Upconversion Luminescence with Bis-pyclen Yb(III) Chelates: Crown vs. Linear Polyether Linkers in Discrete Heteropolynuclear Architectures.

Ligands combining two lateral bis-pyridyl-phosphonated-pyclens were synthesized, using a flexible linear pegylated linker (L2) or a bulkier K22 crown-ether (L3). A functionalized pyridyl-phosphonated-pyclen (L1) was also prepared as a mononuclear analogue. Coordination behavior of lanthanide cations was studied via NMR titration with Lu for L1, and UV/Vis and luminescence spectroscopy with Yb for L2/L3.

Exploring the Limits of Ligand Rigidification in Transition Metal Complexes with Mono--Functionalized Pyclen Derivatives.

We report the synthesis of a new family of side-bridged pyclen ligands. The incorporation of an ethylene bridge between two adjacent nitrogen atoms was reached from the pyclen-oxalate precursor described previously. Three new side-bridged pyclen macrocycles, H, , and H, were obtained with the aim to assess their coordination properties toward Cu and Zn ions.

Multistep synthesis of a novel copper complex with potential for Alzheimer's disease diagnosis.

Positron emission tomography (PET) imaging of Aβ plaques, is recognized as a tool for the diagnosis of Alzheimer's disease. As a contribution to the development of new strategies for early diagnosis of the disease, using PET medical imaging technique, a new copper complex, the [Cu(TE1PA-ONO)] was synthesized in ten steps. The key step of our strategy is the coupling of a monopicolinate-N-alkylated cyclam-based ligand with a moiety capable of recognizing Aβ plaques via a successful and challenging Buchwald-Hartwig coupling reaction.

Synthesis and Photophysical Properties of Lanthanide Pyridinylphosphonic Tacn and Pyclen Derivatives: From Mononuclear Complexes to Supramolecular Heteronuclear Assemblies.

Synthetic methodologies were developed to achieve the preparation of ligands and consisting of tacn- and pyclen-based chelators decorated with pyridinylphosphonic pendant arms combined with ethylpicolinamide or acetate coordinating functions, respectively. Phosphonate functions have been selected for their high affinity toward Ln ions compared to their carboxylated counterparts and for their steric hindrance that favors the formation of less-hydrated complexes. Thanks to regiospecific -functionalization of the macrocyclic backbones, the two ligands were isolated with good yields and implicated in a comprehensive photophysical study for the complexation of Eu, Tb, and Yb.

["New Modalities in Cancer Imaging and Therapy" XVth edition of the workshop organized by the network "Tumor Targeting, Imaging, Radiotherapies" of the Cancéropôle Grand-Ouest, 5-8 October 2022, France].

The fifteenth edition of the international workshop organized by the "Tumour Targeting and Radiotherapies network" of the Cancéropôle Grand-Ouest focused on the latest advances in internal and external radiotherapy from different disciplinary angles: chemistry, biology, physics, and medicine. The workshop covered several deliberately diverse topics: the role of artificial intelligence, new tools for imaging and external radiotherapy, theranostic aspects, molecules and contrast agents, vectors for innovative combined therapies, and the use of alpha particles in therapy.

Design of Bifunctional Pyclen-Based Lanthanide Luminescent Bioprobes for Targeted Two-Photon Imaging.

In the past, Lanthanide Luminescent Bioprobes (LLBs) based on pyclen-bearing π-extended picolinate antennas were synthesized and demonstrated well-adapted optical properties for biphotonic microscopy. The objective of this work is to develop a strategy to design bifunctional analogues of the previously studied LLBs presenting an additional reactive chemical group to allow their coupling to biological vectors to reach deep targeted two-photon bioimaging. Herein, we elaborated a synthetic scheme allowing the introduction of a primary amine on the position of the macrocyclic pyridine unit.

Tuning the lipophilic nature of pyclen-based 90Y3+ radiopharmaceuticals for β-radiotherapy.

Pyclen-dipicolinate chelates proved to be very efficient chelators for the radiolabeling with β--emitters such as 90Y. In this study, a pyclen-dipicolinate ligand functionalized with additional C12 alkyl chains was synthesized. The radiolabeling with 90Y proved that the addition of saturated carbon chains does not affect the efficiency of the radiolabeling, whereas a notable increase in lipophilicity of the resulting 90Y radiocomplex was observed.

