Energetics of direct and water-mediated proton-coupled electron transfer

Proton-coupled electron transfer (PCET) is an elementary chemical reaction crucial for biological oxidoreduction. We perform quantum chemical calculations to study the direct and water-mediated PCET between two stacked tyrosines, TyrO(?) + TyrOH → TyrOH + TyrO(?), to mimic a key step in the catalytic reaction of class Ia ribonucleotide reductase (RNR). The energy surfaces of electronic ground and excited states are separated by a large gap of ~20 kcal mol(-1), indicative of an electronically adiabatic transfer mechanism. In response to chemical substitutions of the proton donor, the energy of the transition state for direct PCET shifts by exactly half of the change in energetic driving force, resulting in a linear free energy relation with a Br?nsted slope of ?. In contrast, for water-mediated PCET, we observe integer Br?nsted slopes of 1 and 0 for proton acceptor and donor modifications, respectively. Our calculations suggest that the π-stacking of the tyrosine dimer in RNR results in strong electronic coupling and adiabatic PCET. Water participation in the PCET can be identified perturbatively in a Br?nsted analysis.     

Easily accessible non-aromatic heterocycles with handles: 4-bromo-2,3-dihydrofurans from 1,2-dibromohomoallylic alcohols

The first general preparation of 4-bromo-2,3-dihydrofurans is reported. These non-aromatic heterocycles containing a useful coupling handle are accessed via Cu-catalyzed intramolecular cyclization of 1,2-dibromohomoallylic alcohols, which are themselves available in just two steps from aromatic and aliphatic aldehydes and ketones. Molecular dynamics simulations using the simple substrates and key geometric parameters provide a rationale for the selectivities observed. The synthetic utility of the 4-bromodihydrofurans is also demonstrated.

The first general preparation of 4-bromo-2,3-dihydrofurans is reported.     

Solvent-Free Mechanochemical Synthesis of High Transition Biphenyltetracarboxydiimide Liquid Crystals

A series of high temperature alkyl and alkoxy biphenyltetracarboxydiimide liquid crystals have been prepared under ball mill method using solvent-free mechanochemical approach. The thermal properties of the prepared compounds were investigated by deferential scanning calorimetry (DSC) measurements and the textures were identified by polarized optical microscope (POM). The compounds showed smectic mesomorphic behaviour. The results showed the increasing nature of transition temperature Cr-SmC with chain length with increments of the SmC mesophase range. However, the mesophase range of the SmA was decreased with the terminal chain length either for the alkyl or alkoxy terminal groups. Moreover, the DFT theoretical calculations have been conducted give a detailed projection of the structure of the prepared compounds. A conformational investigation of the biphenyl part has been studied. A deep illustration of the experimental mesomorphic behaviour has been discussed in terms of the calculated aspect ratio. A projection of the frontier molecular orbitals as well as molecular electrostatic potential has been studied to show the effect of the polarity of the terminal chains on the level and the gap of the FMOs and the distribution of electrostatic charges on the prepared molecules.     

Development of a Fluorescent Enzyme-Linked DNA Aptamer-Magnetic Bead Sandwich Assay and Portable Fluorometer for Sensitive and Rapid Leishmania Detection in Sandflies

A fluorescent peroxidase-linked DNA aptamer-magnetic bead sandwich assay is described which detects as little as 100 ng of soluble protein extracted from Leishmania major promastigotes with a high molarity chaotropic salt. Lessons learned during development of the assay are described and elucidate the pros and cons of using fluorescent dyes or nanoparticles and quantum dots versus a more consistent peroxidase-linked Amplex Ultra Red (AUR; similar to resazurin) fluorescence version of the assay. While all versions of the assays were highly sensitive, the AUR-based version exhibited lower variability between tests. We hypothesize that the AUR version of this assay is more consistent, especially at low analyte levels, because the fluorescent product of AUR is liberated into bulk solution and readily detectable while fluorophores attached to the reporter aptamer might occasionally be hidden behind magnetic beads near the detection limit. Conversely, fluorophores could be quenched by nearby beads or other proximal fluorophores on the high end of analyte concentration, if packed into a small area after magnetic collection when an enzyme-linked system is not used. A highly portable and rechargeable battery-operated fluorometer with on board computer and color touchscreen is also described which can be used for rapid (<1 h) and sensitive detection of Leishmania promastigote protein extracts (～100 ng per sample) in buffer or sandfly homogenates for mapping of L. major parasite geographic distributions in wild sandfly populations.     

