Scholarlink

<p>Cavity size plays a decisive role in governing host–guest interactions in cyclodextrin-based inclusion systems. In this study, the encapsulation behavior of 4-aminopyridine (4-AP) with α- and β-cyclodextrins (α-CD and β-CD) was systematically investigated to elucidate the relationship between cavity dimensions, binding thermodynamics, and functional performance. Inclusion complex formation was confirmed by ^1H NMR, UV–visible, FTIR, fluorescence spectroscopy, and ESI–MS analyses, revealing distinct cavity-dependent binding modes. Pronounced upfield shifts of inner cavity protons (H3 and H5), along with guest proton perturbations, indicated deeper inclusion and stronger stabilization of 4-AP within the β-CD cavity compared to α-CD.</p><p>Thermodynamic parameters demonstrated enhanced binding affinity and stability for the β-CD complex, consistent with its optimal cavity size. Density functional theory (DFT) calculations further corroborated the experimental findings, providing insights into inclusion geometry, interaction energies, and non-covalent stabilization, while reduced density gradient (RDG) analysis confirmed the dominance of van der Waals and hydrogen bonding interactions. In vitro release studies revealed a cavity size–dependent modulation of drug release, with β-CD complexes exhibiting more sustained release profiles relative to α-CD and free 4-AP, indicating improved encapsulation efficiency and controlled delivery behavior.</p><p>Importantly, biological evaluations demonstrated that cyclodextrin inclusion significantly influences functional activity. Antioxidant and antimicrobial assays showed enhanced activity for the inclusion complexes, particularly for β-CD, compared to the free drug, highlighting the role of improved stability and molecular dispersion. Furthermore, in vitro cytotoxicity studies using A549 human lung adenocarcinoma cells confirmed that β-CD encapsulation leads to superior biological response, attributable to optimized release and stronger host–guest interactions.</p><p>Overall, this study establishes a direct correlation between cyclodextrin cavity size, binding energetics, release behavior, and biological function, demonstrating that cavity size–dependent control of host–guest interactions can be strategically exploited to enhance drug performance.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Exploring cavity size-dependent control of host–guest interactions in cyclodextrins: linking spectroscopy, binding thermodynamics to release and biological function of 4-Aminopyridine

  • 期刊论文

  • 发表日期：

    2026年6月3日

查看全文
  • Koushik Baul,
  • Priyanka Roy,
  • Subhankar Choudhury,
  • Biswanath Karmakar,
  • Dibakar Ghosh,
  • Swarnendu Roy,
  • Sangita Dey,
  • Anoop Kumar,
  • Saurav Sarkar,
  • Gouranga Nandi,
  • Mahendra Nath Roy

摘要

Cavity size plays a decisive role in governing host–guest interactions in cyclodextrin-based inclusion systems. In this study, the encapsulation behavior of 4-aminopyridine (4-AP) with α- and β-cyclodextrins (α-CD and β-CD) was systematically investigated to elucidate the relationship between cavity dimensions, binding thermodynamics, and functional performance. Inclusion complex formation was confirmed by ^1H NMR, UV–visible, FTIR, fluorescence spectroscopy, and ESI–MS analyses, revealing distinct cavity-dependent binding modes. Pronounced upfield shifts of inner cavity protons (H3 and H5), along with guest proton perturbations, indicated deeper inclusion and stronger stabilization of 4-AP within the β-CD cavity compared to α-CD.

Thermodynamic parameters demonstrated enhanced binding affinity and stability for the β-CD complex, consistent with its optimal cavity size. Density functional theory (DFT) calculations further corroborated the experimental findings, providing insights into inclusion geometry, interaction energies, and non-covalent stabilization, while reduced density gradient (RDG) analysis confirmed the dominance of van der Waals and hydrogen bonding interactions. In vitro release studies revealed a cavity size–dependent modulation of drug release, with β-CD complexes exhibiting more sustained release profiles relative to α-CD and free 4-AP, indicating improved encapsulation efficiency and controlled delivery behavior.

Importantly, biological evaluations demonstrated that cyclodextrin inclusion significantly influences functional activity. Antioxidant and antimicrobial assays showed enhanced activity for the inclusion complexes, particularly for β-CD, compared to the free drug, highlighting the role of improved stability and molecular dispersion. Furthermore, in vitro cytotoxicity studies using A549 human lung adenocarcinoma cells confirmed that β-CD encapsulation leads to superior biological response, attributable to optimized release and stronger host–guest interactions.

Overall, this study establishes a direct correlation between cyclodextrin cavity size, binding energetics, release behavior, and biological function, demonstrating that cavity size–dependent control of host–guest interactions can be strategically exploited to enhance drug performance.