Accuracy of enthalpy and entropy determination using the kinetic method: are we approaching a consensus?

We determined the gas-phase acidity of methylthioacetic acid (MTA) in a triple-quadrupole mass spectrometer using the Cooks' kinetic method with the consideration of entropy effects. The negatively charged proton-bound dimers were generated by electrospray ionization. Collisioninduced dissociation was applied to the dimer ions and the product ion ratios were measured at four different collision energies. The gas-phase acidity (⌬H acid ) of MTA was determined to be 340.0 Ϯ 1.7 kcal/mol using the extended kinetic method and 339.8 Ϯ 1.7 kcal/mol using the standard kinetic method. The entropy term is insignificant in this case and can be ignored. The standard kinetic method yielded a free energy of deprotonation of MTA (⌬G acid ) of 333.0 Ϯ 1.7 kcal/mol. The entropy of the acid dissociation, ⌬S acid , was estimated to be 22.8 cal/mol K. Theoretical prediction at the B3LYP/6-31 ϩ G* level of theory gives a similar value for ⌬H acid of 338.9 kcal/mol. In the gas-phase, MTA is a stronger acid than methoxyacetic acid, although in solution, MTA is a weaker one. , and as a model to study electron-transfer reactions in substituted alkyl sulfides [3]. A recent study of natural food flavors found that MTA is one of the biotransformation products of the cysteine-aldehyde conjugate by baker's yeast [4]. MTA has a similar structure as that of methoxyacetic acid, CH 3 OCH 2 CO 2 H. Both methoxyacetic acid and MTA have been used to study solvent and substituent effects on the acidity of substituted acetic acids [5,6]. In aqueous solution, MTA (pK a ϭ 3.7) is a slightly weaker acid than methoxyacetic acid (pK a ϭ 3.5) [6]. In the gas-phase, methoxyacetic acid has an acidity (⌬H acid ) of 341.9 kcal/mol [7,8], while the acidity of MTA is unknown. In this paper, we report on the first determination of the gas-phase acidity of MTA by using the Cooks' kinetic method [9,10] and theoretical calculations. ExperimentalThe gas-phase acidity (⌬H acid ) of MTA was determined by using the extended Cooks' kinetic method in which entropy effects were taken into consideration [11][12][13]. Selected applications of using the extended kinetic method to determine thermochemical quantities can be found in the current literature [14 -19]. Briefly, a series of proton-bound dimers ([A·H·A i ] Ϫ ) of deprotonated MTA (HA) with a set of conjugate bases of reference acids (HA i ) were generated in the mass spectrometer. The reference acids all have known gas-phase acidities. Each proton-bound dimer was activated by collisions with argon atoms and underwent competitive unimolecular dissociations to produce two ionic products, A Ϫ and A i Ϫ , with rate constants of k and k i , respectively, Scheme 1.With the assumption that there are no reverse activation barriers for both dissociation channels, the natural logarithm of the ratio of the rate constants can be expressed by eq 1, where R is the ideal gas constant, T eff is the effective temperature of the activated dimer ion, and ⌬H and ⌬H i are the gas-phase acidities of MTA and the reference acid, respective...

Section: Discussionmentioning

confidence: 99%

Determination of the gas-phase acidity of methylthioacetic acid using the Cooks’ kinetic method

Ren

Patel

2005

“…Since it was first proposed by Cooks and Kruger in 1977° [26]°the°applicability°of°the°kinetic°method°to thermochemical analysis has been extensively discussed° [27][28][29][30][31][32][33][34][35].°The°kinetic°method°can°be°applied°to the determination of gas phase acidities by examination of competitive dissociation of proton bound dimer anions. This is achieved by equating the ratio of the rate constants (k x /k y ) for the dissociation channels of the dimer, such as the phospholipid dimer shown in Scheme 3, with the ratio of the observed ion abundances (I x /I y ) in the tandem mass spectrum.…”

Section: The Kinetic Methodsmentioning

confidence: 99%

A comparison of the gas phase acidities of phospholipid headgroups: Experimental and computational studies

