Eric F. Strittmatter

Dissociation energetics and mechanisms of leucine enkephalin (M+H)+ and (2M+X)+ ions (X=H, Li, Na, K, and Rb) measured by blackbody infrared radiative dissociation

The dissociation kinetics of protonated leucine enkephalin and its proton and alkali metal bound dimers were investigated by blackbody infrared radiative dissociation in a Fouriertransform mass spectrometer. From the temperature dependence of the unimolecular dissociation rate constants, Arrhenius activation parameters in the zero-pressure limit are obtained. Protonated leucine enkephalin dissociates to form b4 and (M-H2O)+ ions with an average activation energy (Ea) of 1. 1 eV and an A factor of 1010. 5 s−1. The value of the A factor indicates that these dissociation processes are rearrangements. The b4 ions subsequently dissociate to form a4 ions via a process with a relatively high activation energy (1.3 eV), but one that is entropically favored. For the cationized dimers, the thermal stability decreases with increasing cation size, consistent with a simple electrostatic interaction in these noncovalent ion-molecule complexes. The Ea and A factors are indistinguishable within experimental error with values of ∼1.5 eV and 1017 s−1, respectively. Although not conclusive, results from master equation modeling indicate that all these BIRD processes, except for b4 → a4, are in the rapid energy exchange limit. In this limit, the internal energy of the precursor ion population is given by a Boltzmann distribution and information about the energetics and dynamics of the reaction are obtained directly from the measured Arrhenius parameters.

Dissociation Energies of Deoxyribose Nucleotide Dimer Anions Measured Using Blackbody Infrared Radiative Dissociation

The dissociation kinetics of deprotonated deoxyribose nucleotide dimers were measured using blackbody infrared radiative dissociation. Experiments were performed with noncovalently bound dimers of phosphate, adenosine (dAMP), cytosine (dCMP), guanosine (dGMP), thymidine (dTMP), and the mixed dimers dAMP · dTMP and dGMP · dCMP. The nucleotide dimers fragment through two parallel pathways, resulting in formation of the individual nucleotide or nucleotide + HPO3 ion. Master equation modeling of this kinetic data was used to determine threshold dissociation energies. The dissociation energy of (dGMP · dCMP - H)− is much higher than that for the other nucleotide dimers. This indicates that there is a strong interaction between the nucleobases in this dimer, consistent with the existence of Watson-Crick hydrogen bonding between the base pairs. Molecular mechanics simulations indicate that Watson-Crick hydrogen bonding occurs in the lowest energy structures of (dGMP · dCMP - H)−, but not in (dAMP · dTMP - H)−. The trend in gas phase dissociation energies is similar to the trend in binding energies measured in nonaqueous solutions within experimental error. Finally, the acidity ordering of the nucleotides is determined to be dTMP < dGMP < dCMP < dAMP, where dAMP has the highest acidity (largest ΔGacid).

The role of proton affinity, acidity, and electrostatics on the stability of neutral versus ion-pair forms of molecular dimers

Abstract Ion-pair formation via proton transfer from an acidic hydrogen of one functional group to a basic functional group plays an important role in the structure and reactivity of biomolecules in the gas phase. The relative stabilities of the ion-pair and the neutral-pair forms of five dimers composed of a basic molecule and a trifluoroacetic acid molecule were compared using density-functional calculations. The proton affinity of the basic molecules investigated ranged from 246 to 254 kcal/mol. The gas phase acidity of trifluoroacetic acid is 323.8 kcal/mol. The results of the B3LYP (6−311++G∗∗) calculations indicate that the structures of the dimers change from a neutral pair to an ion pair as the proton affinity of the bases increases. This result is consistent with previous blackbody infrared radiative dissociation experiments on protonated trimolecular complexes (or trimers) consisting of two basic molecules and trifluoroacetic acid, which indicates that the predominant structure of the trimer changes from a charge-solvation structure to a salt bridge structure with the increasing gas phase basicity of the base. The electrostatic character of the interaction between the basic molecule and the trifluoroacetic acid molecule was determined using the natural energy-decomposition analysis (NEDA) program. In the ion pair, a majority (69%–77%) of the attractive energy of the dimer is comprised of the electrostatic component. Two models are derived that include the acidity of the acidic molecule, the proton affinity of the basic molecule, and an electrostatic binding term for both the ion pair and the neutral pair. Several nonelectrostatic interaction terms can be replaced by a single correction or constant term so that both models, one using NEDA electrostatic terms and the other using integration of point-charge interactions, provide reasonably accurate results. This indicates that electrostatic models similar to the ones used here may be useful in studying salt bridge formation in larger molecules.

Computational approach to the proton affinities of Glyn (n = 1–10)

Abstract The proton affinities of a series of polyglycines were calculated as a function of molecular size up to Gly 10 . Molecular mechanics calculations using the Merck molecular mechanics force field were used to find lowest energy structures. These structures were used as starting geometries for both semiempirical and density functional calculations. Local density approximation density functional theory (DFT) (Slater exchange/VWN correlation or S-VWN, 6-31G∗) was used to refine the geometries obtained from the mechanics. B3LYP (6-31G∗) energies were calculated using these S-VWN geometries. The results of these calculations are compared to previously measured experimental data. The average deviation between the B3LYP and S-VWN proton affinities and the experimentally measured values of Fenselau and co-workers [J. Am. Soc. Mass Spectrom. 3 (1992) 863] are 4.0 and 2.0 kcal/mol, respectively. Better agreement to the experimentally measured values is obtained if the proton affinities are normalized to that of glycine. As expected, the DFT values are in better agreement than the semiempirical (AM1 and PM3) values. For the semiempirical methods, the average deviation from the proton affinities measured by Fenselau and co-workers (all data normalized to glycine) is ∼4.5 kcal/mol. For proton affinities calculated with B3LYP hybrid functionals, this average deviation is only 1.2 kcal/mol (this deviation does not directly reflect the accuracy of the calculations since there are errors in both the experimental and calculated values). For pentaglycine, optimization was performed at the B3LYP 6-311G∗∗ level; the proton affinity differed by only 1 kcal/mol over that calculated at the 6-31G∗ level. This suggests that the lower basis set is sufficient for this application. The energies of the zwitterionic forms of Gly n ( n = 4, 5, 7, and 10) were compared to those of the simple protonated form. The zwitterion form of each polyglycine was found to be less stable at all levels of theory. These results suggest that it is possible to obtain accurate thermochemical data using mechanics and DFT calculations even for these relatively large molecules.