A Heterobimetallic Ruthenium–Gadolinium Complex as a Potential Agent for Bimodal Imaging

Abstract

Trinuclear heterobimetallic Ln(III)-Ru(II) complexes (Ln = Eu, Gd) based on a 1,10-phenanthroline ligand bearing a diethylenetriaminepentaacetic acid (DTPA) core have been synthesized and fully characterized by a range of experimental techniques. The (17)O NMR and proton nuclear magnetic relaxation dispersion (NMRD) measurements of Gd(III)-Ru(II) show that, in comparison to the parent Gd-DTPA, this complex exhibits improved relaxivity, which is the result of an increase of the rotational correlation time. Relaxometry and ultrafiltration experiments indicate that the 1,10-phenanthroline ligand has a high affinity for noncovalent binding to human serum albumin, which results in a high relaxivity r(1) of 14.3 s(-1) mM(-1) at 20 MHz and 37 °C. Furthermore, the Ln(III)-Ru(II) complexes (Ln = Eu, Gd) show an intense light absorption in the visible spectral region due to metal-to-ligand charge transfer (MLCT) transitions. Upon excitation into the MLCT band at 440 nm, the complexes exhibit a bright-red luminescence centered at 610 nm, with a quantum yield of 4.7%. The luminescence lifetime equals 540 ns and is therefore long enough to exceed the fluorescent background. Monometallic lanthanide complexes have also been synthesized, and the Eu(III) analogue shows a characteristic red luminescence with a quantum yield of 0.8%. Taking into account the relaxometric and luminescent properties, the developed Gd(III)-Ru(II) complex can be considered as a potential in vitro bimodal imaging agent.

Lanthanide(III) Complexes of Diethylenetriaminepentaacetic Acid (DTPA)–Bisamide Derivatives as Potential Agents for Bimodal (Optical/Magnetic Resonance) Imaging

“…Luminescence lifetimes in H 2 O lie in the range of 0.54–0.57 ms for Eu III and 1.49–1.58 ms for Tb III complexes and are more or less independent of the nature of the ligand (Table 2). The τ values are typical for the corresponding lanthanide complexes with DTPA–bisamide derivatives 7a,20. In D 2 O, luminescence lifetimes increase by a factor of approximately 4.7 and 2 for Eu III and Tb III , respectively.…”

Lanthanides: Supramolecular Chemistry

“…Along a similar vein, Parac-Vogt and coworkers prepared a trinuclear mixed Ru II 2 -Ln III system (Ln = Eu or Gd) where the ligand (22) contained two 1,10-phenanthroline groups for Ru II complexation and a central octadentate acyclic amino-carboxylate group for Ln III complexation ( Figure 10). 37 The synthesis of the trinuclear system began with formation of the Ln III complex followed by reaction of this with Ru II (bpy) 2 to give the desired trinuclear system [Ru 2 (bpy) 4 ·22·Ln] 4+ . The [Ru 2 (bpy) 4 ·22·Eu] 4+ complex was red luminescent, displaying both Eu III and Ru II centered emission, whereas the [Ru 2 (bpy) 4 ·22·Gd] 4+ displayed both relaxometric and luminescent properties, and is thus is considered a potential bimodal imaging agent for in vivo studies.…”

Assembly of near infra-red emitting upconverting nanoparticles and multiple Gd(iii)-chelates as a potential bimodal contrast agent for MRI and optical imaging

“…The large paramagneticity of gadolinium(III) and its long electron relaxation times make it an ideal ion as a CA for T 1 -weighted MRI measurements. Several routes have been explored, including conjugation of CA to macromolecular entities such as dendrimers and polymers, [2][3][4][5][6][7] interaction with proteins, such as human serum albumin (HSA), [8][9][10][11] the incorporation of CA into micelles or liposomes, [12][13][14][15][16] formation of gadolinium(III) or manganese(II) based nanoparticles [17][18][19][20] or via synthesis of large molecules [21][22][23][24] that hold multiple paramagnetic ions in a supramolecular structure. Presently many medically applicable gadolinium che-lates are being used as positive CAs, of which 2-[4,7,10-tris-(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetate (DOTA) forms a kinetically inert and a thermodynamically stable complex with gadolinium(III).…”

“…Altering the tumbling rate of the complex has been widely used as a method for enhancing the proton relaxivities. [21][22][23][37][38][39][40] Lanthanide ions have very interesting optical properties since they exhibit sharp emission lines and have long luminescence lifetimes. 25 Due to the high spatial resolution, the lack of ionizing radiation and penetration limitations, MRI is widely used as a preoperative technique to visualize the soft tissue in the human body.…”