Cryptophanes xenon

Cryptophane A (47) binds xenon in its cavity in C2D2CI4, as evidenced by the Xe NMR spectrum of the insertion complex. In a racemic mixture of 47, addition of Eu(hfc)3 gives rise to two Xe signals, showing an effective chiralization of a neutral xenon atom. ... 

Xe NMR spectra for a xenon layer frozen on EtOH or H20/EtOH were used to obtain time-resolve imaging of melting and dissociation processes.682 129Xe NMR spectra gave information on the interaction of xenon with a dissymmetrical cryptophane ((Xe)2 bis-cryptophane) complex.683... 

Hydrazine can be stabilized by formation of an inclusion compound with hydroquinone.58 Uncomplexed anhydrous hydrazine can be explosive. Highly toxic dimethyl sulfate can be handled more easily as an inclusion compound with toxic 18-crown-6. Both of these toxic compounds could be avoided through the use of dimethyl carbonate (as described in Chap. 2). Reactive intermediates, such as benzyne, have been stabilized by generating them inside hosts.59 Even the noble gas xenon can be trapped reversibly by hosts such as a cryptophane, 4-ferf-butyl-calix[4]arene or a-cyclodextrin.60... 

The relatively high xenon affinity of functionalized cryptophanes, with dissociation constants in the micromolar range, has been successfiiUy appUed in the development of Xe biosensors. ... 

Unlike CTVs, cryptophanes are able to bind small guest molecules in solution as weU as within solid-state complexes. In solution, cryptophanes show particularly strong affinity for small molecules including methane, chloroform, dichloromethane, and xenon. 

Xenon. [Xe/cryptophane] complexation dynamics have been investigated by Xe one-dimensional EXSY NMR experiments. ... 

This review is dedicated to the synthesis of water-soluble cryptophanes and of the closely related hemicryptophane derivatives that were developed more recently. The study of their binding properties with different species and some peculiar properties related to their chiral structure are also described. A particular attention is given to xenon-cryptophane complexes since, as above mentioned, these complexes have played a major role in the development of water-soluble cryptophane derivatives. We describe in a concise manner the different approaches, which have been reported in the literature to introduce hydrophilic moieties onto the cryptophane structure. Finally, we report some physical properties of the water-soluble cryptophane complexes. This mainly concerns the study of their binding properties with neutral molecules or charged species. The preparation of enantiopure cryptophanes has also contributed to the development of this field. Indeed, it was stressed that cryptophanes exhibit remarkable chiroptical and binding properties in water [11]. These properties are also described. The last part of this review is devoted to hemicryptophane derivatives, which are closely related to the cryptophane structure and which allow the functionalization of the inner space of the molecular cavity. These show a renewed interest in their applications in chiral recognition and supramolecular catalysis. 

In recent time the number of water-soluble cryptophanes reported in the literature has increased substantially. The main reason for this arises from the rapid development of the xenon-cryptophane complexes aimed at designing biosensors for MRI applications. Nevertheless, it seems important to distinguish between two types of water-soluble cryptophanes. The first series of water-soluble cryptophanes are made from a cryptophane skeleton, which has been properly modified in order to significantly enhance its solubility in water. For instance, the hexa-carboxylate cryptophane 1 (Fig. 21.2), whose synthesis is reported below (Scheme 21.1), is sparingly soluble in neutral water and very soluble in basic solution (Na0H/H20). The second class of water-soluble cryptophanes is made of lipophilic cryptophane cores, which have been adequately functionalized in order to make the whole molecule soluble in water. For example, cryptophanol-A 2, when suitably substituted by hydrosoluble moiety at the phenol function, belongs to this second class of molecule (Fig. 21.2). Original cryptophane biosensors have been prepared by this way and will be described in more detail below. 

LP) NMR techniques at or even below the micromolar scale. For instance, compound 8 has been used to demonstrate that the xenon in-out exchange process with 8 occurs via a degenerate process [18]. Schroder et al. also reported the study of Xe 8 as a sensor to study membrane fluidity and membrane composition [19,20]. Independently, Frechet et al. demonstrated that the introduction of several Xe 8 cryptophane complexes inside a PAMAM dendritic structure allowed a significant gain (by a factor 8) in sensitivity of the Xe NMR signal [21]. 

Schroder et al. synthesized the two dendronized cryptophanes, 12 and 13, to enhance the solubility of the host in water at neutral pH [23]. They are formed from a bis-functionalized cryptophane containing two carboxylic acid groups, each of which are located on a distinct CTB xmit (Fig. 21.6). Polyglycerol substituents were then added to afford water-soluble cryptophanes that are expected to show high biocompatibility and to provide multi-functionality on the outer surface of the molecules for subsequent reactions. This approach appears promising for the design of new xenon-biosensors for biological studies. It is noteworthy that the synthesis of the cryptophane precursor has never been fully described. 

Rousseau et al. reported the preparation of the water-soluble cryptopahne-111 31 for xenon biosensing application [32]. The synthesis of this compound (Scheme 21.5) first requires the introduction of a reactive function on compound 25 that can be used for subsequent reactions. Thus, a single bromine atom was introduced on the cryptophane-111 skeleton to give rise to cryptophane 32. In turn, a halogen-metal exchange reaction allowed for the introduction of a carboxylic acid... 

To date, cryptophane-111 derivatives are the best molecular hosts for xenon with unprecedentedly high binding constants. However, their use as xenon carriers for MRI application is questionable since the exchange dynamics of xenon is much slower than for cryptophane-A based biosensors. This point is cmcial for designing efficient xenon biosensor since small quantities of biosensor have to be detected in solution in a very short time. 

Xenon-Biosensors from Mono-functionalized Cryptophane-A... 

---