Organic molecules partition coefficient calculation simulator

• Grant number: 05/05218-8
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2006
• End date: August 31, 2009
• Field of knowledge: Physical Sciences and Mathematics - Computer Science - Computer Systems
• Principal Investigator: Andréa Lucia Braga Vieira Rodrigues
• Grantee: Andréa Lucia Braga Vieira Rodrigues
• Host Institution: Pró-Reitoria de Pós-Graduação e Pesquisa. Universidade de Sorocaba (UNISO). Sorocaba , SP, Brazil

Abstract

Drug partition coefficient (PC) is a quantitative measure that supplies information about its polarity and, in many cases, drives its distribution in the different biological spaces in the human body. When a drug is submitted to a binary solvent system (such as n-octanol/water) it is often distributed between the two phases and its PC value is calculated dividing its concentration in the n-octanol phase by its concentration in the water phase, thus, the largest its lipophilicity, the bigger its PC value. The PC can be determined by three different methods: using "shake flask" (SF) practical method, by high pressure liquid chromatography (HPLC) or through calculation. The scope of this work is to create a calculation processing tool involving different organic molecules using adjusted methods in terms of predictive capacity, i.e., those that allows calculated values close to practical ones. The PC calculation methods is based on molecular fragmentation allowing sub-units that possesses reliable PC values and including the correction terms due to intramolecular interaction. Thus, to automatize PC calculation the consecrated method of Rekker will be adopted and a system will be implemented that processes de PC calculation using an algorithm representing the structural molecular formula and searching the contribution of the fragments and the correction terms in the data base. The computational method allows studies of hundreds of molecules, allowing in the future, corrections in terms of deviation and calculus re-dimention in order to optimize its preditivity characteristic. (AU)