Monoprotonated form

An extremely low rate of neutralization was found for the hexapyridino-tetraazatrimacrocycle [7] (Takemura et al., 1991). The monoprotonated form [7]-H could be isolated as its hydroxide The neutralization of the iM-located proton took half a year, forming a complex in which a water molecule is bound on the inside. 

The formation of the [M(HA)](" 1>+ complex was confirmed in independent pH-metric experiments in the case of copper(II). These studies also provided evidence that ascorbic acid is coordinated to the metal center in its monoprotonated form. Because of relatively fast redox reactions between iron(III) and ascorbic acid, similar studies to confirm the formation of [Fe(HA)]2+ were not feasible. However, indirect kinetic evidence also supported the formation of the [M(HA)](" 1>+ complex in both systems (6). 

When the EGB is an anion or a dianion, irreversible follow-up reaction of the deprotonated substrate, S , is the only way by which an unfavorable proton transfer equilibrium can be driven toward products. A disadvantage is that when the follow-up reaction of S is with an added electrophile, competing reaction between the EGB and the electrophile is often observed. Or - if the EGB is a dianion - the monoprotonated form may react with the electrophile. 

Both the formation and hydrolysis rates of chelates will generally be pH-dependent. Let us compare the behavior of a chelating ligand L with its monoprotonated form LH+. Each will exist in predominant amounts at particular pH s and usually have separate and distinct reactivities. 

A kinetic smdy of the acylation of ethylenediamine with benzoyl chloride (110) in water-dioxane mixtures at pH 5-7 showed that the reaction involves mainly benzoylation of the monoprotonated form of ethylenediamine. Stopped-flow FT-IR spectroscopy has been used to study the amine-catalysed reactions of benzoyl chloride (110) with either butanol or phenol in dichloromethane at 0 °C. A large isotope effect was observed for butanol versus butanol-O-d, which is consistent with a general-base-catalysed mechanism. An overall reaction order of three and a negligible isotope effect for phenol versus phenol- /6 were observed and are consistent with either a base- or nucleophilic-catalysed mechanism. Mechanistic studies of the aminolysis of substituted phenylacetyl chlorides (111) in acetonitrile at —15 °C have revealed that reactions with anilines point to an associative iSN2 pathway. ... 

It should be emphasized that the interpretation of the present results depended on the assumption that the substances were present in solution in one form only ( the di-anion of eosin and the monoprotonated form of proflavine) and that no association or dissociation occurred in the excited states. A full investigation should have included the dependence of the absorption and luminescence spectra on pH, concentration, and solvent. With this reservation in mind, the following tentative conclusions have been drawn from the present results ... 

Figure 5-5 Near ultraviolet absorption spectra of cytidine, uridine, adenosine, and guanosine. 1. Monoprotonated form of cytidine (for which pKa = 4.2). 2. Neutral form (pH 7) of cytidine. 3. Neutral form of uridine (for which pKa = 9.2). 4. Monoanionic form of uridine. 5. Monoprotonated form of adenosine (pKa = 3.5). 6. Neutral form of adenosine. 7. Neutral form of guanosine (pKa = 9.2). 8. Monoanion of guanosine.

Either of the two protons might dissociate first as the pH is raised (Eq. 6-75). However, the two microscopic dissociation constants pK x and pKB are distinctly different. The result is that at 25°C in the neutral (monoprotonated) form 80% of the molecules carry a proton on the N, while the other 20% are protonated on the less basic - O. Notice that the subscripts a and b used in this discussion do not refer to acidic and basic but to the individual dissociation steps shown in Eq. 6-75. Microscopic constants will always be indicated with asterisks in this discussion. 

