Field-Dependent ¹H Relaxometry as a General Probe of Hydration Dynamics in Paramagnetic Ln3+ Complexes

Abstract

Hydration dynamics at metal centres govern the reactivity of chemical and biological systems and are central to the function of paramagnetic probes. Nuclear magnetic resonance (NMR) offers powerful multinuclear and multifield approaches to interrogate exchange processes across broad kinetic regimes. However, established methodologies require high sample concentrations, limiting access to poorly soluble, high-molecular-weight, or scarce complexes. Here we introduce a concentration-efficient relaxometric strategy that enables direct determination of water-exchange dynamics in paramagnetic complexes through the simultaneous analysis of longitudinal and transverse ¹H relaxation rates over an extended magnetic field range. This approach provides quantitative access to exchange kinetics while requiring only dilute solutions. We validate the method using the [Ln(DTPA)]^2- and [Ln(AAZTA)]^-series, two prototypical systems in which lanthanide contraction modulates coordination number and hydration state in distinct ways. The DTPA complexes display the expected progressive acceleration of water exchange toward the heavier lanthanides, consistent with a dissociative interchange mechanism. In contrast, the AAZTA analogues exhibit a pronounced deceleration of exchange for the heavier ions, reflecting changes in coordination environment and hydration equilibria. The method faithfully captures these opposing trends, demonstrating its sensitivity to subtle structural variations across the series. Beyond reproducing established behaviour, this strategy expands experimental access to metal-water exchange kinetics under conditions previously inaccessible to conventional ¹⁷O NMR techniques. Its direct relevance to MRI contrast agent development enables rational optimization of next-generation probes for high-field imaging. More broadly, the methodology is readily extendable to transition-metal systems, offering a general platform to interrogate hydration dynamics in coordination chemistry.