Octadentate Picolinic Acid‐Based Bispidine Ligand for Radiometal Ions

Abstract

The synthesis of the octadentate bispidine ligand bearing two picolinic acid pendant arms (H bispa ), and its coordination chemistry with radionuclides relevant for nuclear medicine, namely indium(III) ( In), lutetium(III) ( Lu), and lanthanum(III) (as surrogate for Ac), are reported. The non-radioactive metal complexes of the N O -type bispa ligand were characterized by H and C NMR spectroscopy, elemental analysis, mass spectrometry and single-crystal X-ray analysis. Experimental structural data, computational analysis, complex stabilities determined by potentiometric titration, and "radiostabilities" determined by competition studies in the presence of human serum reveal complex stabilities of H bispa comparable to those of the macrocyclic "gold standard" DOTA. After an incubation time of 1 day, 86 and 87 % of [ Lu(bispa )] and [ Lu(DOTA)] , respectively, remain intact. Importantly, unlike DOTA, H bispa is radiolabeled quantitatively with In and Ac under ambient conditions, which is an essential aspect when working with heat-sensitive antibodies as targeting vectors. In the case of In , room temperature radiolabeling of H bispa yields molar activities as high as 70 MBq nmol within 10 minutes. These are promising results for radiopharmaceutical applications of H bispa .

Sensing Zn2+ in Aqueous Solution with a Fluorescent Scorpiand Macrocyclic Ligand Decorated with an Anthracene Bearing Tail

“…Scorpiand type aza-macrocyclic ligands, that is aza-macrocyclic ligands with coordinating tails [1], and their metal complexes have attracted considerable interest thanks to the numerous uses they have been tested for, including but not limited to various biomedical applications [2,3] (MRI contrast agents [4,5], radioisotopes complexation and radiolabelling [6][7][8][9], radiotherapy [10][11][12][13][14], chelation therapy [15][16][17], antiproliferative treatments [18][19][20][21], enzyme mimicking [22][23][24][25][26][27][28][29]), catalysis [30][31][32][33][34][35][36] and chemosensing [37][38][39][40][41][42][43].…”

“…Here, we describe the synthesis of the new conjugated chemosensor L ( Figure 1) and its behaviour in sensing Zn(II) ions in water. L is a scorpiand type molecule constituted by a macrocyclic [9]aneN 3 (1,4,7-triazacyclononane) binding unit connected to an anthracene fluorophore through a linker containing an additional nitrogen donor. [9]aneN 3 has been widely used for the construction of chemosensors thanks to its peculiar coordination properties and the availability of consolidated synthetic procedures for its symmetric and non-symmetric functionalization [52].…”

An Eighteen‐Membered Macrocyclic Ligand for Actinium‐225 Targeted Alpha Therapy

“…[ 225 Ac(macropa)] + remained intact over 7t o 8dayswhen challenged with either excess La 3+ ions or human serum, and did not accumulate in any organ after 5hin healthy mice.Abifunctional analogue,macropa-NCS,was conjugated to trastuzumab as well as to the prostate-specific membrane antigen-targeting compound RPS-070. [11][12][13][14] Although ah ighly promising bispidine-based chelator has recently been disclosed, [15] the 12-membered tetraaza macrocycle H 4 DOTA (Figure 1b)i s currently the state of the art for the chelation of the 225 Ac 3+ ion. In LNCaP xenograft mice, 225 Ac-macropa-RPS-070 was selectively targeted to tumors and did not release free 225 Ac over 96 h. These findings establish macropa to be ah ighly promising ligand for 225 Ac chelation that will facilitate the clinical development of 225 Ac TATf or the treatment of soft-tissue metastases.…”

Highly Dynamic and Tunable Behavior of 1D Coordination Polymers Based on the Bispidine Ligand

“…Bispidines were first synthesized by Carl Mannich almost a century ago, and are still being investigated for their properties . The basic bispidine scaffold, having two aliphatic aminic N‐donor atoms, can be used to construct efficient metal binders by the addition of ancillary metal‐binding sites, thus obtaining tetra‐, penta‐, hexa‐, and octa‐dentate species . Despite the fact that there exist approximately two hundred metal complexes reported in the CSD to date, no example of CPs made with bispidine derivatives has yet been reported.…”