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) x 10(4 )M(-1) , K-a = (6.81 +/- 0.33) x 10(4) M-1 , and K-a = (5.09 +/- 0.98) x 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.

Automated summary

A new water-soluble derivative was synthesized and used for supramolecular drug delivery, showing promising results in releasing anticancer drugs. The drugs could be effectively released by overexpressed molecules in cancer cells.