Rigid MIIL2Gd2III (M = Fe, Ru) complexes of a terpyridine-based heteroditopic chelate:: A class of candidates for MRI contrast agents

Rigid chelates of high-molecular weight, [M(tpy-DTTA)(2)](6-) (M = Fe, Ru), are obtained upon self-assembly around one M-II ion of two terpyridine-based molecules substituted in the 4'-position with the polyaminocarboxylate diethylenetriamine-N,N,N,N-tetraacetate, tpy-DTTA(4-). The protonation constants of tpy-DTTA(4-) (log K-1 = 8.65(4), log K-2 = 7.63(4), log K-3 = 5.25(6), log K-4 = 3.30(7)) and [Fe(tpy-DTTA)(2)](6-) (log K-1 = 8.40(4), log K-2 = 7.26(4)) have been determined by potentiometry, H-1 NMR and UV-vis titrations. The thermodynamic stability constant log K-GdL of [Fe(tpy-DTTA)(2)Gd-2(H2O)(4)] measured at 25 degrees C by potentiometry is 10.87. This relatively low value is due to the direct linkage of the polyaminocarboxylate part to the electron-withdrawing terpyridine. UV-vis absorbance spectra of [M(tpy-DTTA)2Gd2(H2O)4] and H-1 NMR spectra of [M(tpy-DTTA)(2)Eu-2(H2O)(4)] revealed similar solution behavior of the Fe and Ru complexes. An Id water-exchange mechanism (Delta V-double dagger = +6.8 +/- 1 cm(3) mol(-1)) with a rate constant of k(ex)(298) = (5.1 +/- 0.3) x 10(6) s(-1) has been found for [Fe(tpy-DTTA)(2)Gd-2(H2O)(4)] by O-17 NMR. A slow rotational correlation time (tau(RO) = 410 +/- 10 ps) and the presence of two water molecules (q = 2) in the coordination inner-sphere of each Gd-III ion have also been determined for this complex. A remarkably high relaxivity has been observed for both [M(tpy-DTTA)(2)Gd-2(H2O)(4)] complexes (at 20 MHz and 37 degrees C, r(1) = 15.7 mM(-1) s(-1) for the Fe complex, and r(1) = 15.6 mM(-1) s(-1) for the Ru complex).