| Abstract: | A number of isomers and analogs of the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) were examined for their lipophilic behavior. Their partition coefficients in the 1-octanol/H2O system were measured by centrifugal partition chromatography (CPC), which, being much faster and markedly more precise than the classical shake-flask method, proved a very promising alternative for assessing lipophilicity. A smaller-than-expected lipophilicity was shown by the ortho-isomer of MPP+ (M2PP+) and is explained in terms of electronic effects and rigidity, as revealed by UV and NMR spectroscopy, and conformational analysis. Implications of lipophilicity in modulating the in vivo dopaminergic neurotoxicity of the examined compounds are also discussed. |