Pyclen-Based Ligands Bearing Pendant Picolinate Arms for Gadolinium Complexation.

We report the synthesis of two pyclen-based regioisomer ligands (pyclen = 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene) functionalized with picolinic acid pendant arms either at positions () or () of the macrocyclic fragment.

Expanding the Scope of Pyclen-Picolinate Lanthanide Chelates to Potential Theranostic Applications.

A family of three picolinate pyclen-based ligands, previously investigated for the complexation of Y and some lanthanide ions (Gd, Eu), was studied with Tb and Lu in view of potential radiotherapeutic applications. The set of six Tb and Lu complexes was synthesized and fully characterized. The coordination properties in the solid state and in solution were thoroughly studied.

Enabling Indium Channels for Mass Cytometry by Using Reinforced Cyclam-Based Chelating Polylysine.

The synthesis of a polylysine polymer functionalized with the previously reported astonishingly inert [In()] chelate was performed. A biotin end group allowed the conjugation to biotinylated beads by the intermediary of a fluorescein isothiocyanate/neutravidin receptor. High quality imaging mass cytometry trials, based on In detection were performed to highlight the behavior of the material.

Pyclen-Based Ln(III) Complexes as Highly Luminescent Bioprobes for and One- and Two-Photon Bioimaging Applications.

In addition to the already described ligand , two pyclen-based lanthanide chelators, and , bearing two specific picolinate two-photon antennas (tailor-made for each targeted metal) and one acetate arm arranged in a dissymmetrical manner, have been synthesized, to form a complete family of lanthanide luminescent bioprobes: [Eu], [Sm], [Yb], [Tb], and [Dy]. Additionally, the symmetrically arranged regioisomer was also synthesized as well as its [Eu] complex to highlight the astonishing positive impact of the dissymmetrical -distribution of the functional chelating arms. The investigation clearly shows the high performance of each bioprobe, which, depending on the complexed lanthanide, could be used in various applications.

Cationic Biphotonic Lanthanide Luminescent Bioprobes Based on Functionalized Cross-Bridged Cyclam Macrocycles.

Cationic lanthanide complexes are generally able to spontaneously internalize into living cells. Following our previous works based on a diMe-cyclen framework, a second generation of cationic water-soluble lanthanide complexes based on a constrained cross-bridged cyclam macrocycle functionalized with donor-π-conjugated picolinate antennas was prepared with europium(III) and ytterbium(III). Their spectroscopic properties were thoroughly investigated in various solvents and rationalized with the help of DFT calculations.

Picolinate-appended tacn complexes for bimodal imaging: Radiolabeling, relaxivity, photophysical and electrochemical studies.

Based on our previous works involving two 1,4,7-triazacyclononane (tacn)-based ligands Hno2py1pa (1-Picolinic acid-4,7-bis(pyridin-2-ylmethyl)-1,4,7-triazacyclononane) and Hno1pa (1-Picolinic acid-1,4,7-triazacyclononane), we report here the synthesis of analogues bearing picolinate-based π-conjugated ILCT (Intra-Ligand Charge Transfer) transition antenna (HL1, HL2), using regiospecific N-functionalization of the tacn skeleton and their related transition metal complexes (e.g. Cu, Zn and Mn).

Highly Stable and Inert Complexation of Indium(III) by Reinforced Cyclam Dipicolinate and a Bifunctional Derivative for Bead Encoding in Mass Cytometry.

H cb-te2pa, a cross-bridged cyclam functionalized by two picolinate arms, was used for the formation of an incredible inert In chelate. The inertness of the complex was evaluated by UV/Vis experiments in several competitive media and was highlighted by the comparison with [In(dota)] and [In(dtpa)] (H dota = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, H dtpa = diethylenetriamine pentaacetic acid), which are currently used in biological applications. For the first time, a bifunctional analogue of H cb-te2pa was prepared by C-functionalization to keep its coordination properties intact.

Expanding the Family of Pyclen-Based Ligands Bearing Pendant Picolinate Arms for Lanthanide Complexation.

