A novel series of complexones with bis- or biazole structure as mixed ligands of paramagnetic contrast agents for MRI

We describe the syntheses, physicochemical properties and biological evaluation of a novel series of complexones containing bis- or biazoles moieties and two iminodiacetic acid units as novel ligands for paramagnetic lanthanides. The complexones were prepared by reaction of the corresponding 1,1'-bishaloethylbi- or bispyrazoles with methyl iminodiacetate and subsequent NaOH hydrolysis. 1,1'-Bisbromoethyl precursors were obtained by direct alkylation with an excess of 1,2-dibromoethane, or by heating the corresponding alcohol in HCl. Sigmoidal binding isotherms and MO calculations supported as most stable structures in solution, those containing two Gd(III) atoms bound per molecule of complexone with half saturation values S(0.5) (M(-1), 22 degrees C, pH 7.2) in the range 6.5 10(-6)