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The protein α-synuclein, implicated in Parkinson''s disease, was studied by combining nano-electrospray ionization (N-ESI) mass spectrometry and ion mobility. It was found that both the charge-state distribution in the mass spectra and the average protein shape deduced from ion mobility data, depend on the pH of the spray solution. Negative-ion N-ESI of pH 7 solutions yielded a broad charge-state distribution from −6 to −16, centered at −11, and ion mobility data consistent with extended protein structures. Data obtained for pH 2.5 solutions, on the other hand, showed a narrow charge-state distribution from −6 to −11, centered at −8, and ion mobilities in agreement with compact α-synuclein structures. The data indicated that there are two distinct families of structures: one consisting of relatively compact proteins with eight or less negative charges and one consisting of relatively extended structures with nine or more charges. The average cross section of a-synuclein at pH 2.5 is 33% smaller than for the extended protein sprayed from pH 7 solution. Significant dimer formation was observed when sprayed from pH 7 solution but no dimers were observed from the low pH solution. A plausible mechanism for aggregate formation in solution is proposed. [Copyright &y& Elsevier]

Noncovalent peptide-peptide and peptide-water interactions in small model systems were examined using an electrospray mass spectrometer equipped with a high-pressure drift cell. The results of these aggregation and hydration experiments were interpreted with the aid of molecular mechanics (MM) and density functional theory (DFT) calculations. The systems investigated include bare deprotonated monomers and dimers [P1,2-H]- and hydrated deprotonated monomers and dimers [P1,2-H]-.(H2O)n for the peptides dialanine (P = AA) and diglycine (P = GG). Mass spectra indicated that both peptides AA and GG form exclusively dimer ions in the electrospray process. Monomeric ions were generated by high- energy injection of the dimers into the drift cell. Temperature-dependent hydration equilibrium experiments carried out in the drift cell yielded water binding energies ranging from 11.7 (first water molecule) to 7.1 kcal/mol (fourth water) for [AA-H]- and 11.0 to 7.4 kcal/mol for [GG-H]-. The first water molecule adding to the dimer ions [AA-H]-.(AA) and [GG-H]-(GG) is bound by 8.4 and 7.5 kcal/mol, respectively. The hydration mass spectra for the monomers and dimers provide a means to compare the ability of water and a neutral peptide to solvate a deprotonated peptide [P-H]-. The data indicate that a similar degree of solvation is achieved by four water molecules, [P-H]-(H2O)4, or one neutral peptide, [P-H]-(P). Temperature-dependent kinetics experiments yielded activation energies for dissociation of the dimers [AA-H]-.(AA) and [GG-H]-.(GG) of 34.9 and 32.2 kcal/mol, respectively. MM and DFT calculations carried out for the dialanine system indicated that the dimer binding energy is 24.3 kcal/mol, when the [AA-H]- and AA products are relaxed to their global minimum structures. However, a value of 38.9 kcal/mol is obtained if [AA-H]- and AA dissociate but retain the structures of the moieties in the dimer, suggesting the transition state occurs early in the dissociation process. Similar results were found for the diglycine dimer. [ABSTRACT FROM AUTHOR]

Gas-phase clustering reactions of CoCp+ with H2 and with CH4 were investigated using temperature-dependent equilibrium experiments. In both systems, the CoCp+ ion was found to form strong interactions with two ligands. The first and second H2 groups cluster to CoCp+ with bond energies of 16.2 and 16.8 kcal/mol, respectively, while the first and second CH4 groups cluster to CoCp+ with bond energies of 24.1 and 12.1 kcal/mol, respectively. These bond energies are in good agreement with those determined by density functional theory (DFT). Molecular geometries for the four clusters determined with DFT are also presented. Weak experimental bond energies of 0.9 kcal/mol for the third H2 and 2.2 kcal/mol for the third CH4 clustering to CoCp+ suggest these ligands occupy the second solvation shell of the ion. In addition to clustering in the methane system, H2-elimination from CoCp(CH4)2+ was observed. The mechanism for this reaction was investigated by collision-induced dissociation experiments and DFT, which suggest the predominate H2-elimination product is (c-C5H6)Co+&z.sbnd;C2H5. Theory indicates that dehydrogenation requires the active participation of the Cp ring in the mechanism. Transfer of H and CH3 groups to the C5-ring ligand allows the metal center to avoid the high-energy Co(IV) oxidation state required when it forms two covalent bonds in addition to its interaction with a C5-ring ligand. [Copyright &y& Elsevier]

