Proton cryptates

The kinetics of formation and dissociation of the Ca2+, Sr2+ and Ba2+ complexes of the mono- and di-benzo-substituted forms of 2.2.2, namely (214) and (285), have been studied in water (Bemtgen et al., 1984). The introduction of the benzene rings causes a progressive drop in the formation rates the dissociation rate for the Ca2+ complex remains almost constant while those for the Sr2+ and Ba2+ complexes increase. All complexes undergo first-order, proton-catalyzed dissociation with 0bs — kd + /ch[H+]. The relative degree of acid catalysis increases in the order Ba2+ < Sr2+ < Ca2+ for a given ligand. The ability of the cryptate to achieve a conformation which is accessible to proton attack appears to be inversely proportional to the size of the complexed metal cation in these cases. 

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 hexaethylenetetraamine 12 has been created as a proton cryptate and proven by its X-ray structure<99ACIE956>. Related but larger macrocyclic cages have been formed in order to encapsulate metal ions<99ACIE959>. 

Proton cryptates are obtained by internal protonation, the cavity concealing the protons very efficiently especially in the case of the protonated forms 11 and 12 of the smaller cryptand 6 [2.29,2.30]. 

The remarkable protonation features of 21 led to the formulation of the diproto-nated species as the water cryptate, [H20 cr 21, 2H+] 25, in which the water molecule accepts two +N-H---0 bonds from the protonated nitrogens and donates two 0-H---N bonds to the unprotonated ones [2.17, 2.96], The second protonation of 21 is facilitated by the substrate it represents a positive cooperativity effect, mediated by H20, in which the first proton and the effector molecule water set the stage both structurally and energetically for the fixation of a second proton. When 21 is tetraprotonated it forms the chloride cryptate cryptate [Cl c 21,4H+] 26, in which the included anion is bound by four +N-H---X- hydrogen bonds [2.97] (see also Chapt. 3). 

Spherical recognition of halide ions is displayed by protonated macropolycyclic polyamines. Thus, macrobicyclic diamines yield katapinates [3.9]. Anion cryptates are formed by the protonated macrobicyclic 16-6H+ [2.52] and macrotricyclic 21-4H+ [2.97] polyamines, with preferential binding of F and Cl- respectively in an octahedral and in a tetrahedral array of hydrogen bonds. 

Figure 4.20 19F NMR spectrum of 4.44- (n-Bu)4N+F 0.5 1 after heating at 150 °C for 1 h in DMSO-c/6 followed by storage at 25 °C for 10 d. The resonances from left to right correspond to anion cryptates with respectively 0, 1, 2, 3, 4, 5 and 6 NH protons replaced by deuterium. The observed multiplicity follows the standard formula multiplicity = 2n/+ 1 where n is the number of H nuclei remaining and /is the nuclear spin quantum number of H, i.e. xh. (Reproduced with permission from [38] 2004 American Chemical Society).

Menif, R. Reibenspies, J. Martell, A. E. Synthesis, protonation constants, and copper(II) and cobalt(II) binding constants of a new octaaza macrobicylic cryptand (MX)3crystal structures of the cryptand and of the carbonato-bridged dinuclear copper(II) cryptate, Inorg. Chem. 1991, 30, 3446-3454. 

Earlier discussion [12] of the structures of protonated cryptand/oxoanion assemblies was based on consideration of H-bonds between the encapsulated anion and the NH+ donors of the ciyptand. These interactions are assumed to be responsible for retention of the guest anion in the host ciyptand cavity, both in the sohd state and in solution. We have shown that, in all cases, anion cryptates exhibit at least three, and often more, direct H-bond NH+-Oanion contacts tethering the included oxoanion within the crypt. 

Diaza[12]coronand-4 (21) was condensed with diethylene glycol bismesylate 22 in the presence of butyllithium. Precipitation, occuring during the reaction course, afforded the proton cryptate 24 H+ c= [1.1.1] in 40% yield. It should be noted that [1.1.1] was obtained only in 10% yield via the high-dilution method 23). Lithium promoted cyclization was excluded (as an alternative mechanism) by an additional experiment in which KH served as a base instead of BuLi. Identical yield was achieved, indicating that intramolecular hydrogen bonding was responsible of the cyclization. 

A derivative of the (bpy.bpy.bpy) cryptand, obtained by modifying one of the chains, Lbpy, forms a di-protonated cryptate with EuCb in water at acidic pH, [EuCl3(H2Lbpy)]2+ in which the metal ion is coordinated to the four bipyridyl and two bridgehead nitrogen atoms, and to the three chlorine ions (Fig. 4.25). The polyamine chain is not involved in the metal ion coordination, due to the binding of the two acidic protons within this triamine subunit. In solution, when chlorides are replaced by perchlorate ions, two water molecules coordinate onto the Eu(III) ion at low pH and one at neutral pH, a pH at which de-protonation of the amine chain occurs, allowing it to coordinate to the metal ion. As a result, the intensity of the luminescence emitted by Eu(III) is pH dependent since water molecules deactivate the metal ion in a non-radiative way. Henceforth, this system can be used as a pH sensor. Several other europium cryptates have been developed as luminescent labels for microscopy. 

Fig. 4.25. Structure of the protonated cryptate [EuCl3(H2L)]2+. Redrawn from C. Bazzicalupi et al., Chem.

---