The two monoprotonated forms of pyridoxine are the tautomeric pair shown in Eq. 6-75 and whose concentrations are related by the tautomeric ratio, R = [neutral form]/[dipolar ion], a pH-independent equilibrium constant with a value of 0.204/0.796 = 0.26 at 25°C.75 Evaluation of microscopic constants for dissociation of protons from compounds containing non-identical groups depends upon measurement of the tautomeric ratio, or ratios if more than two binding sites are present. In the case of pyridoxine, a spectrophotometric method was used to estimate R. 

The UV-visible absorption spectrum of the monoprotonated form of PLP was divided mathematically into individual bands for the aldehyde with dipolar ionic ring (+), the aldehyde tautomer with an uncharged ring (0) and the hydrate of the dipolar ion. The following fractions were estimated (Harris et al, 1976, Biochem. Biophys. Acta. 521,181-194. 

The lack of ring deformation on the first N protonation in the predeformed TV-alkylporphyrins renders them more basic [pX3 as 5.64 for (TV-Me)H(TPP)] than the planar porphyrins [pX3 a 4.38 for H2(TPP)], whereas their pX4 values (3.85) are identical because their monoprotonated forms have already been distorted.149... 

Diprotonated 2,4-pentanediol 10 loses water and rearranges to form 1,3-dimethyl allyl cation [Eq. (4.6)]. Diprotonated 2,5-hexanediol 11, above — 30°C, rearranges to a mixture of protonated cis- and tra .v-2,5-dimethyltetrahydrofurans [Eq. (4.7)]. This would seem to indicate that there is a significant amount of the monoprotonated form present or that the carbocation formed can easily lose a proton before ring formation occurs. 

Further support for the involvement of the superelectrophile (162) was obtained from experimental studies establishing the effect of acidity on the rearrangement. The yield of methyl isopropyl ketone from pivaldehyde is found to increase in proportion to acidity (Table 5) with complete conversion occurring at Hq —10.9. The pKa for the protonated pivaldehyde is estimated to be —8.0, indicating that more than half of the aldehyde is in its monoprotonated form (161) at Ho —10.9. Thus, protosolvation of the monoprotonated species (161) should lead to the formation of the superelectrophile (162) albeit in low concentrations. 

As a caveat to the use of NICS values as the sole determinant of aromaticity, Sastry and co-workers <2003JMT(663)145> have examined the use of this parameter for a range of heteroaromatic systems, including phosphinine 1 and its monoprotonated form 16. Their conclusion is that NICS values should not be used as the sole criterion for aromaticity for heteroaromatic molecules containing group III and IV row main group elements. 

Fig. 9.6 Absorption spectra of three ionic forms of tryptophanase in 0.1 M phosphate. A, the diprotonated, low pH form B, the monoprotonated form C, the unprotonated, high pH species. The spectra were resolved with log-normal curves. (Reproduced with permission from Metzler et al.,J. Biol Chem., 266,...

Fig. 31 Crystal structures of (a) the nickel(II) complex of the monoprotonated form of 18 [Nin(18H)]3+ [65] C-H hydrogen atoms omitted for clarity and (b) the [Cun(18)]2+ complex [66] all hydrogen atoms omitted for clarity...

At present some preliminary evidence has been obtained which suggests that sapphyrins can bind anions other than fluoride. In fact, an X-ray diffraction study shows that NJ binds to the monoprotonated form of sapphyrin [157]. Specifically, as shown in Fig. 29, the monoprotonated sapphyrin, H4Sap Nj, does not complex azide anion in an in-plane fashion but in an end-on manner, with the terminal azide nitrogen atom being 1.13 A above the sapphyrin plane [157]. Nonetheless, this atom is still vsdthin typical hydrogen bonding distance (2.8 to 3,0 A) of at least four of the five pyrrolic nitrogens [59, 173-176]. 

DDIEN. For DDPA at pH = 7.0, the ligand is most likely a mixture of the unprotonated and monoprotonated forms, with the percentage of the neutral form decreasing as the charge of the surfactant decreases from CTAB (+1) to SDS (-1) (32-34). The values of Kl vary by less than a factor of two among the three surfactants... 

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