Octopus cyclophane

Fig. 3A-C. Space-filling models of artificial receptors, each being capable of providing a large hydrophobic cavity A octopus cyclophane 4 B steroid cyclophane 6 C cage-type cyclophane 8...

Unique inclusion behavior in reflection of the induced-fit binding mechanism is observed when an organic stock solution of octopus cyclophane 3 is injected into an aqueous medium containing ANS for the host-guest complexation study [17], A circular dichroism (CD) spectrum does not undergo any change for 3 upon complexation with ANS, indicating that the conformation around l-... 

Formation of the hybrid assemblies of peptide lipid 9 with the octopus cyclophanes (3 and 4) and the steroid cyclophanes (5 and 6) was also character-... 

Each of the hybrid systems, composed of steroid cyclophane 6 and octopus cyclophanes 3 and 4 in combination with lipid 9, also exhibits effective guestbinding in comparison with the cyclophane-free system as reflected in the fluorescence features of ANS and TNS, which are similar to those shown in Fig. 6. On the other hand, the hybrid assembly formed with a steroid derivative, the monomeric analogue of 5 with respect to the steroid fragment, and lipid 9 in a molar ratio of 1 10 does not enhance the fluorescence intensities of the guests to any significant extent. 

The steroid cyclophanes provide less polar microenvironments for ANS and TNS by forming the hybrid assemblies with the peptide lipid. To our surprise, the microenvironment around the ANS molecule incorporated into the hybrid assembly formed with lipid 9 and steroid cyclophane 5 is equivalent to that provided by hexane ( = 0.009). In contrast, the microscopic polarity experienced by TNS in the identical hybrid assembly is as polar as 1-pentanol ( = 0.568). On the other hand, the hybrid assembly formed with lipid 9 and steroid cyclophane 6 binds the TNS molecule in a less polar microenvironment than ANS. Meanwhile, both of the octopus cyclophanes and their hybrid assemblies formed with the peptide lipid incorporate both guest molecules into the comparable binding sites with respect to the microenvironmental polarity. 

The hydrophobic cavity provided by the octopus cyclophane is significantly flexible, and capable of performing molecular recognition toward hydrophobic guest molecules of various bulkiness through the induced-fit mechanism, not only in aqueous solution but in the bilayer membrane formed with a synthetic peptide lipid. However, such a flexible hydrophobic cavity seems to be unfavorable for size-sensitive molecular discrimination. 

The steroid cyclophane also provides a sizable and well-desolvated hydro-phobic cavity in aqueous media in a manner as observed for the octopus cyclophane. The molecular recognition ability of the steroid cyclophane is inferior to that of the octopus cyclophane in aqueous solution due to the structural rigidity of steroid segments of the former host. When the steroid cyclophane is embedded in the bilayer membrane to form a hybrid assembly, however, the steroid cyclophane becomes superior to the octopus cyclophane with respect to functions as an artificial cell-surface receptor, performing marked guest discrimination. 

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 azacyclophane 18 is built according to the same general pattern which has been successfully applied in the construction of esterolytic octopus-like molecular catalysts The design features and catalytic properties of functionalized octopus cyclophanes 22 and related structures have been reviewed in depth recently... 

Fig. 3 An example of artificial holoenzyme formed with the octopus cyclophane (6) and the hydrophobic vitamin derivative (7).

Murakami, Y. Kikuchi, J. Ohno, T. Hayashida, O. Kojima, M. Syntheses of macrocyclic enzyme models. 7. Octopus cyclophanes having L-aspartate residues as novel water-soluble hosts. Aggregation behavior and induced-fit molecular recognition. J. Am. Chem. Soc. 1990.112 (21). 7672-7681. 

Molecular Recognition of Hydrophobic Ammonium Substrates by a Cationic Octopus Cyclophane Bearing Noncovalently Bound Pyridoxal-5 -phosphate ... 

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 order to get further insight into the inclusion behavior of the octopus cyclophane, we now prepared a new water-soluble octopus cyclophane and studied its guest-binding behavior for constitution of a vitamin B -dependent holoenzyme model. 

Upon addition of the amine (AA) to the aqueous solution containing 1 and PLP, the extent of the Schiff-base (SB) formation was monitored by electronic absorption spectroscopy. A typical example of the spectral change is shown in Figure 1. Clear isosbestic points were observed for all the measurements. The apparent SB formation constants ( sb) defined by equation (1) were evaluated according to the Benesi-Hildebrand relationship in a manner that has been reported elsewhere [6]. The Ksb values in the absence of the octopus cyclophane were also evaluated. The... 

As is apparent from Figure 1, SB shows two absorption bands with maxima at 400 and 318 nm, which are assigned to two tautomeric isomers, C and D in Scheme 2, respectively [7]. Since the relative intensities of these bands sensitively vary depending on the medium polarity, the microenvironmental polarity provided by the octopus cyclophane can be estimated. Figure 2 shows electronic absorption spectra of the SB species formed with PLP and octylamine in the presence and absence of 1, While SB is present exclusively in form C in an aqueous phase, form D is remarkably favored in the presence of 1 the microenvironmental polarity in the cavity of 1 is roughly equivalent to that provided by 2-propanol. Accordingly, it is apparent that PLP bound to the hydrophilic site of the octopus cyclophane moves into a more hydrophobic domain of the host molecule via formation of SB with the hydrophobic alkylammonium substrate as schematically illustrated in Figure 3. 

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. 

Fig. 3. Schematic representation for hydrophobic incorporation of the PLP Schiff-base into the octopus cyclophane.

Murakami, Y., J. Kikuchi, and O. Hayashida - Molecular recognition of hydrophobic ammonium substrates by a cationic octopus cyclophane bearing noncovalently bound pyridoxal-5 -phosphate a vitamin Bg-dependent holo iZ3mie model 91... 

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