THE USE OF MOLECULAR-ORBITAL INDEXES TO PREDICT THE SURFACE-PROPERTIES OF PHARMACEUTICAL POWDERS

The electron density, frontier electron density and superdelocalisabil ity indices have been calculated for the total molecular structures, a nd the parts of the molecules which are anticipated to be involved in hydrogen bonding interactions. The models used comprised of an homolog ous series (alkyl p-hydroxybenzoates), materials related by a common r ing structure, but with differing substituents (imidazoles), and three related comparatively large molecular weight drugs (HMG-CoA reductase inhibitors). Surface energies were determined from contact angle data with water, using Neumann's equation of state. No relationship was se en between data for total molecular orbital indices for the molecules and measured contact angles or derived surface energies. However, when the hydrogen bonding atoms of the molecules were selected, a good lin ear correlation was observed for all three types of molecule between s uperdelocalisability and bath contact angle and surface energy. This i s expected as the hydrogen bonding regions are probably especially imp ortant in interactions with water. Two (of 16) molecules were outliers from the general relationship. These were one of the HMG-CoA reductas e inhibitors and methyl p-hydroxybenzoate. It is possible that the hig h molecular weight of the first of these molecules was the cause of an error in calculation of the molecular orbital indices (due to optimis ation to a secondary minimum). For the methyl p-hydroxybenzoate, there are considerable data in the literature to indicate that this materia l has idiosyncratic properties. Its curious behaviour is examined with consideration to possible crystal packing energy differences over oth er members in the series. The data presented here give encouragement t hat the surface properties of a wide range of different materials may be predicted from molecular structure, however, there are inevitable o utliers which will mean that predictions will have to be confirmed wit h practical observations, until modelling approaches have been develop ed further and adequately validated.