Investigating the Complexation of the Pb²⁺/Bi³⁺ Pair with Dipicolinate Cyclen Ligands

Abstract

The complexation properties toward Pb(2+) and Bi(3+) of the macrocyclic ligands 6,6'-((1,4,7,10-tetraazacyclododecane-1,7-diyl)bis(methylene))dipicolinic acid (H2do2pa) and 6,6'-((4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diyl)bis(methylene))dipicolinic acid (H2Me-do2pa) have been investigated. A new three-step synthesis of H2do2pa following the bisaminal methodology has also been developed. The X-ray structures of [Pb(Me-do2pa)]·6H2O and [Bi(Me-do2pa)](NO3)·H2O show that the two metal ions are eight-coordinated by the ligand. The two complexes exist as the racemic Δ(δδδδ)/Λ(λλλλ) mixture both in the solid state and in solution, as indicated by NMR and DFT studies. The stability constants of the lead(II) and bismuth(III) complexes of the two ligands were determined in 0.5 M KCl using potentiometric and spectrophotometric techniques. The stability constants determined for the complexes of Pb(2+) are relatively high (log KML = 16.44 and 18.44 for H2do2pa and H2Me-do2pa, respectively) and exceptionally high for the complexes of Bi(3+) (log KML = 32.0 and 34.2 for H2do2pa and H2Me-do2pa, respectively). The [Pb(Me-do2pa)] complex presents rather fast formation and very good kinetic inertness toward transchelation. Additionally, the [Bi(Me-do2pa)](+) complex was found to present a remarkably fast complexation rate (full complexation in ∼2 min at pH 5.0, acetate buffer) and a very good kinetic inertness with respect to metal ion dissociation (half-life of 23.9 min in 1 M HCl), showing promise for potential applications in α-radioimmunotherapy.

Exciplex Formation and Aggregation Induced Emission in Di‐(N‐benzyl)cyclen and Its Complexes – Selective Fluorescence with Lead(II), and as the Cadmium(II) Complex, with the Chloride Ion

“…The nitrogen donors of the cyclen moiety form a plane with the Pb lying above it, while the two perchlorates are coordinated to the Pb, pushed to one side by the π contacted benzyl from an adjacent complex individual. The Pb–N bond lengths to the cyclen part of the macrocycle average 2.502 Å, somewhat shorter than the average of 2.65 ± 0.04 Å found in the CSD for Pb–N bonds in five structures containing Pb II bound to a cyclen moiety . The Pb–O bonds to the two perchlorates are rather long at 3.069(4) and 2.934(4) Å, which is typical of bonds near the stereochemically active lone pair on Pb II ,, , if the lone pair is located between the two Pb–O bonds.…”

“…The Pb–O bonds to the two perchlorates are rather long at 3.069(4) and 2.934(4) Å, which is typical of bonds near the stereochemically active lone pair on Pb II ,, , if the lone pair is located between the two Pb–O bonds. The difference appears to be due to the fact that the cyclen‐based ligands in the five reported structures all have pendent donor groups that raise the C.N. of the Pb II to 8, as compared with C.N.…”

Optimizing labelling conditions of 213Bi-DOTATATE for preclinical applications of peptide receptor targeted alpha therapy

“…The activation energy for the DOTA ring inversion process is in the order of 65 kJ/mol (Lima et al 2015 ). The initial dose rate by the α-radiation in the vial with 100 MBq 213 Bi amounts 165 mGy/s, which corresponds to an absorbed energy rate of 0.13 mJ/s in 800 μL with 7 nmol compound, or 19 kJ/mol.s.…”

Intracellular Transport Studies of Picolinate Macrocyclic Copper and Lanthanide Complexes

“…[Eu(do2pa)] + (Figure ) is a cyclen‐based bispicolinate used as analogue of potential MRI CA [Gd(do2pa)] + . The octodentate ligand do2pa encloses the metal, resulting in a remarkably kinetically stable configuration . Furthermore, one water molecule is available for exchange in the inner‐sphere, improving longitudinal and transverse relaxation enhancement of water protons for the Gd 3+ complex.…”