RELAXOMETRIC, STRUCTURAL, AND DYNAMIC NMR-STUDIES OF DOTA-LIKE LN(III) COMPLEXES (LN=LA, GD, HO, YB) CONTAINING A P-NITROPHENYL SUBSTITUENT

We report here the synthesis of the ligand tris(carboxymethyl)-1,4,7,1 0-tetraazacyclododecane (3) and its La(III), Gd(III), Ho(III), and Yb( III) complexes. The introduction of the p-nitrophenyl substituent on t he methylenic carbon of one acetate group does not alter the overall c helating ability of 3 with respect to the parent DOTA ligand. The [Gd( 3)](-) complex displays a slightly higher relaxivity than that of [Gd( DOTA)](-), mainly as a consequence of a longer molecular reorientation al correlation time (tau(R)), due to the increased molecular dimension of the complex, and of limited changes to the other relaxation parame ters. A further increase of relaxivity has been observed upon formatio n of an inclusion compound with beta-cyclodextrin. The solution struct ure and dynamics were thoroughly investigated by high-resolution NMR s pectroscopy. Of the four possible enantiomeric pairs that could be pre sent in the solutions of monosubstituted derivatives of [Ln(DOTA)](-) complexes, the proton spectra of Ho and Yb derivatives are consistent with the occurrence of only two isomeric species whose structures have been elucidated through analysis of dipolar shifts and 2D-EXSY data. In both species the bulky aromatic group has replaced the acetate prot on pointing outward from the coordination cage. Unlike in the DOTA cas e, in [Ln(3)](-) complexes the isomerization process involves the inve rsion of the ethylenic groups of the macrocycle rather than the motion of the acetate arms. This behavior is rationalized in terms of steric crowding at the substituent site: minimization of the steric interact ions between the aromatic group and the macrocyclic ring protons resul ts in both structural and dynamic selectivity. Interestingly, in the c ase of the diamagnetic La(III) complex the variable temperature behavi or of the C-13 NMR spectra is consistent with an exchange process invo lving one major species and at least one minor isomer of very low conc entration, whose relative population increases with temperature. This causes a persistent exchange broadening of the resonances over a wide range of temperatures.