Crystallographic and Computational Characterisation of the Potential PET Tracer 1,4,7‐Triazacyclononane‐1,4,7‐tri(methylenephosphonato)gallium(III)

The macrocyclic chelator 1,4,7‐triazacyclononane‐1,4,7‐tri(methylenephosphonic acid) (H6NOTP) has shown significant promise for use in positron emission tomography with the positron‐emitting radionuclide 68Ga3+. We report the X‐ray crystal structure of the neutral complex 1,4,7‐triazacyclononane‐1,4,7‐tri(methylenephosphonato)gallium(III) ([Ga(H3NOTP)]), which crystallised in the centrosymmetric space group P21/n. The coordination geometry of the Ga3+ ion is distorted octahedral with three macrocyclic amine N donor atoms and three singly deprotonated phosphonato O donor atoms. Two discrete enantiomers, Δ(λλλ)‐SSS and Λ(δδδ)‐RRR, are present as a racemate within the unit cell. Intermolecular hydrogen bonds between phosphonic acid groups of adjacent complexes form a two‐dimensional sheet network. Density functional theory (DFT) calculations supported the observation of complexes with low electric field gradient values with slight but significant deviations from ideal octahedral geometry. The DFT calculations were also used to investigate the influence of intermolecular interactions and ligand protonation states on the coordination environment and surface charge distribution. The macrocyclic complex 1,4,7‐triazacyclononane‐1,4,7‐tri(methylenephosphonato)gallium(III) [Ga(H3NOTP)] was characterised by X‐ray crystallography and DFT calculations. Intermolecular interactions and ligand protonation states influenced the coordination environment and surface charge distribution of the complex. The phosphonate groups provided a coordination environment around the Ga3+ ion that was closer to ideal octahedral than several related 1,4,7‐triazacyclononane Ga3+ complexes that have been investigated for radiopharmaceutical applications.