The Scope of Application of Macrocyclic Polyamines Beyond Metal Chelation

Abstract

Recent advances in the use of radiometals for both imaging and therapy has spurred on the development of an original chemistry that endows radionuclide‐chelating molecular cages with ever sharper physicochemical properties. Macrocyclic polyamines (MPAs) such as cyclen and DOTA are among the most frequently encountered cages for the design of new radiotracers, owing to their versatile chemistry that makes them customizable molecular tools. The idea of using MPAs for alternative purposes has recently emerged, with an eye towards benefiting from their unique topology, versatility, symmetry and water‐solubility. This review summarizes strategies that have been recently implemented in which MPAs are used as multivalent molecular platforms for constructing sophisticated suprastructures that found applications in various fields, from materials chemistry to chemical biology. These original approaches are invaluable in that they successfully expand the scope of applications of MPAs far beyond their restricted roles of metal chelating appendages.

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

“…Anthracene-9-carbaldehyde (0.41 g, 2 mmol) was added in small portions in 1 h to a stirred solution of 1-(2-aminoethyl)-1,4,7-triazacyclononane (0.34 g, 2 mmol) in 100 cm 3…”

“…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].…”

DNA Junction Ligands Trigger DNA Damage and Are Synthetic Lethal with DNA Repair Inhibitors in Cancer Cells

“…[71][72][73] From lab curiosity, this field became an intensive research area thanks to the impetus provided by the pioneering works of M. J. Hannon and coworkers, 40,[44][45][74][75] which laid solid foundations for the design of efficient TWJ ligands. To date, only few families of compounds have been studied for their ability to interact specifically with TWJ, including Hannon's supramolecular cylinders (vide supra) along with poly-aza-macrocyles, 55,76 triptycene derivatives, [77][78] azacryptands, 43 azacyclophanes and metallacages, 41 and calix [3]carbazoles. 79 In the present work, we go a step further demonstrating that TWJ ligands do have therapeutic value, showing that finely selected TWJ ligands damage DNA in human cancer cells and are amenable to chemically induced synthetic lethality strategies upon association with inhibitors of DNA repair.…”

Solid phase synthesis in the development of magnetic resonance imaging probes

“…39 SPS is instrumental in the development of these specific probes, showing how it can be utilised as a special tool in the synthesis of molecular imaging agents and of similar compounds for applications unrelated to metal chelation. 40 To expand on the elegance of the SPS methodology and its application potential, this review aims to provide a concise overview of the strategies employed in the development of MRI CAs using it and evaluate the outlook of the approach in future CA synthesis. Focus will be placed in areas related to polyaminopolycarboxylate ligands for T 1 -weighted imaging, CEST and bioresponsive MRI CAs.…”