Calculating log P(oct) with no missing fragments; The problem of estimating new interaction parameters

摘要

The solvation forces which determine the equilibrium of a solute between water and a non-polar solvent, such as octanol, cannot be assigned on an atom-by-atom basis in the solute structure. The program CLOGP defines the hydrophobic hydrocharbon portions of any structure in such a way that he remaining polar fragments are unambiguously defined and of a manageable size. Early versions required that each polar fragment thus defined be present in a measured solute before it could be used in calculations of log P(oct), but in versions 4.0 or greater, these can be calculated ab initio; i.e.' from scratch'. An equally important step in calculating log P(oct) for solutes with unmeasured fragments is estimating their propensity for electronic, steric, and/or hydrophobic interactions with other polar fragments which may also be present. The combined error of estimation of a new fragment value and its interaction with others appears to be less than ± 0.5.