Effects of Structure on 1‐Octanol/Water Partitioning Behavior of Aliphatic Amines and Ammonium Ions

<jats:title>Abstract</jats:title><jats:p>The partition coefficients of 45 neutral aliphatic amines and the ion‐pair formation‐partition equilibrium constants with picrate of 66 aliphatic ammonium ions, determined using a 1‐octanol/water system, were analyzed by means of free‐energy‐related substituent constants and the multiple regression technique. The hydrophobic, electronic, steric, and hydrogen bonding effects of N‐substituents governing the partitioning behaviors were quantitatively separated by means of an equation: log K = a∑π + ρ<jats:sub>I</jats:sub>∑σ<jats:sub>I</jats:sub> ∑δ<jats:sub>i</jats:sub>E<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tex2gif-stack-1.gif" xlink:title="urn:x-wiley:09318771:media:QSAR19850040403:tex2gif-stack-1" /> (R<jats:sub>i</jats:sub>) + bn<jats:sub>H</jats:sub> + c, where K is the equilibrium constant, and ρ<jats:sub>I</jats:sub>, δ<jats:sub>i</jats:sub>, b, and c are susceptibility constants and the intercept. ∑π and ∑σ<jats:sub>I</jats:sub>, are, respectively, the sum of the hydrophobic π values and the inductive electronic σ<jats:sub>I</jats:sub> values of three or four N‐substituents. E<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tex2gif-stack-2.gif" xlink:title="urn:x-wiley:09318771:media:QSAR19850040403:tex2gif-stack-2" /> (R<jats:sub>i</jats:sub>) is a modified steric constant derived from the Dubois E′<jats:sub>s</jats:sub> value considering the branching effect of N‐substituents, R<jats:sub>j</jats:sub>, in which i = 1 ∼ 3 for amines and i = 1 ∼ 4 for ammonium ions. R<jats:sub>i</jats:sub> is classified according to the relative magnitude of E<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tex2gif-stack-3.gif" xlink:title="urn:x-wiley:09318771:media:QSAR19850040403:tex2gif-stack-3" /> values so that E<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tex2gif-stack-4.gif" xlink:title="urn:x-wiley:09318771:media:QSAR19850040403:tex2gif-stack-4" /> (R<jats:sub>1</jats:sub>) ≤ E<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tex2gif-stack-5.gif" xlink:title="urn:x-wiley:09318771:media:QSAR19850040403:tex2gif-stack-5" /> (R<jats:sub>2</jats:sub>) ≤ E<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tex2gif-stack-6.gif" xlink:title="urn:x-wiley:09318771:media:QSAR19850040403:tex2gif-stack-6" /> (R<jats:sub>3</jats:sub>) ≤ E<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tex2gif-stack-7.gif" xlink:title="urn:x-wiley:09318771:media:QSAR19850040403:tex2gif-stack-7" /> (R<jats:sub>4</jats:sub>). n<jats:sub>H</jats:sub> is the number of NH hydrogens of the (conjugate) ammonium ion. It was shown that the definitely intermolecular type of steric effect in the ion‐pairing is nicely elucidated with the E<jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/tex2gif-stack-8.gif" xlink:title="urn:x-wiley:09318771:media:QSAR19850040403:tex2gif-stack-8" /> constant of component N‐substituents.</jats:p>