Cryptophanes water-soluble

The above methods furnish cryptophanes provided with methoxy substituent at the periphery of the cyclotriveratrylene caps. These hosts are soluble in organic solvents such as halogenated hydrocarbons but are insoluble in water or in alcoholic solvents. A way to make them water-soluble would be to incorporate... 

Figure 56 A water-soluble cryptophane for binding alkylanunonium guests [78]...

L. G. Garel, B. Lozach, J.-P. Dutasta, A. Collet, Remarkable effect of receptor size on the binding of acetylcholione and related ammonium ions to water-soluble cryptophanes, J. Am. Chem. Soc., 1993, 115, 11652-11653. 

Canceill, J. Lacombe, L. Collet. A. Water-soluble cryptophane binding lipophilic guests in aqueous solution. J. Chem. Soc.. Chem. Commun. 1987, 219-221. 

Bouchet A, Brotin T, Cavagnat D, Buffeteau T (2010) Induced chiroptical changes of a water-soluble cryptophane by encapsulation of guest molecules and counterion effects. Chem Eur J 16 4507 518... 

Bouchet A, Brotin T, Linares M, Agren H, Cavagnat D, Buffeteau T (2011) Conformational effects induced by guest encapsulation in an enantiopure water-soluble Cryptophane. J Oig Chem 76 1372-1383... 

Even in lipophilic solvents where hydrophobic effects and interactions are minimized, the cryptophanes strongly, reversibly and selectively complex neutral guests of complementary size such as the halogenomethanes. For example, enantio-selective complexation of CHFClBr by (140) has also been reported (138a). The water-soluble cryptophane (141) scavenges trace amounts of halogenomethanes from water. 

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. 

The sparingly water-soluble carboxylic acid cryptophane 8 was prepared from cryptophanol-A 2. Although its solubility is very limited in water, the Xe 8 complex can be easily detected in water thanks to high sensitivity laser-polarized... 

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. 

Scheme 21.3 Synthesis of a water-soluble cryptophanes for the complexation of human carbonic anhydrase [reaction conditions (a) HCIO4, MeOH, rt, 14 h, 48 % (b) Sulfonamide linker, CUSO4,...

Fig. 21.8 Structure of the pH sensitive water-soluble cryptophane biosensor 24...

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... 

Scheme 21.4 Synthesis of the water-soluble cryptophane- 111 (29) from compound (25) (reaction conditions (a) CH2ClBr (excess), DMF, 80 ° C,...

Scheme 21.5 Synthesis of the water-soluble cryptophane-111 31 from 25 (reaction conditions (a) NBS, CHCI3, 24 h, rt, 64 % (b) THF, /i-BuLi, CO2,1 h, 27 % (c) DMSO, 34, PyBOP, DIEA in NMP then TFA 0.1 %, 43 %)...

Recently, Brotin et al. reported the synthesis of novel water-soluble cryptophanes based on the cryptophane-223 skeleton (Scheme 21.6) [33]. The design of such new cryptophane hosts was motivated by the need for fast and easy preparation of cryptophane biosensors and the critical requirement for producing sizable amounts of compounds if future in-vivo experiments are envisaged. The cryptophane-223 skeleton has been used as starting material and new functionalities were introduced on the central carbon atom of the propylenedioxy linker. The authors have described two different approaches to cryptophane-223 35... 

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