Adhesive π-Clamping within Synthetic Multifunctional Pores

We report the design, synthesis, and evaluation of synthetic multifunctional pores with adhesive, that is, electron-deficient naphthalenediimide (NDI) π-clamps at their inner surface. We find that, in lipid bilayer membranes, comparable synthetic pores with and without π-clamps have similar, nanomolar activity. Functional relevance of adhesive π-clamping within synthetic pores is demonstrated by means of an innovative in situ blocker screening method. The obtained line of experimental evidence includes (a) different blockage efficiency with and without π-clamps (quantified as clamping factors), (b) increasing clamping factors with increasing blocker charge (supportive ion pairing), and, most importantly, (c) increasing clamping factors with increasing aromatic electron donor−acceptor interactions. The availability of advanced synthetic multifunctional pores with refined active sites is important for practical applications in domains such as drug discovery (enzyme inhibitor screening) and diagnostics (mult...