Quantification of solvent effects on molecular recognition in polyhedral coordination cage hosts

Abstract

A water-soluble cubic coordination cage (H w) has been prepared, which is isostructural with a previously reported organic-soluble cage (H) apart from the hydroxy groups on the external surface which render it water-soluble. These two cages act as hosts for small organic molecules which bind via a combination of (i) hydrogen-bonding interactions with specific sites on the internal surface of the cages; (ii) nonpolar interactions such as aromatic and van der Waals interactions between aromatic rings in the guest and the cage internal surface; and (iii) solvophobic interactions. By comparing DG values for guest binding in water (using H w) and MeCN (using H), and using pairs of related guests that differ in the presence or absence of an aromatic ring substituent, it is possible to construct thermodynamic cycles that allow quantification of the solvophobic contribution to binding. Specifically, this is the difference between the solvophobic contributions to DG in water and MeCN associated with desolvation of both guest and the internal surface of the cage when complexation occurs. A highly consistent value of ca. À10 kJ mol À1 is determined for this solvophobic contribution to DG associated with the aromatic ring in water compared to MeCN, which correlates very well with what would be expected based on the free energy changes associated with transfer of toluene from MeCN to water. Thus, all three contributions to guest binding listed above can be separately quantified. The ability to prepare related pairs of guests with the presence or absence of a wide range of substituents provides a potentially general way to quantify the solvophobic contributions to guest binding of these substituents.

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

“…[23][24][25] The presence of hydroxyl groups on the external surface renders the cage water-soluble, whilst the hydrophobic interior cavity (volume ≈ 400 Å 3 ) allows binding 4 of hydrophobic organic guests that are a good shape / size match for the cavity with binding constants of up to 10 8 M -1 in water. 13,23,26 Windows in the centre of each face allow ingress / egress of guests. Importantly, only neutral guests bind strongly: cationic (protonated amines) or anionic (carboxylate) guests bind much more weakly as they are hydrophilic and preferentially solvated by bulk water, which means that pH can be used to control uptake and release of ionisable guests.…”

“…1, with a Co(II) ion at each vertex of an approximate cube and a bridging ligand spanning every edge. [23][24][25] The presence of hydroxyl groups on the external surface renders the cage water-soluble, whilst the hydrophobic interior cavity (volume ≈ 400 Å 3 ) allows binding 4 of hydrophobic organic guests that are a good shape / size match for the cavity with binding constants of up to 10 8 M -1 in water. 13,23,26 Windows in the centre of each face allow ingress / egress of guests.…”

“…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.…”

Guest Binding and Catalysis in the Cavity of a Cubic Coordination Cage

“…To this end, we prepared a modified ligand L w , which bears CH 2 OH groups at the C 4 position of every pyridyl ring (Figure 1b 16 (Figure 3b) which, by virtue of the twenty-four hydroxyl groups on the external surface, is now water-soluble, and this has been the focus of our recent guest binding studies. 7 The importance of the hydrophobic effect on guest binding was immediately apparent on comparing binding properties of the same guests in the original MeCN-soluble cage and the new water-soluble cage: for example, the binding constant for coumarin increases by two orders of magnitude from 78(«20) M ¹1 in MeCN to 7600(«900) M ¹1 in D 2 O. 7 Two different investigations allowed us to confirm the role of the hydrophobic effect by showing that the free energy of binding for the guests has a contribution that scales precisely with the hydrophobic surface area of the guest.…”

“…7 The importance of the hydrophobic effect on guest binding was immediately apparent on comparing binding properties of the same guests in the original MeCN-soluble cage and the new water-soluble cage: for example, the binding constant for coumarin increases by two orders of magnitude from 78(«20) M ¹1 in MeCN to 7600(«900) M ¹1 in D 2 O. 7 Two different investigations allowed us to confirm the role of the hydrophobic effect by showing that the free energy of binding for the guests has a contribution that scales precisely with the hydrophobic surface area of the guest. 7,8 Firstly, we compared binding of the two guests 1 and 2 ( Figure 4) in both MeCN and water; the guests differ by the presence of the additional aromatic ring in 2, which provides an additional hydrophobic surface area of 39 ¡ 2 .…”