Imidazoles protonation

Figure 45. Imidazole proton conductors—both as free molecules and attached to a polymer backbone.

Imidazole proton conductors have been explored as water replacement solvents and have also been attached to polymer backbones to replace the acid/ water complex in current PEMs (Figure 45). 

To summarize, the more hydrophobic phenolic compounds are extracted better than the less hydrophobic ones, and the extraction is maximal at pH < pfCg. In general, for all the compounds distribution ratios are relatively high and comparable to those achieved with conventional active solvents like 1-octanol. This may be attributed to the ability of IL s imidazolic proton at Cj to hydrogen bonding and specific solvation of the phenolic molecule. 

Fig. 17. Proton NMR spectra of native MbnICN and reconstituted DeutMbmCN (Fig. 2). The resonance assignments are (a) ring methyls, (6) mesoprotons, (c, d) methylene protons of the propionate groups, (/) —CH protons of the vinyl groups (/D) 2,4-protons in DeutMbIIICN, (x) tentatively assigned to the imidazole protons of the axial histidine. The f-resonances were assigned from their absence in Deut-MblnCN, the other resonances from their intensities and their presence in both spectra. (Reproduced from ref. (98))...

Bello-Roufai, M. and Midoux, P. (2001) Histidylated polylysine as DNA vector elevation of the imidazole protonation and reduced cellular uptake without change in the polyfection efficiency of serum stabilized negative polyplexes. Bioconjug. Chem., 12, 92-99. 

Evidence for the tetrahedral intermediate includes a Hammett p constant of+2.1 for the deacylation reaction of substituted benzoyl-chymotrypsins and the formation of tetrahedral complexes with many inhibitors, such as boronates, sulfonyl fluorides, peptide aldehydes, and peptidyl trifluoromethyl ketones. In these last the chemical shift of the imidazole proton is 18.9 ppm, indicating a good low-barrier H-bond, and the pJQ of the imidazolium is 12.1, indicating that it is stabilized by 7.3 kcal mol 1 compared to substrate-free chymotrypsin. The imidazole in effect is a much stronger base, facilitating proton removal from the serine. 

The amine-imine and the lactam-lactim tautomerisms may, of course, be coupled with the shift of the imidazole proton on the purine skeleton. In polysubstituted derivatives, e.g., in 8-azaguanine, all the different types of tautomerisms may be intermingled. 

This precaution stated, a simultaneous theoretical investigation of the essential spectroscopic features of the lactam and lactim forms of the three fundamental monohydroxypurines yields some interesting results. These are summarized in Table XII, together with the corresponding experimental data, which in the case of lactim forms refer to the methoxy derivatives. As in all these compounds there is besides the lactam-lactim tautomerism, the possibility of an oscillation of the imidazole proton between the different N atoms of the ring system, Table XII indicates the exact tautomeric form or forms to which the calculations refer. In case of the lactam forms these are the most probable tautomers of such forms obtained in the study described in the next section. For the lactim forms they are the a priori most probable ones. 

Another interesting electronic property which may be studied comparatively for the lactam and lactim forms of hydroxypurines is their dipole moment. A difficulty occurs, however, due to the fact that dipole moments are, on the one hand, extremely sensitive to the position of the imidazole proton and, on the other, they are also very sensitive, in the lactim form, to the C-O-H angle. Any hindrance to the free rotation of the O-H bond may therefore have a very strong influence on the value of the moment. For these reasons we shall limit ourselves here to a few general qualitative remarks. 

Whatever be the difficulties in dealing satisfactorily with the problem of the lactam-lactim tautomerism in hydroxypurines, the predominance of the lactam tautomer granted, there remains the problem of the detailed structure of the most probable lactam form for each isomer. The problem is essentially that of the site of location of the imidazole proton. From that point of view forms 34-38 have to be considered for 2-hydroxypurine, forms 39—42 for 6-hydroxypurine (hypoxanthine), and forms 43-45 for 8-hydroxypurine. There are, in addition, some betaine tautomeric forms but these are probably of low stability and will not be considered further. Before describing the results of theoretical calculations, it may be useful to indicate that from the experimental point of view we may, in this respect, turn again for significant evidence to infrared spectroscopy... 

Because of the presence of a carbonyl and an amino group and the possibilities for the imidazole proton to oscillate between nitrogens N-7, N-9, and N-3, the molecule of guanine offers numerous and complex possibilities of tautomerization. Among those two have received special attention. 

A much more curious case is that of the N(3)H tautomer (61) of guanine that we have studied (at least to begin with) in which the imidazole proton is shifted to position 3, a proton remaining attached to position 1. It is thus an N(1)H-N(3)H tautomer. Such a structure... 

Maciejewska" has published 13C CP/MAS NMR spectra of 2-methyl-4-(4-X-phenylazo)imidazoles. Proton transfer phenomena can occur in imidazoles. Depending on the nature and orientation of the substituent X it was possible to identify one tautomer for X = H, Br and N02 and two tautomers for X = OCH3. Solid 2-methyl-4-(4-X-phenylazo)imidazoles form hydrogen-bonded chains with N—H- N bonds and C—H- O or C—H- N interactions. 

Barlin and Batterham223 have studied the effects of solvent on chemical shifts of the anionic and cationic species of imidazoles. Protonation shifts, obtained by direct comparison of spectra in deuteriochloroform and trifluoroacetic acid, observed for 1-methyl-imidazoles are consistent with stabilization of the resulting cations by an amidinium-type resonance (47). Thus, for 1-methylimidazole, which... 

In the anionic form of xanthine (as a sodium salt) no hydrogen appears at N-3 or N-7 and the data has been interpreted by assignment of the canonical structures (Scheme 1) (69BCJ3099). It is interesting to note that in this case all the forms are assigned as 9H tautomers, the imidazole proton in solution usually being assigned to N-7. 

The base DMAP below protonates on the sp nitrogen that is perpendicular to the pi system and not the lone pair involved in conjugation with the pyridine ring. Likewise, imidazole protonates on the lone pair not involved in the aromaticity of the ring system. 

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