Spherands

The AMBER-based approach used to model cyclic polyethers and cryptands has also been applied to the study of the Li+, Na+, and K+ complexes of three spherands (Fig. 14.3)12641. Experimentally determined metal ion selectivities were successfully reproduced. A similar AMBER-based model, used for molecular mechanics and dynamics of a cyclic urea-based spherand, was also successful in reproducing its metal ion selectivity12651. A number of new conformations of the spherand, including the global energy minimum, were located using molecular dynamics12651. 

These macrocycles show the highest stability constants known for certain alkali metal ions, and remarkable selectivity. For example, when the ionic diameter (1) for the guest metal cations becomes too large for the preformed cavity no complexation occurs. The three spherands (84)-(86) bind only Na and Li no binding to could be detected (81). This behaviour is in contrast to that of crowns and cryptands in which size-related peak selectivity is found. 

Semi-rigid hemispherands (81,82) have also been recently synthesized which 

These host molecules exhibit very high stability constants for alkali metal ions and are highly selective. For example, whereas the spherands (84) and (85) show Li over Na selectivity (factors of 600 and 360 respectively), impressive selectivities of Na over Li are exhibited by cryptahemispherand (89) (420000) and bridged hemispherand (91) (9500) (90) exhibits over Na selectivity of 11000. 

Caution Carry out all procedures in a well-ventilated hood, and wear disposable vinyl or latex gloves and chemical-resistant safety goggles. 

The following procedure for the synthesis of spherand 1 by dimerization of 1,1 3, 1 -terphenyl 5 is representative for this type of spherand ring closure reaction. 

All reactions should be carried out in oven-dried glassware (electric oven, 110°C, 2 h) under a nitrogen or argon atmosphere. 

Assemble a 250 mL triple-necked flask, stirrer bar, thermometer, dropping funnel and argon ballon in a solid C02-acetone bath (-78°C). 

Weigh 15 g of dry Fe(acac)3 in a 5 L triple-necked round-bottomed flask equipped with a reflux condenser. Add 1.7 L of dry benzene and reflux while vigorously stirring under argon. 

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From the kinetic point of view the facts are different and the order is reverse, ie, the rigid highly preorganized spherands are slow, as contrasted with the flexible barely preorganized podands that are fast both in formation and decomposition of the receptor—substrate (host—guest) complex (20,21). 

Fig. 7. Crown type and analogous receptor molecules of different varieties (1) crown ethers (2) cryptands (3) a podand (4) a spherand and (5) the natural...

Fig. 3. Crown compounds/cryptands and analogous inclusion hosts. (1 4) Crown macro rings bicyclic cryptands (5) [37095-49-17, (6) [31250-06-3J, (7) [31364-42-8] (8) [23978-09-8]-, (9) spherical cryptand [56698-26-1]-, (10) cylindrical cryptand [42133-16-4]-, (11) apodand [57310-75-5]-, and (12) a spherand...

Inclusions of Other Grown Analogues. A variety of crown analogues and hybrid modifications (24—28) with other topological features (lariat ethers (31,32), octopus molecules (33), spherands (eg, (12) (34), torands (35)) including chiral derivatives (36) have been prepared and demonstrated to show particular inclusion properties such as chiroselective inclusion (Fig. 4) (37) or formation of extremely stable complexes (K ">(LR) for (12)... 

The spherand prepared by Cram and coworkers was designed to have a relatively small molecular cavity and appeared to prefer complexation with Li and Na over larger cations like K", Rb, etc. Tlie spheroidal cryptand prepared by Lehn ° involved strategy employed previously but the spherand 24 was prepared by quite a different approach. 

Chapter 8 Macrobicyclic, macrotricyclic, or polycyclic compounds including crypt-ands, spherands, etc. 

X 10 forNa+,2.8 X 10 for, and 1.3 x 10 for Li These constants were of a magnitude that persuaded the authors to liken the binding properties of these calixar-enes to cryptands and spherands. 

The problem of molecular recognition has attracted biologically oriented chemists since Emil Fischer s lock-and-key theory l0). Within the last two decades, many model compounds have been developed micelle-forming detergents11, modified cyclodextrins 12), many kinds of crown-type compounds13) including podands, coronands, cryptands, and spherands. Very extensive studies using these compounds have, however, not been made from a point of view of whether or not shape similarity affects the discrimination. 

Sensitization of ArNJ in spectroscopy 280 f. Serendipity, in scientific discoveries 213,217 ff. Silver halide photography 283 Spherands 294 f. 

Cyclophanes or 7r-spherands have played a central role in the development of supramolecular chemistry forming an important class of organic host molecules for the inclusion of metal ions or organic molecules via n-n interactions. Particular examples are provided by their applications in synthesis [80], in the development of molecular sensors [81], and the development of cavities adequate for molecular reactions with possible applications in catalysis [82]. The classical organic synthesis of cyclophanes can be quite complex [83], so that the preparation of structurally related molecules via coordination or organometallic chemistry might be an interesting alternative. 

Li" " and Na+ (preferentially Na" ), but not K", Mg or Ca. Molecules such as these, whose cavities can be occupied only by spherical entities, have been called spherands. Other types are calixarenes (e.g., 22). There is significant hydrogen bonding involving the phenolic OH units in [4]calixarenes, but this diminishes as the size of the cavity increases in larger ring calixarenes. There are also calix[4]-arenes, which have been shown to have conformational isomers (see p. 167) in... 

The hemispherands, spherands, calixarenes, and related derivatives. A number of hosts for which the pre-organization criterion is half met (the hemispherands) (Cram et al., 1982) or fully met (the spherands) (Cram, Kaneda, Helgeson Lein, 1979) have been synthesized. An example of each of these is given by (251) and (252), respectively. In (251), the three methoxyl groups are conformationally constrained whereas the remaining ether donors are not fixed but can either point in or out of the ring. This system binds well to alkali metal ions such as sodium and potassium as well as to alkylammonium ions. The crystal structure of the 1 1 adduct with the f-butyl ammonium cation indicates that two linear +N-H - 0... 

It is of interest to compare the cyclodextrins with the spherands, since each consists of cyclic oligomers composed of rigid structural units such that enforced cavities result. However, they differ in that the spherands... 

Fig.9.10 Tetrahedral hosts with Td symmetry, (a) Lehn s spherand, (b) Vogtle s spheraphane, (c) Saalfrank s metal-based cage.

In addition to macrocyclic hosts discussed above, many other molecules capable of selective complexation have been synthesized. They belong to so-called macrocyclic chemistry [30] encompassing crown ethers discussed in this Chapter, cryptands 61-63 [21], spherands 70 [31], cyclic polyamines 71 [32], calixarenes 18 [5], and other cyclophane cages such as 72 [33] to name but a few. Hemicarcerand 5 [2b] discussed in Chapter 1 and Section 7.3 also belongs to this domain. Typical macrocyclic host molecules are presented in Chapter 7. 

Spherands, hemispherands, and other similar macrocycles capable of inclusion complex formation [33]... 

Figure 7.2.8. The template synthesis leading to spherand after demetallation.

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