Self-assembling heteropolymetallic complexes as MRI contrast agents.

Magnetic resonance imaging (MRI) is currently routinely used as a diagnostic tool in various medical procedures. In recent years, many efforts have been directed towards contrast agents with an increased efficiency and higher organ specificity. Our approach in achieving such goals explores the slow-down of the rotational motion of these contrast agents by forming large molecular weight supramolecular structures. A promising class of supramolecular structures is formed by the so-called metallostars. These are metal complexes built by self-assembly containing a central p- or d-metal ion and multiple peripheral lanthanide(III) ions. A luminescent central metal ion allows obtaining bimodal contrast agents. For the synthesis of the complexes, novel ditopic ligands were developed containing a DTPA derivative as a binding unit for the lanthanide(III) ion and a catechol, 8-hydroxyquinoline or 1,10-phenantroline derivative as a binding unit for respectively a Ti(IV), Al(III) and Ru(II) ion. All complexes were fully characterized together with a complete relaxometric and luminescence examination. By exception of the catechol-based metallostar which lacks promising photophysical properties in its present form, all other complexes show in aqueous solutions bright luminescence ranging from blue-green to red emission together with high quantum yields. In addition, they have higher relaxivities at stronger magnetic field strengths compared to the commercially available contrast agents. For these reasons, all complexes can be considered as potential probes for bimodal imaging.nrpages: 164status: publishe

Self-assembled heteropolymetallic complexes as MRI contrast agents

poster presentation by Geert Dehaenstatus: publishe

Development of a metallostar MRI contrast agent based on a DTPA derivative of 8-hydroxyquinoline

poster presentation by Elke Debroyestatus: publishe

Development of a metallostar MRI contrast agent based on a DTPA derivative of 8-hydroxy-quinoline

Poster presented by Elke Debroyestatus: publishe

Self-assembled heteropolymetallic complexes as MRI contrast agents

Oral presentation by Geert Dehaenstatus: publishe

(Tetracycline)europium(III) Complex as Luminescent Probe for Hydrogen Peroxide Detection

Luminescence spectra of aqueous solutions containing a fixed concentration of tetracycline (TC) and increasing concentrations of Eu3+ were recorded both in the absence and presence of hydrogen peroxide (H2O2). In H2O2-free solutions in which the Eu/TC molar ratio was varied from 1 : 1 to 8 : 1, the 5D0 --> 7F0 transition consisted of only one peak at 580 nm. In the presence of H2O2, an extra peak appeared in the spectrum at 578 nm when the Eu/TC molar ratios were above 2.5. A detailed analysis of this spectral region revealed that at lower Eu/TC molar ratios (up to 2 : 1), the 5D0 --> 7F0 transition experienced a slight blue shift. This indicates that at low Eu/TC molar ratios, the presence of H2O2 leads to two different environments of the trivalent europium ions, which most likely form bridged peroxide complexes with hydrogen peroxide (mu-H2O2 ligand). Luminescence spectra measured in the presence of molybdate ions, which catalytically decompose H2O2, led to the disappearance of the extra europium(III) site that was formed in the presence of H2O2. The intensity of the hypersensitive 5D0 --> 7F2 transition did not linearly depend on the H2O2/TC molar ratio. For H2O2/TC ratios up to 10, a sharp linear increase of the peak intensity was observed, but with further increase of the H2O2 concentration, the intensity remained nearly constant. For H2O2/TC ratios above 100, the intensity of this transition even started to decrease, which limits the use of the (tetracycline)europium(III) system to quantify hydrogen peroxide in solution.status: publishe

A Self-Assembled Complex with a Titanium(IV) Catecholate Core as a Potential Bimodal Contrast Agent

International audienceA ditopic chelating ligand (H(6)4) that bears catechol and diethylenetriamine-N,N,N',N'',N''-pentaacetate (DTPA) has been designed and shown to specifically bind lanthanide(III) ions at the DTPA core ([Ln(H(2)4)(H(2)O)](-)) and further self-assemble with titanium(IV), thereby giving rise to the formation of a supramolecular metallostar complex with a lanthanide(III)-to-titanium(IV) ratio of 3:1, [(Ln4)(3)Ti(H(2)O)(3)](5-) (Ln=La, Eu, Gd). The efficacy of the metallostar complex as a potential bimodal optical/magnetic resonance imaging (MRI) agent has been evaluated. Nuclear magnetic relaxation dispersion (NMRD) measurements for the [(Gd4)(3)Ti(H(2)O)(3)](5-) complex have demonstrated an enhanced r(1) relaxivity that corresponds to 36.9 s(-1) mM(-1) per metallostar molecule at 20 MHz and 310 K, which is a result of a decreased tumbling rate. The ability of the complex to bind to human serum albumin (HSA) was also examined by relaxometric measurements. In addition, upon UV irradiation the [(Gd4)(3)Ti(H(2)O)(3)](5-) complex exhibits broad-band green emission in the range 400-750 nm with a maximum at 490 nm. Taking into account the high relaxivity and luminescence properties, the [(Gd4)(3)Ti(H(2)O)(3)](5-) complex is a good lead compound for the development of efficient bimodal contrast agents

