Shape-, Size-, and Functional Group-Selective Binding of Small Organic Guests in a Paramagnetic Coordination Cage

Abstract

The host-guest chemistry of the octanuclear cubic coordination cage [Co(8)L(12)](16+) (where L is a bridging ligand containing two chelating pyrazolyl-pyridine units connected to a central naphthalene-1,5-diyl spacer via methylene "hinges") has been investigated in detail by (1)H NMR spectroscopy. The cage encloses a cavity of volume of ca. 400 Å(3), which is accessible through 4 Å diameter portals in the centers of the cube faces. The paramagnetism of the cage eliminates overlap of NMR signals by dispersing them over a range of ca. 200 ppm, making changes of specific signals easy to observe, and also results in large complexation-induced shifts of bound guests. The cage, in CD(3)CN solution, acts as a remarkably size- and shape-selective host for small organic guests such as coumarin (K = 78 M(-1)) and other bicyclic molecules of comparable size and shape such as isoquinoline-N-oxide (K = 2100 M(-1)). Binding arises from two independent recognition elements, which have been separately quantified. These are (i) a polar component arising from interaction of the H-bond accepting O atom of the guest with a convergent group of CH protons inside the cavity that lie close to a fac tris-chelate metal center and are therefore in a region of high electrostatic potential; and (ii) an additional component arising from the second aromatic ring (aromatic/van der Waals interactions with the interior surface of the cage and/or solvophobic interactions). The strength of the first component varies linearly with the H-bond-accepting ability of the guest; the second component is fixed at approximately 10 kJ mol(-1). We have also used (1)H-(1)H exchange spectroscopy (EXSY) experiments to analyze semiquantitatively two distinct dynamic processes, viz. movement of the guest into and out of the cavity and tumbling of the guest inside the host cavity. Depending on the size of the guest and the position of substituents, the rates of these processes can vary substantially, and the rates of processes that afford observable cross-peaks in EXSY spectra (e.g., between free and bound guest in some cases; between different conformers of a specific host·guest complex in others) can be narrowed down to a specific time window. Overall, the paramagnetism of the host cage has allowed an exceptionally detailed analysis of the kinetics and thermodynamics of its host-guest behavior.

Highly efficient catalysis of the Kemp elimination in the cavity of a cubic coordination cage

“…These pockets 5 lie at the two diagonally opposed fac tris-chelate metal sites where there is a convergent array of inwardly-directed ligand C-H atoms in regions of relatively high electrostatic potential. 37 From the structure, we can see that there are CH•••N and CH•••O hydrogen bonds between the guest and the internal surface of the cage (Fig. 4b).…”

“…Fig. 4c), 23,24,26,27,37 which would position hydroxide close to the CH of the substrate constrained in the cavity. If these sites around the cage are saturated with hydroxide ions at pD 8.5 due to the high positive charge, increasing the pD to 11.4 will not result in an increase in the local hydroxide concentration and the rate of the reaction should therefore be independent of pD in this range.…”

“…As the reaction proceeds the transition state involves a buildup of negative charge on the O atom, which could be stabilised by adjacent H-bond donors. 31,37 However, the H-bond donor pocket on the interior surface of the cage cavity is less effective at stabilising H-bond acceptor sites than is water: a carbonylcontaining guest in this pocket is actually destabilised relative to solvation by water by about 7 kJ mol -1 , 26 and the penalty must be even larger for a negatively charged transition state. The interior of the cage therefore provides a poorer medium than water for the reaction because of preferential solvation of the developing negative charge by water, and the weak binding of the product anion underlines this.…”

Binding of Hydrophobic Guests in a Coordination Cage Cavity is Driven by Liberation of “High‐Energy” Water

“…We can imagine that displacing the first water molecule from a cluster of ten, and transferring it to the bulk solution, results in a change in hydrogen‐bonding that is not the same as would arise from displacement of the fifth, or tenth, water molecule. As the guests in Scheme 1 fall within a fairly narrow size range (between 31 and 43 % of the cavity volume),11, 12 it is reasonable that the incremental effect of the extra methylene group in each pairwise comparison is similar in each case.…”

“…The paramagnetism of the cage complexes greatly facilitates this by dispersing the individual 1 H resonances over a range of nearly 200 ppm, with the Co II ions acting as excellent shift agents 10, 11, 13, 22. This allows similar but slightly different signals for a particular 1 H environment associated with empty and guest‐containing cages to be distinguished and integrated separately (Figure 4 a).…”