Deprotonation Protonation

Hydrogen exchange, in thiazole, especially deuteration, has been quantitatively investigated (379,380), but the mechanism of the reaction carried out at acidic or neutral pH corresponds to a protonation-deprotonation process (380), different from electrophilic substitution and is discussed in section I.3.E. 

The effect of pH is rarely of use for pK measurement it is more often of use in identifying the site of protonation/deprotonation when several basic or acidic sites are present. Knowing the incremental substitutent effects Z of amino and ammonium groups on benzene ring shifts in aniline and in the anilinium ion (40), one can decide which of the nitrogen atoms is protonated in procaine hydrochloride (problem 24). 

As discussed in the three preceding sections, the key intermediate in diazotizations is the A-nitroso derivative of the primary amine, the formation of which is usually the rate-determining step of diazotization. The subsequent steps are faster and therefore not easily accessible to study. The sequence of protonation, deprotonation, protonation, and dehydration in Scheme 3-36 seems to be the most reasonable mechanism. 

In the structure, we could not identify any residues in the vicinity of the cluster except the histidine ligands that are likely to undergo redox-dependent protonation/deprotonation (9)... 

Eq. (18)]. Similar protonation-deprotonation reactions are known in other systems (46, 146). 

For larger cryptands [6] (Cox et al., 1978), the protonation/deprotonation kinetics have also been measured. Table 4 lists the kinetic and the equilibrium data for such cryptands. When compared to the neutralization of protonated tertiary amines by OH, the reaction of the second smallest protonated cryptand [2.1.1] H is 10 to 10 times slower (Cox et al., 1978), indicating a strong shielding and possibly an i -orientation of the proton. For the [2.2.1] cryptand, no k and k-i values could be calculated, probably due to a fast pre-equilibrium between in,in- and m,OMt-conformations. 

Mammalian metallothioneins typically bind seven metal ions in cluster structures, with bridging sulfur groups, as seen in the x-ray structure of the Cd5Zn2MT complex (86). It is therefore difficult to develop a simple formation-constant description for the binding of metal ions to MT (87), considering that protonation-deprotonation equilibria of the free protein itself should also be taken into account. However, the usefulness of Table VIII as a guide to the affinity of metal ions for mercapto donor ligands is seen in that the ability of metal ions to... 

Electrochemical methods have been used extensively to elucidate the mechanism of reduction of tetrazolium salts. In aprotic media, the first step is a reversible one-electron reduction to the radical 154 as confirmed by ESR spectroscopy.256,266 As shown in Scheme 26, this radical can then disproportionate to the tetrazolium salt and the formazan anion (166) or take up another electron to the formazan dianion (167). The formation of the dianion through a direct reduction or through the intermediate tetrazolyl anion (168) has also been proposed.272-28 1,294 In aqueous solutions, where protonation/deprotonation equilibria contribute to the complexity of the reduction process, the reduction potentials are pH dependent and a one-electron wave is seldom observed. 

According to this scheme, 192 first affords the anion 195 in an initial protonation/ deprotonation equilibrium 195 then undergoes rate-determining unimolecular decomposition to the metaphosphorimidate 197, which reacts fast with water to give the phosphoric acid 197. 

Spectacular differences in absorption/excitation spectra are often observed for the dyes that exist in protonation-deprotonation equilibria. Their straightforward application is for pH sensing and also for designing the reporters, in which the shifting of such equilibrium by external proton donor or acceptor group is involved in sensing event. 

Changes in shape are not, of course, the only factors that can prevent electron-return. Other factors, such as a change in solvation or chemical reactions such as protonation, deprotonation, unimolecular break-down, rearrangement, etc., are summarised in Schemes 1 and 2. Some consequences of electron return are presented in Scheme 3. Here, AB stands for any species suffering the effects of radiation, including positive or negative ions as well as neutral molecules. 

If during the ionization the amount of energy deposited on the molecule is low, as occurs in soft techniques, i.e. Cl, ESI, DESI and MALDI, the mass spectrum is very simple. It is characterized by protonated/deprotonated molecules, and eventually few adduct ions but very few or no fragment ions. This implies that it is easy to obtain the molecular weight of the analyte under investigation, but structural information is missing. As an example, the ESI mass spectrum of a small molecule is reported in Figure 2.20. There are two main ions one at m/z 556 and another at m/z 578. As the mass spectrum has been obtained in positive... 

