Nouveaux chélates [triazacyclononane-métaux de transition] (synthèse, complexation et premières applications)

Les polyazamacrocycles trouvent de nombreuses applications dans le domaine de la complexation de cations métalliques ou d'anions. Le laboratoire à longtemps étudié la fonctionnalisation des dérivés tétraazamacrocycliques et leurs propriétés de complexation. Afin d'accroître le savoir-faire du laboratoire et d'explorer de nouvelles propriétés de complexation des polyamines cycliques, nous nous sommes intéressé à transposer ce savoir à la fonctionnalisation d'un macrocycle plus petit : le tacn. Ce travail repose sur la mise au point d'une nouvelle stratégie de fonctionnalisation sélective du tacn et la synthèse de nouveaux dérivés. Les composés obtenus ont permis l'étude de leurs propriétés de complexation vis-à-vis de différents métaux de transition. Les propriétés de complexes de cuivre (II) ont été étudiées pour des applications en imagerie TEP ou en radioimmunothérapie. La détection de zinc (II) basée sur une détection IRM par de nouvelles sondes ditopiques tacn-do3a a été étudiée. La complexation de fer (II) pour des applications en transition de spin ont également permis de déterminer les propriétés de complexation de dérivés du tacn.The polyazamacrocycles have many applications in the field metal cations or anions complexation. Our laboratory studied the functionalization of tetraazamacrocyclic derivatives and their complexation properties during a long time. To enhance the expertise of our laboratory and to explore new properties of complexation of cyclic polyamines, we were interested in transpose his expertise to the functionalization of a smaller macrocycle: the tacn. This work is based on the development of a new synthetic strategy of selective functionalization of tacn and the synthesis of new derivatives. The complexation properties of this new functionalized macrocycles with different transition metals were also studied. The properties of copper (II) complexes have been studied for applications in Positron Emission Tomography (PET) imaging or radioimmunotherapy (RIT). The detection of zinc (II) based on Magnetic Resonance Imaging (MRI) detection by new ditopic probes tacn-do3a has been studied. Complexation of iron (II) for applications in spin crossover also revealed the complexation properties of the tacn derivatives.BREST-SCD-Bib. electronique (290199901) / SudocSudocFranceF

On the Dissociation Pathways of Copper Complexes Relevant as Pet Imaging Agents

[Abstract] Several bifunctional chelators have been synthesized in the last years for the development of new 64Cu-based PET agents for in vivo imaging. When designing a metal-based PET probe, it is important to achieve high stability and kinetic inertness once the radioisotope is coordinated. Different competitive assays are commonly used to evaluate the possible dissociation mechanisms that may induce Cu(II) release in the body. Among them, acid-assisted dissociation tests or transchelation challenges employing EDTA or SOD are frequently used to evaluate both solution thermodynamics and the kinetic behavior of potential metal-based systems. Despite of this, the Cu(II)/Cu(I) bioreduction pathway that could be promoted by the presence of bioreductants still remains little explored. To fill this gap we present here a detailed spectroscopic study of the kinetic behavior of different macrocyclic Cu(II) complexes. The complexes investigated include the cross-bridge cyclam derivative [Cu(CB-TE1A)]+, whose structure was determined using single-crystal X-ray diffraction. The acid-assisted dissociation mechanism was investigated using HClO4 and HCl to analyse the effect of the counterion on the rate constants. The complexes were selected so that the effects of complex charge and coordination polyhedron could be assessed. Cyclic voltammetry experiments were conducted to investigate whether the reduction to Cu(I) falls within the window of common bioreducing agents. The most striking behavior concerns the [Cu(NO2Th)]2+ complex, a 1,4,7-triazacyclononane derivative containing two methylthiazolyl pendant arms. This complex is extremely inert with respect to dissociation following the acid-catalyzed mechanism, but dissociates rather quickly in the presence of a bioreductant like ascorbic acid.The authors thank Ministerio de Ciencia e Innovación (PID2019-104626GB-I00) and Xunta de Galicia (ED431B 2020/52) for generous financial support. R.U.-V. thanks Xunta de Galicia (Grant ED481A-2018/314) for funding her PhD contract. V. P. and R. T. acknowledge the Ministère de l'Enseignement Supérieur et de la Recherche and the Centre National de la Recherche Scientifique. L.V. thanks CACTI (Universidade de Vigo) for X-ray measurementsXunta de Galicia; ED431B 2020/52Xunta de Galicia; ED481A-2018/31

Isomerism as a remarkable tool for the design of new potentially bridging macrocycle ligands: Synthesis and characterization of the [Cu(4-L1)](NO3)2·2H2O polymeric chain (4-L1=mono-N (4-picolyl)cyclen)

International audienceA new coordination complex [Cu(4-L1)](NO3)2.2H2O (1) based on the mono-N (4-picolyl)cyclen (4-L1) has been prepared and characterized by X-ray diffraction. The structure of 1 can be described as a monodimensional coordination polymer in which the macrocycle ligand acts as bridging ligand

Proton-sponge behaviour of new pendant armed cross-bridged bis-cyclens: Synthesis, NMR, X-ray, and potentiometric investigations

International audienceThe synthesis via bis-aminal derivatives and proton-sponge behaviour of new constrained bis-cyclens in which each macrocyclic subunit is alkylated with an alcohol function is presented and highlighted with NMR spectra, X-ray data and corroborated by potentiometric investigations

