Terpyridine-Based Heteroditopic Ligand for RuIILn3III Metallostar Architectures (Ln = Gd, Eu, Nd, Yb) with MRI/Optical or Dual-Optical Responses

A new ditopic ligand (L) based on a 2,2':5 '',4 ''-terpyridine unit substituted in the 2 '',6 '' positions with iminodiacetate arms has been designed and synthesized for the construction of Ru(II)L(3)Ln(3)(III) supramolecular architectures. The two components of this system, a 2,2'-bipyridine unit for RuII coordination and a pyridine-bis(iminodiacetate) core for LnIII coordination, are tightly connected via a covalent C-arom(py)-C-arom(py) bond. The paramagnetic and photophysical properties of the corresponding tetrametallic (RuL3Gd3III)-L-II complex have been evaluated, highlighting the potential of this metallostar structure to act as a bimodal MRI/optical imaging agent. Variable-temperature O-17 NMR and proton nuclear magnetic relaxation dispersion (NMRD) measurements showed that this complex exhibits (i) a remarkable relaxivity per metallostar molecule, particularly at clinical and high magnetic fields (r(1)(310K) = 51.0 and 36.0 mM(-1) s(-1) at 20 and 300 MHz, respectively) and (ii) a near-optimal residence lifetime of Gd-III coordinated water molecule (tau(310K)(M) = 77.5 ns). This is the result of the presence of two inner-sphere water molecules in the Gd-III components of the metallostar and a slow tumbling rate of the molecule (tR(310K) = 252 ps). Upon excitation in the visible domain (lambda(exc) = 472 nm), the Ru-II component of the complex exhibits a bright-red luminescence centered at 660 nm with a quantum yield of 2.6% in aqueous solutions at pH 7.4. Moreover, this (RuL3Gd3III)-L-II assembly is also characterized by a high kinetic inertness in biological media (PBS and human serum solutions) and a high photostability (photobleaching). Finally, preliminary photophysical studies on RuL3Nd3 and RuL3Yb3 assemblies revealed that the Ru-II center acts as an effective sensitizer for Ln(III)-based luminescence in the near-IR region. The Nd-III species was found to be the most effective at quenching the 3MLCT luminescence of the Ru center.