Chelator free gallium-68 radiolabelling of silica coated iron oxide nanorods via surface interactions

The commercial availability of combined magnetic resonance imaging (MRI)/positron emission tomography (PET) scanners for clinical use has increased demand for easily prepared agents which offer signal or contrast in both modalities. Herein we describe a new class of silica coated iron–oxide nanorods (NRs) coated with polyethylene glycol (PEG) and/or a tetraazamacrocyclic chelator (DO3A). Studies of the coated NRs validate their composition and confirm their properties as in vivo T₂ MRI contrast agents. Radiolabelling studies with the positron emitting radioisotope gallium-68 (t1/2 = 68 min) demonstrate that, in the presence of the silica coating, the macrocyclic chelator was not required for preparation of highly stable radiometal-NR constructs. In vivo PET-CT and MR imaging studies show the expected high liver uptake of gallium-68 radiolabelled nanorods with no significant release of gallium-68 metal ions, validating our innovation to provide a novel simple method for labelling of iron oxide NRs with a radiometal in the absence of a chelating unit that can be used for high sensitivity liver imaging

Phosphate and polyphosphate anion recognition by a dinuclear copper(ii) complex of an unsymmetrical squaramide

[Abstract] In the search for receptors suitable for the recognition of phosphate or polyphosphate anions, a new unsymmetrical squaramide-based ligand bearing dipicolylamine (dpa) and ethylpiperazine units (L) was designed and prepared. The acid–base reactions of L, its copper(II) complexation behaviour and the binding of phosphate and polyphosphate anions by the copper(II) complexes used as receptors were evaluated. 1H and 13C NMR titrations of L performed in D2O allowed the determination of its protonation sequence. The ligand L is able to coordinate two copper(II) cations forming thermodynamically stable dinuclear complexes likely having two water molecules bound to each metal centre, as supported by DFT calculations. Coordinated water molecules can be replaced by the O-donors of the phosphate/polyphosphate anions. The potentiometric studies showed that at 2 : 1 Cu2+ : L ratio the dinuclear [Cu2LH−1]3+ species predominates from pH ∼ 5 to ∼7, and hydroxodinuclear species prevail at pH > 7. 1H NMR experiments in both H2O/D2O 9 : 1 v/v and in DMSO proved that copper(II) coordination provokes deprotonation of the squaramide NH bound to the ethylpiperazine moiety, resulting in [Cu2LH−1]3+ species. The dicopper(II) complexes of L, [Cu2LH−i]4−i, were used as the receptor for the uptake of some phosphate and polyphosphate anions. The receptor presents very high association constants with HPPi3− and ATP4− and the determined Keff showed that at physiological pH ATP4− is selectively taken from an aqueous solution containing phenylphosphate (PhPO42−), aminoethylphosphate (Haep−), AMP2– and ADP3−, but HPPi3− strongly interferes. DFT calculations suggest that the strong interaction with HPPi3− and ATP4− is related to the simultaneous coordination of the polyphosphate unit to the two copper(II) centres.This work was partially supported by Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020 – Programa Operacional Competitividade e Internacionalização (POCI) and by national funds through FCT. The NMR data were acquired at CERMAX, ITQB-NOVA, Oeiras, Portugal with equipment funded by FCT, project AAC 01/SAICT/2016. C. V. Esteves thanks FCT for the PhD fellowship SFRH/BD/89501/2012 and Project LISBOA-01-0145-FEDER-007660 for a last fellowshipPortugal. Fundação para a Ciência e a Tecnologia; LISBOA-01-0145-FEDER-007660Portugal. Fundação para a Ciência e a Tecnologia; AAC 01/SAICT/2016Portugal. Fundação para a Ciência e a Tecnologia; SFRH/BD/89501/201

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

Polyamine Drug Discovery. Edited by Patrick Woster and Robert A. Casero, Jr.

International audienc

Picolinate cross-bridged cyclam, chelate with metallic cations and use thereof

PCT/EP2014074415 - 2014-11-12The present invention relates to chelates resulting from the complexation of picolinate cross-bridged cyclams of formula (I), wherein the substituents L1-L4 and R1-R4 are defined as in the claims, with metallic cations. The invention further relates to picolinate cross-bridged cyclam ligands of formula (I). Another object of the invention is the use of chelates of the invention in nuclear medicine and the use of ligands of the invention in cations detection or epuration of effluents

Methods for Preparing Functional Tetraazacycloalkane Compounds using a Specific Cyclic Bisaminal Compound

Special C-functionalized cyclic bisaminal compounds having formula (I) or (II), their salts or solvates, methods for their preparation, their uses, and methods for preparing functional tetraazacycloalkane compounds implementing such cyclic bisaminal compounds

Nouvelles synthèses de polyazacycloalcanes, complexation, épuration des eaux / liquides

DIJON-BU Sciences Economie (212312102) / SudocSudocFranceF

Picolinate cross-bridged cyclam, chelate with metallic cations and use thereof

PCT/EP2014074415 - 2014-11-12The present invention relates to chelates resulting from the complexation of picolinate cross-bridged cyclams of formula (I), wherein the substituents L1-L4 and R1-R4 are defined as in the claims, with metallic cations. The invention further relates to picolinate cross-bridged cyclam ligands of formula (I). Another object of the invention is the use of chelates of the invention in nuclear medicine and the use of ligands of the invention in cations detection or epuration of effluents

Methods for Preparing Functional Tetraazacycloalkane Compounds using a Specific Cyclic Bisaminal Compound

Special C-functionalized cyclic bisaminal compounds having formula (I) or (II), their salts or solvates, methods for their preparation, their uses, and methods for preparing functional tetraazacycloalkane compounds implementing such cyclic bisaminal compounds