Water Soluble Cryptophanes Showing Unprecedented Affinity for Xenon:  Candidates as NMR-Based Biosensors

Abstract

Cryptophanes bearing OCH(2)COOH groups in place of the methoxy groups represent a new class of xenon-carrier molecules soluble in water at biological pH. By using (1)H and (129)Xe NMR (thermally- and laser-polarized dissolved gas), the structural and dynamical behaviors of these host molecules as well as their interaction with xenon are studied. They are shown to exist in aqueous solution under different conformations in very slow exchange. A saddle form present for one of these conformations could explain the (1)H NMR spectra. Whereas the cryptophanes in such a conformation are unable to complex xenon, unprecedented high binding constants are found for cryptophanes in the other canonical crown-crown conformation. These host molecules could therefore be valuable candidates for biosensing using (129)Xe MRI.

Strongly underestimated dispersion energy in cryptophanes and their complexes

“…The latter conformation has already been described for cryptophane-A derivatives and larger cryptophanes 16,28,29 . To determine the conformation of impl-1, a mixture of CHCl 3 @1 in 1,2-C 6 D 4 Cl 2 was heated at 423 K for 12 h to completely remove CHCl 3 from the solution.…”

Temperature‐Controlled Molecular Depolarization Gates in Nuclear Magnetic Resonance

“…When using temperature to control depolarization transfer, three effects should be considered: First, increasing temperature increases the exchange rate of xenon with the cage molecules (6,9,10). Second, the binding constant of the cage-xenon complex tends to increase as temperature increases (11), making more xenon susceptible to selective saturation.…”

“…Second, the use of low-bandwidth pulses is an important step for reading out different sensor signals in the same system (multiplexing, (7,10)). …”

“…Biosensor detection now includes features of MRI thermometry (13)-which could be used to monitor hyperthermia in oncologic therapy (14)-but the concept of a transpletor also illustrates increased sensitivity at body temperature. Moreover, this concept can be applied to other problems that rely on exchangeable NMR-detected guests to reveal properties of the host structure or indirect detection of competing guests (6,10,15,16). Such experiments would facilitate studies of the exchange dynamics of other nanostructure hosts (alternative cages, carbon nanotubes, zeolites (17)).…”

Rotaxane probes for protease detection by 129Xe hyperCEST NMR

“…129 Xe NMR is a versatile tool that can take advantage of hostguest interactions that can reflect the molecular environment. 8,9 By use of spin-exchange optical-pumping for hyperpolarizing xenon, signals can be increased by more than four orders of magnitude, allowing for extremely sensitive detection. 10,11 The polarizability of 129 Xe atoms makes their chemical shifts highly sensitive to their environment, and thus they can be used to detect changes in temperature, pH, and liquid crystal ordering.…”