Recent Advances in Lanthanide Based Nano-Architectures as Probes for Ultra High-Field Magnetic Resonance Imaging.

Paramagnetic Lanthanide ions incorporated into nano- architectures are emerging as a versatile platform for Magnetic Resonance Imaging (MRI) contrast agents due to their strong contrast enhancement effects combined with the platform capability to include multiple imaging modalities. This short review examines the application of lanthanide based nanoarchitectures (nanoparticles and nano- assemblies) in the development of multifunctional probes for single and multimodal imaging involving high field MRI as one imaging modality.

High-Field MRI Contrast Agents and their Synergy with Optical Imaging: the Evolution from Single Molecule Probes towards Nano-architectures.

Contrast agents for magnetic resonance imaging have historically been based on paramagnetic metal complexes, particularly Gd3+ chelates, which tend to lose their contrast enhancement ability with increasing magnetic field strength. Emerging high-field MRI applications require the development of novel contrast agents that exhibit high relaxation enhancement as a function of magnetic field strength. Paramagnetic ions such as Dy3+ , Tb3+ or Ho3+ incorporated into supramolecular or inorganic nano-architectures represent promising platforms for the development of high field MRI contrast agents. Furthermore, such platforms allow facile inclusion of multiple imaging modalities, therapeutic loading, and targeting vectors. This Minireview examines the application of contrast agents for high-field MRI, which range from single molecules to nanoparticles. Approaches to create multimodal agents by combining high-field MRI contrast properties with another imaging modality are also discussed.

A Magnetic Chameleon: Biocompatible Lanthanide Fluoride Nanoparticles with Magnetic Field Dependent Tunable Contrast Properties as a Versatile Contrast Agent for Low to Ultrahigh Field MRI and Optical Imaging in Biological Window.

A novel type of multimodal, magnetic resonance imaging/optical imaging (MRI/OI) contrast agent was developed, based on core-shell lanthanide fluoride nanoparticles composed of a ß-NaHoF4 core plus a ß-NaGdF4:Yb3+ , Tm3+ shell with an average size of ∼24 nm. The biocompatibility of the particles was ensured by a surface modification with poly acrylic acid (PAA) and further functionalization with an affinity ligand, folic acid (FA). When excited using 980 nm near infrared (NIR) radiation, the contrast agent (CA) shows intense emission at 802 nm with lifetime of 791±3 µs, due to the transition 3 H4 →3 H6 of Tm3+ . Proton nuclear magnetic relaxation dispersion (1 H-NMRD) studies and magnetic resonance (MR) phantom imaging showed that the newly synthesized nanoparticles, decorated with poly(acrylic acid) and folic acid on the surface (NP-PAA-FA), can act mainly as a T1 -weighted contrast agent below 1.5 T, a T1 /T2 dual-weighted contrast agent at 3 T, and as highly efficient T2 -weighted contrast agent at ultrahigh fields. In addition, NP-PAA-FA showed very low cytotoxicity and no detectable cellular damage up to a dose of 500 µg mL-1 .

A Eu(III) tetrakis(ß-diketonate) dimeric complex: photophysical properties, structural elucidation by Sparkle/AM1 calculations, and doping into PMMA films and nanowires.

Reaction of Ln(III) with a tetrakis(diketone) ligand H4L [1,1'-(4,4'-(2,2-bis((4-(4,4,4-trifluoro-3-oxobutanoyl) phenoxy)methyl)propane-1,3-diyl)bis(oxy)bis(4,1-phenylene))bis(4,4,4-trifluorobutane-1,3-dione)] gives new podates which, according to mass spectral data and Sparkle/AM1 calculations, can be described as dimers, (NBu4[LnL])2 (Ln = Eu, Tb, Gd:Eu), in both solid-state and dimethylformamide (DMF) solution. The photophysical properties of the Eu(III) podate are compared with those of the mononuclear diketonate (NBu4[Eu(BTFA)4], BTFA = benzoyltrifluoroacetonate), the crystal structure of which is also reported. The new Eu(III) dimeric complex displays bright red luminescence upon irradiation at the ligand-centered band in the range of 250-400 nm, irrespective of the medium. The emission quantum yields and the luminescence lifetimes of (NBu4[EuL])2 (solid state: 51% ± 8% and 710 ± 2 µs; DMF: 31% ± 5% and 717 ± 1 µs) at room temperature are comparable to those obtained for NBu4[Eu(BTFA)4] (solid state: 60 ± 9% and 730 ± 5 µs; DMF: 30 ± 5% and 636 ± 1 µs). Sparkle/AM1 calculations were utilized for predicting the ground-state geometries of the Eu(III) dimer. Theoretical Judd-Ofelt and photoluminescence parameters, including quantum yields, predicted from this model are in good agreement with the experimental values, proving the efficiency of this theoretical approach implemented in the LUMPAC software (http://lumpac.pro.br). The kinetic scheme for modeling energy transfer processes show that the main donor state is the ligand triplet state and that energy transfer occurs on both the (5)D1 (44.2%) and (5)D0 (55.8%) levels. Furthermore, the newly obtained Eu(III) complex was doped into a PMMA matrix to form highly luminescent films and one-dimensional nanowires having emission quantum yield as high as 67%-69% (doping concentration = 4% by weight); these materials display bright red luminescence even under sunlight, so that interesting photonic applications can be foreseen.

4,4,5,5,5-Pentafluoro-1-(9H-fluoren-2-yl)-1,3-pentanedione complex of Eu3+ with 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene oxide as a promising light-conversion molecular device.

A novel beta-diketone ligand, 4,4,5,5,5-pentafluoro-1-(9H-fluoren-2-yl)-1,3-pentanedione (Hpffpd), which contains a polyfluorinated alkyl group, as well as a long conjugated fluorene unit, and a chelate phosphine oxide ligand, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene oxide (DDXPO) were synthesized and utilized for the synthesis of two new europium complexes [Eu(pffpd)3(C2H5OH)(H2O)] 1 and [Eu(pffpd)3(DDXPO)] 2. For comparison, the [Eu(pffpd)3(DPEPO)] 3 complex was also synthesized involving a known chelate phosphine oxide, bis(2-(diphenylphosphino)phenyl) ether oxide (DPEPO). The synthesized complexes have been characterized by various spectroscopic techniques and their solid-state photophysical properties were investigated. The single-crystal X-ray diffraction analyses of 2 and 3 revealed that these complexes are mononuclear, and that the central Eu3+ ion is surrounded by eight oxygen atoms, six of which are from the three bidentate fluorinated beta-diketonates, and the other two oxygen atoms from the chelate phosphine oxide. The coordination polyhedra can be described as distorted square antiprism. Compound 2 has a solid-state photoluminescence quantum yield of 48%, which is about two times higher than that of compound 3 (28%). This may be due to the fact that DDXPO in 1 has the mezzo first triplet excited state energy level (T1) between the first singlet excited energy level (S1) and T1 of Hpffpd, which may support one more additional energy transfer from the T1 energy level of DDXPO to that of Hpffpd, and consequently improves the energy transfer in the Eu3+ complex. Furthermore, DDXPO (average Eu-O = 2.34 A) in complex 2 coordinates more strongly with the central Eu3+ as compared to DPEPO in complex 3 (average Eu-O = 2.38 A) which can improve the energy transfer between the ligands and central metal ion, and consequently enhances the photoluminescence efficiency of the corresponding Eu3+ complex.