A series of gas-phase experiments and extensive theoretical modeling was done on the family of singly protonated peptides AARAA, Ac-AARAA, and AARAA-OMe. (AARAA)H[sup+] underwent extensive H/D exchange with D[sub2]O, whereas the other two peptides with blocked termini did not, implying that a salt bridge was involved in the H/D exchange process. Ion mobility measurements and complementary molecular modeling unambiguously identified the 300 K structures of all three protonated peptides as charge solvation structures, not salt bridges. High-level density functional theory calculations indicated the global minimum of (AARAA)H[sup+] was a charge solvation structure with the lowest-energy salt bridge structure 4.8 kcal/mol higher in energy. Uptake of the first five water molecules of hydration at 260 K showed near identical propensities for all three peptides consistent with a common structural motif. Quantitative measurements of δH° and δS° for the first two waters of hydration were very similar for all three peptides, again suggestive of a common structure. A detailed search of the potential energy surface for the singly hydrated (AARAA)H[sup+] using molecular mechanics and density functional theory approaches indicated a charge solvation structure was the global minimum, but now the lowest-energy salt bridge structure was only 1.8 kcal/mol higher in energy. Importantly, a low-energy transition state connecting the charge solvation and the salt bridge structures was found where the D[sub2]O molecule facilitated H/D exchange via the relay mechanism. This "relay" transition state was 7 kcal/mol below the (AARAA)H[sup+] + D[sub2]O asymptotic energy, suggesting that facile H/D exchange could occur in this system. There was no equivalent low-lying relay mechanism transition state for the (Ac-AARAA)[sup+] and (AARAA-OMe)H[sup+] peptides, consistent with the fact that H/D exchange was not observed. Hence, the combined experimental and theoretical methods confirmed that a salt bridge was involved in the H/D exchange by D[sub2]O of (AARAA)H[sup+], but it existed only as a kinetic intermediate, not as a global minimum structure. These findings suggest that caution must be observed in drawing structural conclusions from H/D exchange only. A prescription is given here for understanding both the structural and H/D exchange mechanistic aspects of bare and singly hydrated peptides. [ABSTRACT FROM AUTHOR]

The sequential addition of water molecules to a series of small protonated peptides was studied by equilibrium experiments using electrospray ionization combined with drift cell techniques. The experimental data were compared to theoretical structures of selected hydrated species obtained by molecular mechanics simulations. The sequential water binding energies were measured to be of the order of 7-15 kcal/mol, with the largest values for the first water molecule adding to either a small nonarginine containing peptide (e.g., protonated dialanine) or to a larger peptide in a high charge state (e.g., triply protonated neurotensin). General trends are (a) that the first water molecules are more strongly bound than the following water molecules, (b) that very small peptides (2-3 residues) bind the first few water molecules more strongly than larger peptides, (c) that the first few water molecules bind more strongly to higher charge states than to lower charge states, and (d) that water binds less strongly to a protonated guanidino group (arginine containing peptides) than to a protonated amino group. Experimental differential entropies of hydration were found to be of the order of -20 cal/mol/K although values vary from system to system. At constant experimental conditions the number of water molecules adding to any peptide ion is strongly dependent on the peptide charge state (with higher charge states adding proportionally more water molecules) and only weakly dependent on the choice of peptide. For small peptides molecular mechanics calculations indicate that the first few water molecules add preferentially to the site of protonation until a complete solvation shell is formed around the charge. Subsequent water molecules add either to water molecules of the first solvation shell or add to charge remote functional groups of the peptide. In larger peptides, charge remote sites generally compete more effectively with charge proximate sites even for the first few... [ABSTRACT FROM AUTHOR]

