Improving the stability and inertness of Cu(ii) and Cu(i) complexes with methylthiazolyl ligands by tuning the macrocyclic structure

Abstract

A tacn based ligand bearing two methylthiazolyl arms (no2th) was synthesized with the aim to find ligands forming very stable and inert complexes with Cu(ii) and Cu(i) in aqueous medium for radiopharmaceutical applications. The no2th ligand was efficiently prepared following the orthoamide intermediate synthesis. The complexes with Cu(2+) and Zn(2+) were obtained and analyzed by X-ray diffraction. The [Cu(no2th)](2+) complex presents a pentacoordinated distorted square pyramidal coordination geometry, while the metal ion in [Zn(no2th)](2+) adopts a hexacoordinated distorted trigonal prismatic geometry involving the coordination of a perchlorate counter ion. The acid-base properties of no2th have been studied using potentiometric titrations, and the stability constants of Cu(2+) and Zn(2+) complexes were determined by potentiometric and UV-vis titrations using H4edta as a competitor ligand. The stability constant determined for the Cu(2+) complex is rather high (log KCuL = 20.77 and pCu = 17.15), and moreover no2th exhibits a high selectivity for copper(ii) in relation to zinc(ii). The kinetics of the copper(ii) complexation process is very fast even in acidic medium. In addition, the [Cu(no2th)](2+) complex was found to be inert under rather harsh conditions (up to 2 M HCl and 60 °C), displaying a very high half-life time of about 15 days in 2 M HCl at 90 °C. The electrochemical reduction of the copper(ii) complex in water leads to the reversible formation of a stable copper(i) species. Spectroscopic studies performed by NMR, UV-vis and EPR, assisted by theoretical calculations, show that the [Cu(no2th)](2+) complex presents a structure in solution similar to that observed in the solid state. When compared to its cyclam di-N-methylthiazolyl counterpart, the results reported in this paper unambiguously show that replacing the cyclam unit by a tacn moiety improves the stability and inertness of its Cu(ii) and Cu(i) complexes.

Transient versus Static Electron Spin Relaxation in Mn2+ Complexes Relevant as MRI Contrast Agents

“…Generally, the nonhybrid TPSS functional provides smaller absolute D values than the hybrid B3LYP and TPSSh functionals. The TPSS0 functional was included in this investigation because it was found recently that it provides calculated g - and A -tensors in better agreement with the experimental EPR data than TPSSh. , However, TPSS0 leads to rather erratic results in the present case. Overall, the results presented in Table show that the ZFS parameters in Mn 2+ complexes are rather difficult to predict with DFT, which is in line with previous studies that provided accuracies of ∼0.1 cm –1 .…”

Amphiphilic Distyrylbenzene Derivatives as Potential Therapeutic and Imaging Agents for Soluble and Insoluble Amyloid β Aggregates in Alzheimer’s Disease

“…Based on this strategy, the amphiphilic compound LS-4 contains a hydrophilic azamacrocycle, 2,4-dimethyl-1,4,7-triazacyclononane (Me 2 HTACN), and a hydrophobic distyrylbenzene derivative known to exhibit high binding affinity for the Aβ species (Figure ). , The novel asymmetric distyryl stilbene derivative contains fragments resembling the FDA-approved PET imaging agent [ 18 F]­florbetaben, the symmetric distyrylbenzene structure of compound DF-9 and the related methoxy-X04–which have been widely used in detecting amyloid plaques, ,, as well as the 2-methoxy-phenol fragment reminiscent of o-vanillin that was shown to inhibit the formation of Aβ oligomers and also exhibit antioxidant properties . Notably, a similar type of unsymmetric distyrylbenzene structure has been used for membrane potential sensor development, yet it has never been utilized for binding to or detecting Aβ species related to AD.…”

Palladium Goes First: A Neutral Asymmetric HeteroditopicN,PLigand Forming Pd-3d Heterobimetallic Complexes

“…In addition, three irreversible reduction processes are observed at −1.15, −1.40, and −1.97 V. Interestingly, complex 7 has four irreversible reduction processes at −0.40, −1.27, −1.57, and −1.89 V and two irreversible oxidations at 0.13 and −0.57 V. The Cu I/II redox couple appears at E PC = −0.40 V and E PA = −0.57 V, though this process is not reversible due to the expected change of the coordination geometry of Cu I (see Figure S76). , …”