Cryptates stability

Troxler and Wipff determined conformational preferences of free ligands and solvation patterns of the host-guest complexes for cryptand 222 and their metal cation complexes in acetonitrile. The calculations were carried out with the AMBER force field and also with Aqvist s ion parameters the two sets of results were then compared. When AMBER was used, the relative order of cryptate stabilities and the recognition ability of the cryptand 222 to select K from among Li, Na, Rb, and Cs cations were in qualitative agreement with experimental data. The results obtained with Aqvist s parameters were comparable to or better than those obtained with the AMBER force field. In general, complexes of alkali cations and cryptand 222 are more stable in nonaqueous solvents such as acetonitrile than in water, in part because of the reduced energy cost for cation desolvation upon complexation.i -i i... 

Cryptate stability and lability vary substantially with the nature of M+ and cryptand as is exemplified by the data obtained in dimethyl-formamide shown in Table 1. It is also found that cryptate stability and lability are considerably affected by the nature of the solvent as is exemplified by the [Na.C2IC5] " data in Table 2. 

The stability of cryptate complexes. The cage topology of the cryptands results in them yielding complexes with considerably enhanced stabilities relative to the corresponding crown species. Thus the K+ complex of 2.2.2 is 105 times more stable than the complex of the corresponding diaza-crown derivative - such enhancement has been designated by Lehn to reflect the operation of the cryptate effect this effect may be considered to be a special case of the macrocyclic effect mentioned previously. 

The dissociation rates for a number of alkali metal cryptates have been obtained in methanol and the values combined with measured stability constants to yield the corresponding formation rates. The latter increase monotonically with increasing cation size (with cryptand selectivity for these ions being reflected entirely in the dissociation rates - see later) (Cox, Schneider Stroka, 1978). 

In water, the relatively low stability of the alkali metal and alkaline earth cryptates (except those for which there is a near-optimal fit of the cation in the intramolecular cavity) has resulted in difficulties in undertaking a wide-ranging kinetic study in this solvent. However, in non-aqueous media, the stability constants are larger and most of the studies have been performed in such media. 

Rate constants for reaction of Ca2+aq with macrocycles and with cryptands (281,282,291) reflect the need for conformational changes, considerably more difficult for cryptands than for crown ethers, which may be considerably slower than formation of the first Ca2+-ligand bond. Ca2+aq reacts with crown ethers such as 18-crown-6 with rate constants of the order of 5 x 107M 1 s, with diaza crown ethers more slowly (286,326). The more demanding cryptands complex Ca2+ more slowly than crown ethers (kfslow reaction for cryptands with benzene rings fused to the macrocycle. The dominance of kA over kt in determining stability constants is well illustrated by the cryptates included in Table X. Whereas for formation of the [2,1,1], [2,2,1], and [2,2,2] cryptates kf values increase in order smoothly and gently, the k( sequence Ca[2,l,l]2+ Ca[2,2,l]2+ Ca[2,2,2]2+ determines the very marked preference of Ca2+ for the cryptand [2,2,1] (290). 

Kinetics of H+-promoted dissociation of the Ni2+ complex of a tetra-dentate aza-oxa-cryptate derived from tren, conducted in acidic aqueous acetonitrile, indicate that its dissociation rate is smaller than that of [Ni(tren)(H20)2]2+, despite the much higher thermodynamic stability of the tren complex a kinetic cryptate effect is invoked to rationalize this (288). 

The study of Lehn s cryptands has shown that a three-dimensional arrangement of binding sites leads to very stable inclusion complexes (cryptates) with many cations. For example, the stability constant for K+ in methanol/water (95/5) is five orders of magnitude higher with [2.2.2]-cryptand [37] (log K 9.75 Lehn and Sauvage, 1975) than with [2.2]-cryptand [38] (log... 

The proportion of the /rans-O-alkylated product [101] increases in the order no ligand < 18-crown-6 < [2.2.2]-cryptand. This difference was attributed to the fact that the enolate anion in a crown-ether complex is still capable of interacting with the cation, which stabilizes conformation [96]. For the cryptate, however, cation-anion interactions are less likely and electrostatic repulsion will force the anion to adopt conformation [99], which is the same as that of the free anion in DMSO. This explanation was substantiated by the fact that the anion was found to have structure [96] in the solid state of the potassium acetoacetate complex of 18-crown-6 (Cambillau et al., 1978). Using 23Na NMR, Cornelis et al. (1978) have recently concluded that the active nucleophilic species is the ion pair formed between 18-crown-6 and sodium ethyl acetoacetate, in which Na+ is co-ordinated to both the anion and the ligand. 

