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.