title: Whole-molecule calculation of log p based on molar volume, hydrogen bonds, and simulated 13C NMR spectra.
abstract: The prediction of Log P is usually accomplished using either substructure or whole-molecule approaches. However, these methods are complicated, and previous whole-molecule approaches have not been successful for the prediction of Log P in very complex molecules. The observed chemical shifts in nuclear magnetic resonance (NMR) spectroscopy are related to the electrostatics at the nucleus, which are influenced by solute-solvent interactions. The different solvation effects on a molecule by either water or methanol have a strong effect on the NMR chemical shift value. Therefore, the chemical shift values observed in an aqueous and organic solvent should correlate to Log P. This paper develops a rapid, objective model of Log P based on molar volume, hydrogen bonds, and differences in calculated 13C NMR chemical shifts for a diverse set of compounds. A partial least squares (PLS) model of Log P built on the sum of carbon chemical shift differences in water and methanol, molar volume, number of hydrogen bond donors and acceptors in 162 diverse compounds gave an r2 value of 0.88. The average r2 for 10 training models of Log P made from 90% of the data was 0.87+/-0.01. The average q2 for 10 leave-10%-out cross-validation test sets was 0.87+/-0.05.
authors.affiliation: Division of Systems Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079, USA.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Schnackenberg
authors.forename: Richard D
authors.initials: RD
authors.lastname: Beger
mesh_terms: D002247:Carbon Isotopes / Q000737:chemistry; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D000432:Methanol / Q000737:chemistry; D008956:Models, Chemical; D012997:Solvents / Q000737:chemistry; D055672:Static Electricity; D014867:Water / Q000737:chemistry
chemical_list: D002247:Carbon Isotopes; D012997:Solvents; D014867:Water; D000432:Methanol