R-807

The prediction of drug solubility in various pure and mixed solvents and the octanol-water partition coefficient (K_OW) are evaluated using the recently revised conductor-like screening segment activity coefficient (COSMO-SAC) model.The solubility data of 51 drug compounds in 37 different solvents and their combinations over a temperature range of 273.15 K to 323.15 K (300 systems, 2918 data points) are calculated from the COSMO-SAC model and compared to experimentsThe solubility data cover a wide range of solubility from (10^-1 to 10^-6) in mole fraction.When only the heat of fusion and the normal melting temperature of the drug are used, the average absolute error from the revised model is found to be 236 %, a significant reduction from that (388 %) of the original COSMO-SAC model.When the pure drug properties (heat of fusion and melting temperature) are not available, predictions can still be made with a similar accuracy using the solubility data of the drug in any other solvent or solvent mixtureThe accuracy in prediction of the solubility in a mixed solvent can be greatly improved (average error of 70 %), if the measured solubility data in one pure solvent is used.Also, the standard deviation in log K_OW of 89 drugs, whose values range from -3.7 to 5.25, is found to be 1.14 from the revised COSMO-SAC model.Our results show that the COSMO-SAC model can provide reliable predictions of properties of pharmaceuticals and is a useful tool for drug discovery.

The stainable polyphosphate bodies in five species of algae epiphytic on Cladophora glomerata were enumerated. The algal populations, two species of diatoms, two species of blue-green algae, and a red alga, were collected at various distances from a point source of phosphorus enrichment in Lake Huron. Populations assayed had accumulated polyphosphate bodies and exhibited different levels of maximum polyphosphate body abundance. Numbers of polyphosphate bodies per unit cell volume were least in the diatoms, greatest in the blue-greens, and intermediate in the red alga. No significant differences were found between subpopulations of the same species growing in different portions of the epiphyte community matrix at one location. The subpopulation growing at the location farthest from the point source of phosphorus had substantially fewer polyphosphate bodies than subpopulations of the same species closer to the point source. The ecology and growth relationships of Cladophora communities in the Laurentian Great Lakes has been studied extensively, largely because of the potential for offensive overgrowth in localities receiving phosphorus enrichment. Although abundance of Cladophora generally is related to phosphorus loading, certain aspects of seasonal growth apparently are mediated by other factors. Presently it is not clear if the commonly observed mid-summer decline in Cladophora growth is due to genetically pre-determined maturation effects, or to competition for critical resources by epiphytic communities which develop upon the maturing Cladophora stands. Due to the complex and highly structured form of the community developed upon Cladophora, the latter aspect of Cladophora ecology is difficult to address experimentally. In the following, we report the results of an investigation of one possibly important competitive process, sequestering of phosphorus beyond immediate growth requirements by populations epiphytic on Cladophora. Several specific questions were considered: (1) is there appreciable luxury consumption of phosphorus by epiphyte communities; (2) is the amount of phosphorus sequestered dependent upon ambient phosphorus levels; (3) is this ability to sequester phosphorus restricted to, or more prevalent in, certain major autecological groups of epiphytic organisms; 1 We thank L. Sicko-Goad for her review of this manuscript, guidance, and suggestions. Drs. Martin Auer and Raymond Canale deserve recognition for aid in obtaining partial funding of this project by United States Environmental Protection Agency Contract No. R806/600-01-0. Additional funding for this study was by United States Environmental Protection Agency Contract No. R807/450-01-0. Contribution No. 375, Great Lakes Research Division. 2 Present address: Department of Biology, University of Louisville, Louisville, Kentucky