Specific formation of isocyanide iron complexes by reaction of primary carbamoyl ferrates with oxalylchloride

cited By 4International audienceReaction of primary carbamoyl ferrates (CO)4Fe[C(O)NHR] - (R=Me, Et, allyl, decyl, cyclohexyl, t-butyl, benzyl, phenyl) with 1/2 equiv. of oxalylchloride affords cis-bis-carbamoyl intermediates: (CO) 4Fe[C(O)NHR]2 which thermally give rise, in good yields, to the mono-isocyanide complexes (CO)4Fe(CNR). The mechanism of the reaction is discussed. Via a similar process, an alkoxycarbamoyl intermediate (CO)4Fe[C(O)NHR](CO2Me) affords Fe(CO)5 and 1,3-dialkylurea. © 2003 Elsevier Science B.V. All rights reserved

exo-Diastereoisomer of 10-aryl-1,4,7-triazabicyclo[5.2.1]decane as intermediary in specific derivatisation of triazacyclononane

International audienceReaction of triazacyclononane (tacn) and aromatic aldehydes leads to aminal adducts, which exhibit onlythe exoconfiguration. In these aminal compounds, secondary amine function possesses a higher re-activity towards electrophilic reactants than the two nitrogen atoms linked to aminal carbon, giving riseto the specific derivatisation of tacn by different functionalised groups. Study of this behaviour alsopermits the access to a ditopic tacn-cyclam bicyclic polyamine

Cyclen based bis-macrocyclic ligands as phosphates receptors. A potentiometric and NMR study

cited By 31International audienceThe host-guest interaction between orthophosphate, pyrophosphate and triphosphate anions and four cyclen based bis-macrocycles ligands possessing ortho-(BOC), meta-(BMC), para-xylenyl (BPC) or 2,6-pyridinyl (BPyC) linker was investigated by potentiometric measurements and NMR spectroscopy. Each ligand gave protonated species in aqueous solution that further formed ternary complexes after binding with anions; these complexes were analyzed as a result of hydrogen bond formation and Coulombic attraction between the organic host and the inorganic guest. The equilibrium constants for all the detected species are reported and the selectivity, illustrated with species distribution diagrams, is discussed. The results unambiguously showed the importance of the distance between the two cyclen cores and underlined, especially for the triphosphate species, the contribution of the nitrogen atom of the pyridinyl spacer as a supplementary anchoring point in acidic medium. © The Royal Society of Chemistry 2005

Bioconjugated chelates based on (methylpyridinyl)tacn: synthesis, 64Cu labeling and in vitro evaluation for prostate cancer targeting

International audienceAbstract Three new bifunctional copper chelators based on the 1,4,7-triazacyclononane (tacn) platform have been synthesized and conjugated to peptide. The first one is constituted of the tacn with two methylpyridinyl and one methylthiazolyl carboxylic acid pendant arms, while, in the second and third ones, the macrocycle is functionalized by three methylpyridinyl groups, with an additional hexynoic acid chain on a carbon of one or two pyridine rings. These three bifunctional chelators have been conjugated to the antagonist JMV594 peptide for targeting the gastrin releasing peptide receptor (GRP-r), which is overexpressed in prostate cancer. The resulting monomeric bioconjugates have shown their efficiency to be radiolabeled with β+ emitter 64Cu, and the hydrophilicity and PC-3 cell internalisation properties of these radiolabeled conjugates have been studied. PC-3 cell binding affinity of mono- and dimeric metal-free and natCu metallated conjugates have been evaluated by IC50 measurements. The results demonstrate the potential of these methylpyridinyl tacn derivatives for radiopharmaceutical applications

Dinuclear spin-crossover complexes based on tetradentate and bridging cyanocarbanion ligands

Spin-crossover (SCO) Fe(II) dinuclear complexes of formula [Fe2(tmpa)2(μ2-tcpd)2]·0.8(CH3OH) (1·MeOH) and [Fe2(andmpa)2(μ2-tcpd)2]·2CH3OH (2·MeOH) (tmpa = tris(2-pyridylmethyl)amine, andmpa = bis(2-pyridylmethyl)aminomethyl)aniline, (tcpd)(2-) = 2-dicyanomethylene-1,1,3,3-tetracyanopropanediide) have been synthesized and characterized by infrared spectroscopy, X-ray diffraction, and magnetic measurements. The crystal structure determinations of the two complexes (1·MeOH and 2·MeOH) and the desolvated complex 1 (from 1·MeOH) revealed a neutral centrosymmetrical dinuclear structure in which the (tcpd)(2-) cyanocarbanion acts as a double μ2-bridging ligand between two [FeL](2+) (L = tmpa (1), andmpa (2)) units involving two free coordination sites in the cis configuration. Examination of the shortest intermolecular contacts in 1·MeOH and 1 reveals no significant hydrogen bonding between the dinuclear units, while in 2·MeOH these units are held together by significant hydrogen bonds between one of the uncoordinated nitrile groups and the anilate function, giving rise to 1D supramolecular structure. The three dinuclear complexes 1, 2·MeOH, and 2 exhibit SCO behaviors which have been evidenced by the thermal evolutions of the χmT product and by the average values of the six Fe-N distances for 1 and 2·MeOH, that reveal a gradual conversion with transition temperatures (T1/2) at ca. 352 K (1), 196 K (2), and 180 K (2·MeOH). For the solvated 1·MeOH, the sharp SCO transition observed around 365 K was induced by the desolvatation process above 330 K during the magnetic measurements.Bistabilité magnétique dans de nouveaux systèmes moléculaires à base de ligands anioniques pontant