Cyclophane binding affinity

Molecular shuttle 154+ consists of a tetracationic cyclophane macrocycle, a linear thread containing two hydroquinol stations and a polyether spacer. The macrocycle binds the stations via n - n and charge-transfer interactions between the electron-poor cyclophane and the electron-rich hydroquinols. As explained above, because both stations are energetically degenerate (they are chemically identical) the macrocyclic unit has no preference for either of them and randomly shuttles between them, in this case at a rate of k = 2360 s 1 in (CDs CO at 34 °C, measured by JH NMR spectroscopy. It was already noted in Stoddart s seminal 1991 paper that including two stations of different binding affinity in the thread could allow a stimuli-induced change of position of the macrocycle in a molecular shuttle. 

Smithrud DB, Wyman TB, Diederich E. Enthalpically driven cyclophane arene inclusion complexation - Solvent-dependent calorimetric studies. J. Am. Chem. Soc. 1991 113 5420-5426. Gilson MK, Zhou HX. Calculation of protein-ligand binding affinities. Annu. Rev. Biophys. Biomol. Struct. 2007 36 21 2. Karplus M, McCammon JA. Molecular dynamics simulations of biomolecules. Nat Struct Biol 2002 9 646-652. 

It is widely known that tetrathiafulvalene (15) - commonly known as TTF -can be easily oxidized to its radical cation and then on to its dicationic state. Previous research [36] from our laboratories had shown that reduction of the tetracationic cyclophane CBPQT4+ reduces enormously its binding affinity for 7i-electron-rich guests. In the light of this knowledge, it was considered possible to develop a pseudorotaxane-based switch in which the switching process is not only controlled and monitored electrochemically, but in which it can be accomplished [37] in one of two ways. 

Diederich and coworker have synthesized chiral receptors that possess additional carboxylate residues that are suitable for the complexation of disaccharides [54]. Cyclophanes 141-143 were prepared via a stepwise approach involving chain elongation steps followed by a single intramolecular cyclization reaction. The complexation of these receptors with two disaccharides was investigated by H NMR spectroscopy and showed that the incorporation of the methyl carboxylate groups in 142 increased the assodation relative to the unfunctionalized derivative 141. A subsequent publication reported on the detailed binding affinities of square cydo-... 

Some authors based their approach to selective binding of the more lipophilic a-amino acids in water on hydrophobic effects using water-soluble, cavity-containing cyclophanes for the inclusion of only the apolar tail under renouncement of any attractive interaction of the hosts with the zwitterionic head . Kaifer and coworkers made use of the strong affinity of Stoddart s cyclobis(paraquat-p-phenylene) tetracation 33 for electron-rich aromatic substrates to achieve exclusive binding of some aromatic a-amino acids (Trp, Tyr) in acidic aqueous solution [48]. Aoyama et al. reported on selectivities of the calix[4]pyrogallolarene 34 with respect to chain length and t-basicity of aliphatic and aromatic amino acids, respectively [49]. Cyclodextrins are likewise water-soluble and provide a lipophilic interior. Tabushi modified )S-cyclodextrin with a 1-pyrrolidinyl and a carboxyphenyl substituent to counterbalance the... 

Very recently, nice recognition of free and AT-acetylated amino acids (Gly, Ala, Phe) and some structurally related guests by a dicationic cyclophane-type A/,Ar -dibenzylated chiral derivative (4) of a bisisoquinoline alkaloid S,S-(+)-tetrandine (3 DBT) has been studied by NMR titration in water [31]. In contrast to other macrocyclic hosts, DBT shows high affinity and large enan-tioselectivity (K(S)/K(R)> 10) toward the smaller N-acetylalanine and binds the larger phenylalanine more weakly and nonselectively. The binding specificity of DBT was rationalized on the basis of molecular mechanics calculations. 

Fig. 27. The rationale behind the design of an electrochemically switchable [2]catenane. The neutral form of TTF is bound very strongly within the cyclophane CBPQT4+. However, when it is oxidized to either of its cationic forms, TTF shows no affinity whatsoever for the cyclophane. 1,5-Dimethoxynaphthalene exhibits moderate binding toward the cyclophane. All binding constants Ka were measured in acetonitrile at 298 K...

Adding aUcaU metal iodide salts as templates induced modest changes in product distribution [36]. The most significant shift in library composition was induced by sodium iodide, which doubled the concentration of tetramer and pentamer in the reaction mixture. Binding constants were not measured however, the relative affinities of the amplified cyclophane macrocycles for the different metal alkali were studied by electrospray ionization-mass spectrometry (electrospray ionization ESI-mass spectrometry MS), finding good agreement with the main amplification observed. The yield of cychc tetramer was increased by the addition of sodium in the cases of the MEM and di(p-methoxybenzyl) monomers, and these were found to bind sodium preferentially in the ESl-MS study [109]. 

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