Highly stable host-guest complexation of 4-aminoquinoline-based tweezer-type host molecule with chlorin e6

Abstract

Host-guest systems that function under physiologically relevant conditions possess considerable potential to contribute to biological and biomedical applications. We previously developed a 4-aminoquinoline (4-AQ)-based tweezer-type host molecule that forms stable complexes with heme and protoporphyrin IX (PPIX) in DMSO/HEPES buffer (pH 7.4) (2:3, v/v), respectively. However, the binding study including the determination of association constants of the 4-AQ-based tweezer-type host molecule under more physiologically relevant conditions was not possible although it was one of the most important parts of our studies. In this paper, we report a new host-guest system based on the 4-AQ-based tweezer-type host molecule and chlorin e6 (Ce6). The 4-AQ-based tweezer-type host molecule formed a highly stable host-guest complex not only in DMSO/HEPES buffer (pH 7.4) (2:3, v/v) but also in more physiologically relevant conditions (HEPES buffer or phosphate-buffered saline, pH 7.4, 1.0% (v/v) DMSO). Their association constants for a 1:1 complex were determined to be 10⁶–10⁷ M^− 1 under the investigated aqueous media. These results were first obtained using Ce6 as the guest molecule instead of heme and PPIX because Ce6 at low concentrations preferentially exists in a monomeric form in water at neutral pH. The study findings provide useful information for the future molecular design, evaluation, and applications of host-guest systems between tweezer-type host molecules and their appropriate guest molecules in aqueous media.