Imidazole group protonation

Substitution of a protonated imidazole group by an azide anion permits an azido-carboxylic ester to be obtained in good yield [137]... 

Studies on the effect of pH on peroxidase catalysis, or the heme-linked ionization, have provided much information on peroxidase catalysis and the active site structure. Heme-linked ionization has been observed in kinetic, electrochemical, absorption spectroscopic, proton balance, and Raman spectroscopic studies. Kinetic studies show that compound I formation is base-catalyzed (72). The pKa values are in the range of 3 to 6. The reactions of compounds I and II with substrates are also pH-dependent with pKa values in a similar range (72). Ligand binding (e.g. CO, O2 or halide ions) to ferrous and ferric peroxidases is also pH-dependent. A wide range of pKa values has been reported (72). The redox potentials of Fe3+/Fe2+ couples for peroxidases measured so far are all affected by pH. The pKa values are between 6 and 8, indicative of an imidazole group of a histidine residue (6, 31-33),... 

Octahedral with axial unidentate carboxylate groups. 2 imidazole groups have displacement of protons Me compound has trans py molecules and chelating carboxylates (N.B. 

On the basis of the above data, a tentative hypothesis has been advanced for the observed asymmetric induction. The carbonyl oxygen of benzaldehyde forms a H-bond with the piperazine ring NH of the histidine, the imidazole is protonated by the HCN, and the resulting cyanide ion attacks the si face of the activated carbonyl group since the re face is blocked by the phenyl ring of the phenylalanine, as seen in the Fig. 1. 

Evidence for the formation of Meisenheimer-type adducts from a purine system has been obtained by Liotta in two cases.43 The addition of t-BuO to 6-(2-hydroxyethoxy)-9-methoxymethyIpurine in t-BuOH, as monitored by H-NMR spectroscopy, causes an upfield shift of both pyrimidine and imidazole ring protons and the conversion of two absorptions of the methylene protons of the CH2CH2OH group to a broad absorption of the dioxolane ring, in agreement with the formation of the spiro adduct 19. Similarly, adduct 20 was formed from 6-methoxy-9-methoxymethylpurine by slow reaction with MeCT in 7-BuOH. 

The tautomeric ratio of B to A for histidine in water (Eq. 2-6) has been estimated, using 15N- and 13C-NMR, as 5.0 when the a-amino group is proto-nated and as 2.5 when at high pH it is unprotonated.17 This tautomerism of the imidazole group is probably important to the function of many enzymes and other proteins for example, if Ne of structure A (Eq. 2-6) is embedded in a protein, a proton approaching from the outside can induce the tautomerism shown with the release of a proton in the interior of the protein, perhaps at the active site of an enzyme. The form protonated on Ns (B of Eq. 2-6), which is the minor form in solution, predominates in some positions within proteins.18... 

At pH 7 the weakly basic imidazole group of histidine may be partially protonated. Both the -SH group of cysteine and the phenolic -OH of tyrosine are weakly acidic and will dissociate and thereby acquire negative charges at a sufficiently high pH. 

The equilibrium constant for Eq. 9-102, calculated from the pKa of 7.0 for imidazole, is 10 7 M. Since Keq is also the ratio of the overall rate constants for the forward and reverse reactions, we see that for the forward reaction kj = 10 7 x 1.5 x 1010 = 1.5 x 103 s . This slow rate results from the fact that in the intermediate complex (in brackets in Eq. 9-102) the proton is on the imidazole group most of the time. For a small fraction of the time it is on the coordinated molecule HzO but reverts to being on the imidazole many times before the imidazole and OH3+ separate (see also Eqs. 9-97 and 9-98). Because of this unfavorable equilibrium within the complex, the diffusion-controlled rate of proton transfer from a protonated imidazole to water is far less than for proton transfer in the reverse direction. 

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