Molecular bowls for inclusion complexation of toxic anticancer drug methotrexate.

ABSTRACT: We describe the preparation and study of novel cavitands, molecular bowls 1⁶⁺ and 2⁶⁺, as good binders of the anticancer drug methotrexate (MTX). Molecular bowls are comprised of a curved tribenzotriquinacene (TBTQ) core conjugated to three macrocyclic pyridinium units at the top. The cavitands are easily accessible via two synthetic steps from hexabromo-tribenzotriquinacene in 25% yield. As amphiphilic molecules, bowls 1⁶⁺ and 2⁶⁺ self-associate in water by the nucleation-to-aggregation pathway (NMR). The bowls are preorganized, having a semi-rigid framework comprising a fixed bottom with a wobbling pyridinium rim (VT NMR and MD). Further studies, both experimental (NMR) and computational (DFT and MCMM), suggested that a folded MTX occupi

SUBMITTER: Karmakar P 

PROVIDER: S-EPMC11220613 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature