A Journey to the Total Synthesis of Daptomycin

Daptomycin, the first antibiotic of its class, provides a new structural motif for the development of new antibiotics. Recently, we have completed the total synthesis of daptomycin. The development of the successful synthetic strategy is described here, including the application of serine/threonine ligation mediated peptide cyclization to the daptomycin macrocyclization.     

NVU dynamics. II. Comparing to four other dynamics

In the companion paper [T. S. Ingebrigtsen, S. Toxvaerd, O. J. Heilmann, T. B. Schr?der, and J. C. Dyre, "NVU dynamics. I. Geodesic motion on the constant-potential-energy hypersurface," J. Chem. Phys. (in press)] an algorithm was developed for tracing out a geodesic curve on the constant-potential-energy hypersurface. Here, simulations of NVU dynamics are compared to results for four other dynamics, both deterministic and stochastic. First, NVU dynamics is compared to the standard energy-conserving Newtonian NVE dynamics by simulations of the Kob-Andersen binary Lennard-Jones liquid, its WCA version (i.e., with cut-off's at the pair potential minima), and the Lennard-Jones Gaussian liquid. We find identical results for all quantities probed: radial distribution functions, incoherent intermediate scattering functions, and mean-square displacement as function of time. Arguments are presented for the equivalence of NVU and NVE dynamics in the thermodynamic limit; in particular, to leading order in 1∕N these two dynamics give identical time-autocorrelation functions. In the final part of the paper, NVU dynamics is compared to Monte Carlo dynamics, to a diffusive dynamics of small-step random walks on the constant-potential-energy hypersurface, and to Nose?-Hoover NVT dynamics. If time is scaled for the two stochastic dynamics to make single-particle diffusion constants identical to that of NVE dynamics, the simulations show that all five dynamics are equivalent at low temperatures except at short times.     

Isomorph Invariance of Higher-Order Structural Measures in Four Lennard–Jones Systems

In the condensed liquid phase, both single- and multicomponent Lennard–Jones (LJ) systems obey the “hidden-scale-invariance” symmetry to a good approximation. Defining an isomorph as a line of constant excess entropy in the thermodynamic phase diagram, the consequent approximate isomorph invariance of structure and dynamics in appropriate units is well documented. However, although all measures of the structure are predicted to be isomorph invariant, with few exceptions only the radial distribution function (RDF) has been investigated. This paper studies the variation along isomorphs of the nearest-neighbor geometry quantified by the occurrence of Voronoi structures, Frank–Kasper bonds, icosahedral local order, and bond-orientational order. Data are presented for the standard LJ system and for three binary LJ mixtures (Kob–Andersen, Wahnström, NiY2). We find that, while the nearest-neighbor geometry generally varies significantly throughout the phase diagram, good invariance is observed along the isomorphs. We conclude that higher-order structural correlations are no less isomorph invariant than is the RDF.     

Ring opening of aziridines by aromatic thiols followed by amino-substitution

Ring opening of 2-aziridinecarboxylic acid methyl ester by a number of aromatic thiols under solvent-free and non-catalytic conditions resulted in bis-arylsulfanyl propanoic acid esters.     

Forces acting on water droplets falling in oil under the influence of an electric field: numerical predictions versus experimental observations

The combination of an electric field and a moderate turbulent flow is a promising technique for separating stable water–oil emulsions. Field-induced charges on the water droplets will cause adjacent droplets to align with the field and attract each other. The present work describes the forces that influence the kinematics of droplets falling in oil when exposed to an electric field. Mathematical models for these forces are presented and discussed with respect to a possible implementation in a multi-droplet Lagrangian framework. The droplet motion is mainly due to buoyancy, drag, film-drainage, and dipole–dipole forces. Attention is paid to internal circulations, non-ideal dipoles, and the effects of surface tension gradients.Experiments are performed to observe the behavior of a droplet falling onto a stationary one. The droplet is exposed to an electric field parallel to the direction of the droplet motion. The behavior of two falling water droplets exposed to an electric field perpendicular to the direction of their motion is also investigated until droplet coalescence. The droplet motion is recorded with a high-speed CMOS camera. The optical observations are compared with the results from numerical simulations where the governing equations for the droplet motion are solved by the RK45 (Runge Kutta) Fehlberg method with step-size control and low tolerances. Results, using different models, are compared and discussed in detail. A framework is otlined to describe the kinematics of both a falling rigid spherical particle and a fluid droplet under the influence of an electric field.     

Communication: thermodynamics of condensed matter with strong pressure-energy correlations

We show that for any liquid or solid with strong correlation between its NVT virial and potential-energy equilibrium fluctuations, the temperature is a product of a function of excess entropy per particle and a function of density, T = f(s)h(ρ). This implies that (1) the system's isomorphs (curves in the phase diagram of invariant structure and dynamics) are described by h(ρ)/T = Const., (2) the density-scaling exponent is a function of density only, and (3) a Gru?neisen-type equation of state applies for the configurational degrees of freedom. For strongly correlating atomic systems one has h(ρ) = ∑(n)C(n)ρ(n/3) in which the only non-zero terms are those appearing in the pair potential expanded as ν(r) = ∑(n)ν(n)r(-n). Molecular dynamics simulations of Lennard-Jones type systems confirm the theory.     

A high resolution sonar for sea-bed imaging

A sonar system for making three-dimensional topographic images of the sea-bed is described. The system applies a sectorial scan within each range cell by electronic beam forming. It is designed to resolve 128 beams each separated by 0.5° to cover a 64° sector. The beam forming is facilitated by a real-time Fourier transform of the signal samples from the multielement receiving transducer array. The Fourier transform is implemented as a chirp transform using surface acoustic wave reflective array devices.The design and measured performance of the transducers, and the beam former are discussed in some detail.     

NVU dynamics. I. Geodesic motion on the constant-potential-energy hypersurface

An algorithm is derived for computer simulation of geodesics on the constant-potential-energy hypersurface of a system of N classical particles. First, a basic time-reversible geodesic algorithm is derived by discretizing the geodesic stationarity condition and implementing the constant-potential-energy constraint via standard Lagrangian multipliers. The basic NVU algorithm is tested by single-precision computer simulations of the Lennard-Jones liquid. Excellent numerical stability is obtained if the force cutoff is smoothed and the two initial configurations have identical potential energy within machine precision. Nevertheless, just as for NVE algorithms, stabilizers are needed for very long runs in order to compensate for the accumulation of numerical errors that eventually lead to "entropic drift" of the potential energy towards higher values. A modification of the basic NVU algorithm is introduced that ensures potential-energy and step-length conservation; center-of-mass drift is also eliminated. Analytical arguments confirmed by simulations demonstrate that the modified NVU algorithm is absolutely stable. Finally, we present simulations showing that the NVU algorithm and the standard leap-frog NVE algorithm have identical radial distribution functions for the Lennard-Jones liquid.