Comparison of structures and energies of CH52+• with CH4+• and their possible role in superacidic methane activation

Contrary to previous theoretical studies at the UHF/6-31G* level, the methonium radical dication CH52+ is not a Cs symmetrical structure with a 2e—3c bond but a C2v symmetrical structure 1 with two 2e—3c bonds (at the UHF/6-31G**, UMP2/6-31G**, and UQCISD(T)/6-311G** levels). The Cs symmetrical structure is not even a minimum at the higher level of calculations. The four hydrogen atoms in 1 are bonded to the carbon atom by two 2e—3c bonds and the fifth hydrogen atom by a 2e—2c bond. The unpaired electron of 1 is located in a formal p-orbital (of the sp2-hybridized carbon atom) perpendicular to the plane of the molecule. Hydrogen scrambling in 1 is however extremely facile, as is in other C1 cations. It is found that the protonation of methane to CH5+ decreases the energy for subsequent homolytic cleavage resulting in the exothermic (24.1 kcal/mol) formation of CH4+•. Subsequent reaction with neutral methane while reforming CH5+ gives the methyl radical enabling reaction with excess methane to ethane and H2. The overall reaction is endothermic by 11.4 kcal/mol, but offers under conditions of oxidative removal of H2 an alternative to the more energetic carbocationic conversion of methane.

Fractionation factors and activation energies for exchange of the low barrier hydrogen bonding proton in peptidyl trifluoromethyl ketone complexes of chymotrypsin

NMR investigations have been carried out of complexes between bovine chymotrypsin Aα and a series of four peptidyl trifluoromethyl ketones, listed here in order of increasing affinity for chymotrypsin: N-Acetyl-l-Phe-CF3, N-Acetyl-Gly-l-Phe-CF3, N-Acetyl-l-Val-l-Phe-CF3, and N-Acetyl-l-Leu-l-Phe-CF3. The D/H fractionation factors (φ) for the hydrogen in the H-bond between His 57 and Asp 102 (His 57-Hδ1) in these four complexes at 5°C were in the range φ = 0.32–0.43, expected for a low-barrier hydrogen bond. For this series of complexes, measurements also were made of the chemical shifts of His 57-Hɛ1 (δ2,2-dimethylsilapentane-5-sulfonic acid 8.97–9.18), the exchange rate of the His 57-Hδ1 proton with bulk water protons (284–12.4 s−1), and the activation enthalpies for this hydrogen exchange (14.7–19.4 kcal⋅mol−1). It was found that the previously noted correlations between the inhibition constants (Ki 170–1.2 μM) and the chemical shifts of His 57-Hδ1 (δ2,2-dimethylsilapentane-5-sulfonic acid 18.61–18.95) for this series of peptidyl trifluoromethyl ketones with chymotrypsin [Lin, J., Cassidy, C. S. & Frey, P. A. (1998) Biochemistry 37, 11940–11948] could be extended to include the fractionation factors, hydrogen exchange rates, and hydrogen exchange activation enthalpies. The results support the proposal of low barrier hydrogen bond-facilitated general base catalysis in the addition of Ser 195 to the peptidyl carbonyl group of substrates in the mechanism of chymotrypsin-catalyzed peptide hydrolysis. Trends in the enthalpies for hydrogen exchange and the fractionation factors are consistent with a strong, double-minimum or single-well potential hydrogen bond in the strongest complexes. The lifetimes of His 57-Hδ1, which is solvent shielded in these complexes, track the strength of the hydrogen bond. Because these lifetimes are orders of magnitude shorter than those of the complexes themselves, the enzyme must have a pathway for hydrogen exchange at this site that is independent of dissociation of the complexes.

Equilibrium constants and free energies in unfolding of proteins in urea solutions

A novel thermodynamic approach to the reversible unfolding of proteins in aqueous urea solutions has been developed based on the premise that urea ligands are bound cooperatively to the macromolecule. When successive stoichiometric binding constants have values larger than expected from statistical effects, an equation for moles of bound urea can be derived that contains imaginary terms. For a very steep unfolding curve, one can then show that the fraction of protein unfolded, B̄, depends on the square of the urea concentration, U, and is given by \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}\bar {B}=\frac{{\mathit{A}}^{{\mathit{2}}}_{{\mathit{1}}}{\mathit{e}}^{{\mathrm{{\lambda}}}n\bar {B}}{\mathit{U}}^{{\mathit{2}}}}{{\mathrm{1\hspace{.167em}+\hspace{.167em}}}{\mathit{A}}^{{\mathrm{2}}}_{{\mathrm{1}}}{\mathit{e}}^{{\mathrm{{\lambda}}}\bar {B}}{\mathit{U}}^{{\mathrm{2}}}}{\mathrm{.}}\end{equation*}\end{document} A12 is the binding constant as B̄→ 0, and λ is a parameter that reflects the augmentation in affinities of protein for urea as the moles bound increases to the saturation number, n. This equation provides an analytic expression that reproduces the unfolding curve with good precision, suggests a simple linear graphical procedure for evaluating A12 and λ, and leads to the appropriate standard free energy changes. The calculated ΔG° values reflect the coupling of urea binding with unfolding of the protein. Some possible implications of this analysis to protein folding in vivo are described.

Direct measurement of salt-bridge solvation energies using a peptide model system: implications for protein stability.

The solvation energies of salt bridges formed between the terminal carboxyl of the host pentapeptide AcWL- X-LL and the side chains of Arg or Lys in the guest (X) position have been measured. The energies were derived from octanol-to-buffer transfer free energies determined between pH 1 and pH 9. 13C NMR measurements show that the salt bridges form in the octanol phase, but not in the buffer phase, when the side chains and the terminal carboxyl group are charged. The free energy of salt-bridge formation in octanol is approximately -4 kcal/mol (1 cal = 4.184 J), which is equal to or slightly larger than the sum of the solvation energies of noninteracting pairs of charged side chains. This is about one-half the free energy that would result from replacing a charge pair in octanol with a pair of hydrophobic residues of moderate size. Therefore, salt bridging in octanol can change the favorable aqueous solvation energy of a pair of oppositely charged residues to neutral or slightly unfavorable but cannot provide the same free energy decrease as hydrophobic residues. This is consistent with recent computational and experimental studies of protein stability.

Optical evidence for the unification of active galactic nuclei and quasi-stellar objects.

There is a variety of optical evidence for some unification of different types of active galactic nuclei and quasi-stellar objects (QSOs). The case is very strong for the unification of at least some Seyfert galaxies, where polarization data show that the type assigned to the Seyfert galaxy must depend on viewing direction. It has been proposed that Fanaroff-Riley type 2 (FR2) radio galaxies are quasars seen in a direction from which the quasar is obscured, and there is some limited direct evidence for this picture. The broad absorption line QSOs may be normal QSOs seen from a special direction. Some of the sources observed to have high luminosities in the far infrared could be obscured QSOs and active nuclei. Mergers and interactions are likely to play an important role in nuclear activity, and active galaxies and QSOs could change their apparent types through these encounters followed by subsequent evolution.