El. Piatnitski et al., Highly organized spherical hosts that bind organic guests in aqueous solution with micromolar affinity: Microcalorimetry studies, CHEM-EUR J, 6(6), 2000, pp. 999-1006
Two novel closed-shell hemicarcerand-like hosts with spherical cavities of
11 Angstrom diameter that are soluble in aqueous solution were constructed.
The binding of xylenes, aryl ethers, polyaromatic compounds, ferrocene der
ivatives, and bicyclic aliphatic compounds were examined by NMR spectroscop
y and microcalorimetry. NMR binding studies indicated that binding depended
upon guest hydrophobicity and shape. No binding was detected for guests in
which a charge must be desolvated as part of inclusion or for guests that
can not fit within the cavity of the host. Three complexes 2.naphthalene, 2
.pxylene, and 2.ferrocene were isolated and found to be indefinitely stable
in the solid phase and in aqueous solution. The binding constants for thes
e complexes are estimated to be greater than 10(8) M-1. Thirteen guests wer
e examined by microcalorimetry with binding constants ranging between 10(7)
and 10(3) M-1. A comparison of results obtained here with those from previ
ous work with beta-cyclodextrin and cyclophane hosts, along with analysis o
f the entropy-enthalpy compensation data, indicate that there is a higher d
egree of guest desolvation with this host structure than with open-shell ho
sts. This accounts at least partially for the increase in affinity observed
with these closed-shell hosts. Replacing a hydroxy group in the host porta
l with a hydrogen atom does not affect the binding constant, a finding cons
istent with the guest residing deeply buried within the host cavity. It was
observed that aromatic guests are bound with higher affinity than aliphati
c ones in agreement with results that point to the importance of London dis
persion forces in the association of aromatic components in face-to-edge or
ientations. The correlation of changes in NMR chemical shift with microcalo
rimetry data supports a model in which increased CH-pi interactions strengt
hen association between host and guest due to the dominant role of van der
Waals dispersion forces. Remarkably, the binding constant for the 1,4 isome
r of dimethoxybenzene is 32 times higher than for the 1,2 isomer, and even
greater discrimination is observed between the xylene guests since the bind
ing constant for p-xylene is 80 times greater than that for o-xylene. This
discrimination between isomeric guests by a rigid host indicates that chang
es in specific hydrophobic interactions have substantial effects upon bindi
ng affinity.