Structure of cationized glycine, gly.m (m = be, mg, ca, sr, ba), in the gas phase: intrinsic effect of cation size on zwitterion stability.

Interactions between divalent metal ions and biomolecules are common both in solution and in the gas phase. Here, the intrinsic effect of divalent alkaline earth metal ions (Be, Mg, Ca, Sr, Ba) on the structure of glycine in the absence of solvent is examined. Results from both density functional and Moller-Plesset theories indicate that for all metal ions except beryllium, the salt-bridge form of the ion, in which glycine is a zwitterion, is between 5 and 12 kcal/mol more stable than the charge-solvated structure in which glycine is in its neutral form. For beryllium, the charge-solvated structure is 5-8 kcal/mol more stable than the salt-bridge structure. Thus, there is a dramatic change in the structure of glycine with increased metal cation size. Using a Hartree-Fock-based partitioning method, the interaction between the metal ion and glycine is separated into electrostatic, charge transfer and deformation components. The charge transfer interactions are more important for stabilizing the charge-solvated structure of glycine with beryllium relative to magnesium. In contrast, the difference in stability between the charge-solvated and salt-bridge structure for magnesium is mostly due to electrostatic interactions that favor formation of the salt-bridge structure. These results indicate that divalent metal ions dramatically influence the structure of this simplest amino acid in the gas phase.

Effects of Gas-Phase Basicity on the Proton Transfer between Organic Bases and Trifluoroacetic Acid in the Gas Phase: Energetics of Charge Solvation and Salt Bridges.

The unimolecular dissociation pathways and kinetics of a series of protonated trimer ions consisting of two organic bases and trifluoroacetic acid were investigated using blackbody infrared radiative dissociation. Five bases with gas-phase basicities (GB) ranging from 238.4 to 246.2 kcal/mol were used. Both the dissociation pathways and the threshold dissociation energies depend on the GB of the base. Trimers consisting of the two most basic molecules dissociate to form protonated base monomers with an E(0) ~ 1.4 eV. Trimers consisting of the two least basic molecules dissociate to form protonated base dimers with an E(0) ~ 1.1-1.2 eV. These results indicate that the structures of the trimers change as a function of the GB of the basic molecule. The predominant structure of the protonated trimers consisting of the two most basic molecules is consistent with a salt bridge in which both of the basic molecules are protonated, and the trifluoroacetic acid molecule is deprotonated, whereas the predominant structure of the protonated trimers consisting of the two least basic molecules are consistent with charge-solvated complexes in which the proton is shared. The structure of the trimer consisting of the base of intermediate basicity is less clear; it dissociates to form primarily protonated base dimer, but has an E(0) ~ 1.2 eV. These results are consistent with the structure of this trimer as a salt bridge, but the resulting dissociation A(-). BH(+) product does not appear to be stable as an ion pair in the dissociative transition state.

Structures of protonated arginine dimer and bradykinin investigated by density functional theory: further support for stable gas-phase salt bridges.

The gas-phase structures and energetics of both protonated arginine dimer and protonated bradykinin were investigated using a combination of molecular mechanics with conformational searching to identify candidate low-energy structures, and density functional theory for subsequent minimization and energy calculations. For protonated arginine dimer, a good correlation (R = 0.88) was obtained between the molecular mechanics and EDF1 6-31+G* energies, indicating that mechanics with MMFF is suitable for finding low-energy conformers. For this ion, the salt-bridge or ion-zwitterion form was found to be 5.7 and 7.2 kcal/mol more stable than the simple protonated or ion-molecule form at the EDF1 6-31++G** and B3LYP 6-311++G** levels. For bradykinin, the correlation between the molecular mechanics and DFT energies was poor (R = 0.28), indicating that many low-energy structures are likely passed over in the mechanics conformational searching. This result suggests that structures of this larger peptide ion obtained using mechanics calculations alone are not necessarily reliable. The lowest energy structure of the salt-bridge form of bradykinin is 10.6 kcal/mol lower in energy (EDF1) than the lowest energy simple protonated form at the 6-311G* level. Similarly, the average energy of all salt-bridge structures investigated is 13.6 kcal/mol lower than the average of all the protonated forms investigated. To the extent that a sufficient number of structures are investigated, these results provide some additional support for the salt-bridge form of bradykinin in the gas phase.

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 delta Gacid).

Activation energies for dissociation of double strand oligonucleotide anions: evidence for watson-crick base pairing in vacuo.

