Unified mechanism

An alternative, single mechanism for both bases may be formulated, however, by taking into account the differences in basicity (piCa = 5.25 and 11.01, for Py and EtsN, respectively [148]), and hydrophobicity between the two bases. A quantitative measure of the latter property is given by logP, the partition coefficient of the solute between n-octanol and water (logP = log([solute] octanol/[solute]water)> 0.65 and 1.45 for Py and EtsN, respectively [149]. This unified mechanism is shown in Fig. 4, where B refers to the base employed. 

Fig. 4 A unified mechanism for the reaction of cellulose with tosyl chloride in the presence of base (pyridine and/or triethylamine)...

Experiments with terminal acetylenes, isolation of an intermediate acetal, alkyne hydratation studies, and ab initio calculations provide substantiation of a unified mechanism that rationalizes the reactions in which the complex formation between the alkyne and the iron(III) halides is the activating step (Scheme 12) [27]. 

Properly folded native proteins tend to aggregate less than when unfolded. Solution additives that are known to stabilize the native proteins in solution may inhibit aggregation and enhance solubility. A diverse range of chemical additives are known to stabilize proteins in solution. These include salts, polyols, amino acids, and various polymers. Timasheff and colleagues have provided an extensive examination of the effects of solvent additives on protein stability [105]. The unifying mechanism for protein stabilization by these cosolvents is related to their preferential exclusion from the protein surface. With the cosolvent preferentially excluded, the protein surface is... 

In a very recent paper (47), Amer and Shapiro concluded that the thermal degradation oY PVC powder in the temperature range 170-210°C proceeded in such a way that HC1 catalysis was an integral part of the overall process. They proposed a unified mechanism consisting of three steps namely random generation of a single double bond in the cis configuration,... 

McAnaney TB, Zeng W, Doe CFE, Bhanji N, Wakelin S, Pearson DS, Abbyad P, Shi XH, Boxer SG, Bagshaw CR (2005) Protonation, photobleaching, and photoactivation of yellow fluorescent protein (YFP 10C) a unifying mechanism. Biochemistry 44 5510-5524... 

Fromm, M. F., Kim, R. B., Stein, M., Wilkinson, G. R., Roden, D. M., Inhibition of P-glycoprotein-mediated drug transport a unifying mechanism to explain the interaction between digoxin and quinidine, Circulation 1999, 99, 552-557. 

Scheme 7 Unified mechanism of rearrangement and fragmentation of ((-substituted radical...

Yan Y, Bariev NA, Haley RH, Berger SL, Marmorstein R (2000) Crystal structure of yeast Esal suggests a unified mechanism for catalysis and substrate binding by histone acetyltransferases. Mol Cell 6 1195-1205... 

Steric effects, molecular rearrangements, anchimeric assistance, and the use of tracer techniques have provided useful information about the nature of catalytic sites of aluminas and have led to a unified mechanism of their action. 

Available evidence suggests that a single unifying mechanism does not exist but rather that various vasodilators may act at different places in the series of processes that couple excitation of vascular smooth muscle cells with contraction. For example, the vasodilators known as calcium channel antagonists block or limit the entry of calcium through voltage-dependent channels in the membrane of vascular smooth muscle cells. In this way, the calcium channel blockers limit the amount of free intracellular calcium available to interact with smooth muscle contractile proteins (see Chapter 14). 

Recently, Jacobs (48) proposed a unified mechanism incorporating this dissociative sublimation step. He imagines the step towards the adsorbed state to be accomplished by proton transfer. At low temperatures, both NH3 and HCIO4 desorb but recombine in the gas phase to form gaseous NH4CIO4—i.e., pure sublimation occurs. At low temperatures and increased pressures, NH3 does not desorb but remains physically... 

Similar 1,2-migration/cyclization is observed in the reaction of 5-hexynyl tosylate 92a with zincates (equation 44)61. In addition to the exo-cyclization leading to (alkyli-dene)cyclopentane 93a, endo-cyclization occurs competitively to give cyclohexene 94a, which is a major product in the reaction with PthZnl.i. In the reaction of the phenyl-substituted derivative 92b, two endo-cyclization products 94b and 94 (1 1) were obtained as well as exo-cyclization product 93b. A unified mechanism in which the -electrons of the alkynylzincate 95 participate in exo- and endo-cyclization (Scheme 8) has been proposed to rationalize these observations. The intermediacy of cyclohexyne 96 was verified... 

Daggett, V., Fersht, A.R. (2003) Is there a unifying mechanism for protein folding Trends Biochem. Sci. 28, 18-25. 

It appears difficult to propose a unified mechanism to explain all experimental observations of the cyclotrimerization of acetylene. The most common pathway, studied mainly with cobalt complexes,72 73 involves a metallacyclopentadiene intermediate ... 

The detailed mechanism, or mechanisms, of the solvolysis of acid chlorides is still a matter of dispute. There are at least four possible mechanisms, (a)-(d) below, all of which have been proposed either to act separately or in various combinations, and there is a unified mechanism, that of Minato93 which will be discussed later. The bimolecular mechanisms (a) and (b) differ in that (a) includes a tetrahedral intermediate whereas (b) does not. The former is commonly accepted as the most likely for the bimolecular mechanism and the arguments against (b) have been stated in the introduction. There is, however, good evidence for (A), at least in the case of the hydrolysis of chloracetyl chloride94. The acylium ion mechanism (c) and the hydrated carbonium ion mechanism (d) are both unimolecular mechanisms. Whereas the acylium ion XXVII has never been directly observed in hydrolysis or alcoholysis reactions, it is favoured as an intermediate by many workers, although it is kinetically indistinguishable from XXVIII. 

This, although correctly predicting the direction of the variation in apparent order in solvent for benzoyl chloride hydrolysis at 25°C in changing from 2.9 (2-5% water/dioxan) to 1.15 (5-15% water/acetone) does not do so unambiguously. The unified mechanism of Minato is, nevertheless, a very valuable contribution and may be preferred on the grounds that it uses the hydrated carbonium ion rather than the acylium ion, a species which although undoubtedly known, has never, to the knowledge of the present author, been detected in the media used for hydrolysis. However, there is still no evidence to decide between the mechanism of Minato and a combination of routes (a) or (6), and (d) (p. 227). 

Porter NA, Lehman LS, Weber BA, Smith KJ (1981) Unified mechanism for polyunsaturated fatty acid autoxidation. Competition of peroxy radical hydrogen atom abstraction, p-scission, and cyclization. J Am Chem Soc 103 6447-6455... 

Brownlee, M., 2005, The pathobiology of diabetic complications a unifying mechanism. Diabetes 54, 1615-1625. 

Ross CA (2002) Polyglutamine pathogenesis emergence of unifying mechanisms for Huntington s disease and related disorders. Neuron 35 819-822. 

Figure 14 Unified mechanism of xylyl hydroxylation reactions, accounting for Cu202 intermediate [11] formation and copper-mediated N.I.H. shift (1,2-migration) reactions.

Numerous mechanistic studies of aluminum neurotoxicity have been performed, but the main sites of action have not been discerned as discussed in Section 2.4.2 and by Strong et al. (1996). Additional studies could help identify a single unifying mechanism that can explain and reconcile the wide variety of pathological, neurochemical, and behavioral effects of aluminum induced by oral exposure and in various model systems (e.g., intracerebral and intracistemal administration), but these kinds of studies are unlikely to better characterize neurotoxicity NOAELs and LOAELs relevant to MRL assessment. The relationship between aluminum exposure and neurotoxicity is an active area of research. 

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