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Pyridine‐Based Lanthanide Complexes Combining MRI and NIR Luminescence Activities

Identifieur interne : 000523 ( France/Analysis ); précédent : 000522; suivant : 000524

Pyridine‐Based Lanthanide Complexes Combining MRI and NIR Luminescence Activities

Auteurs : Célia S. Bonnet [France] ; Frédéric Buron [France] ; Fabien Caillé [France] ; Chad M. Shade [États-Unis] ; Bohuslav Drahoš [France] ; Laurent Pellegatti [France] ; Jian Zhang [États-Unis] ; Sandrine Villette [France] ; Lothar Helm [Suisse] ; Chantal Pichon [France] ; Franck Suzenet [France] ; Stéphane Petoud [France, États-Unis] ; Éva T Th [France]

Source :

RBID : ISTEX:DFF753055D2C0A0FB767F013D03B716A22AC291B

Descripteurs français

English descriptors

Abstract

A series of novel triazole derivative pyridine‐based polyamino–polycarboxylate ligands has been synthesized for lanthanide complexation. This versatile platform of chelating agents combines advantageous properties for both magnetic resonance (MR) and optical imaging applications of the corresponding Gd3+ and near‐infrared luminescent lanthanide complexes. The thermodynamic stability constants of the Ln3+ complexes, as assessed by pH potentiometric measurements, are in the range log KLnL=17–19, with a high selectivity for lanthanides over Ca2+, Cu2+, and Zn2+. The complexes are bishydrated, an important advantage to obtain high relaxivities for the Gd3+ chelates. The water exchange of the Gd3+ complexes (kex298=7.7–9.3×106 s−1) is faster than that of clinically used magnetic resonance imaging (MRI) contrast agents and proceeds through a dissociatively activated mechanism, as evidenced by the positive activation volumes (ΔV≠=7.2–8.8 cm3 mol−1). The new triazole ligands allow a considerable shift towards lower excitation energies of the luminescent lanthanide complexes as compared to the parent pyridinic complex, which is a significant advantage in the perspective of biological applications. In addition, they provide increased epsilon values resulting in a larger number of emitted photons and better detection sensitivity. The most conjugated system PheTPy, bearing a phenyl–triazole pendant on the pyridine ring, is particularly promising as it displays the lowest excitation and triplet‐state energies associated with good quantum yields for both Nd3+ and Yb3+ complexes. Cellular and in vivo toxicity studies in mice evidenced the non‐toxicity and the safe use of such bishydrated complexes in animal experiments. Overall, these pyridinic ligands constitute a highly versatile platform for the simultaneous optimization of both MRI and optical properties of the Gd3+ and the luminescent lanthanide complexes, respectively.

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DOI: 10.1002/chem.201102310


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ISTEX:DFF753055D2C0A0FB767F013D03B716A22AC291B

