Novel host-guest binding motifs based on negatively charged carboxylatopillar[5]arene and carboxylatopillar[6]arene (CP5A and CP6A) with N,N'-bis(4-pyridylmethyl)-1,4-diamino-butane dihydrochloride (C4N4Cl(2)) were constructed. According to the integrated results of H-1 NMR, 2D NOESY, and fluorescence titration experiments, we demonstrated that the molecular recognition between CP5A or CP6A with different cavity sizes and C4N4Cl(2) in water not only has high stability constants but also has pH-responsiveness.