An oxygen-17 dynamic NMR study of the Pr–DOTA complex

Abstract

The complex between ¹⁷O-enriched DOTA (tetraazacyclododecanetetraacetic acid) and praseodymium(III) (Pr³⁺) was studied in aqueous solution by variable-temperature ¹⁷O NMR at 14.1 T. pH effects as well as the influence of metal ions free in solution were investigated. At low temperature, the so-called TSAP and SAP conformations give rise to distinct signals for the oxygen atoms coordinated to the metal ion (O₂); coalescence occurs between 20 and 30 °C. In contrast, a single signal was detected for the noncoordinated oxygen atoms (O₁) in the entire investigated temperature range, i.e. between −3 and 135 °C. At high temperature, the spectra exhibit signal broadening that reveals the interchange of the O₁ and O₂ oxygen atoms of the carboxylate groups. The linewidths measured for O₁ were deconvolved into contributions from quadrupole relaxation and chemical exchange, allowing the corresponding activation barriers to be determined. The present ¹⁷O dynamic NMR study provides the first quantitative experimental data characterizing the interchange of the oxygen atoms in a DOTA chelate of a lanthanide metal ion. The activation entropy of this process is negligible and the activation enthalpy is found to range between 66 and 77 kJ mol⁻¹, depending on the pH and the presence of free Pr³⁺ ions in solution. These data support the results of a previous computational study according to which the exchange mechanism involves the internal rotation of the carboxylate groups.