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

Abstract

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 the exchange ("phosphonate rotation") in model Ln(III) complexes of monophosphonate H4dota analogue which alters phosphorus atom chirality of coordinated phosphonate monoester. Combination of macrocycle-based isomerism with P-based chirality leads to several diastereoisomers. The (non)-coordinated oxygens were distinguished through 17O-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 (k2-PO2)- coordination. It was observed on complexes of large Ln(III) ions in twisted-square antiprism diastereoisomers. The process energy increases for smaller Ln(III) ions (298ΔG‡(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 for MRI and protein paramagnetic NMR probes. It demonstrates usefulness of 17O NMR to study solution dynamics in complexes involving phosphorus acid derivatives. The results 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.