Hydrophobic interaction cyclophane

In a completely different approach to metal-templated receptors, Schwa-bacher et al. have prepared a series of bis(amino add) derivatives like (57) which, on addition of transition metals such as mckel(II) or cobalt(II), dimerize to form cyclophane-like macrocycles (58) that are capable of substrate recognition in water [68]. These designs have the advantage that the metal can provide electrostatic binding to polar substituents on the substrate in addition to the primarily hydrophobic interactions [69]. 

Crown compounds having cyclophane-skeletons and called crownophanes , are reviewed. They form characteristic host-guest complexes due to their crown-cyclophane hybrid structures. Significant stabilization of complexes is often reported through the ion-dipole, cation-aromatic n-electron and n-n stacking interactions, size-and-shape complementarity, and hydrophobic interaction. 

For binding to occur, a host must possess suitable binding sites with favourable electronic properties such as polarity and hydrogen bond donor/acceptor abilities that complement those of the guest. Cyclophanes such as I, calixarenes II, homocalixarenes IH, and resor-cinarenes FV fulfil these requirements (Scheme 12.1). Cucurbiturils V are water soluble container molecules without aromatic subunits. Therefore, both electrostatic interaction other than cation- r interaction and hydrophobic interaction play a dominant role. 

With water as solvent, hydrophobic interactions can be used to drive complex formation. Cyclodextrins were widely used to study hydrophobic binding, and they often show enantioselectivity. However, strong enantiodiscrim-ination is rare, especially for less-functionalized substrates. synthetic water-soluble receptors gave similar results. For example, cyclophane 65 bound the enantiomers of menthol 66 in the ratio 5 4. - while macrocycle 67 bound Naproxen derivatives 68 in D20/Me0H (60 40) with 1.9 ] enantioselectivity. " ... 

Organic compounds usually have hydrophobic moieties, and therefore, hosts capable of forming complexes with organic guests by hydrophobic interactions are extremely attractive. Earlier studies on cyclophanes such as 1 [2] and 2 [3] have suggested that they form inclusion complexes with hydrophobic guests in aqueous solution. 

Key words. Cyclophane, pyridoxal-5 -phosphate, Schiff-base, vitamin B, hydrophobic interaction,... 

Hydrophobic effects arise from the exclusion of non-polar groups or molecules from aqueous solution. This situation is more energetically favourable because water molecules interact with themselves or with other polar groups or molecules preferentially. This phenomenon can be observed between dichloromethane and water which are immiscible. The organic solvent is forced away as the intersolvent interactions between the water molecules themselves are more favourable than the hole created by the dichloromethane. Hydrophobic interactions play an important role in some supramolecular chemistry, for example, the binding of organic molecules by cyclophanes and cyclodextrins in water (see Chapter 2, Sections 2.7.1 and 2.7.5, respectively). Hydrophobic effects can be split into two energetic components, namely an enthalpic hydrophobic effect and an entropic hydrophobic effect. 

Pseudopolyrotaxanes incorporating cycloalkanes [35], CDs [36,37], cyclourethanes [38], cyclophanes [39], and crown ethers [29] have all been prepared following route D. Hydrophobic interactions assist [40] the threading of a-cyclodextrin (a-CD) (64) onto polyamine 72 in aqueous... 

There are several types of natural and synthetic molecular hosts, such as cyclodextrin and cyclophane, that are shaped to accommodate neutral and charged organic molecules in the three-dimensional cavity. The inclusion complexation by molecular hosts is driven by various weak forces like van der Waals, hydrophobic, hydrogen bonding, ion-dipole, and dipole-dipole interactions, and therefore the molecular recognition process seems much more complicated. In expanding the scope of the present theory, it is intriguing and inevitable to perform the extrather-... 

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... 

In order to construct a hydrophobic three-dimensional cavity that is in-tramolecularly limited in space, we have prepared cage-type cyclophanes by linking macrocyclic rings. First we prepared a macropolycyclic host, which is constructed with two rigid macrocyclic skeletons of different size, tetraaza[3.3.3.3]paracyclophane as the larger one and tetraazacyclotetradecane as the smaller one, and four flexible hydrocarbon chains that connect the two macrocycles [40]. The flexibility of four hydrocarbon chains connecting the two macrocycles allows the induced-fit host-guest interaction in aqueous media. 

The cage-type peptide cyclophanes (7 and 8) exhibit discrimination toward steroid hormones, as effected by hydrophobic and n-n interactions. In addition, the chirality-based discrimination between a- and -estradiol as well as between D- and L-amino acids bearing an aromatic moiety is performed on the basis of their capacity of forming efficient hydrogen bonding with the host molecules in aqueous media [41, 43]. 

The monophthalocyanines 106 and 107 show a weak aggregation tendency in chloroform. The latter has a self-dimerization constant of 1,175 M-1. By contrast, the donor-acceptor bis(phthalocyanine) 99 exhibits a much stronger aggregation tendency with a dimerization constant of 1.1 x 106 M-1 in chloroform. It is believed that in addition to the hydrophobic effect, the two phthalocyanine halves of compound 99 may be considered as donor and acceptor subunits that interact with each other. As revealed by electron microscopy, 99 forms one-dimensional nanoaggregates through intermolecular interactions between its complementary donor and acceptor phthalocyanine units as shown in Fig. 8. The dimerization constant of 99 is about one order of magnitude lower than that observed for the hetero-dimerization of 106 and 107, which may be due to the cyclophane step that hinders the formation of columnar aggregates of double phthalocyanine dimer. 

The problem of binding purely covalent substrates is expectedly difficult because of the lack of centers capable of providing a strong electrostatic attraction. For these compounds it is necessary to elaborate receptors able to bind substrates effectively via van der Waals interactions, which are much weaker than the Coulomb forces operating in the previously mentioned complexes. A set of models designed for this purpose is shown in Scheme 4.68. Cyclophanes of the general formula 226 have been synthesized as hosts for aromatic hydrocarbons. The presence of a hydrophobic cavity of... 

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