The dissociation kinetics of a series of complementary and noncomplementary DNA duplexes, (TGCA)(2) (3-), (CCGG)(2) (3-), (AATTAAT)(2) (3-), (CCGGCCG)(2) (3-), A(7)*T(7) (3-), A(7)*A(7) (3-), T(7)*T(7) (3-), and A(7)*C(7) (3-) were investigated using blackbody infrared radiative dissociation in a Fourier transform mass spectrometer. From the temperature dependence of the unimolecular dissociation rate constants, Arrhenius activation parameters in the zero-pressure limit are obtained. Activation energies range from 1.2 to 1.7 eV, and preexponential factors range from 10(13) to 10(19) s(-1). Dissociation of the duplexes results in cleavage of the noncovalent bonds and/or cleavage of covalent bonds leading to loss of a neutral nucleobase followed by backbone cleavage producing sequence-specific (a - base) and w ions. Four pieces of evidence are presented which indicate that Watson-Crick (WC) base pairing is preserved in complementary DNA duplexes in the gas phase: i. the activation energy for dissociation of the complementary dimer, A(7)*T(7) (3-), to the single strands is significantly higher than that for the related noncomplementary A(7)*A(7) (3-) and T(7)*T(7) (3-) dimers, indicating a stronger interaction between strands with a specific base sequence, ii. extensive loss of neutral adenine occurs for A(7)*A(7) (3-) and A(7)*C(7) (3-) but not for A(7)*T(7) (3-) consistent with this process being shut down by WC hydrogen bonding, iii. a correlation is observed between the measured activation energy for dissociation to single strands and the dimerization enthalpy (-DeltaH(d)) in solution, and iv. molecular dynamics carried out at 300 and 400 K indicate that WC base pairing is preserved for A(7)*T(7) (3-) duplex, although the helical structure is essentially lost. In combination, these results provide strong evidence that WC base pairing can exist in the complete absence of solvent.

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 Fourier-transform 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 b(4) and (M-H(2)O)(+) ions with an average activation energy (E(a)) of 1.1 eV and an A factor of 10(10.5) s(-1). The value of the A factor indicates that these dissociation processes are rearrangements. The b(4) ions subsequently dissociate to form a(4) 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 E(a) and A factors are indistinguishable within experimental error with values of approximately 1.5 eV and 10(17) s(-1), respectively. Although not conclusive, results from master equation modeling indicate that all these BIRD processes, except for b(4) --> a(4), 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.

Effects of charge state on fragmentation pathways, dynamics, and activation energies of ubiquitin ions measured by blackbody infrared radiative dissociation.

Blackbody infrared radiative dissociation spectra of the (M + 5H)5+ through (M + 11H)11+ ions of the protein ubiquitin (8.6 kDa) formed by electrospray ionization were measured in a Fourier-transform mass spectrometer. The 5+ ion dissociates exclusively by loss of water and/or ammonia, whereas the 11+ charge state dissociates only by formation of complementary y and b ions. These two processes are competitive for intermediate charge state ions, with the formation of y and b ions increasingly favored for the higher charge states. The y and b ions are formed by cleavage of the backbone amide bond on the C-terminal side of acidic residues exclusively, with cleavage adjacent to aspartic acid favored. Thermal unimolecular dissociation rate constants for the dissociation of each of these charge states were measured. From the temperature dependence of these rates, Arrhenius activation parameters in the rapid energy exchange limit are obtained. The activation energies (Ea) and preexponential factors (A) for the 5+, 8+, and 9+ ions are 1.2 eV and 10(12) s-1, respectively. These values for the 6+ and 7+ ions are 0.9-1.0 eV and 10(9) s-1, and those for the 10+ and 11+ ions are 1.6 eV and 10(16)-10(17) s-1. Thus, with the exception of the 5+ ion, the higher charge states of ubiquitin have larger dissociation activation energies than the lower charge states. The different A factors observed for production of y and b ions from different precursor charge states indicate that they are formed by different mechanisms, ranging from relatively complex rearrangements to direct bond cleavages. These results clearly demonstrate that the relative dissociation rates of large biomolecule ions by themselves are not necessarily a reliable indicator of their relative dissociation energies, even when similar fragment ions are formed.

Unimolecular reaction kinetics in the high-pressure limit without collisions.

Molecular activation by blackbody photons, first postulated in 1919 by Perrin, plays a dominant role in the unimolecular dissociation of large ions trapped at low pressure in a Fourier-transform mass spectrometer. Under readily achievable experimental conditions, molecular ions of the protein ubiquitin equilibrate with the blackbody radiation field inside the vacuum chamber. The internal energy of a population of these ions is given by a Boltzmann distribution. From the temperature dependence of unimolecular dissociation rate constants measured in the zero-pressure limit, Arrhenius activation parameters equal to those in the high-pressure limit are obtained.