Real-time, noninvasive assessment of glomerular filtration rate (GFR) is essential not only for monitoring critically ill patients at the bedside, but also for staging and monitoring patients with chronic kidney disease. In our pursuit to develop exogenous luminescent probes for dynamic optical monitoring of GFR, we have prepared and evaluated Eu(3+) complexes of several diethylenetriamine pentaacetate (DTPA)-monoamide ligands bearing molecular "antennae" to enhance metal fluorescence via intramolecular ligand-metal fluorescence resonance energy transfer process. The results show that Eu-DTPA-monoamide complex 18b, which contains a quinoxanlinyl antenna, exhibits large (ca. 2700-fold) Eu(3+) fluorescence enhancement. Indeed, complex 18b exhibits the highest fluorescent enhancement observed thus far in the DTPA-type metal complexes. The renal clearance property was assessed using the corresponding radioactive (111)In complex 18a, and the data suggest that this complex clears via a complex mechanism that includes glomerular filtration.

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derivative of diethylenetriaminepentaacetic acid (DTDTPA, Scheme 1). The extensive characterization reveals that the resulting nanoparticles (Au@DTDTPA) are composed of a gold core (about 2.4 nm) embedded in a multilayered shell of DTDTPA. If this capping molecule (DTDTPA) is not anchored on gold particles by both sulfur atoms, they allow however the formation of a robust multilayered shell with inter and intralayer disulfide bonds. Up to about 150 Gd 3þ ions can be entrapped in this organic shell. These particles exhibit therefore a high relaxivity (r 1 ¼ 585 vs 3.0 mM À1 s À1 for DTPA:Gd), rendering them very attractive as contrast agents for MRI. After intravenous injection of Au@ DTDTPA-Gd (9 mg/mL, $60 Gd per particle) in the tail of a mouse, these particles could be followed up by MRI since they induce a strong enhancement of the positive contrast of the MR images. They accumulated first in kidneys and then in the bladder and no undesirable uptake by liver, lungs or spleen was observed. This biodistribution was confirmed by ICP analysis but also by in vivo X ray computed tomography imaging, which was carried out at the ESRF (Grenoble, France) on the medical beamline. Owing to the high atomic number of gold and the high density of the particle, Au@DTDTPA-Gd nanoparticles strongly absorb the X ray radiation and can therefore replace iodinated compounds. This study shows that Au@DTDTPA-Gd nanoparticles are well suited for in vivo dual modality magnetic resonance and X-ray computed tomography imaging. Molecular and cellular imaging with MRI and paramagnetic contrast agents requires some kind of bifunctional agent with high efficiency. These contrast agents are then coupled to backbones with high-affinity ligands having a known localization profile. They are then used as targeting agents for the in vivo visualization of molecular events occurring at cellular level. The efficiency of a Gd(III)-contrast agent can be increased by increasing its relaxivity without compromising with its thermodynamic stability, kinetic inertness and water solubility. The observed relaxivity of an MR agent depends on several factors such as electronic properties of the Gd-ion, exchange of water molecules (directly bound to Gd; inner sphere, and that diffusing in proximity; outer sphere), rotational diffusion, and the ion-to-water proton distance [4] with a modification of nitro alcohols as the starting materials. We have determined the crystal structures of Gd(III) and Eu(III)-complexes by X-ray crystallography that shows dimeric forms (Fig. 1), where one carboxylato group from each ligand forms a bridge between two metal centers. However, in solutions these complexes show monomeric structures with two water molecules associated with Gd complex [4]. For the ability of these complexes to act as bifunctional contrast agents, these chelates have been conjugated to other bio-relevant or synthetic molecules by functionalization of the -OH groups using Suzuki coupling reactions. Other approaches involve converting the -OH group into amine,...

heteroatom in each heterocyclic ring 883 7.22.9.1.2 With two heteroatoms in one heterocyclic ring and one in the other 884 7.22.9.2 Synthesis of Compounds with a Central Five-membered Ring 885 7.22.9.2.1 With one heteroatom in each heterocyclic ring 885 7.22.9.2.2 With two heteroatoms in one heterocyclic ring and one in the other 886 875 876 Tricyclic Systems: Central Carbocyclic Ring, 5-and 6-membered Rings 7.22.9.2.3 With two heteroatoms in each heterocydic ring 886 7.22.9.3 Synthesis of Compounds with a Central Six-membered Ring 886 7.22.9.3.1 With one heteroatom in each heterocydic ring 886 7.22.9.3.2 With two heteroatoms in one heterocydic ring and one in the other 894 7.22.9.3.3 With two heteroatoms in each heterocydic ring 900 7.22.9.3.4 With more than two heteroatoms in either heterocydic ring 900 7.22.9.4 Synthesis of Compounds with a Central Seven-membered Ring 902 7.22.9.4.1 With one heteroatom in each heterocydic ring 902 7.22.9.4.2 With two heteroatoms in one heterocydic ring and one in the other 903 7.22.10 RING SYNTHESIS BY TRANSFORMATION OF ANOTHER RING 903 7.22.11 SYNTHESIS OF PARTICULAR CLASSES OF COMPOUNDS 905 7.22.11.1 Benzo-separated Purines 905 7.22.11.2 Furocoumarins and Furochromones 911 7.22.11.2.1 Synthesis using chromium carbene complexes 911 7.22.11.2.2 Other methods 912 7.22.11.3 Ellipticines 913 7.22.11.3.1 Synthesis using cydoaddition reactions 913 7.22.11.3.2 Other methods 914 7.22.11.4 Pyrroloquinolinequinone and Related Compounds 914 7.22.12 IMPORTANT COMPOUNDS AND APPLICATIONS 915 7.22.12.1 Benzo-separated Purines 915 7.22.12.2 Furocoumarins and Furochromones 916 7.22.12.3 Ellipticines 917 7.22.12.4 Pyrroloquinolinequinones and Related Compounds 917 7.22.12.5 Ergolides