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 1:1 with association constants of Ka = (7.67 ± 0.34) × 104 M−1, Ka = (6.81 ± 0.33) × 104 M−1, and Ka = (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.

Donor‐Acceptor Tribenzotriquinacene‐Based Molecular Wizard Hats Bearing Three ortho‐Benzoquinone Units

“…In the past decades, the chemistry of tribenzotriquinacene (TBTQ) has been developed in a large variety of ways. [1][2][3][4][5][6][7][8][9][10][11][12] Besides functionalization of the four bridgeheads and the six outer (peripheral) arene positions, such as in the key derivative 1 (Figure 1), [13,14] activation of the six inner arene positions offer a great potential, especially for π-extension of the bowl-(or hat-) shaped polyaromatic TBTQ framework. [1,5a,15] Threefold bridging of the (extended) bays by ortho-phenylene units, giving wizard-hat-shaped congeners, and full annulation with a nonaphenylene jacket, like in 2, have been achieved in recent years.…”

pH-Responsive fluorescent supramolecular nanoparticles based on tetraphenylethylene-labelled chitosan and a six-fold carboxylated tribenzotriquinacene

“…Similar to those macrocyclic acceptors, tribenzotriquinacene (TBTQ) derivatives, a class of versatile host molecules with a bowl-shaped C 3v -symmetric skeleton, are capable of effectively encapsulating guest molecules [ 9 – 15 ]. In recently published studies [ 16 – 17 ], we have successfully synthesized two water-soluble hexacarboxylated tribenzotriquinacene derivatives, 2,2',2'',2''',2'''',2'''''-((12d-methyltribenzotriquinacene-2,3,6,7,10,11-hexayl)hexakis(oxy))hexaacetate ( TBTQ-C 6 ) and 2,2',2'',2''',2'''',2'''''-((((12d-methyltribenzotriquinacene-2,3,6,7,10,11-hexayl)hexakis(oxy))hexakis(methylene))hexakis(1 H -1,2,3-triazole-4,1-diyl))hexaacetate ( TBTQ-CB6 ), which act as host molecules to bind to guest molecules to construct pH-responsive supramolecular vesicles and molecule-scale drug carriers, respectively. Both of them exhibited pH-responsive properties, with the host–guest binding disintegrating when the pH of the solution is adjusted to 5.5 and the binding regenerated when the pH is restored to 7.4.…”