The sequential association energies for one through six water molecules clustering to Na[sub 2]I[sup +], as well as one and two water molecules clustering to Na[sub 3]I[sub 2, sup +], are measured. The association energies show a pairwise behavior, indicating a symmetric association of water molecules to the linear Na[sub 2]I[sup +] and Na[sub 3]I[sub 2, sup +] ions. This pairwise behavior is well reproduced by Density Functional Theory (DFT) calculations. DFT calculations also suggest that a significant separation of charge for the Na-I ion pair occurs when four or more water molecules cluster to a single sodium center. Two different solvent-separated ion pairs have been identified with the DFT calculations. Experiments also show that the dissolution processes, loss of a neutral Nal unit, occurs when six or more water molecules have been added to Na[sub 2]I[sup +] cluster. However, one or two water molecules are able to detach an Nal unit from the Na[sub 3]I[sub 2, sup +] cluster. The difference in solubility of the Na[sub 2]I[sup +] and Na[sub 3]I[sub 2, sup +] ions is due to the difference in the energies required to lose an Nal unit from these two species. The experiment also confirms that the loss of a neutral Nal unit, instead of an Na[sup +] ion, occurs during the dissolution processes of Na[sub 3]I[sub 2, sup +]. The microsolvation schemes proposed to explain our experimental observations are supported by DFT and phase space theory (PST) calculations. [ABSTRACT FROM AUTHOR]

Provides information on a study which used equilibrium methods to measure the binding energies of two dihydrogen ligands. Discussion on the activation of the ... bonds; In-depth look at the ground-state B+(1SO) ions; Methodology used to conduct the study; Results of the study.

The article presents the study on the conformational differences and stability of Syrian hamster prion protein (PrP)(90-231). It notes that PrPc is degraded in proteinase K which has high thermal stability. The study suggests that there may be PrPc structure aspects important to the stable structure of PrPSc.

This article focuses on the catalytic activity of gold clusters on magnesium oxide films used in the oxidation of carbon monoxide. While several studies show a strong dependence of the catalytic activity on the deposited cluster size, the eventual size and shape of the metal clusters once they were deposited on the substrate was not measured directly in either case. Positive ion clusters are extracted and accelerated through a skimmer in an argon carrier gas. Gold monomers are highly mobile on the rutile surface, leading to aggregation into larger clusters.

The combination of ion mobility, mass spectrometry and molecular mechanics calculations provides a powerful method for diastereomer determination. Information about the olefinic linkage connectivity was obtained using ion mobility experiments and molecular mechanics calculations. In the ion mobility experiments, sodiated ions of trans-1,2-bis([2,2]paracyclophanyl)ethene, formed by MALDI, are mass selected and injected at low energy into a drift cell. The ions are rapidly thermalized by collisions with the helium gas and travel through the drift cell under the influence of a weak electric field.

A letter to the editor is presented regarding the role of the aggregation of the amyloid β protein (Aβ) in Alzheimer's disease development.

The article informs that oxytocin (OT) was the first peptide hormone to have its sequence determined and the first to be chemically synthesized in its biologically active form. OT is well characterized for its role in the reproductive cycle, where it stimulates smooth muscle contractions in the uterus during labor and the mammary glands during lactation. OT is further implicated to play a pivotal role in the complex process of "affiliation" in mammals (maternal behavior, infant separation distress, and mate formation). The peptide consists of nine amino acids, and an amidated C-terminus. The secondary structure is characterized by a disulfide bridge that links the first and sixth residues, which results in the formation of a 20-atom ring.