A Cylindrical Capsule

It was not until we had in hand a nonspherical (or more specifically, a cylindrical) capsule that additional mles governing coencapsulated molecules emerged. On the table with the tennis ball and softball, this capsule would resemble a can for three tennis balls and it has been used to demonstrate many features of molecules at close range. The synthesis and various renderings of this capsule s structure are shown in Fig. 7.4, and our initial experiments in filling its space showed the preferential encapsulation of two different molecules [5]. 

An extreme example, involving a large and small combination, is shown with anthracene and methane in Fig. 7.5. Neither molecule alone is encapsulated but when both are present, the capsule takes up exactly one of each. 

---

Fig. 46 The formation of a cylindrical capsule and its energy minimised structure containing two toluene guest molecules. Reprinted with permission from [131]. Copyright 2002 American Chemical Society...

Iodine-125 sources. Iodine-125 is widely used for permanent implants in radiotherapy. The encapsulation consists of a 0.05 mm thick titanium tube welded at both ends to form a cylindrical capsule of dimensions 4.5 x 0.8 mm. Iodine-125 decays exclusively by electron capture to an excited state of Technetium-125, which then emits a 35.5 keV photon. Characteristic x-rays in the range of 27 to 35 keV also are produced due to the electron capture and internal conversion processes. 

Figure 6.2 a) Cylindrical capsule A. b) Softball capsule B. In the modelled structures some substituents, hydrogen atoms and hydrogen bonds have been omitted for clarity. Reproduced with permission from 12 /] Copyright 2002 Wiley-VCH Verlag GmbH ... 

Shivanyuk A, Rebek J (2002) The inner solvation of a cylindrical capsule. Chem Commun 20 2326-2327... 

Palmer LC, Zhao Y-L, Houk KN, Rebek J Jr (2005) Diastereoselection of chiral acids in a cylindrical capsule. Chem Commun 29 3667-3669... 

Barrett ES, Dale TJ, Jr. Rebek J (2007) Self-assembly dynamics of a cylindrical capsule monitored by fluorescence resonance energy transfer. J Am Chem Soc 129(28) 8818-8824... 

F. 7.4 Left Stmcture of a cylindrical capsule. The peripheral alkyl groups, R = C11H23, are not shown but impart solubility in organic solvents. Center The space available inside the capsule is a tapered cavity with a volume of 425 A. Right A belt of eight bifurcated hydrogen bonds holds the capsule together... 

Pirt [16] described a diffusion capsule for the addition of a solute at a constant rate to a liquid medium. The diffusion capsule consists of a small cylindrical container that can be completely filled with solution and then sealed with a small semipermeable membrane at one end. The device was designed for obtaining the low substrate feed rates required for multiple cultures of microbes. 

T. Heinz, D.M. Rudkevich, J. Rebek, Jr, Pairwise selection of guests in a cylindrical molecular capsule of nanometre dimensions , Nature 1998, 394,764-766. 

For these tests, Clark placed a small charge of HE in a No 8 detonator shell and pressed it under a reinforcing capsule at 3400 psi. The detonator was placed centrally in a cylindrical oaken shield, with its long axis parallel to and... 

However, great care must be taken in choosing an appropriate sample holder and a suitable sample geometry.9 Cylindrical capsules machined from high-purity PTFE, enclosed in long polyethylene straws, allow the measurement of compressed polycrystalline samples or even solutions. Polycrystalline samples need to be pulverized so that preferential orientation can be avoided. The sample should be placed into a cylindrically shaped sample holder. Air-sensitive compounds can be sealed in small tubes from synthetic quartz glass. The field- and temperature-dependent contribution of the sample holder must be known precisely. 

Fig. 15 Homodimeric cylindrical capsule held together by means of a seam of 16 hydrogen bonds. R groups have been removed for clarity...

Coencapsulation is a process that limits the space provided to trapped guests and obliges them to sense reciprocally simply because they cannot avoid each other. Chirality is a feature related to the spatial distribution of objects, therefore any symmetric closed space becomes chiral if a chiral object is placed in it (Fig. 27A). This simple concept is then applied to spherical and cylindrical capsules in both cases the correct orientation of two chiral guests is necessary to allow interactions between the asymmetric centers of the two partners. In... 

Fig. 28 Hydrocarbon encapsulation in the achiral cylindrical capsule occurs forcing the guest to assume a helical conformation in order to fit the available space...

The easiest combination of two chiral guests in the cylindrical capsule comes by the double encapsulation of racemic species with adequate size, shape and polarity to be accommodated in pairs, giving two diastereoisomeric complexes, the homochiral couple (R) - (R)/(S) - (S) and the heterochiral (R) -(S) combination. ( )-trans-1,2-Cyclohcxancdiol has all the above requisites and showed a 1.2 ratio between the two complexes in favor of the heterochiral combination [60]. This observation may be related to the preference in nature for centrosymmetric crystals or, alternatively stated, the higher melting points of racemates vs. enantiopure compounds where the resolution is driven by the less soluble pair [61,62], In the cylindrical capsule a single couple of chiral molecules is extrapolated from the bulk and the interactions between the two is governed by the shape of the cavity and their goodness of fit within the cavity. 

Fig. 29 Coencapsulation of three chiral molecules into an achiral cylindrical capsule leads to the formation of three racemic diastereoisomeric complexes. Their reciprocal ratio is a function of the enantiopurity of the guest...

We also devised a system that uses acid/base control of expansion and contraction of the capsules and their guests. A number of studies with the cylindrical capsule defined its application as a reaction vessel [77,78] but the conformational flexibility [79] of normal alkanes as guests (which adopt shapes complementary to their hosts) offered an opportunity to create what we termed a spring-loaded device. 

Due to the liquid state of the silicone prepolymer, silicone polymers are prepared as preformed sheets and tubing or any other shape by first mixing the drug with the silicone polymer and a catalyst (e.g., stannous octoate). Then, the mixture is cast as a sheet or in a mold followed by curing overnight. For example, Norplant is a set of flexible, closed cylindrical capsules (2.4 x 34 mm) of Silastic silicone polymer containing levonorgestrel for fertility control for 5 years. The capsules are inserted under the skin of the upper arm. 

---