Conformational effects on the host-guest interaction between amino acids modified pyrene and γ-cyclodextrin

The folding behavior of guest molecules plays a critical role in determining host-guest interaction patterns in supramolecular systems. This study presents a systematic investigation of how amino acid side chains control the folding conformations of pyrene-based guests and thereby direct their recognition by γ-cyclodextrin. Through comprehensive analysis, we demonstrate that extended conformations enable stable inclusion within the cyclodextrin cavity, as evidenced by the emergence of a characteristic excimer fluorescence band at 480 nm, while progressively folded structures lead to weakened interactions due to steric hindrance. The self-shielding effect in rigidly folded molecules, driven by intramolecular π-π stacking between the pyrene core and the aromatic side chain, completely suppresses host-guest complexation. This mechanistic insight is quantitatively supported by molecular dynamics simulations, which reveal that the spatial dimensions of the folded conformers exceed the capacity of the γ-cyclodextrin cavity. These findings establish molecular folding as a key design parameter for programming supramolecular recognition, providing new strategies for controlling molecular assembly through side chain engineering.