Accelerating chemical reactions: exploring reactive free-energy surfaces using accelerated ab initio molecular dynamics

A biased potential molecular dynamics simulation approach, accelerated molecular dynamics (AMD), has been implemented in the framework of ab initio molecular dynamics for the study of chemical reactions. Using two examples, the double proton transfer reaction in formic acid dimer and the hypothetical adiabatic ring opening and subsequent rearrangement reactions in methylenecyclopropane, it is demonstrated that ab initio AMD can be readily employed to efficiently explore the reactive potential energy surface, allowing the prediction of chemical reactions and the identification of metastable states. An adaptive variant of the AMD method is developed, which additionally affords an accurate representation of both the free-energy surface and the mechanism associated with the chemical reaction of interest and can also provide an estimate of the reaction rate.     

Enantioselective total syntheses of (-)-taiwaniaquinone H and (-)-taiwaniaquinol B by iridium-catalyzed borylation and palladium-catalyzed asymmetric α-arylation

We report a concise, enantioselective total synthesis of (-)-taiwaniaquinone H and the first enantioselective total synthesis of (-)-taiwaniaquinol B by a route that includes asymmetric palladium-catalyzed α-arylation of a ketone with an aryl bromide that was generated by sterically controlled halogenation via iridium-catalyzed C-H borylation. This asymmetric α-arylation creates the benzylic quaternary stereogenic center present in the taiwaniaquinoids. The synthesis was completed efficiently by developing a Lewis acid-promoted cascade to construct the [6,5,6] tricyclic core of an intermediate common to the synthesis of a number of taiwaniaquinoids. Through the preparation of these compounds, we demonstrate the utility of constructing benzylic quaternary stereogenic centers, even those lacking a carbonyl group in the α-position, by asymmetric α-arylation.     

Integrable Nonlinear Equations for Water Waves in Straits of Varying Depth and Width

A considerable amount of information is currently available on the creation and propagation of large solitary waves in marine straits. In order to be able to analyze such data we develop a theoretical model, extending previous one-dimensional models to the case of straits with varying width and depth, and nonvanishing vorticity. Starting from the Euler equations for a three-dimensional homogeneous incompressible inviscid fluid, we derive, in the quasi-one-dimensional long-wave and shallow-water approximation, a generalized KadomtsevPetviashvili (GKP) equation, together with its appropriate boundary conditions. In general, the coefficients of this equation depend on the form of the bottom and on the vorticity; the sides of the straits figure only in the boundary conditions. Under certain restrictions on the vorticity and the geometry of the straits we reduce the GKP equation to one of several completely integrable partial differential equations, in order to study the evolution of solitons which originate in the straits.     

Concerning the design of capacitively driven induction coil guns

The authors consider the design of capacitively driven, multisection, electromagnetic coil launchers, or coil guns, taking their transient behavior into account. A lumped-parameter computer simulation is developed to predict the performance of the launcher system. It is shown that a traveling electromagnetic wave can be generated on the barrel by the resonance of drive coils and their capacitors. More than half of the energy initially stored in the capacitor bank can be converted into kinetic energy of the projectile in one shot, and an additional quarter can be utilized in subsequent shots, if the launcher dimensions, resonant frequency, and firing sequence are properly selected. The projectile starts smoothly from zero initial velocity and with zero initial sleeve current. Section-to-section transitions which have significant effects on the launcher performance are also discussed. Experimental results were obtained with a small model and are in good agreement with theoretical predictions     

Arnol′d Diffusion in a Pendulum Lattice

The main model studied in this paper is a lattice of pendula with a nearest‐neighbor coupling. If the coupling is weak, then the system is near‐integrable and KAM tori fill most of the phase space. For all KAM trajectories the energy of each pendulum stays within a narrow band for all time. Still, we show that for an arbitrarily weak coupling of a certain localized type, the neighboring pendula can exchange energy. In fact, the energy can be transferred between the pendula in any prescribed way. © 2014 Wiley Periodicals, Inc.     

Some algebraic structures for diffusion in social networks

Restrictions on influence structures discussed by Buskens and Yamaguchi (1999) and others lead the states of possible distributions of information to form an algebraic structure of a lattice that is closed under union. From an examination of such a lattice of distribution, it is possible to recreate an influence network that is not observed directly. Finally, it is noted that these structures are different from those examined via Galois lattices; therefore, if these diffusion processes occur, Galois lattices do not recreate the actual social structure underlying this diffusion.     

Theoretical optimization of Irinotecan-based anticancer strategies in the case of drug-induced efflux

The anticancer drug Irinotecan (CPT11) is known to trigger the induction of ATP-Binding Cassette (ABC) transporters, responsible for the efflux of the drug and its metabolites outside of the cells. The drug-modulated overexpression of those transporters prevents its accumulation in the intracellular medium, therefore decreasing its efficacy. A critical clinical concern lies in the design of CPT11-based therapeutic strategies which eradicate a maximum number of cancer cells despite their ability to become resistant. In order to address this issue, we supplemented an existing mathematical model of CPT11 molecular pharmacokinetics–pharmacodynamics (PK–PD) with a new model of CPT11-induced overexpression of ABC transporters. We then theoretically optimized exposure to CPT11 given as a single agent or combined either with ABC transporter inhibitors, or with inhibitors of nuclear factors whose activation is responsible for transporter overexpression. We firstly considered a cancer cell population endowed with the ability of inducing their transporters. For any drug combination, we concluded that the highest concentration of CPT11 should be administered in order to kill a maximum number of cancer cells, despite the triggering of resistance. We then considered a population of healthy cells which were assumed to be identical to cancer cells except that they were not able to become resistant. Optimal schemes were defined as the ones which maximized DNA damage in cancer cells under the constraint of DNA damage in healthy cells not exceeding a tolerability threshold. The optimal therapeutic strategy consisted in combining CPT11 with ABC transporter inhibitors as it achieved a complete reversal of resistance by means of the lowest concentrations of CPT11.     

On congruences of-normal semigroups-normal semigroups

Communicated by G. Lallement