Lipophilic hexadentate Gallium, indium and iron complexes of new phenolate derivatized cyclohexanetriamine ligands as potential in vivo metal transfer reagents

The compounds (RsalH2)3tachH3 (R=H, NO2, OMe) have been synthesized by Schiff base condensation between cis-1,3,5-triaminocyclohexane and a substituted salicylaldehyde, followed by reduction with KBH4. Reaction of these compounds with gallium(III), indium(III) and iron(III) salts neutral hexacoordinate N3O3 complexes of type M(RsalH2)3tach (M = Ga, In, Fe). The complexes have been characterized by a combination of infrared, 1H and 13C[1H] NMR and mass spectroscopy. The distribution coefficient between 1-octanol and water indicate that complexes are lipophilic. The electronic absorption spectra of the high spin Fe(III) complexes show LMCT bands in the 450-500 nm range. The structures of (RsalH2)3tachH3 (R=H, NO2, OMe), and In(SalH2)3 tach have been confirmed by single-crystal X-ray crystallography. Solutions of the three ligands ((salH2)3tach, (NO2salH2)3tach) and (MeOsalH2)3tach) complexed to radioactive 59 were prepared in a fashion similar to solutions of ligands complexed with non-radioactive iron, except on a much smaller scale. Biodistribution data for 59Fe(RsalH2)3tach (R=H, NO2, and OMe) complexes over a 24 hour period ere obtained. These 24 hour data show that the complexes are more effectively cleared from the body than is the control solution of 59Fe. These data will be discussed and possible medical applications for these compounds will be offered. (authors), 2 tabs., 1 figs., 7 refs