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

ABSTRACT

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 11 with association constants of K a = (7.67 ± 0.34) × 104 M-1, K a = (6.81 ± 0.33) × 104 M-1, and K a = (5.09 ± 0.98) × 105 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.