Novel structural molecular-chemical models

The molecule sulfur hexafluoride (SFA has recently challenged both molecular spectroscopy with its unexpected rotational spectra 29) and electronic structure theories with novel correlation effects (30,31,5). The electronic structure must explain the molecule s high stability, octahedral symmetry, and, most importantly, provide a simple picture of the bonding. At first glance, the traditional chemical models do not appear to be appropriate because sulfur seemingly forms six bonds to fluorines, yet the sulfur s2pA valence configuration allows for at most two covalent bonds. 

In the following section, the calculation of the VolSurf parameters from GRID interaction energies will be explained and the physico-chemical relevance of these novel descriptors demonstrated by correlation with measured absorption/ distribution/metabolism/elimination (ADME) properties. The applications will be shown by correlating 3D molecular structures with Caco-2 cell permeabilities, thermodynamic solubilities and metabolic stabilities. Special emphasis will be placed on interpretation of the models by multivariate statistics, because a rational design to improve molecular properties is critically dependent on an understanding of how molecular features influence physico-chemical and ADME properties. 

Chart 8 Chemical structures of the CA4 boronic acid bioisostere (9) and of MDL-27048. The former was proposed by a structure-based molecular modeling study, the latter was used to elaborate a virtual screening protocol for the identification of novel chalcone CSI... 

---