Imidazoles proton affinity

MO studies (AMI and AMI-SMI) on the tautomerism and protonation of 2-thiopurine have been reported [95THE(334)223]. Heats of formation and relative energies have been calculated for the nine tautomeric forms in the gas phase. Tire proton affinities were determined for the most stable tautomers 8a-8d. Tire pyrimidine ring in the thiones 8a and 8b has shown a greater proton affinity in comparison with the imidazole ring, or with the other tautomers. In solution, the thione tautomers are claimed to be more stabilized by solvent effects than the thiol forms, and the 3H,1H tautomer 8b is the most stable. So far, no additional experimental data or ab initio calculations have been reported to confirm these conclusions. 

Computations performed on an N-methylated imidazole showed that the presence of the methyl group increases the proton affinity of the other nitrogen. In contrast, a peptide substituent at a carbon adjacent to the nitrogen decreases its proton affinity. This can be explained by the conjugation stabilization of the peptide-substituted neutral form, which is absent in the protonated form. This result seems to indicate that heteroatomic rings linked by... 

Electronic structure of imidazol-2-ylidene in the lowest singlet and triplet states proton affinity... 

The topic of low-barrier hydrogen bonds (LBHBs) and the question of how they are involved in enzyme function has been discussed heavily in the literature recently. Hydrogen bonds between two bases of nearly matched proton affinity often exhibit strongly perturbed bond lengths and spectroscopic parameters it remains somewhat unclear exactly how the spectroscopic parameters reflect total energy or reactivity. In this study, we report H NMR chemical shift data and surveys of structural preferences for the well-studied 0-H---0 systems, and also for less studied, but biologically important N-H-0 systems, in particular the imidazole and imidazolium functionality. The H shifts also show interesting trends in comparison with O-H-O motifs, which will require further scrutiny. 

The gas-phase proton affinity of the IV-heterocyclic carbene l-ethyl-3-methyl-imidazol-2-ylidene has been determined as 251.3 4 kcalmol-1 using the kinetic method, a value which makes the carbene one of the strongest bases reported thus far.160 Density functional theory calculations have been carried out at the B3FYP/ 6-31+G(d) level to compare the high experimental value with that estimated theoretically. 

The general strategy for generating radical adducts to heterocyclic molecules relies on selective protonation of a suitable neutral precursor to prepare a cation of a well-defined structure. The gas-phase acid is chosen so as to attack only the most basic site in the molecule, or alternatively, non-selective protonation can be used to prepare a mixture of ions. For example, protonation of imidazole with NH4+ occurs selectively on the imine nitrogen atom (N-l), which has the highest proton affinity and is the only position that can be protonated by an exothermic reaction (Scheme 22) [239]. 

Arad et al. (1990) simulated the reaction sequence of papain by constructing several enzyme-substrate models with molecular mechanics and following reaction paths with semiempirical quantum mechanics. AMBER force field (Weiner et al., 1986a) was employed for the construction. AMI (Dewar et al, 1985) results for proton affinities of the modeled molecules were compared to 4-31G and to experiments. AMI underestimates the proton affinities of methanethiol and of imidazole but overestimates the proton affinity of methanol. However, the proton transfer reactions from methanol to imidazole and from methanethiol to imidazole are overestimated by only 6 and 11 kcal/mol, respectively, and PT from imidazolium to formamide is underestimated by 6 kcal/mol. 

Table 1 Proton affinities (kcal mol ) and pK values of imidazoles.

The gas-phase basicity (intrinsic basicity) for pyrazoles and imidazoles has been determined, as have their thermodynamic and kinetic basicities and proton affinities [127]. 

Sulkowski E. 1996. Immobilized metal-ion affinity chromatography imidazole proton pump and chromatographic sequelae I. Proton pump, J. Mol. Recognit., 9, 389-393. 

The shapes of the titration curves of weak electrolytes are identical, as Figure 2.13 reveals. Note, however, that the midpoints of the different curves vary in a way that characterizes the particular electrolytes. The pV, for acetic acid is 4.76, the pV, for imidazole is 6.99, and that for ammonium is 9.25. These pV, values are directly related to the dissociation constants of these substances, or, viewed the other way, to the relative affinities of the conjugate bases for protons. NH3 has a high affinity for protons compared to Ac NH4 is a poor acid compared to HAc. 

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