Le document en format XML

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<term>Animal studies</term>
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<term>C5tpy</term>
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<term>Cell culture</term>
<term>Cell proliferation</term>
<term>Cell proliferation index</term>
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<term>Epsilon value</term>
<term>Epsilon values</term>
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<term>Excitation wavelengths</term>
<term>Experimental data</term>
<term>Experimental data points</term>
<term>Fluorescence intensity</term>
<term>Fluorescence spectra</term>
<term>Full paper</term>
<term>Gdc5tpy</term>
<term>Gddtpa</term>
<term>Gdpy</term>
<term>Glioma cells</term>
<term>Gmbh</term>
<term>Good quantum yields</term>
<term>Hela cells</term>
<term>Hepes</term>
<term>Hepes buffer</term>
<term>Higher energy</term>
<term>Higher temperatures</term>
<term>Hydration number</term>
<term>Imaging</term>
<term>Imaging applications</term>
<term>Imaging modality</term>
<term>Imaging probe</term>
<term>Imaging techniques</term>
<term>Inner sphere</term>
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<term>Ligand</term>
<term>Ligand excitation</term>
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<term>Lower energies</term>
<term>Lower energy</term>
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<term>Lowest excitation</term>
<term>Luminescence</term>
<term>Luminescence activities</term>
<term>Luminescence lifetimes</term>
<term>Luminescence properties</term>
<term>Luminescent</term>
<term>Luminescent lanthanide complexes</term>
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<term>Metal cation</term>
<term>Methoxy group</term>
<term>Mmol</term>
<term>Mmol eupy</term>
<term>Optical properties</term>
<term>Other hand</term>
<term>Paper table</term>
<term>Parent pyridinic</term>
<term>Petoud</term>
<term>Phetpy</term>
<term>Phosphorescence spectra</term>
<term>Photon</term>
<term>Physical properties</term>
<term>Positive activation volumes</term>
<term>Positive values</term>
<term>Potentiometric</term>
<term>Preliminary communication</term>
<term>Pressure dependence</term>
<term>Proliferation index</term>
<term>Protonation</term>
<term>Protonation constants</term>
<term>Pyridine</term>
<term>Pyridine nitrogen atom</term>
<term>Pyridine ring</term>
<term>Pyridinic</term>
<term>Pyridinic ligands</term>
<term>Quantum yields</term>
<term>Relaxation</term>
<term>Relaxation rates</term>
<term>Resonance imaging</term>
<term>Room temperature</term>
<term>Rotational</term>
<term>Rotational correlation time</term>
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<term>Same order</term>
<term>Same range</term>
<term>Sensitizer</term>
<term>Significant changes</term>
<term>Significant effect</term>
<term>Significant shift</term>
<term>Significant variation</term>
<term>Simultaneous optimization</term>
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<term>Structural changes</term>
<term>Such bishydrated complexes</term>
<term>Suzenet</term>
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<term>Titration curves</term>
<term>Toth</term>
<term>Toxicity</term>
<term>Transaminase activity</term>
<term>Transition state</term>
<term>Transverse relaxation rate</term>
<term>Transverse relaxation rates</term>
<term>Triazole</term>
<term>Triazole derivatives</term>
<term>Triazole ring</term>
<term>Triplet states</term>
<term>Vander elst</term>
<term>Variable pressure</term>
<term>Variable temperature</term>
<term>Verlag</term>
<term>Verlag gmbh</term>
<term>Versatile platform</term>
<term>Vital organs</term>
<term>Vivo</term>
<term>Vivo application</term>
<term>Vivo experiments</term>
<term>Vivo toxicity</term>
<term>Vivo toxicity studies</term>
<term>Water exchange</term>
<term>Water exchange process</term>
<term>Water exchange rate</term>
<term>Water molecules</term>
<term>Weinheim</term>
<term>Weinheim chem</term>
</keywords>
<keywords scheme="Teeft" xml:lang="en">
<term>Absolute quantum yields</term>
<term>Absorption spectra</term>
<term>Activation volume</term>
<term>Affinity constants</term>
<term>Angew</term>
<term>Animal studies</term>
<term>Apparent maxima</term>
<term>Aqueous solution</term>
<term>Aqueous solutions</term>
<term>Bimodal</term>
<term>Bimodal imaging probes</term>
<term>Bioconjugate chem</term>
<term>Biological applications</term>
<term>Bishydrated</term>
<term>Bishydrated chelate</term>
<term>Bishydrated complexes</term>
<term>Blood samples</term>
<term>Body weight</term>
<term>Bruker avance</term>
<term>C5tpy</term>
<term>Cation</term>
<term>Cell culture</term>
<term>Cell proliferation</term>
<term>Cell proliferation index</term>
<term>Cell viability</term>
<term>Cellular toxicity</term>
<term>Central nitrogen atom</term>
<term>Chelate</term>
<term>Chem</term>
