The fast multipole boundary element method for molecular electrostatics: An optimal approach for large systems

We propose a fast implementation of the boundary element method for solving the Poisson equation, which approximately determines the electrostatic field around solvated molecules of arbitrary shape. The method presented uses computational resources of order O(N) only, where N is the number of elements representing the dielectric boundary at the molecular surface. The method is based on the Fast Multipole Algorithm by Rokhlin and Greengard, which is used to calculate the Coulombic interaction between surface elements in linear time. We calculate the solvation energies of a sphere, a small polar molecule, and a moderately sized protein. The values obtained by the boundary element method agree well with results from finite difference calculations and show a higher degree of consistency due to the absence of grid dependencies. The boundary element method can be taken to a much higher accuracy than is possible with finite difference methods and can therefore be used to verify their validity. © 1995 by John Wiley & Sons, Inc.     

Viscosity of liquid mixtures: the Vesovic-Wakeham method for chain molecules

New expressions for the viscosity of liquid mixtures, consisting of chain-like molecules, are derived by means of Enskog-type analysis. The molecules of the fluid are modelled as chains of equally sized, tangentially joined, and rigid spheres. It is assumed that the collision dynamics in such a fluid can be approximated by instantaneous collisions. We determine the molecular size parameters from the viscosity of each pure species and show how the different effective parameters can be evaluated by extending the Vesovic-Wakeham (VW) method. We propose and implement a number of thermodynamically consistent mixing rules, taking advantage of SAFT-type analysis, in order to develop the VW method for chain molecules. The predictions of the VW-chain model have been compared in the first instance with experimental viscosity data for octane-dodecane and methane-decane mixtures, thus, illustrating that the resulting VW-chain model is capable of accurately representing the viscosity of real liquid mixtures.     

Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[e][1,4]oxazepin-2(3H)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro

Acute myeloid leukemia (AML) is the most aggressive type of blood cancer, and there is a continued need for new treatments that are well tolerated and improve long-term survival rates in patients. Induction of differentiation has emerged as a promising alternative to conventional cytotoxic chemotherapy, but known agents lack efficacy in genetically distinct patient populations. Previously, we established a phenotypic screen to identify small molecules that could stimulate differentiation in a range of AML cell lines. Utilising this strategy, a 1,5-dihydrobenzo[e][1,4]oxazepin-2(3H)-one hit compound was identified. Herein, we report the hit validation in vitro, structure-activity relationship (SAR) studies and the pharmacokinetic profiles for selected compounds.     

Structural reinvestigation of ammonium hypophosphite: was dihydrogen bonding observed long ago?

The past decade has seen the explosive emergence of "dihydrogen bonds", interactions between the electrons of M-H sigma-bonds, where M is less electronegative than H (M = Al, B, Ga, Ir, Mo, Mn, Os, Re, Ru, W) and traditional proton donors. But 70 years ago, such an interaction was proposed by Zachariasen and Mooney [J. Chem. Phys. 1934, 2, 34-37] on the basis of their single-crystal X-ray diffraction structure (heavy atoms positions only) of ammonium hypophosphite (NH(4)H(2)PO(2)). We redetermined this structure at high resolution with a focus on the hydrogen atoms, using a modern diffractometer equipped with a CCD detector. Molecular orbital calculations were performed to investigate the charge density and the bond polarity of the P-H bonds and to assess their potential for participation in dihydrogen bonds. Neither the theory nor the X-ray structure supports the original claim of H...H interactions in this salt.     

Chloroindate(III) ionic liquids: recyclable media for Friedel-Crafts acylation reactions

Chloroindate(III) ionic liquids are versatile reaction media for Friedel-Crafts acylation reactions; the system is catalytic and totally recyclable, using an aqueous workup, with no leaching of the indium into the product phase.     

Long-Range 31P-31P Spin Coupling Constants in the 31P NMR Spectra of Phosphite Triesters

Abstract

Data are presented on the magnitudes of ⁵ J _pp and ⁶ J _PP spin-spin coupling constants in the ³¹P NMR spectra of a variety of novel polyphosphite triesters.