Importance of ligand design in lanthanide azamacrocyclic complexes relevant to biomedical applications

Synthesis and characterization of a novel [52Mn]Mn-labelled affibody based radiotracer for HER2+ targeting

“…However, for the complexes intended for in vivo use, it is slowly being accepted that their inertness is more crucial than their thermodynamic stability. 30,31 Therefore we have also accessed the rate of dissociation of the complexes at pH = 6.0 in the presence of high (25-fold) Zn( ii ) excess by using a previously proposed R 2 relaxometric protocol. 3 Transverse relaxivity changes as a function of time for the Mn( ii ) complexes of BFCs are depicted in Fig.…”

Rearmed Bifunctional Chelating Ligand for 225Ac/155Tb Precision-Guided Theranostic Radiopharmaceuticals─H4noneunpaX

“…Global deprotection and cleavage from the resin was carried out using a standardized TFA cleavage cocktail to give the cyclized Fmoc-protected peptides 16 and 17 , which were isolated by RP-HPLC. To allow selective functionalization of the N-terminus of each peptide, the side chain primary amine group on Lys was first protected using Boc 2 O prior to N α -Fmoc cleavage with 20% piperidine in DMF to give compounds 18 and 19 . This approach maximized the purity of the Tyr 3 -TATE peptides prior to incorporating the bifunctional chelator.…”

“…Clear differences in the interatomic bond distances between the backbone donor atoms and central Bi 3+ ion are apparent in the structures of the two metal complexes, Figure 6. Specifically, the Bi−N(1) and Bi−O (5) bond distances in [Bi(noneunpaX)] − are elongated at 2.794 and 2.768 Å, respectively, compared to [Bi(noneunpa)] − , wherein the equivalent donor distances are 2.661 and 2.698 Å. This deviation in bonding is a result of the increased steric constraints induced by anchoring two large picolinic acid donors to the same terminal nitrogen atom N(1), consequently disfavoring coordination of the large Bi 3+ ion (ionic radius = 1.15 Å, CN = 9), 48 in addition to the hard anionic nature of the two acetate units placed on N(2), which are more poorly matched to the intermediate-hardness of the Bi 3+ ion.…”

“…Macrocyclic chelating ligands, such as DOTA, Chart , are well-established as versatile platforms for sequestering different metal ions, forming thermodynamically stable and kinetically inert metal complexes; however, this is often at the expense of specificity/selectivity and requires high temperatures for metal ion incorporation . Notably, significant research studies by the groups of Yang et al , and Wilson et al – have discovered macrocyclic ligands with expanded core frameworks (e.g., crown, macropa, macrodipa), which demonstrate more facile complexation characteristics and show interesting size–selectivity relationships. Furthermore, the bispidine class of chelating ligands, which have been extensively explored by Comba et al, have achieved favorable complexation properties with both large and small metal ions under mild conditions. , Nonmacrocyclic chelating ligands, such as EDTA and DTPA, have been extensively investigated over decades for metal ion chelation owing to their fast complexation kinetics under mild conditions, and their widespread application has been found in the medicinal sector in combination with thermally sensitive drug molecules; , however, such chelators can exhibit fast decomplexation kinetics, leading to poor in vivo stability.…”

“…Given the inherent challenges in the directed synthesis of ligands with symmetric donor substitution and the require-Chart 1. Chemical Structures of Discussed Ligands [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]26,27 ments to often "break" symmetry in the pursuit of bifunctional derivatives for radiopharmaceutical applications, 22 an assessment of the exact impacts of an inverted donor group arrangement on metal ion chelation is warranted. This inverted "syn" constitutional arrangement may give several advantages, particularly in regard to synthesis: protecting group strategies can be circumvented through rational synthetic design, and the incorporation of bifunctional handles within the core framework is synthetically more accessible, allowing for streamlined tuning of the pharmacokinetic profile of new radiopharmaceuticals.…”