Comprehensive Quantitative and Calibration-Free Evaluation of Hyperpolarized Xenon-Host Interaction by Multiparametric NMR

The probing of microscopic environments by hyper-polarized xenon NMR has spurred investigations in supramolecular chemistry as well as important biosensing and molecular imaging applications. While xenon exchange with host structures at micromolar concentrations and below can be readily detected, a quantitative analysis is limited, requiring complementary experimentation by different methodologies and thus lacking completeness and compromising the validity and comparability of numerical results. Here, a new NMR measurement and data analysis approach is introduced for the comprehensive characterization of the host-xenon binding dynamics. The application of chemical exchange saturation transfer of hyperpolarized Xe-129 under parametric modulation of the saturation RF amplitude and xenon gas saturation of the solution enables a delineation of exchange mechanisms and, through modeling, a numerical estimation of the various reaction rate constants (and thus magnetization exchange rate constants), the xenon affinity, and the total host molecule concentration. Only the numerical xenon solubility is additionally required for input, a quantity that has a low impact on the measurement uncertainty and is derivable from metrological data collections. Signal calibration by a reference material may thus be avoided, qualifying the method as calibration-free. For demonstration a xenon exchange with the host cucurbit[6]uril at low concentration is investigated, with the numerical results being validated by standard quantitative NMR data obtained at high concentration. The readiness to evaluate xenon exchange for the one sample at hand and in a single experimental attempt by the proposed method may allow comprehensive quantitative studies in supramolecular chemistry, biomacromolecular structure and dynamics, and sensing.

Automated summary

The probing of microscopic environments by hyper-polarized xenon NMR has led to investigations in supramolecular chemistry and important applications in biosensing and molecular imaging. However, quantitative analysis of xenon exchange with host structures is limited and requires complementary experimentation by different methodologies, compromising the validity and comparability of numerical results. In this study, a new NMR measurement and data analysis approach is introduced for a comprehensive characterization of host-xenon binding dynamics. The proposed method allows for a numerical estimation of reaction rate constants, xenon affinity, and total host molecule concentration, avoiding the need for signal calibration using a reference material.