Design of surface active soluble peptide molecules at the air/water interface

Surface active molecules collect at interfaces and have the potential to be used for water evaporation reduction. The objective of this work is to design surface active soluble peptides that collect at the air/water interface using molecular simulations. Rotational isomeric state Monte Carlo (RISMC) sampling together with a solvation model that we recently invented, the AAD solvation model [Gu, C.; Lustig, S.; Trout, B. J. Phys. Chem. B 2006, 110 (3), 1476-1484] was applied to calculate the adsorption free energy of the peptide molecule at the air/water interface. The results were validated by both molecular dynamics simulations with an explicit solvent model and surface tension measurements on synthesized peptides. It was demonstrated that this approach is able to give a reasonable prediction of surface activity with an approximately 50% hit rate in terms of designed surface active molecules actually being surface active. The relationship between the chemical composition and the surface morphology is also discussed.     

Changes in the intracellular Ca2+ content in human red blood cells in the presence of glycerol

Changes of the intracellular Ca2+ content in human red blood cells (RBCs) in glycerol-containing solutions and after freeze-thawing the cells with glycerol and subsequent deglycerolization were investigated with the Ca2+-sensitive fluorescent dye fluo-4 using fluorescence microscopy. In the glycerol-containing solutions the Ca2+ content increased when compared with a physiological medium (Hepes buffered saline solution (HBSS)). This effect was most likely a result of an inhibition of the Ca2+ pump. After inhibiting the Ca2+ pump using o-vanadate, the Ca2+ uptake was not significantly different in the cells in glycerol-containing and physiological medium. Freeze-thawing and deglycerolization of RBCs resulted in a more pronounced increase in the Ca2+ content. Also in this case, the Ca2+ pump seemed to play a major role.     

Quantum mechanical scattering cross sections and permeability coefficients for ions crossing the human red cell and resting squid axon membranes

Quantum mechanical calculations of elastic scattering cross sections for some permeant ions crossing the human red blood cell and resting axolemma squid axon membranes have been carried out using the three-dimensional spherically symmetric square potential well. Making the assumption that the permeability coefficient is inversely proportional to scattering cross section, we obtain the order of membrane selectivity for the ions as well as values for the permeability coefficients. Despite the relatively simple method used, good agreement between calculated permeability coefficients and data available in the literature is obtained. We suggest that elastic scattering cross section measurements for ions in various membranes would be valuable not only because they give a precise idea about the permeability ratios between ions but they also determine the form of the potential the ions are moving in.     

Computational study of solvent effects on the molecular self-assembly of tetrolic acid in solution and implications for the polymorph formed from crystallization

The solution behavior of a model compound, tetrolic acid (TTA), is studied via molecular dynamics simulations in four organic solvents. The results suggest that strong interactions between TTA and solvent molecules (ethanol or dioxane) prevent the formation of carboxylic acid dimers in solution and thus promote the crystallization of TTA in a catemer-based form or a solvate form. Weak interactions, however, between TTA and solvent molecules (carbon tetrachloride or chloroform) facilitate the formation of carboxylic acid dimers in solution and thus promote the crystallization of a dimer-based crystal. Detailed solvent structure plays an important role in determining the relative stability of various growth synthons in solution and also the barriers along the pathway connecting them. This work illustrates the potential of molecular simulations to aid in the rational selection of solvents to obtain desired polymorphs during crystallization.     

Evidence for a size dependent nucleation mechanism in solid state polymorph transformations

This study applies aimless shooting and likelihood maximization to determine the molecular mechanism in the solid state polymorph transformation in terephthalic acid from over 500 candidate order parameters. The crystals examined here extend the range of crystal sizes considered in our previous work (J. Amer. Chem. Soc. 2007, 129, 4714) and reveal a change in the mechanism with increasing system size. As the crystal size increases beyond that studied in our previous work, the polymorph transformation mechanism changes from a global distortion of the crystal to a local corner nucleation mechanism. In the corner nucleation mechanism, the interfacial area between the two polymorphs is minimized for a given nucleus size. However, this mechanism differs from classical nucleation theory in that the molecular level details are essential to describe the nucleation process, which involves nonspherical domains at the corner of the crystal. These new findings suggest that there is a range of sizes for which corner nucleation is the dominant mechanism of polymorph transitions, thus implying that different mechanistic regimes exist for nucleation based on crystal size. From a computational standpoint, this study demonstrates the utility of aimless shooting and likelihood maximization to identify nonintuitive reaction coordinates in complex systems.     

Femtosecond real-time probing of transition state dynamics in a surface photoreaction: methyl desorption from CH3I on MgO(100)

A novel experimental approach to the investigation of surface adsorbate reaction dynamics is presented. The direct time-resolved monitoring of the surface reaction transition state and product formation dynamics were accomplished via pump-probe mass spectrometry. As an example, methyl iodide molecules adsorbed at submonolayer coverage on an ultrathin magnesia film on Mo(100) were photoexcited to the A-band by ultrafast laser pulse irradiation. Employing time-delayed multiphoton ionization the dynamics of the dissociative methyl iodide transition state and of the emerging methyl photoproduct could be detected with femtosecond resolution. The reaction times deduced from the temporal evolution of the methyl ion mass signal indicate a strong interaction of the methyl fragment with the substrate surface prior to desorption.     

Reactions of nitroheteroarenes with carbanions: bridging aromatic, heteroaromatic, and vinylic electrophilicity

The relative rate constants for the vicarious nucleophilic substitution (VNS) of the anion of chloromethyl phenyl sulfone (1-) with a variety of nitroheteroarenes, for example, nitropyridines, nitropyrroles, nitroimidazoles, 2-nitrothiophene, and 4-nitropyrazole, have been determined by competition experiments. It was shown that nitropyridines are approximately four orders of magnitude more reactive than nitrobenzene. Among the five-membered heterocycles 2-nitrothiophene is the most active followed by nitroimidazoles and 4-nitropyrazole. Nitropyrroles are the least electrophilic nitroheteroarenes with reactivities comparable to nitrobenzene. Quantum chemically calculated methyl anion affinities (B3LYP/6-311G(d,p)//B3LYP/6-31G(d)) of the nitroarenes correlated only moderately with the partial relative rate constants. The correlation of these activities with the LUMO energies of nitroarenes is even worse. By measuring the second-order rate constants of the addition of 1- to nitroarenes and to diethyl arylidenemalonates 10, it was possible to link the electrophilic reactivities of nitroheteroarenes with the comprehensive electrophilicity scale based on the linear-free-energy-relationship log k(20 degrees C)=s(N+E).