BIOSOL · Solvent effects on physico-chemical properties of bioactive compounds: combination of theory with experiments

Recent developments in combinatorial chemistry, high throughput screening, and robotics led to a large number of compounds with potential biological activity. The vast and ever increasing number of possible lead molecules requires prioritizing the most promising compounds. Physicochemical properties of the drugs in solutions determine their pharmacodynamics and pharmacokinetcs and, therefore, are of key importance in the further development process. We propose a multidisciplinary project that includes correlated experimental and theoretical efforts to understand the molecular mechanisms of structural changes of biomolecules and thermodynamics of biomolecular solvation. The Max Planck group has recently proposed new modeling approaches based on the combinations of several methods of computational chemistry as the improved integral equations theory, molecular mechanics and the density functional theory. This approach allows one to predict the physicochemical properties of biomolecules in solution with high accuracy but with low computational cost. We believe that the combination of the novel modeling methods with direct cutting-edge experiments made by other participants should provide new insights on the intriguing problems of biomolecule solvation such as: 1. How solvent properties (type of solvent, temperature, pH, ionic strength, cosolvents, etc) affect physico-chemical properties of bioactive molecular compounds? 2. What are the molecular mechanisms of different solubility pathways for bioactive compounds: in aqueous solutions and what is the role of polimorphism on the solubility pathways? 3. What are the effects of ions (concentration and type of ions present in the solution) and pH on the solvation properties of bioactive compounds? 4. What are the basic molecular principles of solubilisation of ionised and non-ionised compounds in supercritical fluids?5. Can we still operate with such terms as solvation shell and solvated complex in supercritical solvents?