We report a detailed characterization of lanthanide complexes with two azaligands based on the pyclen macrocycle containing two picolinate and one acetate pendant arms. The two picolinate arms are attached to either opposite (L3) or adjacent (L4) amine nitrogen atoms of the macrocyclic platform. The X-ray structures of the Yb complexes show nine coordination of the ligand to the metal ion, a situation that is also observed for EuL4 in the solid state.

Combining a pyclen framework with conjugated antenna for the design of europium and samarium luminescent bioprobes.

The first pyclen based ligand bearing two picolinate intra-ligand charge transfer transition antennae and one acetate arm organized in a dissymmetric manner was synthesized for Eu(iii) and Sm(iii) complexation. The europium complex presents an excellent brightness and biphotonic imaging of T24-cells has been performed using Eu(iii) and the less common Sm(iii) bioprobes.

Kinetics Are Crucial When Targeting Copper Ions to Fight Alzheimer's Disease: An Illustration with Azamacrocyclic Ligands.

Targeting copper ions to either remove or redistribute them is currently viewed as a possible therapeutic strategy in the context of Alzheimer's disease (AD). Thermodynamic parameters, as for instance the copper(II) affinity of the drug candidate or the copper(II) over zinc(II) selectivity, are considered in the design of the drug candidate. In contrast, kinetic factors have been overlooked despite their probable high importance.

Stable and Inert Yttrium(III) Complexes with Pyclen-Based Ligands Bearing Pendant Picolinate Arms: Toward New Pharmaceuticals for β-Radiotherapy.

We report the synthesis of two azaligands based on the pyclen macrocyclic platform containing two picolinate and one acetate pendant arms. The two ligands differ in the relative positions of the pendant functions, which are arranged either in a symmetrical (L3) or nonsymmetrical (L4) fashion. The complexation properties of the ligands toward Y and Y were investigated to assess their potential as chelating units for radiopharmaceutical applications.

A Coordination Chemistry Approach to Fine-Tune the Physicochemical Parameters of Lanthanide Complexes Relevant to Medical Applications.

The geometric features of two pyclen-based ligands possessing identical donor atoms but different site organization have a profound impact in their complexation properties toward lanthanide ions. The ligand containing two acetate groups and a picolinate arm arranged in a symmetrical fashion (L1) forms a Gd complex being two orders of magnitude less stable than its dissymmetric analogue GdL2. Besides, GdL1 experiences a much faster dissociation following the acid-catalyzed mechanism than GdL2.

The role of the capping bond effect on pyclen Y/Y chelates: full control of the regiospecific N-functionalization makes the difference.

Thanks to a smart regiospecific N-functionalization, a pyclen based ligand bearing one picolinate and two acetate arms organized in a dissymmetric manner was synthesized for Y complexation, and compared to its symmetric analogue. The nature of the capping bonds around the metal coordination environment has a dramatic effect on the properties of the chelate, the Y and Y dissymmetric derivatives presenting enhanced thermodynamic stability and kinetic inertness.

Near infrared two photon imaging using a bright cationic Yb(iii) bioprobe spontaneously internalized into live cells.

An Yb(iii) complex based on a dimethyl cyclen macrocyclic ligand functionalized by charge transfer antennae was prepared. This cationic [YbL3] complex is stable and soluble in water and presents interesting photophysical nonlinear properties. It is spontaneously internalized and accumulates in live cells.

Investigation of the complexation of Zr(iv) and Zr(iv) by hydroxypyridinones for the development of chelators for PET imaging applications.

Three hydroxypyridinone (HOPO) positional isomers - 1,2-HOPO (L1H) and its water soluble analogue (L1'H), 3,2-HOPO (L2H) and 3,4-HOPO (L3H) have been investigated for the complexation of Zr(iv). Potentiometric and UV-Vis spectrometric studies show a higher thermodynamic stability for the formation of Zr(L1') in comparison with Zr(L2) and Zr(L3) as well as a higher kinetic inertness in competition studies with EDTA or Fe at a radiotracer concentration with Zr. Besides the low pK of L1H or L1'H (pK = 5.

Pyclen Tri-n-butylphosphonate Ester as Potential Chelator for Targeted Radiotherapy: From Yttrium(III) Complexation to (90)Y Radiolabeling.

The Y(3+) complex of PCTMB, the tri-n-butyl phosphonate ester of pyclen (3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene), was synthesized as well as its Ho(3+) and Lu(3+) analogues.