The interactions of two mono-functionalized sulfonatocalix[4]arenes with
cytochrome c were investigated by structural and thermodynamic methods. The
replacement of a single sulfonate with either a bromo or a phenyl substituent
resulted in altered recognition of cytochrome c as evidenced by X-ray
crystallography. The bromo-substituted ligand yielded a new binding mode in
which a self-encapsulated calixarene dimer contributed to crystal packing. This
ligand also formed a weak halogen bond with the protein. The phenyl-substituted
ligand was bound to Lys4 of cytochrome c, in a 1.7 Å resolution crystal
structure. A dimeric packing arrangement mediated by ligand-ligand contacts in
the crystal suggested a possible assembly mechanism. The different protein
recognition properties of these calixarenes are discussed.