Thomas

Mitchell

Blanksby

2005

Proton-bound dimers consisting of two glycerophospholipids with different headgroups were prepared using negative ion electrospray ionization and dissociated in a triple quadrupole mass spectrometer. Analysis of the tandem mass spectra of the dimers using the kinetic method provides, for the first time, an order of acidity for the phospholipid classes in the gas phase of PE Ͻ PA Ͻ Ͻ PG Ͻ PS Ͻ PI. Hybrid density functional calculations on model phospholipids were used to predict the absolute deprotonation enthalpies of the phospholipid classes from isodesmic proton transfer reactions with phosphoric acid. The computational data largely support the experimental acidity trend, with the exception of the relative acidity ranking of the two most acidic phospholipid species. Possible causes of the discrepancy between experiment and theory are discussed and the experimental trend is recommended. The sequence of gas phase acidities for the phospholipid headgroups is found to (1) have little correlation with the relative ionization efficiencies of the phospholipid classes observed in the negative ion electrospray process, and (2)

“…For example, Tabet and coworkers [13] applied the simplest variant of the kinetic method without considering entropy corrections that are necessary to deal with multifunctional compounds like AAs according to recent consensus in the community [23][24][25][26]]. Bouchoux's PAs for Gly, Ala, Pro, Ser, Lys, and His [14] were derived from GBs determined by the reliable thermokinetic method.…”

Section: Assessment Of the Reliability Of Sources For Pa Datamentioning

confidence: 99%

Revising the proton affinity scale of the naturally occurring α-amino acids

Bleiholder

Suhai

Paizs

2006

130

146

P rotonation energetics of the naturally occurring amino acids (AA) is of current interest because of the importance of proton transfer (PT) reactions in biological systems [1]. Recently, the PAs of amino acids, small peptides, and their derivatives have been successfully used [2][3][4][5][6][7] to explain some fragment ion abundance relationships in the low-energy tandem mass spectra of protonated peptides. Considering appropriate PAs, one can often predict whether the N-or the C-terminal fragment remains charged upon dissociation of the respective parent ions [2]. These predictions require, however, good quality PA data for the fragments involved.The literature on the protonation chemistry of AAs and small peptides was reviewed by Harrison [8] who introduced the recently available, most consistent gasphase basicity (GB) and proton affinity (PA) scales for AAs. Harrison used the following strategy [8] to compile his list. First, he critically evaluated the available literature data on gas-phase basicities of AAs since most of the existing experimental techniques address primarily GBs and not PAs. Then eq 1,was used to convert GBs to PAs applying appropriate ⌬S values. Here, T is the temperature and ⌬S is the protonation entropy. The protonation entropy can be represented as a sum of three terms, involving entropy changes caused by loss of translational (⌬S trans ), rotational (⌬S rot ), and vibrational (⌬S vib ) degrees of freedom, whereby the ⌬S vib term is usually neglected (for more details, see reference [8]). Direct assessment of ⌬S is possible only if the GBs are determined from variable-temperature equilibrium measurements [8]. Such studies have been performed only for Gly, Ala, and Pro; the results suggest that the ⌬S term is dominated by the loss of translational entropy of the free proton for these AAs (⌬S Ϸ ⌬S trans ; ⌬S rot Ϸ 0) [9]. In other words, for those amino acids for which no extra strong H-bond is introduced in the protonated species, ⌬S resulting from changes of the rotational degrees of freedom is negligible (⌬S rot Ϸ 0). The term ⌬S trans can be readily approximated by the Sackur-Tetrode equation (for details see reference [8]), which gives T⌬S trans of Ϫ7.8 kcal mol Ϫ1 for T ϭ 298 K. The ⌬S rot Ϸ 0 approximation is definitely not valid for AAs containing strongly basic side chains like Lys or Arg, for which a strong intramolecular H-bond is introduced in the protonated species (for example, ϪH 2 N ϩ ϪH. . .NH 2 Ϫ for protonated Lys). These strong hydrogen bonds freeze rotational degrees of freedom in the protonated species that can be considered free in the neutral molecules, thus leading to a negative rotational entropy (⌬S rot Ͻ 0). The magnitude of ⌬S rot for AAs is mostly approximated by considering similar molecules for which data from variable temperature equilibrium experiments are available. For example, Harrison approximated ⌬S rot (Lys) using ⌬S rot (1,5-. Unfortunately, no experimental or theoretical information on ⌬S rot for Arg, Gln, Asn, etc. is available. Harrison assume...