Ab initio study of tautomerism and of basicity center preference in histamine, from gas phase to solution—comparison with experimental data (gas phase, solution, solid state)

Abstract

epoc ABSTRACT: Tautomeric and basicity center preferences for isolated neutral and monoprotonated histamine were studied by means of ab initio calculations (HF, MP2 and DFT). The polarizable continuum model (PCM) was applied to the study of the variations of the tautomeric and basicity center preferences in histamine on going from the gas phase to aqueous solution. Twelve solvents of different polarities (from n-heptane to water) were chosen and calculations were performed for geometries optimized at the HF/6-31G* level. In low-polarity solvents and in the gas phase the protonation site is identical. A change of the preferred site of protonation takes place in solvents containing heteroatoms (except tetrachloromethane). Under the same conditions, a variation of the tautomeric preference in the monocation occurs. The ring N 2 -protonated form (ImH þ )-favored in gas phase-is also preferred in non-polar solvents (n-heptane, benzene, tetrachloromethane). The ImH þ form becomes less important in more polar solvents. In such a case, the chain N 3 -protonated form (AmH þ -T 1 ) predominates. For the neutral histamine, solvation has a relatively small influence on the relative energies (variations are less than 1 kcal mol À1 ), and does not change the tautomeric preference (HA-T 2 ). Calculated basicity parameters were compared with those obtained experimentally in the gas phase and in aqueous solution. In the gas phase, the experimental ('macroscopic') basicity parameter (PA) is close to the 'microscopic' PA calculated for the gauche conformation. In aqueous solution, the microscopic pK a order is similar to that of the E prot calculated for the trans conformation. In the solid state, both forms of histamine (neutral and monoprotonated) prefer the trans conformation. Some exceptions occur for complexes with metals.

Gas-phase lithium cation basicity of histamine and its agonist 2-(β-aminoethyl)-pyridine

“…These strong increase of LCBs for bidentate ligands cannot be explained solely by substituent effects (polarizability and field/inductive) of the ethylamino group, because these effects should be smaller than 5 kcal mol −1 . The very high LCB for AEP and HA is attributed to the chelation effect of the lithium cation by two nitrogen basic sites, the ring N-aza and the chain N-amino, similarly as it has been previously reported for the proton [12,[14][15][16][17][18]20]. In the chelated structures, both ligands may take the gauche ('scorpion') conformation of the ethylamino side chain, and histamine may additionally take the HA1 tautomeric form, similarly as it has been observed for a majority of metal cation complexes of histamine in the solid state [16].…”

“…The very high LCB for AEP and HA is attributed to the chelation effect of the lithium cation by two nitrogen basic sites, the ring N-aza and the chain N-amino, similarly as it has been previously reported for the proton [12,[14][15][16][17][18]20]. In the chelated structures, both ligands may take the gauche ('scorpion') conformation of the ethylamino side chain, and histamine may additionally take the HA1 tautomeric form, similarly as it has been observed for a majority of metal cation complexes of histamine in the solid state [16]. The 'scorpion' conformation has been also found for the monoprotonated forms of both ligands in the gas-phase, where the chain N-aza binds the proton and the chain N-amino forms the hydrogen bond [17], as shown in Scheme 1, when M = H. Higher LCB values for pyridine and imidazole than for methylamine suggest that the lithium cation also interacts more strongly with the ring N-aza than with the chain N-amino site in both ligands, HA and AEP (as for the proton), as shown in Scheme 1, when M = Li.…”

“…All frequencies were positive, indicating that the DFT optimized structures correspond to the energy minima. For the neutral ligands HA and AEP, the conformations found previously were considered here as found previously [14,16,17,36]. The energies, enthalpies and Gibbs free energies at 298 K were calculated at the B3LYP/6-31G*//B3LYP/6-31G* level, as well as at the B3LYP/6-311+G**//B3LYP/6-31G* level for comparison.…”

“…Examination of structural data reported for the solid state revealed that histamine easily forms complexes with metal cations [16], e.g., with Cu(I), Cu(II), Ni(II), Cr(III), Co(III), Ca and Pd. Generally, HA plays the role of a bidentate nitrogen ligand in these complexes, where both basic sites, the ring N-aza and the chain N-amino are coordinated to the metal cation.…”

“…In previous papers, our attention was mainly concentrated on the proton-transfer reactions for histamine and its agonist 2-(␤-aminoethyl)-pyridine [12][13][14][15][16][17]. It has been found that similarly to other bidentate nitrogen ligands with a flexible conformation (diamines, aminoamidines, aminoguanidines), HA and AEP exhibit exceptionally high basicity in the gas-phase.…”