<term>Chemical shifts</term>
<term>Click chemistry</term>
<term>Considerable shift</term>
<term>Contrast agents</term>
<term>Contrast media</term>
<term>Control animal</term>
<term>Correlation time</term>
<term>Corresponding complexes</term>
<term>Dalton trans</term>
<term>Detection sensitivity</term>
<term>Different complexes</term>
<term>Different concentrations</term>
<term>Electronic levels</term>
<term>Electronic structure</term>
<term>Emission bands</term>
<term>Endogenous cations</term>
<term>Energy transfer</term>
<term>Epsilon</term>
<term>Epsilon value</term>
<term>Epsilon values</term>
<term>Eupy</term>
<term>Eupy incubation</term>
<term>Exchange rate</term>
<term>Exchange regime</term>
<term>Excitation</term>
<term>Excitation energies</term>
<term>Excitation spectra</term>
<term>Excitation wavelength</term>
<term>Excitation wavelengths</term>
<term>Experimental data</term>
<term>Experimental data points</term>
<term>Fluorescence intensity</term>
<term>Fluorescence spectra</term>
<term>Full paper</term>
<term>Gdc5tpy</term>
<term>Gddtpa</term>
<term>Gdpy</term>
<term>Glioma cells</term>
<term>Gmbh</term>
<term>Good quantum yields</term>
<term>Hela cells</term>
<term>Hepes</term>
<term>Hepes buffer</term>
<term>Higher energy</term>
<term>Higher temperatures</term>
<term>Hydration number</term>
<term>Imaging</term>
<term>Imaging applications</term>
<term>Imaging modality</term>
<term>Imaging probe</term>
<term>Imaging techniques</term>
<term>Inner sphere</term>
<term>Inorg</term>
<term>Kgaa</term>
<term>Kinetic inertness</term>
<term>Lanthanide</term>
<term>Lanthanide cations</term>
<term>Lanthanide complexation</term>
<term>Lanthanide complexes</term>
<term>Lanthanide ions</term>
<term>Large number</term>
<term>Ligand</term>
<term>Ligand excitation</term>
<term>Longitudinal</term>
<term>Longitudinal relaxation rates</term>
<term>Lower energies</term>
<term>Lower energy</term>
<term>Lower excitation energies</term>
<term>Lowest excitation</term>
<term>Luminescence</term>
<term>Luminescence activities</term>
<term>Luminescence lifetimes</term>
<term>Luminescence properties</term>
<term>Luminescent</term>
<term>Luminescent lanthanide complexes</term>
<term>Magnetic resonance</term>
<term>Magnetic resonance imaging</term>
<term>Meopy</term>
<term>Merbach</term>
<term>Metal cation</term>
<term>Methoxy group</term>
<term>Mmol</term>
<term>Mmol eupy</term>
<term>Optical properties</term>
<term>Other hand</term>
<term>Paper table</term>
<term>Parent pyridinic</term>
<term>Petoud</term>
<term>Phetpy</term>
<term>Phosphorescence spectra</term>
<term>Photon</term>
<term>Physical properties</term>
<term>Positive activation volumes</term>
<term>Positive values</term>
<term>Potentiometric</term>
<term>Preliminary communication</term>
<term>Pressure dependence</term>
<term>Proliferation index</term>
<term>Protonation</term>
<term>Protonation constants</term>
<term>Pyridine</term>
<term>Pyridine nitrogen atom</term>
<term>Pyridine ring</term>
<term>Pyridinic</term>
<term>Pyridinic ligands</term>
<term>Quantum yields</term>
<term>Relaxation</term>
<term>Relaxation rates</term>
<term>Resonance imaging</term>
<term>Room temperature</term>
<term>Rotational</term>
<term>Rotational correlation time</term>
<term>Rotational dynamics</term>
<term>Same order</term>
<term>Same range</term>
<term>Sensitizer</term>
<term>Significant changes</term>
<term>Significant effect</term>
<term>Significant shift</term>
<term>Significant variation</term>
<term>Simultaneous optimization</term>
<term>Stability constants</term>
<term>Standard deviation</term>
<term>Structural changes</term>
<term>Such bishydrated complexes</term>
<term>Suzenet</term>
<term>Titration</term>
<term>Titration curves</term>
<term>Toth</term>
<term>Toxicity</term>
<term>Transaminase activity</term>
<term>Transition state</term>
<term>Transverse relaxation rate</term>
<term>Transverse relaxation rates</term>
<term>Triazole</term>
<term>Triazole derivatives</term>
<term>Triazole ring</term>
<term>Triplet states</term>
<term>Vander elst</term>
<term>Variable pressure</term>
<term>Variable temperature</term>
<term>Verlag</term>
<term>Verlag gmbh</term>
<term>Versatile platform</term>
<term>Vital organs</term>
<term>Vivo</term>
<term>Vivo application</term>
<term>Vivo experiments</term>
<term>Vivo toxicity</term>
<term>Vivo toxicity studies</term>
<term>Water exchange</term>
<term>Water exchange process</term>
<term>Water exchange rate</term>
<term>Water molecules</term>
<term>Weinheim</term>
<term>Weinheim chem</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr">
