A stress tensor and QTAIM perspective on the substituent effects of biphenyl subjected to torsion.

The Quantum Theory of Atoms in Molecules (QTAIM) defines quantities in 3D space that can be easily obtained from routine quantum chemical calculations. The present investigation shows that local properties can be related quantitatively to measures traditionally connected to experimental data, such as Hammett constants. We consider the specific case of substituted biphenyl to quantify the effects of a torsion φ, 0.0° ≤ φ ≤ 180.0°, of the C-C bond linking the two phenyl rings for C12 H9 -x, where x = N(CH3 )2 , NH2 , CH3 , CHO, CN, NO2, on the entire molecule. QTAIM interpreted Hammett constants, aΔH(rb ) are introduced and constructed using the difference between the H(rb ) value of C12 H9 -x and the C12 H9 -H, biphenyl which is the reference molecule, with a constant of proportionality a. This investigation unexpectedly yields very good or good agreement for the x groups with the Hammett para-, meta-, and ortho-substituent constants and is checked against para-substituted benzene. We then proceed to present the interpreted substituent constants of seven new biphenyl substituent groups, where tabulated Hammett substituent constant values are not available; y = SiH3 , ZnCl, COOCH3 , SO2 NH2 , SO2 OH, COCl, CB3 . Consistency is found for the QTAIM interpreted biphenyl substituent constants of the seven new groups y independently using the stress tensor polarizability Pσ . In addition, a selection of future applications is discussed that highlight the usefulness of this approach. © 2016 Wiley Periodicals, Inc.

The role of hydrogen bonding in nanocolloidal amorphous silica particles in electrolyte solutions.

Explicit solvent (water) molecular dynamics simulations were undertaken containing three pairs of amorphous silica nanoparticles, having diameters of 2.0nm, 2.4nm and 2.8nm, respectively. Mean forces acting between the silica nanoparticles were calculated in a background electrolyte, i.e., NaCl at four different concentrations. Dependence of the inter-particle potential of mean force on the center of mass separation, silicon to sodium ratio (Si:Na(+)), background electrolyte concentration, number of hydrogen bonds directly linking pairs of silica nanoparticles and the density of charged surface sites, are calculated. The pH was indirectly accounted for via the ratio of silicon to sodium used in the simulations. The close relationship between the variation of the number of hydrogen bonds between the pairs of silica nanoparticles and the inter-particle potential of mean force indicates that the degree of inter-particle hydrogen bonding quantifies, for a given size of nanoparticle, the degree of nanoparticle 'stickiness'. Simulations also show that the number of hydrogen bonds between the charged surface (O(-)) sites and the surrounding water molecules increases with increase in charged sites, in agreement with the interaction behavior of silica nanoparticles usually seen in experiments.

Molecular dynamics simulation of nanocolloidal amorphous silica particles: part III.

Explicit-solvent molecular dynamics simulations were applied to four pairs of amorphous silica nanoparticles, two pairs having a diameter of 2.0 nm and two pairs with diameter 3.2 nm. The silica nanoparticles were immersed in a background electrolyte consisting of Ca(2+) and Cl(-) ions and water and mean forces acting between the pair of silica nanoparticles were extracted at four different background electrolyte concentrations. The pH was indirectly accounted for via the ratio of silicon to sodium used in the simulations. Dependence of the interparticle potential of mean force on the center-of-mass separation and the silicon to sodium ratio (5:1 and 20:1) is demonstrated. A Si:Na(+) ratio of 5:1 gave more repulsive interparticle potentials and lower numbers of internanoparticle or "bridging" hydrogen bonds. Conversely a Si:Na(+) ratio of 20:1 yielded more attractive potentials and higher numbers of bridging hydrogen bonds. The nature of the interaction of the counterions with charged silica surface sites (deprotonated silanols) was also investigated. The effect of the sodium double layer on water ordering was observed. The number of water molecules trapped inside the nanoparticles was investigated, and at the highest background ionic concentrations were found to consistently behave in accordance with there being an osmotic pressure. This study highlights the effect of divalent (Ca(2+)) background ions on the interparticle potentials compared with previous work using monovalent (Na(+)) background ions. Mechanisms of coagulation and the stability of silica nanocolloids found from this work appear to be in agreement with findings from experiments described in the literature.

Molecular dynamics simulation of nanocolloidal amorphous silica particles: Part II.

