title: Insight into the lipophilicity of the aromatic N-oxide moiety.
abstract: OBJECTIVE
  A systematic study to assess the influence of N-oxygenation on the lipophilicity of aromatic weak bases was performed.
  
  
  METHODS
  The methods used were experimental (CPC and shake-flask techniques) and computational (AMI semi-empirical method).
  
  
  RESULTS
  The intrinsic increment in the log P(oct) system for an oxygen atom added to form an aromatic N-oxide, designated as diff(log PN(O) -N), was -1.91, but the presence of para-substituents markedly affected this value. The good linear relationship (r2 = 0.92) between diff(log PN(O) - N), and the electronic density on the oxygen atom suggests that H-bond acceptor basicity is the main structural factor responsible for the variations in lipophilicity of aromatic N-oxides. Partition coefficients of aromatic N-oxides in dodecane/buffer and chloroform/buffer systems also support this hypothesis.
  
  
  CONCLUSIONS
  The solvent-dependent polarity of the N-oxide moiety is mainly due to its marked H-bond acceptor basicity.
authors.affiliation: Institut de Chimie Thérapeutique, Université de Lausanne, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Caron
authors.forename: P A
authors.initials: PA
authors.lastname: Carrupt
authors.forename: B
authors.initials: B
authors.lastname: Testa
authors.forename: G
authors.initials: G
authors.lastname: Ermondi
authors.forename: A
authors.initials: A
authors.lastname: Gasco
mesh_terms: D006860:Hydrogen Bonding; D008055:Lipids / Q000737:chemistry*; D010087:Oxides / Q000737:chemistry*
chemical_list: D008055:Lipids; D010087:Oxides