Dehydron

Note. In abbreviations, a capital P is used to indicate a terminal -PO3H2 group or a non-terminal -PO2H- group (or dehydronated forms). 

Specific acid-catalysed solvolysis of l-methoxy-l,4-dihydronaphthalene or 2-methoxy-l,2-dihydronaphthalene in 25% acetonitrile in water has been found to yield mainly the elimination product, naphthalene, along with a small amount of 2-hydroxy-1,2-dihydronaphthalene, there being no trace of either the 1-hydroxy-1,4-dihydronaphthalene or the rearranged ether. The nucleophilic selectivity, ns/ hoh = 2.1 X 10", between added azide ion and solvent water has been estimated for the relatively stable = 1 x 10 s ) intermediate benzallylic carbocation for which the barrier to dehydronation is unusually low k = 1.6 x 10 ° s ), as evidenced by the large elimination-to-substitution ratio with solvent water as base/nucleophile. The kinetics of acid-catalysed solvolysis of 1-hydroxy-1,4-dihydronaphthalene and 2-hydroxy-1,2-dihydronaphthalene have also been studied. 

Industrial synthesis of nerolidol starts with linalool, which is converted into ger-anylacetone by using diketene, ethyl acetoacetate, or isopropenyl methyl ether, analogous to the synthesis of 6-methyl-5-hepten-2-one from 2-methyl-3-buten-2-ol. Addition of acetylene and partial hydrogenation of the resultant dehydroner-olidol produces a mixture of cis- and trans-nerolidol racemates. 

The Meyer reaction is intrinsically reversible. As the pH rises and arsenite becomes progressively dehydronated, it becomes an increasingly good nucleophile, whereas it becomes an increasingly good leaving group as the pH falls and the C—As bond can break (see 75, p. 987). 

A number of investigations of the reaction of cis-Pt with GSH have been published (76, 187-189, 191), but due to the complexity of the system, i.e., because of amine release, the reaction products still have not been characterized unambiguously. It has been suggested that [Pt(GS)2] (187) with coordination via S and dehydronated peptide N atoms, or [cis-PT(NH3)2(GS)(H20)] (191), is formed. On the other hand, it has been proved recently that eventually a polymeric structure is formed with formula [Pt(GS)2] (76, 188, 189), involving loss of NH3. Combining the results of the two most detailed studies (188,189), it is likely that initially intermediate species such as [cis-Pt(NH3)2(GS)Cl] and [Pt2(NH3)4(GS)2] (see Fig. 12) can indeed be formed. These unstable products lose NH3 upon standing, eventually forming the polymeric [Pt(GS)2] with coordination exclusively via the S atom, but with several different Pt—S and Pt—S—Pt environments. 

This is a new recommendation. Note that it implies that all uses with respect to acids and bases involving tbe normal isotopic mixture of h. 2H. and 3H would require the use of hydron, i.c., the hydron affinity of bases, Brpnsied acids are hydron donors, etc. Wc have retained the current usage of proton affinity, etc., because the recommendation came out as this book was going to press. The reader should note however that hydron is already receiving some European usage, as in "GS = GSH dehydronated at the thiol group."]... 

Protein side groups, such as thiolate, imidazole, carboxylates some examples are given in Figure 1 in many cases dehydronation (i.e., loss of a hydron, H+) takes place upon binding to a metal. 

A pathway that can lead to loss of specificity involves hydronation of the vinyl ligand at the carbon atom remote from the metal. This gives rise to an alkylidene species and consequent formation of a carbon-carbon single bond. Of course, dehydronation can occur to regenerate the vinyl species, but free rotation about this carbon-carbon single bond in the alkylidene would be expected to lead to a mixture of cis- and irans-vinyl species. Surprisingly, this need not be the case. 

Ser642 has abstracted a hydron from Ca a carbanion has been formed. That Sei642 has a dehydronated hydroxyl group implies that its pAa... 

A mechanism for the oxidation of carbon monoxide at cluster C has been proposed [139] in it CO and water bind to the cluster (Figure 6a). By analogy with cyanide binding, water is proposed to bind to the high-spin Ni(II) and CO to an iron atom of the cluster. After dehydronation of the water molecule the resulting hydroxide attacks the CO to form -COOH. Dehydronation of this spe-... 