<term>Taux de change</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">A series of novel triazole derivative pyridine‐based polyamino–polycarboxylate ligands has been synthesized for lanthanide complexation. This versatile platform of chelating agents combines advantageous properties for both magnetic resonance (MR) and optical imaging applications of the corresponding Gd3+ and near‐infrared luminescent lanthanide complexes. The thermodynamic stability constants of the Ln3+ complexes, as assessed by pH potentiometric measurements, are in the range log KLnL=17–19, with a high selectivity for lanthanides over Ca2+, Cu2+, and Zn2+. The complexes are bishydrated, an important advantage to obtain high relaxivities for the Gd3+ chelates. The water exchange of the Gd3+ complexes (kex298=7.7–9.3×106 s−1) is faster than that of clinically used magnetic resonance imaging (MRI) contrast agents and proceeds through a dissociatively activated mechanism, as evidenced by the positive activation volumes (ΔV≠=7.2–8.8 cm3 mol−1). The new triazole ligands allow a considerable shift towards lower excitation energies of the luminescent lanthanide complexes as compared to the parent pyridinic complex, which is a significant advantage in the perspective of biological applications. In addition, they provide increased epsilon values resulting in a larger number of emitted photons and better detection sensitivity. The most conjugated system PheTPy, bearing a phenyl–triazole pendant on the pyridine ring, is particularly promising as it displays the lowest excitation and triplet‐state energies associated with good quantum yields for both Nd3+ and Yb3+ complexes. Cellular and in vivo toxicity studies in mice evidenced the non‐toxicity and the safe use of such bishydrated complexes in animal experiments. Overall, these pyridinic ligands constitute a highly versatile platform for the simultaneous optimization of both MRI and optical properties of the Gd3+ and the luminescent lanthanide complexes, respectively.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>France</li>
<li>Suisse</li>
<li>États-Unis</li>
</country>
<region>
<li>Pennsylvanie</li>
</region>
<settlement>
<li>Pittsburgh</li>
</settlement>
<orgName>
<li>Université de Pittsburgh</li>
</orgName>
</list>
<tree>
<country name="France">
<noRegion>
<name sortKey="Bonnet, Celia S" sort="Bonnet, Celia S" uniqKey="Bonnet C" first="Célia S." last="Bonnet">Célia S. Bonnet</name>
</noRegion>
<name sortKey="Buron, Frederic" sort="Buron, Frederic" uniqKey="Buron F" first="Frédéric" last="Buron">Frédéric Buron</name>
<name sortKey="Caille, Fabien" sort="Caille, Fabien" uniqKey="Caille F" first="Fabien" last="Caillé">Fabien Caillé</name>
<name sortKey="Caille, Fabien" sort="Caille, Fabien" uniqKey="Caille F" first="Fabien" last="Caillé">Fabien Caillé</name>
<name sortKey="Drahos, Bohuslav" sort="Drahos, Bohuslav" uniqKey="Drahos B" first="Bohuslav" last="Drahoš">Bohuslav Drahoš</name>
<name sortKey="Pellegatti, Laurent" sort="Pellegatti, Laurent" uniqKey="Pellegatti L" first="Laurent" last="Pellegatti">Laurent Pellegatti</name>
<name sortKey="Pellegatti, Laurent" sort="Pellegatti, Laurent" uniqKey="Pellegatti L" first="Laurent" last="Pellegatti">Laurent Pellegatti</name>
<name sortKey="Petoud, Stephane" sort="Petoud, Stephane" uniqKey="Petoud S" first="Stéphane" last="Petoud">Stéphane Petoud</name>
<name sortKey="Petoud, Stephane" sort="Petoud, Stephane" uniqKey="Petoud S" first="Stéphane" last="Petoud">Stéphane Petoud</name>
<name sortKey="Petoud, Stephane" sort="Petoud, Stephane" uniqKey="Petoud S" first="Stéphane" last="Petoud">Stéphane Petoud</name>
<name sortKey="Pichon, Chantal" sort="Pichon, Chantal" uniqKey="Pichon C" first="Chantal" last="Pichon">Chantal Pichon</name>
<name sortKey="Suzenet, Franck" sort="Suzenet, Franck" uniqKey="Suzenet F" first="Franck" last="Suzenet">Franck Suzenet</name>
<name sortKey="Suzenet, Franck" sort="Suzenet, Franck" uniqKey="Suzenet F" first="Franck" last="Suzenet">Franck Suzenet</name>
<name sortKey="T Th, Eva" sort="T Th, Eva" uniqKey="T Th E" first="Éva" last="T Th">Éva T Th</name>
<name sortKey="T Th, Eva" sort="T Th, Eva" uniqKey="T Th E" first="Éva" last="T Th">Éva T Th</name>
<name sortKey="T Th, Eva" sort="T Th, Eva" uniqKey="T Th E" first="Éva" last="T Th">Éva T Th</name>
<name sortKey="Villette, Sandrine" sort="Villette, Sandrine" uniqKey="Villette S" first="Sandrine" last="Villette">Sandrine Villette</name>
</country>
<country name="États-Unis">
<region name="Pennsylvanie">
<name sortKey="Shade, Chad M" sort="Shade, Chad M" uniqKey="Shade C" first="Chad M." last="Shade">Chad M. Shade</name>
</region>
<name sortKey="Petoud, Stephane" sort="Petoud, Stephane" uniqKey="Petoud S" first="Stéphane" last="Petoud">Stéphane Petoud</name>
<name sortKey="Zhang, Jian" sort="Zhang, Jian" uniqKey="Zhang J" first="Jian" last="Zhang">Jian Zhang</name>
</country>
<country name="Suisse">
<noRegion>
<name sortKey="Helm, Lothar" sort="Helm, Lothar" uniqKey="Helm L" first="Lothar" last="Helm">Lothar Helm</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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