Nickel-Catalyzed Kumada Cross-Coupling Reactions of Benzylic Sulfonamides

Herein, we report a Kumada cross-coupling reaction of benzylic sulfonamides. The scope of the transformation includes acyclic and cyclic sulfonamide precursors that cleanly produce highly substituted acyclic fragments. Preliminary data are consistent with a stereospecific mechanism that allows for a diastereoselective reaction.     

Effect of flexibility on hydrophobic behavior of nanotube water channels

Carbon nanotubes can serve as simple nonpolar water channels. Here we report computer simulations exploring the relationship between the mechanical properties of such channels and their interaction with water. We show that on one hand, increasing the flexibility of the carbon nanotubes increases their apparent hydrophobic character, while on the other hand the presence of water inside the channel makes them more resistant to radial collapse. We quantify the effect of increasing flexibility on the hydrophobicity of the nanotube water channel. We also show that flexibility impedes water transport across the nanotube channel by increasing the free-energy barriers to such motion. Conversely, the presence of water inside the nanotube is shown to affect the energetics of radial collapse in a water nanotube, an ostensibly mechanical property. We quantify the magnitude of the effect and show that it arises from the formation of energetically favorable low-dimensional water structures inside the nanotube such as one-dimensional wires and two-dimensional sheets.     

Photodecomposition of Chloroform Catalyzed by Unmodified MCM‐41 Mesoporous Silica

Unactivated MCM‐41 mesoporous silica catalyzes the photodecomposition of chloroform to phosgene and hydrogen chloride under near‐UV (λ > 360 nm) irradiation. The rate of photodecomposition increases toward an asymptotic limit as the O₂ partial pressure is increased. Deuterochloroform does not decompose under the same experimental conditions. Low concentrations of both cyclohexane and ethanol quench the photodecomposition, whereas water, up to its solubility limit, does not. Dissolved tetraalkylammonium salts suppress photodecomposition. The data are consistent with a mechanism in which light absorption by an SiO₂ defect yields an electron‐deficient oxygen atom, which then abstracts hydrogen from chloroform. The resulting CCl₃ radicals react with oxygen to form a peroxy radical that decomposes, eventually yielding phosgene and hydrogen chloride.     

Convergence and error estimation in free energy calculations using the weighted histogram analysis method

The weighted histogram analysis method (WHAM) has become the standard technique for the analysis of umbrella sampling simulations. In this article, we address the challenges (1) of obtaining fast and accurate solutions of the coupled nonlinear WHAM equations, (2) of quantifying the statistical errors of the resulting free energies, (3) of diagnosing possible systematic errors, and (4) of optimally allocating of the computational resources. Traditionally, the WHAM equations are solved by a fixed-point direct iteration method, despite poor convergence and possible numerical inaccuracies in the solutions. Here, we instead solve the mathematically equivalent problem of maximizing a target likelihood function, by using superlinear numerical optimization algorithms with a significantly faster convergence rate. To estimate the statistical errors in one-dimensional free energy profiles obtained from WHAM, we note that for densely spaced umbrella windows with harmonic biasing potentials, the WHAM free energy profile can be approximated by a coarse-grained free energy obtained by integrating the mean restraining forces. The statistical errors of the coarse-grained free energies can be estimated straightforwardly and then used for the WHAM results. A generalization to multidimensional WHAM is described. We also propose two simple statistical criteria to test the consistency between the histograms of adjacent umbrella windows, which help identify inadequate sampling and hysteresis in the degrees of freedom orthogonal to the reaction coordinate. Together, the estimates of the statistical errors and the diagnostics of inconsistencies in the potentials of mean force provide a basis for the efficient allocation of computational resources in free energy simulations.     

Surface‐Assisted Cyclodehydrogenation; Break the Symmetry,Enhance the Selectivity

Selectivity in chemical reactions is a major objective in industrial processes to minimize spurious byproducts and to save scarce resources. In homogeneous catalysis the most important factor which determines selectivity is structural symmetry. However, a transfer of the symmetry concept to heterogeneous catalysis still requires a detailed comprehension of the underlying processes. Here, we investigate a ring‐closing reaction in surface‐confined meso‐substituted porphyrin molecules by scanning tunneling microscopy, temperature‐programmed desorption, and computational modeling. The identification of reaction intermediates enables us to analyze the reaction pathway and to conclude that the symmetry of the porphyrin core is of pivotal importance regarding product yields.