Metal ion size profoundly affects H₃glyox chelate chemistry

The bisoxine hexadentate chelating ligand, H₃glyox was investigated for its affinity for Mn²⁺, Cu²⁺ and Lu³⁺ 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 ]_free 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 Mn²⁺ complex. H₃glyox labels [^52gMn]Mn²⁺, [⁶⁴Cu]Cu²⁺ and [¹⁷⁷Lu]Lu³⁺ at ambient conditions with apparent molar activities of 40 MBq μmol^-1, 500 MBq μmol^-1 and 25 GBq μmol^-1, respectively. Collectively, these initial investigations provide insight into the effects of metal ion size and charge on the chelation with the hexadentate H₃glyox and indicate that further investigations of the Mn²⁺-H₃glyox complex in ^52g/55Mn-based bimodal imaging might be worthwhile.