Cryptophane-Xenon Complexes in Organic Solvents Observed through NMR Spectroscopy

Abstract

The interaction of xenon with cryptophane derivatives is analyzed by NMR by using either thermal or hyperpolarized noble gas. Twelve hosts differing by their stereochemistry, cavity size, and the nature and the number of the substituents on the aromatic rings have been included in the study, in the aim of extracting some clues for the optimization of (129)Xe-NMR based biosensors derived from these cage molecules. Four important properties have been examined: xenon-host binding constant, in-out exchange rate of the noble gas, chemical shift, and relaxation of caged xenon. This work aims at understanding the main characteristics of the host-guest interaction in order to choose the best candidate for the biosensing approach. Moreover, rationalizing xenon chemical shift as a function of structural parameters would also help for setting up multiplexing applications. Xenon exhibits the highest affinity for the smallest cryptophane, namely cryptophane-111, and a long relaxation time inside it, convenient for conservation of its hyperpolarization. However, very slow in-out xenon exchange could represent a limitation for its future applicability for the biosensing approach, because the replenishment of the cage in laser-polarized xenon, enabling a further gain in sensitivity, cannot be fully exploited.

Effect of pH and Counterions on the Encapsulation Properties of Xenon in Water‐Soluble Cryptophanes

“…These observations are strikingly different to the case of compound 1 or other cryptophane-A derivatives, [13] which always are in fast exchange conditions on the proton chemical shift time scale, revealing exchange rates at least one order of magnitude faster (for instance its value is 100 Hz for compound 1). A series of 1 H-EXSY experiments performed on the solutions of compound 2 in the presence of the noble gas and different counterions have allowed exchange characterization through the monitoring of the volume of one or several cross-peaks assigned to pure exchange with the mixing time.…”

“…[13] A dedicated chemistry has been developed to further increase the xenon binding constants. [14] However, the hydrophobic character of these aromatic cage molecules can be problematic in the biosensing approach, since to obtain a water-soluble biosensor the insertion of a hydrophilic spacer is required.…”

MRI Thermometry Based on Encapsulated Hyperpolarized Xenon

“…Recently, 12 different cryptophane complexes dissolved in 1,1,2,2-[D 2 ]tetrachloroethane were examined with regard to their temperature dependence of the chemical shift. [22] These cryptophane cages were sorted in 4 different groups according to their temperature dependence (ca. 0.084 ppm 8C À1 to 0.3 ppm 8C…”

Xenon-based molecular sensors in lipid suspensions

“…Some interaction between the hydrophobic xenon-binding moiety (a cryptophane molecule) that has been targeted to a cell surface receptor and the hydrophobic interior of the cell membrane is likely. Studies have been conducted on cryptophanes in hydrophobic organic solvents [6,7] and in human plasma [8], but there has been no previous report on the interaction of cryptophanes with lipid vesicles.…”