicity of nucleophile desolvation and bond formation for the alpha-nucleophile.

Extraction of potassium p-nitrophenoxide with macrocyclic crown ethers and cryptands from aqueous medium into diverse organic solvents: a systematic evaluation.

A systematic study has been made of the extraction of potassium p-nitrophenoxide from aqueous medium into a number of organic solvents that are immiscible or partly miscible with water, in the presence of several macrocyclic crown ether and cryptand complexing agents. The efficiency of extraction varies extremely widely with the nature of the ligand and the solvent. For some solvent systems, DC-18-C-6 is more efficient than [2.2.2] cryptand as an extradant. The extraction values, however, provide only limited insight into the fundamental reasons behind the observed results. Hence equilibria involved have been considered and the results analysed in terms of the equilibrium constants. The microscopic and macroscopic properties of these systems are discussed.

Methylmercury distribution, metabolism, and neurotoxicity in the mouse brain.

Methylmercury distribution, biotransformation, and neurotoxicity in the brain of male Swiss albino mice were investigated. Mice were orally dosed with [203 Hg]methylmercury chloride (10 mg/kg) for 1 to 9 days. Methylmercury was evenly distributed among the posterior cerebral cortex, subcortex, brain stem, and cerebellum. The The anterior cerebral cortex had a significantly higher methylmercury concentration than the rest of the brain. The distribution of methylmercury's inorganic mercury metabolite was found to be uneven in the brain. The pattern of distribution was cerebellum greater than brain stem greater than subcortex greater than cerebral cortex. The order of the severity of histological damage was cerebral cortex greater than cerebellum greater than subcortex greater than brain stem. There was no correlation between methylmercury distribution in the brain and structural brain damage. However, there was a relationship between the distribution of methylmercury's inorganic mercury metabolite and structural damage in the anterior cerebral cortex (positive correlation) and the anterior subcortex (negative correlation). There was also a positive correlation between the fraction of methylmercury's metabolite of the total mercury present and structural brain damage in the anterior cerebral cortex. This study suggests that biotransformation may have a role in mediating methylmercury neurotoxicity.