Protonation Processes and Electronic Spectra of Histidine and Related Ions

Abstract

A full structural assignment of the neutral, protonated, and deprotonated histidine conformers in the gas phase is presented. A total of 3024 unique trial structures were generated by all combinations of internal single-bond rotamers of these species and optimized at the B3LYP/6-311G* level and further optimized at the B3LYP/6-311++G** level. A set of unique conformers is found, and their relative energies, free energies, dipole moments, rotational constants, electron affinities, ionization energies, and harmonic frequencies are determined. The population ratio of histidine and its tautomer is 1:0.16 at 298 K. Massive conformational changes are observed due to protonation and deprotonation, and the intramolecular H-bonds are characterized with the atoms in molecules theory. The calculated proton dissociation energy, gas-phase acidity, proton affinity, and gas-phase basicity are in excellent agreement with the experiments. The deprotonation and protonation of gaseous histidine both occur on the imidazole ring, explaining the versatile biofunctions of histidine in large biomolecules. The UV spectra of neutral and singly and doubly protonated histidine are investigated with the TDDFT/B3LYP/6-311+G(2df,p) calculations. The S0-S1, S0-S2, and S0-S3 excitations of histidine are mixed pipi*/npi* transitions at 5.37, 5.44, and 5.69 eV, respectively. The three excitation energies for histidine tautomer are 4.85, 5.47, and 5.52 eV, respectively. The three excitations for protonated histidine are mainly npi* transitions at 5.45, 5.67, and 5.82 eV, respectively. The S0-S1 excitation of protonated histidine produces ImH-CbetaH2-CalphaH(COOH)-NH2+, while the S0-S2 and S0-S3 transitions produce ImH-CbetaH2-CalphaH(NH2)-(COOH)+. These data may help to understand the mechanisms of the UV fragmentation of biomolecules.

A first-principles investigation of histidine and its ionic counterparts

“…4. The most stable conformer N τ HA1 is similar to the most stable conformer reported in the literature [54]. The N τ HA1 conformer shows similar type of hydrogen bond (NH-O) reported in aliphatic most stable conformer of cysteine anion [51][52][53].…”

“…The protonation or deprotonation processes induce substantial conformational changes involving the backbone and side chain torsions [54].…”

Structural stabilities of metalated histidines in gas phase and existence of gaseous zwitterionic histidine conformers

“…When the proton associated with the carboxyl of neutral histidine transfers to an imidazole ring directly rather than to the amino group, the histidine also forms a zwitterion tautomer denoted as zHis[N e HN d H]. Preparation of trial structures of the above mentioned tautomers is very similar to that given in previous studies of histidine [22,23] so we give only a brief discussion here. The symmetry of deprotonated carboxyl and protonated amino groups for zHis[N e H] and zHis[N d H] zwitterionic tautomers reduce the degrees of freedom.…”

“…Thus, the ability of accepting protons on both nitrogen atoms, designated as N e and N d , of the imidazole ring leads to multiple forms of zwitterions. [22,23]. When the proton associated with the carboxyl of neutral histidine transfers to an imidazole ring directly rather than to the amino group, the histidine also forms a zwitterion tautomer denoted as zHis[N e HN d H].…”

“…However, lysine, understood to be the second most basic, has not showed any stable zwitterionic forms in the gas phase [21]. Histidine, though with basicity lower than lysine, has potentially multiple zwitterion moieties due to its imidazole side chain [22,23]. Thus, it would be interesting to know whether or not histidine possesses zwitterions in the gas phase and subsequently a systematic search was performed to identify them.…”