Frontiers in radionuclide imaging and therapy, a chemical journey from naturally radioactive elements to targeted theranostic agents

Welcome to this themed issue of Dalton Transactions entitled: ‘Frontiers in Radionuclide Imaging and Therapy; A chemical journey from naturally radioactive elements to targeted theranostic agents’.</p

Phosphonate Chelators for Medicinal Metal Ions

A family of phosphonate-bearing chelators was synthesized to study their potential in metal-based (radio)- pharmaceuticals. Three ligands (H6phospa, H6dipedpa, H6eppy; structures illustrated in manuscript) were fully characterized, including X-ray crystallographic structures of H6phospa and H6dipedpa. NMR spectroscopy techniques were used to confirm the complexation of each ligand with selected trivalent metal ions. These methods were particularly useful in discerning structural information for Sc3+ and La3+ complexes. Solution studies were conducted to evaluate the complex stability of 15 metal complexes. As a general trend, H6phospa was noted to form the most stable complexes, and H6eppy associated with the least stable complexes. Moreover, In3+ complexes were determined to be the most stable, and complexes with La3+ were the least stable, across all metals. Density functional theory (DFT) was employed to calculate structures of H6phospa and H6dipedpa complexes with La3+ and Sc3+. A comparison of experimental 1 H NMR spectra with calculated 1 H NMR spectra using DFT-optimized structures was used as a method of structure validation. It was noted that theoretical NMR spectra were very sensitive to a number of variables, such as ligand configuration, protonation state, and the number/orientation of explicit water molecules. In general, the inclusion of an explicit second shell of water molecules qualitatively improved the agreement between theoretical and experimental NMR spectra versus a polarizable continuum solvent model alone. Formation constants were also calculated from DFT results using potential-energy optimized structures. Strong dependence of molecular free energies on explicit water molecule number, water molecule configuration, and protonation state was observed, highlighting the need for dynamic data in accurate first-principles calculations of metal−ligand stability constants

One and Two Dimensional Pulsed Electron Paramagnetic Resonance Studies of in vivo Vanadyl Coordination in Rat Kidney

The biological fate of a chelated vanadium source is investigated by/n vivo spectroscopic methods to elucidate the chemical form in which the metal ion is accumulated. A pulsed electron paramagnetic resonance study of vanadyl ions in kidney tissue, taken from rats previously treated with bis(ethylmaltolato)oxovanadium(IV) (BEOV) in drinking water, is presented. A combined approach using stimulated echo (3-pulse) electron spin echo envelope modulation (ESEEM) and the two dimensional 4-pulse hyperfine sublevel correlation (HYSCORE) spectroscopies has shown that at least some of the VO2+ ions are involved in the coordination with nitrogen-containing ligands. From the experimental spectra, a 4N hyperfine coupling constant of 4.9 MHz and a quadrupole coupling constant of 0.6 + 0.04 MHz were determined, consistent with amine coordination of the vanadyl ions. Study of VO-histidine model complexes allowed for a determination of the percentage of nitrogen-coordinated VO2+ ions in the tissue sample that is found nitrogen-coordinated. By taking into account the bidentate nature of histidine coordination to VO2+ ions, a more accurate determination of this value is reported. The biological fate of chelated versus free (i.e. salts) vanadyl ion sources has been deduced by comparison to earlier reports. In contrast to its superior pharmacological efficacy over VOSO4, BEOV shares a remarkably similar biological fate after uptake into kidney tissue

Gold amides as anticancer drugs: synthesis and activity studies

Modular gold amide chemotherapeutics: Access to modern chemotherapeutics with robust and flexible synthetic routes that are amenable to extensive customisation is a key requirement in drug synthesis and discovery. A class of chiral gold amide complexes featuring amino acid derived ligands is reported herein. They all exhibit in vitro cytotoxicity against two slow growing breast cancer cell lines with limited toxicity towards normal epithelial cells

Characterization of the potent insulin mimetic agent bis(maltolato)oxovanadium(IV) (BMOV) in solution by EPR spectroscopy

Bis(maltolato)oxovanadium(IV) (abbreviated BMOV or VO(ma)(2)) has been characterized by electron paramagnetic resonance (EPR) spectroscopy in CH(2)Cl(2), H(2)O, MeOH, and pyridine at both room and low temperatures. Spin Hamiltonian parameters for mono- and bis(maltolato)oxovanadium(IV) complexes [VO(ma)](+) (=[VO(ma)(H(2)O)(n)()](+), n = 2 or 3) and VO(ma)(2) (Hma = 3-hydroxy-2-methyl-4-pyrone, maltol) have been obtained by computer simulation (SOPHE). Configurations of solvated vanadyl/maltol complexes, VO(ma)(2)S, in solution (S = solvent) are proposed on the basis of a comparison of their hyperfine coupling constants with those obtained for related vanadium(IV) compounds in the literature. Whereas at room temperature pyridine coordinates to VO(ma)(2) in a position cis to the oxo ligand (cis isomer), in H(2)O or in MeOH solvated and unsolvated cis and trans adducts of VO(ma)(2) are all formed, with the cis isomer dominant. As expected, the coordinating ability was found to be in the order py > H(2)O approximately MeOH > CH(2)Cl(2). In aqueous solutions at room temperature and neutral pH, cis- and trans-VO(ma)(2)(H(2)O) complexes are present as major and minor components, respectively