title: Estimation of alkane-water logP for neutral, acidic, and basic compounds using an alkylated polystyrene-divinylbenzene high-performance liquid chromatography column.
abstract: Reliable HPLC methods are available to estimate octanol-water partition coefficients, but there is no comparable method for alkane-water partition coefficients that is accurate and applicable across a broad span of logP(alk). This study describes a high-throughput method for determining HPLC-logP(alk), a chromatographic parameter closely related to logP(alk), using an alkylated polystyrene-divinylbenzene column and fast acetonitrile gradient. A structurally diverse set of neutral, acidic, and basic compounds was analyzed under ionization-suppressing pH conditions. In this chromatographic system, the relationship between gradient retention time and isocratic logk was essentially linear. Thus, gradient retention time could be used as the sole input needed to determine an apparent logP(alk)by HPLC. HPLC-logP(alk) showed linear correlation (R(2)>0.96, n=59) with reference logP(alk) values from shake-flask measurements over 8 orders of magnitude, ranging from -2.3 to +5.7. Linear solvation energy relationship (LSER) analysis revealed that the relative contributions of intermolecular forces effecting retention in the fast gradient system or its corresponding isocratic variant were highly similar to those governing partition in bulk alkane-water.
authors.affiliation: Hamilton Company, Reno, NV 89502, USA.
authors.forename: Derek A
authors.initials: DA
authors.lastname: Jensen
authors.affiliation: Department of Chemistry and Biochemistry, University of Nevada, Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154, USA. Electronic address: ronald.gary@unlv.edu.
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Gary
mesh_terms: D000473:Alkanes / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D000442:Octanols / Q000737:chemistry*; D011137:Polystyrenes; D014753:Vinyl Compounds; D014867:Water / Q000737:chemistry*
chemical_list: D000473:Alkanes; D000442:Octanols; D011137:Polystyrenes; D014753:Vinyl Compounds; D014867:Water; C004985:divinyl benzene
keywords: Drug discovery; HPLC; Linear solvation energy relationship (LSER); Lipophilicity; Partition coefficient; ΔlogP