Hydrophobic effects cyclophane complexes

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. 

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. 

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 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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