Cyclophanes hydrophobic effects

Nitrogen-bearing cyclophanes like 351 [16] and 352 [17] bind larger organic anions in water due to superposition of the hydrophobic effect and electrostatic attraction. The phenanthridinium hosts like 351 have been found to form the most stable nucleotide complexes known so far. On the other hand, free tetrapyrrolic porphyrins do not bind anions since their cavity is too small to take advantage of the convergent N-H dipoles for the complex stabilization [18]. However, expanded diprotonated porphyrins like sapphyrin 353 were shown to form stable complexes with phosphate [19a] and halide [19b] anions. 

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... 

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. 

Murakami et al. [19] developed an additional vitamin B6 model system with a binding site. They synthesized an octopus cyclophane (27) as a functional model of the protein matrix of transaminase. This cyclophane formed a hydrophobic cavity in water where PLP could be noncovalendy incorporated. Alkylamines having various hydro-phobic chains were employed as substrates, in place of a-amino adds, to evaluate the hydrophobic effect on the Schiff base-forming equilibrium. The Schiff base formation constant was found to depend markedly on the chain length of a substrate in the presence of 27, indicating that the octopus cyclophane can be utilized as an effective ho-loenzyme model capable of forming a ternary complex. 

The tightly bonded inclusion complexes in aqueous solution, between aromatic and aliphatic guests (steroids, among others) and cyclophane receptors with tetra-oxa[ .l.n.l]paracyclophanes and quaternary ammonium cyclophanes is entropically unfavorable and strongly enthalpically driven. The thermodynamic characteristics of tight inclusion complexes differ from those measured for weak apolar association processes, which are characterized by small enthalpic changes and favorable entropic terms. This is the usual interpretation of the so-called hydrophobic effect. 

Cyclophanes Endoacidic, Endobasic, and Endolipophilic Cavities, p. 424 Hydrogen Bonding, p. 658 Hydrophobic Effects, p. 673... 

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. 

We stated that an advantage of cyclophanes and other models is that they allow more detailed dissection of the structural features that promote molecular recognition. Let s examine a couple of cyclophane studies in detail—first, one that again accentuates how complex the hydrophobic effect really is. Figure 4.11 shows the results of a study to determine AH° and AS° for the association reaction of the cyclophane given in Eq. 4.36 and methylquin-... 

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 cage-type cyclophane furnishes a hydrophobic internal cavity for inclusion of guest molecules and exercises marked chiral discrimination in aqueous media. The host embedded in the bilayer membrane is capable of performing effective molecular recognition as an artificial cell-surface receptor to an extent comparable to that demonstarated by the host alone in aqueous media. 

The medium may have a marked effect on the shape of receptor molecules itself. Shape modifications could strongly influence their substrate binding properties, for instance in the case of amphiphilic cyclophane receptors subjected to hydrophobic-hydrophilic factors in aqueous solution. Such medium effects in action are visualized by the solid state structures of two different forms of the water-soluble hexasodium salt of the macrobicyclic cyclophane 66, which could be crystallized in two very different shapes an inflated cage structure 71 building up cylinders disposed in a hexagonal array and a flattened structure 72 stacked in molecular layers separated by aqueous layers in a lamellar arrangement [4.73]. These two... 

A number of studies have made use of functionalized cyclophanes for developing supramolecular catalysts and enzyme models [4.31-4.34, 5.37, 5.38]. Their catalytic behaviour is based on the implementation of electrostatic, hydrophobic and metal coordination features for effecting various reactions in aqueous media. 

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... 

Abstract. The inclusion behavior of the octopus cyclophane constructed with a rigid macrocyclic skeleton and eight hydrocarbon chains was studied in aqueous media by means of fluorescence and electronic absorption spectroscopy. Both hydrophobic and electrostatic interactions came into effect in the host-guest complexation process. The cyclophane acted as an effective apoenzyme model for constitution of an artificial vitamin B -dependent holoenzyme by simultaneous incorporation of pyridoxal-5 -phos-phate and a hydrophobic alkylammonium substrate into the host cavity to give the Schiff-base species, showing the substrate selectivity. 

In conclusion, it became clear that the octopus cyclophane can be utilized as an effective apoenzyme model for constitution of an artificial vitamin B -dependent holoenzyme. The ternary complex is formed with 1, PLP, and a substrate in the initial reaction stage, and then the latter two species bound to 1 undergo Schiff-base formation. Molecular recognition is exercised by the octopus cyclophane in favor of hydrophobic substrates. 

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