Dynamics of Coordinated Phosphonate Group Directly Observed by 17 O‐NMR in Lanthanide( iii ) Complexes of a Mono(ethyl phosphonate) DOTA Analogue

Biological phosphates can coordinate metal ions and their complexes are common in living systems. Dynamics of mutual oxygen atom exchange in the tetrahedral group in complexes has not been investigated. Here, we present a direct experimental proof of exchange (“phosphonate rotation”) in model Ln(III) complexes of monophosphonate H 4 dota analogue which alters phosphorus atom chirality of coordinated phosphonate monoester. Combination of macrocycle‐based isomerism with P ‐based chirality leads to several diastereoisomers. (Non)‐coordinated oxygen atoms were distinguished through 17 O‐labelled phosphonate group and their mutual exchange was followed by various NMR techniques and DFT calculations. The process is sterically demanding and occurs through bulky bidentate (κ 2 ‐PO 2 ) − coordination and was observed only in twisted‐square antiprism (TSA) diastereoisomer of large Ln(III) ions. Its energy demands increase for smaller Ln(III) ions ( 298 Δ G ≠ (exp./DFT)=51.8/52.1 and 61.0/71.5 kJ mol −1 for La(III) and Eu(III), respectively). These results are helpful in design of such complexes as MRI CA and for protein paramagnetic NMR probes. It demonstrates usefulness of 17 O NMR to study solution dynamics in complexes involving phosphorus acid derivatives and it may inspire use of this method to study dynamics of phosphoric acid derivatives (as e. g. phosphorus acid‐based inhibitors of metalloenzymes) in different areas of chemistry.