Metal ion size profoundly affects Hglyox chelate chemistry.

The bisoxine hexadentate chelating ligand, Hglyox was investigated for its affinity for Mn, Cu and Lu ions; all three metal ions are relevant with applications in nuclear medicine and medicinal inorganic chemistry. The aqueous coordination chemistry and thermodynamic stability of all three metal complexes were thoroughly investigated by detailed DFT structure calculations and stability constant determination, by employing UV in-batch spectrophotometric titrations, giving pM values (pM = -log[M ] when [M ] = 1 μM, [L] = 10 μM at pH 7.4 and 25 °C) - pCu (25.2) > pLu (18.1) > pMn (12.0). DFT calculated structures revealed different geometries and coordination preferences of the three metal ions; notable was an inner sphere water molecule in the Mn complex. Hglyox labels [Mn]Mn, [Cu]Cu and [Lu]Lu at ambient conditions with apparent molar activities of 40 MBq μmol, 500 MBq μmol and 25 GBq μmol, respectively. Collectively, these initial investigations provide insight into the effects of metal ion size and charge on the chelation with the hexadentate Hglyox and indicate that further investigations of the Mn-Hglyox complex in Mn-based bimodal imaging might be worthwhile.