Fig. 5. Spectrophotometric titration of the Fe3+/H3L 34 (11) equilibrium system over the pH range 0.69-6.95. Arrows indicate the direction of movement of the spectra (A) with increasing pH and (B) with decreasing pH. Conditions [Fe3+] = [H3LI34] = 2.0 x 10 4mol dm-3, T — 25°C, /j. — 0.10. Two equilibria appear over two distinct pH ranges, indicating two separate protonation/deprotonation events occurring. Reprinted with permission from Ref. (58). Copyright 2007 American Chemical Society.

In this context we postulated that the shift reaction might proceed catalytically according to a hypothetical cycle such as Scheme I. There are four key steps in Scheme I a) nucleophilic attack of hydroxide or water on coordinated CO to give a hydroxycarbonyl complex, b) decarboxylation to give the metal hydride, c) reductive elimination of H2 from the hydride and d) coordination of new CO. In addition, there are several potentially crucial protonation/deprotonation equilibria involving metal hydrides or the hydroxycarbonyl. The mechanistic details have been worked out (but only incompletely) for a couple of the alkaline solution WGSR homogeneous catalysts. In these cases,... 

Chiral tetrahydroisoquinoline derivatives can be obtained by diastereoselective or enatioselective protonation. Deprotonation of lactam 87 with n-BuLi followed by addition of H2O and NH4CI afforded 88 in 92% yield and 97% ee. The stereoselectivity was highly dependent upon the proton source. Further elaboration afforded tetrahydroisoquinoline 89 in >97% ee . The enantioselective protonation of 1-substituted tetrahydroisoquinoline 90 in the presence of chiral amine 91 proceeded in 90-95% yield and 83-86% ee. This methodology was used in an asymmetric synthesis of salsolidine <00SL1640>. 

Whittaker et al. (131) proposed the catalytic cycle for GO shown in Fig. 8. Intriguing protonation-deprotonation steps of the bound alcohol and tyrosinate anion... 

As noted above, biouptake involves a series of elementary processes that take place in the external medium, in the interphasial region, and within the cell itself. One of the most important characteristics of the medium is the chemical speciation of the bioactive element or compound under consideration. Speci-ation not only includes complexation of metal ions by various types of ligands, but also the distribution over different oxidation states, e.g. Fe(II) and Fe(III), and protonation/deprotonation of organic and inorganic acids of intermediate strength. The relationship between speciation and the direct or indirect bioavailability1 of certain species has received a lot of recent attention. 

Compounds with an acidity constant, pK, in the range of 4 to 10, i.e. weak organic acids or bases, are present in two species forms at ambient pH. This pA a.i. range includes aromatic alcohols and thiols, carboxylic acids, aromatic amines and heterocyclic amines [15]. Conversely, alkyl-H and saturated alcohols do not undergo protonation/deprotonation in water (pA iw 14). 

The rate of protonation/deprotonation at the aqua oxo complex, which in principle can proceed via any of the above three pathways, is then given by Eq. (11)... 

The proton transfer processes described above induce interesting effects on the geometry of these metal complexes upon protonation (see also Section II). If it is assumed that the equatorial cyano ligands form a reference plane and are stationary for any of these distorted octahedral cyano oxo complexes, the protonation/deprotonation process as illustrated in Scheme 3 is responsible for the oxygen exchange at the oxo sites. This process effectively induces a dynamic oscillation of the metal center along the O-M-O axis at a rate defined by kmv, illustrated in Fig. 15. This rate of inversion is determined by the rate at which the proton is transferred via the bulk water from the one... 

Figure 6.1 A simple electrostatic adsorption mechanism illustrating the protonation-deprotonation chemistry of surface hydroxyl groups on oxide surfaces (which are neutral at the PZC) and the corresponding uptake of anionic or cationic complexes. Proton transfer to or from the surface can significantly affect the solution pH.

Another key contribution of the Schwarz group was the recognition of the dramatic influence of oxide surfaces on bulk solution pH. In a landmark 1989 paper, Noh and Schwarz [7] demonstrated the method of mass titration, in which successive additions of oxide cause stepwise shifts in solution pH. This procedure is illustrated in Figure 6.7 [7], As indicated in Figure 6.1, the protonation-deprotonation chemistry of the surface hydroxyl groups is coupled to the liquid-phase pH. In mass titration, as the mass (or more appropriately, the surface area) of oxide in solution increases, the solution pH is brought to the PZC of the oxide, at which point no driving force for proton transfer exists... 

The pH shift model of Park and Regalbuto combined (1) a proton balance between the surface and bulk liquid with (2) the protonation-deprotonation chemistry of the oxide surface (single amphoteric site), and (3) a surface charge-surface potential relationship assumed for an... 

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