Carbon chemical shift tensor components in quinolines and quinoline N-oxides

Chemical shift calculations are carried out for the quinoline carbons in 1,8-bis(2-isopropyl-4-quinolyl)naphthalene, 2-isopropylquinoline, amodiaquine, chloroquine, and quinine and the N-oxide of each compound. Ab initio calculations of the isotropic shielding values are in agreement with experimental chemical shifts. The calculations indicate that changes to the principal components of the shielding tensor upon N-oxidation are similar for each compound. Carbons 2, 4, 8, and 10 are largely shielded in each case as the nitrogen is oxidized. For C2, C4, and C10, this shielding is due to a large change in sigma11 and/or sigma22, indicating a change in pi-electron density. For C8, the large shielding change is due mainly to a change in sigma33, indicating a change in sigma-electron density. Upon examination and comparison of the calculated 13C shielding tensor components in the antimalarial drugs versus those in unsubstituted quinolines, it is found that amodiaquine and chloroquine have increased pi-electron density in the ring containing the amino side chain and quinine has increased pi-electron density in the opposite ring, containing the methoxy substituent.