A Self-Assembled Complex with a Titanium(IV) Catecholate Core as a Potential Bimodal Contrast Agent

A ditopic chelating ligand (H64) that bears catechol and diethylenetriamine-N,N,N′,N′′,N′′-pentaacetate (DTPA) has been designed and shown to specifically bind lanthanide(III) ions at the DTPA core ([Ln(H24)(H2O)]−) and further self-assemble with titanium(IV), thereby giving rise to the formation of a supramolecular metallostar complex with a lanthanide(III)-to-titanium(IV) ratio of 3:1, [(Ln4)3Ti(H2O)3]5− (Ln=La, Eu, Gd). The efficacy of the metallostar complex as a potential bimodal optical/magnetic resonance imaging (MRI) agent has been evaluated. Nuclear magnetic relaxation dispersion (NMRD) measurements for the [(Gd4)3Ti(H2O)3]5− complex have demonstrated an enhanced r1 relaxivity that corresponds to 36.9 s−1 mM−1 per metallostar molecule at 20 MHz and 310 K, which is a result of a decreased tumbling rate. The ability of the complex to bind to human serum albumin (HSA) was also examined by relaxometric measurements. In addition, upon UV irradiation the [(Gd4)3Ti(H2O)3]5− complex exhibits broad-band green emission in the range 400–750 nm with a maximum at 490 nm. Taking into account the high relaxivity and luminescence properties, the [(Gd4)3Ti(H2O)3]5− complex is a good lead compound for the development of efficient bimodal contrast agents.status: publishe

A new metallostar complex based on an aluminum(iii) 8-hydroxyquinoline core as a potential bimodal contrast agent

International audienceA ditopic DTPA monoamide derivative containing an 8-hydroxyquinoline moiety was synthesized and the corresponding gadolinium(III) complex ([Gd(H5)(H(2)O)](-)) was prepared. After adding aluminum(III), the 8-hydroxyquinoline part self-assembled into a heteropolymetallic triscomplex [(Gd5)(3)Al(H(2)O)(3)](3-). The magnetic and optical properties of this metallostar compound were investigated in order to classify it as a potential in vitro bimodal contrast agent. The proton nuclear magnetic relaxation dispersion measurements indicated that the relaxivity r(1) of [Gd(H5)(H(2)O)](-) and [(Gd5)(3)Al(H(2)O)(3)](3-) at 20 MHz and 310 K equaled 6.17 s(-1) mM(-1) and 10.9 s(-1) mM(-1) per Gd(III) ion respectively. This corresponds to a relaxivity value of 32.7 s(-1) mM(-1) for the supramolecular complex containing three Gd(III) ions. The high relaxivity value is prominently caused by an increase of the rotational tumbling time τ(R) by a factor of 2.7 and 5.5 respectively, in comparison with the commercially used MRI contrast agent Gd(III)-DTPA (Magnevist®). Furthermore, upon UV irradiation, [(Gd5)(3)Al(H(2)O)(3)](3-) exposes green broad-band emission with a maximum at 543 nm. Regarding the high relaxivity and the photophysical properties of the [(Gd5)(3)Al(H(2)O)(3)](3-) metallostar compound, it can be considered as a lead compound for in vitro bimodal applications

A new metallostar complex based on an aluminum(III) 8-hydroxyquinoline core as a potential bimodal contrast agent

A ditopic DTPA monoamide derivative containing an 8-hydroxyquinoline moiety was synthesized and the corresponding gadolinium(III) complex ([Gd(H5)(H2O)]−) was prepared. After adding aluminum(III), the 8-hydroxyquinoline part self-assembled into a heteropolymetallic triscomplex [(Gd5)3Al(H2O)3]3−. The magnetic and optical properties of this metallostar compound were investigated in order to classify it as a potential in vitro bimodal contrast agent. The proton nuclear magnetic relaxation dispersion measurements indicated that the relaxivity r1 of [Gd(H5)(H2O)]− and [(Gd5)3Al(H2O)3]3− at 20 MHz and 310 K equaled 6.17 s−1 mM−1 and 10.9 s−1 mM−1 per Gd(III) ion respectively. This corresponds to a relaxivity value of 32.7 s−1 mM−1 for the supramolecular complex containing three Gd(III) ions. The high relaxivity value is prominently caused by an increase of the rotational tumbling time τR by a factor of 2.7 and 5.5 respectively, in comparison with the commercially used MRI contrast agent Gd(III)–DTPA (Magnevist®). Furthermore, upon UV irradiation, [(Gd5)3Al(H2O)3]3− exposes green broad-band emission with a maximum at 543 nm. Regarding the high relaxivity and the photophysical properties of the [(Gd5)3Al(H2O)3]3− metallostar compound, it can be considered as a lead compound for in vitro bimodal applications.status: publishe