Orthogonally protected carbohydrate-based scaffolds

A series of orthogonally protected polyaminated carbohydrate scaffolds have been prepared on a multi-gram scale.     

A direct and rapid route to α,α-difluoroacylsilanes from trifluoroethanol

α,α-Difluoroacylsilanes were synthesised directly from a range of allyl ethers of trifluoroethanol via dehydrofluorination/metallation procedures, followed by thermal [3,3]-sigmatropic rearrangement of the intermediate vinylmetals. The scope and limitations of ether synthesis and dehydrofluorination/metallation are described.     

A Conjecture on the Hall Topology for the Free Group

The Hall topology for the free group is the coarsest topologysuch that every group morphism from the free group onto a finitediscrete group is continuous. It was shoen by M.Hall Jr thatevery finitely generated subgroup of the free group is closedfor this topology. We conjecture that if H₁, H₂,...,H_n are finitelygenerated subgroups of the free group, then the product H₁ H₂...H_n is closed. We discuss some consequences of this conjecture.First, it would give a nice and simple algorithm to computethe closure of a given rational subset of the free group. Next,it implies a similar conjecture for the free monoid, which inturn is equivalent to a deep conjecture on finite semigroupsfor the solution of which J. Rhodes has offered $100. We hopethat our new conjecture will shed some light on Rhodes' conjecture.     

Stabilization of a Chiral Dirhodium Carbene by Encapsulation and a Discussion of the Stereochemical Implications

For the first time, the stereochemical course of an asymmetric cyclopropanation can be discussed on the basis of experimental structural information on a pertinent chiral dirhodium carbene intermediate. Key to success was the formation of racemic single crystals of a heterochiral [Rh₂{(S*)‐PTTL}₄{=C(Ar)COOMe}][Rh₂{(R*)‐PTTL}₄] (Ar=MeOC₆H₄; PTTL=N‐phthaloyl‐tert‐leucinate) capsule, which has been characterized by X‐ray diffraction. NMR spectroscopic data confirm that the obtained structural portrait is also relevant in solution and provide additional information about the dynamics of this species. The chiral binding pocket is primarily defined by the conformational preferences of the N‐phthaloyl‐protected amino acid ligands and reinforced by a network of weak interligand interactions that get stronger when chlorinated phthalimide residues are used.     

Attracting cavities for docking. Replacing the rough energy landscape of the protein by a smooth attracting landscape

Molecular docking is a computational approach for predicting the most probable position of ligands in the binding sites of macromolecules and constitutes the cornerstone of structure‐based computer‐aided drug design. Here, we present a new algorithm called Attracting Cavities that allows molecular docking to be performed by simple energy minimizations only. The approach consists in transiently replacing the rough potential energy hypersurface of the protein by a smooth attracting potential driving the ligands into protein cavities. The actual protein energy landscape is reintroduced in a second step to refine the ligand position. The scoring function of Attracting Cavities is based on the CHARMM force field and the FACTS solvation model. The approach was tested on the 85 experimental ligand–protein structures included in the Astex diverse set and achieved a success rate of 80% in reproducing the experimental binding mode starting from a completely randomized ligand conformer. The algorithm thus compares favorably with current state‐of‐the‐art docking programs. © 2015 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.     

Scalable improvement of SPME multipolar electrostatics in anisotropic polarizable molecular mechanics using a general short‐range penetration correction up to quadrupoles

We propose a general coupling of the Smooth Particle Mesh Ewald SPME approach for distributed multipoles to a short‐range charge penetration correction modifying the charge‐charge, charge‐dipole and charge‐quadrupole energies. Such an approach significantly improves electrostatics when compared to ab initio values and has been calibrated on Symmetry‐Adapted Perturbation Theory reference data. Various neutral molecular dimers have been tested and results on the complexes of mono‐ and divalent cations with a water ligand are also provided. Transferability of the correction is adressed in the context of the implementation of the AMOEBA and SIBFA polarizable force fields in the TINKER‐HP software. As the choices of the multipolar distribution are discussed, conclusions are drawn for the future penetration‐corrected polarizable force fields highlighting the mandatory need of non‐spurious procedures for the obtention of well balanced and physically meaningful distributed moments. Finally, scalability and parallelism of the short‐range corrected SPME approach are addressed, demonstrating that the damping function is computationally affordable and accurate for molecular dynamics simulations of complex bio‐ or bioinorganic systems in periodic boundary conditions. © 2016 Wiley Periodicals, Inc.     

On second-order antidiffusive Lagrangian-remap schemes for multispecies kinematic flow models

This paper focuses on the numerical approximation of the solutions of multi-species kinematic flow models. These models are strongly coupled nonlinear first-order conservation laws with various applications like sedimentation of a polydisperse suspension in a viscous fluid, or traffic flow modeling. Since the eigenvalues and eigenvectors of the corresponding flux Jacobian matrix have no closed algebraic form, this is a challenging issue. A new class of simple schemes based on a Lagrangian- Eulerian decomposition (the so-called Lagrangian-remap (LR) schemes) was recently advanced in [4] for traffic flow models with nonnegative velocities, and extended to models of polydisperse sedimentation in [5]. These schemes are supported by a partial numerical analysis when one species is considered only, and turned out to be competitive in both accuracy and efficiency with several existing schemes. Since they are only first-order accurate, it is the purpose of this contribution to propose an extension to second-order accuracy using quite standard MUSCL and Runge-Kutta techniques. Numerical illustrations are proposed for both applications and involving eleven species (sedimentation) and nine species (traffic) respectively.     

Dynamic Aspects and Controllability of the MELiSSA Project: A Bioregenerative System to Provide Life Support in Space

Manmade ecosystems differ from their prototype biosphere by the principle of control. The Earth Biosphere is sustainable by stochastic control and very large time constants. By contrast, in a closed ecosystem such as the micro-ecological life support system alternative (MELiSSA system) developed by the European Space Agency for space exploration, a deterministic control is a prerequisite of sustainable existence. MELiSSA is an integrated sum of interconnected biological subsystems. On one hand, all unit operations in charge of the elementary functions constitutive of the entire life support system are studied until a thorough understanding and mathematical modelling. On the other hand, the systemic approach of complex, highly branched systems with feedback loops is performed. This leads to study in the same perspective, with the same degree of accuracy and with the same language, waste degradation, water recycling, atmosphere revitalisation and food production systems prior to the integration of knowledge-based control models. This paper presents the mathematical modelling of the MELiSSA system and the interface between the control strategy of the entire system and the control of the bioreactors.