Proton affinities from dissociations of proton-bound dimers

109

The proton affinities of the 20 common amino acids have been computed at the G3MP2 level using structures derived from broad conformational searches at a variety of levels including G3MP2. In some cases, the conformational surveys identified more stable species than had been used in previous studies of proton affinities, though the differences in energy are sometimes rather small. The present values are likely the most reliable measure of amino acid proton affinities in the gas phase. An analysis of differences between these values and those obtained experimentally via the kinetic method indicates that the extraction of proton affinities from kinetic method data can potentially lead to large errors linked to the estimation of relative protonation entropies. . As noted by these authors, there is substantial variation in the experimental values reported for these species. The origin of this variability is most likely related to the difficulties of completing thermodynamic measurements in the gas phase on materials with low volatility. As a result, many of the experimental values are from kinetic method measurements and are subject to errors associated with the kinetic method approximation (as well as cumulative errors associated with the development of ladder-type scales). Therefore, in these systems, high-level computational work offers an attractive means of resolving differences in the various experimental measurements.While working on a computational study of the conformational preferences of neutral, gaseous amino acids, we realized that it would be possible to improve on the accuracy of the proton affinities reported by Paizs and coworkers. First, their computational strategy relied on the B3LYP approach to identify global minima and, often, they identified conformations for the neutral amino acids that did not match with those reported in previous computational and experimental studies (apparently in some cases this was the result of the search strategy and in others the computational method). For example, Paizs and coworkers concluded that glycine prefers a structure with an internal hydrogen bond between the carboxylic acid and amine groups. Highlevel ab initio, other B3LYP data [2], and experimental data suggest a structure with a syn carboxyl group and a weak interaction between the amine hydrogens and the carbonyl [3][4][5]. While the energetic impact of this problem is generally minor, we feel it is important to report values based on the most appropriate conformations that can be obtained within a computational method. For the protonated amino acids, this problem is less pronounced because the hydrogen bonding interactions are much stronger; most computational methods identify similar structures as the global minimum. Second, values reported by Paizs and coworkers are at 0 K. We have added a correction for the thermal energy of a proton, which amounts to about 1.5 kcal/mol at 298 K, as well as for the neutral and protonated amino acid. Although these corrections cancel to some extent and while the ge...

Section: Comparison To Experimental Valuesmentioning

confidence: 99%

A reevaluation of computed proton affinities for the common α-amino acids

Gronert

Simpson

Conner

2009

109

“…In order to facilitate interpretation of these data, the gas-phase basicities of the peptides used were ranked by application of the kinetic method first introduced by Cooks°and°coworkers° [17].°Thus,°pairs°of°peptides°were coanalyzed by electrospray at high concentrations. The proton-bound heterodimers so formed were selected and subjected to CID, and the relative abundances of the protonated monomers were determined.…”

Section: Effect Of Ionization Mechanism On Internal Energymentioning

confidence: 99%

Comparison of the effects of ionization mechanism, analyte concentration, and ion “cool-times” on the internal energies of peptide ions produced by electrospray and atmospheric pressure matrix-assisted laser desorption ionization

Konn

Murrell

Despeyroux

et al. 2005

The propensities of a series of peptide ions produced by both electrospray and atmospheric pressure matrix assisted laser desorption ionization (AP-MALDI) to fragment in an ion trap mass spectrometer under various conditions were studied in detail by measuring the extent of fragmentation of precursor ions by collision induced dissociation (CID) as a function of applied resonance excitation RF voltage. For the most basic peptides, the energy required to fragment MH ϩ ions generated by electrospray exceeded that required to fragment equivalent AP-MALDI ions under identical instrumental conditions; the reverse was observed for a peptide incorporating no basic residues, while peptides of intermediate basicity showed little difference between the ionization methods. This correlation between peptide basicity and the difference in the energy required to induce fragmentation of MH ϩ ions generated by AP-MALDI and electrospray is attributed primarily to a trend in the internal energies of the ions generated by AP-MALDI (the greater the difference in gas-phase basicities between the matrix and the analyte the greater the internal energy of the analyte ions produced). Furthermore the internal energies of ions produced by AP-MALDI, but not the equivalent ions formed by electrospray, were observed to decrease with decreasing analyte concentration. We attribute this finding to the cooling effect of endothermic dissociation of analyte ion/matrix molecule clusters following the matrix assisted laser desorption step. Time-resolved analyses (measurement of extent of fragmentation of precursor ions by CID as a function of pre-CID "cool times") revealed that cooling periods in excess of 250 ms were required to achieve internal energy equilibrium through cooling collisions with the helium buffer gas. Furthermore, these analyses demonstrated that, even after these extended cooling times, equivalent ions formed by the two ionization techniques showed different propensities to fragment. We conclude that the two different ionization techniques produce ion populations that may differ in their three-dimensional structure. T he initial internal energy of an ion is determined by the internal energy of the analyte molecule before ionization and the energy deposited during ionization. The additional internal energy that must be acquired during ion activation in order for dissociation to occur is defined by the initial internal energy of the ion. Thus, for a fixed activation energy the extent of ion decomposition is a measure of the initial internal energy of that ion. Therefore, in order to compare the initial internal energies of peptide ions produced by electrospray and AP-MALDI, a series of energyresolved tandem mass spectrometry experiments were performed, in which the extent of decomposition of precursor ions by CID was measured as a function of applied resonance excitation RF voltage.Danell and Glish [1] and Wysocki and coworkers [2] investigated the differences between the internal ener-

