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

The host–guest chemistry of the octanuclear cubic
coordination cage [Co8L12]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 1H NMR spectroscopy. The cage encloses a cavity of volume of ca. 400
Å3, 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 CD3CN 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 1H–1H 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.