Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host-guest interaction for drug delivery.

A new water-soluble hexacarboxylated tribenzotriquinacene derivative ( TBTQ-CB6 ) was synthesized and used as a supramolecular drug carrier to load the model anticancer drugs dimethyl viologen ( MV ) and doxorubicin ( DOX ) via host-guest interactions. The drugs could be effectively released by spermine ( SM ), a molecule overexpressed in cancer cells, through host-guest competitive substitution since TBTQ-CB6 has a stronger binding affinity toward SM than MV and DOX . The host-guest interactions of the complexes of TBTQ-CB6 with MV , DOX and SM were investigated by NMR spectroscopy and fluorescence spectroscopy. The association stoichiometry of the complexes of TBTQ-CB6 with MV , DOX , and SM was found to be 1:1 with association constants of K a = (7.67 ± 0.34) × 10 4 M -1 , K a = (6.81 ± 0.33) × 10 4 M -1 , and K a = (5.09 ± 0.98) × 10 5 M -1 , respectively. The competitive substitution process was visualized by NMR titration. This novel TBTQ-based host-guest drug delivery system may have potential use in supramolecular chemotherapy.