Cavity molecular

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. 

The transition state of concerted Diels-Alder reactions has stringent regio- and stereochemical requirements and can assume settled configurations if the reaction is carried out in a molecular cavity. Cyclodextrins, porphyrin derivatives and cyclophanes are the supramolecular systems that have been most investigated. 

As an approach to biomimetic catalysis, Sanders and colleagues [67] synthesized a series of 1,1,2-linked cyclic porphyrin trimers that allow the stereo- and regiochemistry of the Diels-Alder reaction of 84 and 85 within the molecular cavity to be controlled, thereby producing prevalently or exclusively the endo 86 or the exo 87 adduct. Two examples are illustrated in Scheme 4.18. At 30 °C and in the absence of 88, the reaction furnishes a mixture of diastereoisomers, while the addition of one equivalent of trimer 88 accelerates the reaction 1000-fold and the thermodynamically more stable exo adduct 87 is the sole detectable product. 

Another type of stereoisomerism, called out-in isomerism, is found in salts of tricyclic diamines with nitrogen at the bridgeheads. In cases where k, , and m >6, the N—H bonds can be inside the molecular cavity or outside, giving rise to three isomers, as shown. Simmons and Park ° isolated several such isomers with k, I, and m varying from 6 to 10. In the 9,9,9 compound, the cavity of the in-in isomer is large enough to encapsulate a chloride ion that is hydrogen bonded to the two N—H... 

For sets nos. 1, 2, and 3 of Table XXVII, eq. (1) appears to hold for ionization of ortho substituted benzoic acids (f =. 048 —. 058), with Kj = Pi I= 1.6 . 1. This result is reasonable for field effects transmitted only throu the molecular cavity i.e., the lines of force do not pass through appreciable solvent of high dielectric constant (the solvent is presumably excluded by the close proximity of the CO2H center and the substituent) (36). It is further of interest that eq. (1) fails for the ionization of ortho substituted benzoic acids in solvents of high OH content (sets nos. 4, 5, and 6 of Table XXVII). 

An impressive achievement of this strategy has been the construction of three-dimensional structures. Utilizing branched phenylacetylene sequences, double cyclization yielded macrobicyclic arrays 54 and 55 [43]. The zenith of Moore s approach is macrotricycle 56, a freely hinged system with a sizable 36xl2xl2A molecular cavity [44]. 

E. Buhleier, W. Wehner, and F. Vogtle, Cascade - and nonskid-chain-like syntheses of molecular cavity topologies, Synthesis (1978) 155-158. 

X-ray structure of this compound shows that the ligand adopts a propeller shape. The sodium ion is contained in the molecular cavity and is coordinated to all eight nitrogen atoms (Caron et al., 1985). 

Cryptands of this type are able to exist in three isomeric forms since each of the bridgehead nitrogens may be orientated inwards or outwards with respect to the molecular cavity - the three isomers are thus in-in , in-out , and out-out . In the solid state, 2.2.2 has been shown to have an in-in arrangement (Metz, Moras Weiss, 1976). 

Metalated container molecules can be viewed as a class of compounds that have one or more active metal coordination sites anchored within or next to a molecular cavity (Fig. 2). A range of host systems is capable of forming such structures. The majority of these compounds represent macrocyclic molecules and steri-cally demanding tripod ligands, as for instance calixarenes (42), cyclodextrins (43,44), and trispyrazolylborates (45-48), respectively. In the following, selected types of metalated container molecules and their properties are briefly discussed and where appropriate the foundation papers from relevant earlier work are included. Porphyrin-based hosts and coordination cages with encapsulated metal complexes have been reviewed previously (49-53) and, therefore, only the most recent examples will be described. Thereafter, our work in this field is reported. 

Hindered proton transfer from molecular cavities 184... 

Examples of dramatic reductions in rates of proton removal are found if the acidic proton is protected within a molecular cavity and if an unfavourable conformational change is required to expose the proton to attack by base. This type of complex proton transfer is described in Section 5. 

The most dramatic rate retardations of proton transfers have been observed when the acidic or basic site is contained within a molecular cavity. The first kinetic and equilibrium studies of the protonation of such a basic site were made with large ring bicyclic diamines [72] (Simmons and Park, 1968 Park and Simmons, 1968a). It was also observed (Park and Simmons, 1968b) that chloride ion could be trapped inside the diprotonated amines. The binding of metal ions and small molecules by macrocyclic compounds is now a well-known phenomenon (Pedersen, 1967, 1978 Lehn, 1978). In the first studies of proton encapsulation, equilibrium and kinetic measurements were made with several macrobicyclic diamines [72] using an nmr technique. 

The diamines and their mono- and di-protonated ions can exist in various conformations, in which the nitrogen lone pairs and the protons on nitrogen are directed in (i or i+) or directed out (o or o+) from the molecular cavity. Diprotonated l,10-diazabicyclo[8.8.8]hexacosane, for example, may exist in either of the three forms in equation (79). When the out-out isomer of l,10-diazabicyclo[8.8.8]hexacosane bis hydrochloride (o+ o+) is dissolved in aqueous acidic solution, isomerisation to the in-in isomer (i+ i+) occurs so... 

There is considerable interest in the properties of macrobicyclic cryptands, for example [78] to [81], and particularly in their ability to complex protons, metal ions, and small molecules (Lehn, 1978). In the proton cryptates there exists the possibility of intramolecular +N—H N hydrogen bonding as well as interaction of the proton with the oxygen atoms, and the properties are also strongly influenced by the size of the molecular cavity. In the [l.l.l]-cryptand [78] the molecular cavity is small (Cheney et al., 1978) and... 

For cryptands in which the molecular cavity is larger than in the case of the [l.l.l]-species [78], proton transfer in and out of the cavity can be observed more conveniently. Proton transfer from the inside-monoprotonated cryptands [2.1.1] [79], [2.2.1] [80], and [2.2.2] [81 ] to hydroxide ion in aqueous solution has been studied by the pressure-jump technique, using the conductance change accompanying the shift in equilibrium position after a pressure jump to follow the reaction (Cox et al., 1978). The temperature-jump technique has also been used to study the reactions. If an equilibrium, such as that given in equation (80), can be coupled with the faster acid-base equilibrium of an indicator, then proton transfer from the proton cryptate to hydroxide ion... 

The reactions, with rate coefficients well below the diffusion-limited values, are thought to occur by direct proton transfer from the donor acid into the molecular cavity. The kinetic isotope effect for proton transfer was observed to vary as a function of the pX-value of HA and to pass through a maximum value kHA/kDA 4.0, the maximum occurring for a reaction with ApA" = pA (HA) — pA ([2.1.1]H22+) = ca + 1. A similar large kinetic isotope effect kHA/kDA = 3.9 was observed for protonation of the cryptand by H20 and D20 in the isotopically different solvents (Kjaer et al., 1979). 

Fig. 6 Wave-like ribbon structure of complex 18.p-xylene.l.5(DMF), where DMF=dimethyl-formamide. Guest p-xylene occupies the cavitand molecular cavity, while disordered DMF (only one position shown) occupies the cage created by pendant arms at the lower rim [39]... 

Fig. 17 Section of the helical chain structure found in (C70)(o-carborane)(CTV)(l,2-dichloro-benzene) 34 with C70 guest molecules in each CTV molecular cavity [79]... 

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