Through-Space Paramagnetic NMR Effects in Host–Guest Complexes: Potential Ruthenium(III) Metallodrugs with Macrocyclic Carriers

The
potential of paramagnetic ruthenium­(III) compounds for use as anticancer
metallodrugs has been investigated extensively during the past several
decades. However, the means by which these ruthenium compounds are
transported and distributed in living bodies remain relatively unexplored.
In this work, we prepared several novel ruthenium­(III) compounds with
the general structure Na+[trans-RuIIICl4(DMSO)­(L)]− (DMSO = dimethyl
sulfoxide), where L stands for pyridine or imidazole linked with adamantane,
a hydrophobic chemophore. The supramolecular interactions of these
compounds with macrocyclic carriers of the cyclodextrin (CD) and cucurbit­[n]­uril (CB) families were investigated by NMR spectroscopy,
X-ray diffraction analysis, isothermal titration calorimetry, and
relativistic DFT methods. The long-range hyperfine NMR effects of
the paramagnetic guest on the host macrocycle are related to the distance
between them and their relative orientation in the host–guest
complex. The CD and CB macrocyclic carriers being studied in this
account can be attached to a vector that attracts the drug-carrier
system to a specific biological target and our investigation thus
introduces a new possibility in the field of targeted delivery of
anticancer metallodrugs based on ruthenium­(III) compounds.