Explicit molecular dynamics simulations were applied to a pair of amorphous silica nanoparticles with diameter of 3.2 nm immersed in a background electrolyte. Mean forces acting between the pair of silica nanoparticles were extracted at four different background electrolyte concentrations. The dependence of the interparticle potential of mean force on the separation and the silicon to sodium ratio, as well as on the background electrolyte concentration, are demonstrated. The pH was indirectly accounted for via the ratio of silicon to sodium used in the simulations. The nature of the interaction of the counterions with charged silica surface sites (deprotonated silanols) was also investigated. The effect of the sodium double layer on the water ordering was investigated for three Si : Na(+) ratios. The number of water molecules trapped inside the nanoparticles was investigated as the Si : Na(+) ratio was varied. Differences in this number between the two nanoparticles in the simulations are attributed to differences in the calculated electric dipole moment. The implications of the form of the potentials for aggregation are also discussed.

Molecular dynamics simulation of nanocolloidal amorphous silica particles: Part I.

Explicit molecular dynamics simulations were applied to a pair of amorphous silica nanoparticles in aqueous solution, with diameter of 4.4 nm and with four different background electrolyte concentrations, to extract the mean force acting between the two silica nanoparticles. Dependences of the interparticle forces on the separation and the background electrolyte concentration were demonstrated. The nature of the interaction of the counterions with charged silica surface sites (deprotonated silanols) was investigated. A "patchy" double layer of adsorbed sodium counterions was observed. Dependences of the interparticle potential of mean force on the separation and the background electrolyte concentration were demonstrated. Direct evidence of the solvation forces is presented in terms of changes of the water ordering at the surfaces of the isolated and double nanoparticles. The nature of the interaction of the counterions with charged silica surface sites (deprotonated silanols) was investigated in terms of quantifying the effects of the number of water molecules separately inside each pair of nanoparticles by defining an impermeability measure. A direct correlation was found between the impermeability (related to the silica surface "hairiness") and the disruption of water ordering. Differences in the impermeability between the two nanoparticles are attributed to differences in the calculated electric dipole moment.

2-Aminopurine as a real-time probe of enzymatic cleavage and inhibition of hammerhead ribozymes.

The design, synthesis and study of internally fluorescent hammerhead (HH) ribozymes, where changes in fluorescence parameters directly reflect the progress of the ribozyme's cleavage chemistry, are described. The approach relies on a HH substrate modified at position 1.1, proximal to the cleavage site, with 2-aminopurine (2AP), an intensely fluorescent adenosine isoster. The incorporation of 2AP, an unnatural nucleoside, does not interfere with the ribozyme folding and catalysis. Since 2AP is highly sensitive to environmental changes, its fluorescence is dramatically altered upon ribozyme-mediated cleavage of the substrate. This generates a measurable signal that directly reflects the progress of the ribozyme's reaction in real time. Identical pseudo first order rate constants are obtained for HH constructs using both continuous fluorescence monitoring and radioactive labeling. This rapid and real-time monitoring facilitates the study of ribozyme activity under different conditions (e.g., ionic strength, pH, etc.), and provides a useful assay to rapidly screen potential inhibitors. Three hitherto unknown HH inhibitors are presented and compared to neomycin B and chlortetracycline, two previously studied HH inhibitors. All three new small molecules, neo-acridine, guanidino-neomycin B, and [Delta-(Eilatin)Ru(bpy)(2)](2+), prove to be better inhibitors than neomycin B or chlortetracycline. Investigating HH inhibition under different ionic strengths reveals that the binding of neo-acridine, [Delta-(Eilatin)Ru(bpy)(2)](2+), and chlortetracycline to the HH involves hydrophobic interactions as their RNA affinities are largely unaffected by increasing salt concentrations. In contrast, neomycin B loses more than 50-fold of its inhibitory ability as the NaCl concentration is increased from 50 to 500mM.

tRNA(Phe) binds aminoglycoside antibiotics.

Aminoglycoside antibiotics have recently been found to bind to a variety of unrelated RNA molecules, including sequences that are important for retroviral replication. We report the binding of neomycin B, kanamycin A, and Neo-Neo (a synthetic neomycin-neomycin dimer) to tRNA(Phe). Using thermal denaturation studies, fluorescence spectroscopy, Pb2+-mediated tRNA(Phe) cleavage, and gel mobility shift assays, we have established that aminoglycosides interact with yeast tRNA(Phe) and are likely to induce a conformational change. Thermal denaturation studies revealed that aminoglycosides have a substantial stabilizing effect on tRNA(Phe) secondary and tertiary structures, much greater than the stabilization effect of spermine, an unstructured polyamine. Aminoglycoside-induced inhibition of Pb2+-mediated tRNA(Phe) cleavage yielded IC50 values of: 5 microM for Neo-Neo, 100 microM for neomycin B, > 1 mM for kanamycin A, and > 10 mM for spermine. Enzymatic and chemical footprinting indicate that the anticodon stem as well as the junction of the TpsiC and D loops are preferred aminoglycoside binding sites.