“…These complexes are abbreviated as [M 1 ϩ M 2 ϩ (EOx)], where M 1 ϩ and M 2 ϩ are different alkali metal ions, EO ϭ ethylene oxide unit, and x ϭ degree of polymerization. This study of the doubly cationized PEG has permitted an in situ measure of the relative binding strength of the cumulative ion-dipole bonds when a single PEG molecule coordinates to the s-orbital of two different alkali metal ions.The dissociation of these complexes inside a quadrupole ion trap is a form of the kinetic method [36,37]. In this variation, rather than sandwiching a single cation between two ligands, a single ligand that was large enough to bind two different metal ions was…”

mentioning

confidence: 99%

“…The dissociation of these complexes inside a quadrupole ion trap is a form of the kinetic method [36,37]. In this variation, rather than sandwiching a single cation between two ligands, a single ligand that was large enough to bind two different metal ions was used.…”

mentioning

confidence: 99%

Poly(ethylene glycol) doubly and singly cationized by different alkali metal ions: Relative cation affinities and cation-dependent resolution in a quadrupole ion trap mass spectrometer

Bogan

Agnes

2002

Structural information of gas phase complexes of poly(ethylene glycol) (PEG) cationized by one or two different alkali metal ions is inferred from MS and MS/MS experiments performed with an electrospray quadrupole ion trap mass spectrometer. The rationale for selecting PEG was that its sites for cation binding are non-selective with respect to the repeating monomeric unit of the polymer, but there is selectivity with respect to the formation of an inner coordination sphere specific to each metal ion. The dissociation of [M 1 ϩ M 2 ϩ (EO23)], where EO23 ϭ linear polymer of ethylene oxide, 23 units in length, resulted in loss of one of the alkali metal ions, with preference for loss of the larger cation, with no fragmentation of the PEG backbone for Na, K, Rb, and Cs. Li was not examined in this portion of the study. The selectivity for loss of the larger alkali metal ion was [Na -20]. Factors involved in the solution phase molecular recognition are solvation enthalpy and entropy for both species and the number of atoms from the ligand that are involved with the binding of the metal ion, plus any conformational change of the ligand between its unbound and bound forms [21]. The intrinsic properties of the ion-dipole bonds in these non-covalent complexes are being deduced using a variety of gas phase techniques, including the equilibrium method [22], threshold CID [23][24][25][26], and ion chromatography [27,28].The long chain podands have received comparatively less attention by mass spectrometry [29,30], yet their industrial usage is immense, ranging from the fabrication of materials with varied properties to their use as phase transfer catalysts in industrial processes [31]. Long chain podands are also used as agents for improving bio-compatibility in immunological applications [32][33][34] and as ion channel models [35]. Improved knowledge of the structures formed when long chain podands coordinate with alkali metal ions, and particularly with the ubiquitous Na ϩ and K ϩ , can be of use in improving the applications of these materials.Here we report the uni-molecular dissociation of modest length podands (PEG, M.W. avg ϭ 1000) that were doubly cationized by different alkali metal ions. These complexes are abbreviated as [M 1 ϩ M 2 ϩ (EOx)], where M 1 ϩ and M 2 ϩ are different alkali metal ions, EO ϭ ethylene oxide unit, and x ϭ degree of polymerization. This study of the doubly cationized PEG has permitted an in situ measure of the relative binding strength of the cumulative ion-dipole bonds when a single PEG molecule coordinates to the s-orbital of two different alkali metal ions.The dissociation of these complexes inside a quadrupole ion trap is a form of the kinetic method [36,37]. In this variation, rather than sandwiching a single cation between two ligands, a single ligand that was large enough to bind two different metal ions was