For potassium zeolites, cryptofix 222 and cryptofix 222BB, for example, can be used. The structures together with the stability constants Ks of the complexes (cryptates) of cryptofix 222 and cryptofix 222BB with potassium are shown in... 

Table 2 Structures of Potassium Selective Cryptands Cryptofix 222 and Cryptofix 222BB and the Stability Constants of the Matching Cryptates...

As the results make immediately clear (Tables 7—10), it is among ligands of the macrobicyclic type G (27—44), which give complexes of the [2]-cryptate type, that by far the highest stability constants may be found for any cation. In particular, these optimum Ks values are several decades higher than those of the most stable complexes formed by natural ligands,... 

Much more pronounced is the macrocyclic or [l]-cryptate effect found in 10 as compared with 2 the stability constant for K+ complexation increases by about 104 (in methanol) on ring formation. A similar increase has been observed between copper-(II) complexes of acyclic and macro-cyclic tetra-aza ligands (139). 

Finally, a macrobicyclic or [2]-cryptate effect is found by comparing the stability of the K+ complex of 30 with that of 22, where the solvation shell is completed by solvent molecules (a better model would be a ligand of type 22 bearing a — CH2CH2OCH2CH2OCH3 chain on one nitrogen) a stability increase of more than 105 (in methanol/water, 95/5) is found on introduction of the third bridge. 

Comparing ligands 22 and 38 which contain the same number of binding sites, we note that the special complexation features of 38 result from the cryptate nature of its complexes. Indeed, whereas in complexes of 22 polar solvent molecules may approach the cation from top and bottom, it is much more shielded in complexes of 38. This difference in behaviour is reflected in the corresponding change in ligand thickness (Table 12). The results in Table 11 also display the expected decrease in M2+/M+ stability ratio as the dielectric constant decreases from water to methanol. 

Table 4. Stability constants for the complexes of macroheterobicyclic ligands (cryptates) in aqueous solution (see Lehn et al. (42, 43))... 

Cryptands, 42 122-124, 46 175 nomenclature, 27 2-3 topological requirements, 27 3-4 Cryptate, see also Macrobicyclic cryptate 12.2.2], 27 7-10 applications of, 27 19-22 cylindrical dinuclear, 27 18-19 kinetics of formation in water, 27 14, 15 nomenclature, 27 2-3 spherical, 27 18 stability constants, 27 16, 17 Crystal faces, effect, ionic crystals, in water, 39 416... 

Macrobicyclic cryptate cation selectivity, 27 16-17 complex stability, 27 14-15 kinetic studies, 27 13-14... 

As stated above, systematic names of macrocyclic host molecules were absurdly complicated for routine discussions [22]. Therefore Vogtle proposed the name coronand for crown ethers, and that of coronates for their complexes while cryptand complexes were called cryptates . The corresponding noncyclic analogues are podands such as 64 [23] and podates, respectively. The cumbersome name podando-coronands (and correspondingly podando-coronates ) was proposed for lariat ethers [24] having at least one sidearm like 65. Examples of hemispherands 66 [25], cavitands 25 [26] and those of some other hosts are discussed in Chapter 7 in some detail, whilst the exceptional stability of fragile guests 4 [2a] and 67 [27] in the hemicarcerand 5 cavity are discussed in Chapters 1 and Section 7.3. 

Macropolycyclic ligands containing intramolecular cavities of a three-dimensional nature are referred to as cryptands. The bicyclic cryptands (73) exist in three conformations with respect to the terminal nitrogen atoms, exo-exo, endo-exo and endo-endo 6 these forms can rapidly interconvert via nitrogen inversion but only the endo-endo form has been found in the crystal structures of a variety of complexes372 and for the free ligand ([2.2.2], 73, m = n = / = l).449 In their complexes with alkali and alkaline earth cations, the cryptands exhibit an enhanced stability over the crown ethers and coronands dufe to the macrobicyclic, or cryptate, effect.33 202... 

---