Insight into the lipophilicity of the aromatic N-oxide moiety.
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.
Caron
G
G
Institut de Chimie Thérapeutique, Université de Lausanne, Switzerland.
Carrupt
P A
PA
Testa
B
B
Ermondi
G
G
Gasco
A
A
D006860:Hydrogen Bonding; D008055:Lipids / Q000737:chemistry*; D010087:Oxides / Q000737:chemistry*
D008055:Lipids; D010087:Oxides