An Experimental and Computational Investigation into the Gas-Phase Acidities of Tyrosine and Phenylalanine: Three Structures for Deprotonated Tyrosine

Abstract

Using mass spectrometry and correlated molecular orbital theory, three deprotonated structures were revealed for the amino acid tyrosine. The structures were distinguished experimentally by ion/molecule reactions involving proton transfer and trimethylsilyl azide. Gas-phase acidities from proton transfer reactions and from G3(MP2) calculations generally agree well. The lowest energy structure, which was only observed experimentally using electrospray ionization from aprotic solvents, is deprotonated at the carboxylic acid group and is predicted to be highly folded. A second unfolded carboxylate structure is several kcal/mol higher in energy and primarily forms from protic solvents. Protic solvents also yield a structure deprotonated at the phenolic side chain, which experiments find to be intermediate in energy to the two carboxylate forms. G3(MP2) calculations indicate that the three structures differ in energy by only 2.5 kcal/mol, yet they are readily distinguished experimentally. Structural abundance ratios are dependent upon experimental conditions, including the solvent and accumulation time of ions in a hexapole. Under some conditions, carboxylate ions may convert to phenolate ions. For phenylalanine, which lacks a phenolic group, only one deprotonated structure was observed experimentally when electrosprayed from protic solvent. This agrees with G3(MP2) calculations that find the folded and unfolded carboxylate forms to differ by 0.3 kcal/mol.

Unveiling host–guest–solvent interactions in solution by identifying highly unstable host–guest configurations in thermal non-equilibrium gas phase

“…Third, by adopting the supramolecule/continuum approach, we simulate the structures of perm β-CD/H + /L-Lys complex in solution, thereby finding that the relative thermodynamic stability of perm β-CD/H + /L-Lys complex in solution is the complete reversal of that in the gas phase: The extremely higher Gibbs free energy gas phase structure (Complex I) corresponds to the most stable conformer (Complex A) in solution, and the most stable gas phase conformer (Complex II) becomes a less stable one (Complex B) in solution. This clearly indicates that the origin of the high Gibbs free energy gas phase structure (Complex I) is the configuration (Complex A) of perm β-CD/H + /L-Lys in solution , suggesting that the structure of gas phase host–guest complexes produced by ESI/MS/IRMPD technique 43 may be used as a very useful and accurate guide for probing host–guest–solvent interaction in solution.…”

An Experimental and Computational Study of the Gas-Phase Acidities of the Common Amino Acid Amides

“…Although the GAs of amino acids have been the focus of several studies, 1,2,17,35,36 the only previous report of GAs for amino acid amides is our work with glutamic acid amide and aspartic acid amide. 2 In this prior report, our experimental and computational G3(MP2) level GA values were in excellent agreement, and the calculations confirmed that both amides undergo side chain deprotonation at their carboxylic acid groups.…”

“…Reference compounds were introduced through a leak value at constant pressures, which were in the range of (1.0−11) × 10 −8 mbar. Ion/ molecule reaction times in the FT-ICR cell were varied from 0 to 300 s. Pressures were measured by a calibrated ion gauge, 17,40 and the pressure of each reference compound was corrected for its ionization efficiency, 41 which is determined by polarizabilities calculated with atomic hybrid parameter procedures. 42 The pseudo-first-order decay of precursor ion intensity as a function of reaction time was utilized to obtain experimental rate constants from which GA values were assigned.…”

Effects of ESI conditions on kinetic trapping of the solution-phase protonation isomer of p-aminobenzoic acid in the gas phase

“…[1–6] Furthermore, competing gas-phase (de)protonation sites can have important analytical implications. For instance, if relative abundances of the (de)protonation sites are dependent on experimental conditions, so too might be the observed spectra from tandem mass spectrometry,[7] ion mobility,[8, 9] or infrared spectroscopy.…”