Ultrafast Proton Transport between a Hydroxy Acid and a Nitrogen Base along Solvent Bridges Governed by the Hydroxide/Methoxide Transfer Mechanism.

Aqueous proton transport plays a key role in acid-base neutralization and energy transport through biological membranes and hydrogen fuel cells. Extensive experimental and theoretical studies have resulted in a highly detailed elucidation of one of the underlying microscopic mechanisms for aqueous excess proton transport, known as the von Grotthuss mechanism, involving different hydrated proton configurations with associated high fluxional structural dynamics. Hydroxide transport, with approximately 2-fold-lower bulk diffusion rates compared to those of excess protons, has received much less attention. We present femtosecond UV/IR pump-probe experiments and ab initio molecular dynamics simulations of different proton transport pathways of bifunctional photoacid 7-hydroxyquinoline (7HQ) in water/methanol mixtures. For 7HQ solvent-dependent photoacidity, free-energy-reactivity correlation behavior and quantum mechanics/molecular mechanics (QM/MM) trajectories point to a dominant OH-/CH3O- transport pathway for all water/methanol mixing ratios investigated. Our joint ultrafast infrared spectroscopic and ab initio molecular dynamics study provides conclusive evidence for the hydrolysis/methanolysis acid-base neutralization pathway, as formulated by Manfred Eigen half a century ago. Our findings on the distinctly different acid-base reactivities for aromatic hydroxyl and aromatic nitrogen functionalities suggest the usefulness of further exploration of these free-energy-reactivity correlations as a function of solvent polarity. Ultimately the determination of solvent-dependent acidities will contribute to a better understanding of proton-transport mechanisms at weakly polar surfaces and near polar or ionic regions in transmembrane proton pump proteins or hydrogen fuel cell materials.

Perturbation of the F19-L34 Contact in Amyloid ß (1-40) Fibrils Induces Only Local Structural Changes but Abolishes Cytotoxicity.

We explored structural details of fibrils formed by a mutated amyloid ß (Aß(1-40)) peptide carrying a Phe19 to Lys19 mutation, which was shown to completely abolish the toxicity of the molecule. Computer models suggest that the positively charged Lys19 side chain is expelled from the hydrophobic fibril interior upon fibrillation. This can be accommodated by either a 180° flip of the entire lower ß-strand (model M1) or local perturbations of the secondary structure in the direct vicinity of the mutated site (model M2). This is accompanied by the formation of a new salt bridge between Glu22 and Lys28 in model M1. Experimentally, a novel contact between Phe20 and Leu34 as well as the significant structural perturbation of residues 20-23 could be confirmed. However, the mutated fibrils do not show the formation of any salt bridges. This demonstrates that although morphologically very robust, local perturbations of the Aß(1-40) sequence lead to moderate structural alterations with tremendous impact on the physiological importance of these aggregates, which may suggest alternative strategies for the development of a remedy against Alzheimer's disease.

Combined Experimental and Theoretical Study of the Transient IR Spectroscopy of 7-Hydroxyquinoline in the First Electronically Excited Singlet State.

The photophysics of 7-hydroxyquinoline (7HQ) in protic media results from an interplay of acid-base chemistry, prompted by the effects of photoacidity of the hydroxyl group and photobasicity of the nitrogen atom in the quinoline aromatic system. With ultrafast IR spectroscopic measurements, we follow the proton transfer dynamics of 7HQ in its four possible charged forms in methanol solution. Using deuterated methanol as solvent, we determine deuteron transfer rates from the neutral to the zwitterionic form to be 330 ps, those from the cationic form to the zwitterionic form to be 170 ps, and those from the anionic form to the zwitterionic form to be 600 ps. We compare the observed IR-active fingerprint marker patterns in the electronic ground state and the first electronically excited 1Lb-state with those calculated using density functional theory and time-dependent density functional theory, respectively, and find good correspondence between experimental and calculated transitions. The calculations provide insight into the nature of electronic excitation of these four different charged forms of 7HQ, suggesting the key role of electronic charge distribution changes upon electronic excitation of 7HQ and hydrogen bond changes at the donor hydroxyl and acceptor nitrogen moieties.

Dynamical Dimension to the Hofmeister Series: Insights from First-Principles Simulations.

A systematic characterization of the competing kosmotropic and chaotropic effects of a series of divalent salts on the aqueous H-bonding structure by means of first-principles molecular dynamics simulations is presented. The structural properties are quantified by means of experimental and computed (1) H NMR chemical shifts, whereby the local environments of cations and anions can be discriminated. Complementary to the well-established structural features, a dynamical aspect is added to the concept of kosmotropes and chaotropes. The H-bond dynamics, quantified in terms of the H-bonding autocorrelation functions, shows a good correlation with the structural kosmotropic and chaotropic modifications, which are commonly referred to as the Hofmeister series. The considerably enhanced (reduced) fluctuations of the H-bonding network in the hydration shells around the anions (cations) are a complementary dynamical dimension to the concept of kosmotropic/chaotropic behavior of solvated ions.