This dependency underscores the role of the bases in catalase activity (Figure 21) tuning the metal center (see also Scheme 6), assisting in H202 dehydronation (and hence its binding to Mn) and facilitation, via electronic inductive effects, of 0—0 splitting in Mn(H—O—O—H) intermediates. 

The polymerization of compounds having active methyne groups has also been reported [81] (Eq. 8). The oxidative coupling polymerization of these monomers follows a mechanism similar to that of phenols. The catalytic cycle observed in the polymerization of / -phcnylcncdiaminc with Fe(edta) as the catalyst in an aqueous solution differs from that in the polymerization of phenols as follows The activation of monomers usually involves either electron transfer from the anion or elimination of a hydrogen atom from the monomer. The oxidative polymerization of phenols uses the former mechanism of the electron transfer. In contrast, in the case of the polymerization of aromatic diamines as monomers, the neutral amines are coordinated to the catalyst, followed by the subsequent electron transfer and dehydronation. The dehydronation proceeds by the reaction with 02. Another mechanism has also been proposed where dehydrogenation... 

Full details of a study of leaving group-promoted solvolytic elimination reactions of 1-(1-methyl-l-arylethyl)pyridinium cations in 25 vol.% acetonitrile (aqueous) have been reported. Reactions of (34) and (35) are found to proceed via a common carbocation intermediate of ion-molecule pair type to give the suhstitution product (36) and elimination product (37) (Scheme 4). The total rate of reaction of (35) exceeds that for (34) by 1100-fold, corresponding to a Bronsted parameter of )S g = —0.93, and the fraction of (37) obtained is governed by = 0.12 for the dehydronation (kg) of the ion-molecule pair by the leaving group the product ratio is hardly affected hy the presence of substituted pyridines. For (34) and (35), = 1.85 0.10 (60 °C) and... 

Fig. 1.3 Illustration of the under-wrapping of protein structure. Dehydron pattern of human ubiq-uitin (ribbon display in Fig. 1.1b). Dehydrons are indicated as green segments joining the a-carbons of the paired units, well-wrapped hydrogen bonds (p> 19) are shown in light gray, and the protein backbone is conventionally shown as blue virtual bonds joining the a-carbons of consecutive amino acid units. The displayed structure has 33 backbone hydrogen bonds, of which 11 are dehydrons. Thus, the extent of under-wrapping for this protein is 33%...

Throughout the book, dehydrons will be referred to in different ways depending on the context. Thus, the terms packing defect, wrapping defect, dehydron, structural deficiency, structural vulnerability will be used synonymously. Far from introducing a notational chaos, this name multiplicity bespeaks of the richness of the concept. 

As indicated above, dehydrons have unique physico-chemical properties They represent structural vulnerabilities of the protein, but they also constitute sticky spots promoting the removal of surrounding water [12-14, 19, 21], This latter property could only be established by addressing the following questions How do we effectively demonstrate that a dehydron attracts nonpolar test groups Can we measure the mechanical equivalent of its dehydration propensity ... 

For proteins with comparable surface hydrophobicity, the adsorption uptake correlates strongly with the extent of protein under-wrapping [19]. As an adequate control, only proteins with the same extent of surface hydrophobicity or solvent-exposed nonpolar area were included in the comparative analysis. Hence, the attractive drag exerted by dehydrons on test hydrophobes became accessible. The net gain in Coulomb energy associated with wrapping a dehydron has been experimentally determined to be 4 kJ/mol [19]. The adhesive force exerted by a dehydron on a hydrophobe at 6 A distance is 7.8 pN, a magnitude comparable to the hydrophobic attraction between two nonpolar moieties that frame unfavorable interfaces with water. 

Building on this analysis, we may quantify the net hydrophobicity r] of a hydrogen bond by taking into account the surface flux of the dehydronic field generated by the hydrogen bond. This field is given by = volume of test hydrophobe). Thus, in accord with Gauss theorem we obtain... 

Can we purposely design cooperative drugs that wrap dehydrons in the protein target ... 

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