Detailed studies on the stability, interaction, and microstructure of host‐guest complexes in the vacuum of 5‐fluorouracil (5FU) with β‐cyclodextrin (βCD) were performed using B3LYP with the inclusion of Grimme's dispersion correction GD3 term and 6‐31+G(d,p) basis set. Among several studied 1:1 5FU‐βCD complexes, the one placing the keto tautomer of 5FU vertically in the host cavity and forming N‐H···O_CD and CO···HO_CD hydrogen bonds with hydroxyl groups of the smaller rim of βCD has the highest stability (E_int = −195 kJ/mol). Interestingly, there are no interactions with the inner hydrophobic part of the βCD host cavity. The strength of the intermolecular H‐bonds to the smaller rim of βCD is comparable to those in 5FU‐water and 5FU‐methanol clusters, used as model systems characterizing the noncovalent interactions. Of several studied host‐guest complexes, the inner ones are more stable than the outer systems. Our results reveal that taking dispersion interaction in DFT into account is essential for reliable modeling of the structure, interaction, and stability of 5FU‐βCD complexes. This study is crucial for understanding the interaction of 5FU with βCD in the solid state and additionally suggests the presence of equilibrium between 5FU‐βCD complex and solvated 5FU.

中文翻译：

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5-氟尿嘧啶与β-环糊精的相互作用：具有色散校正的密度泛函理论研究

使用B3LYP对5-氟尿嘧啶（5FU）和β-环糊精（βCD）在真空中的宿主-客体复合物的稳定性，相互作用和微观结构进行了详细研究，其中包括Grimme的色散校正GD3项和6-31 + G（d，p）基集。在几个研究1：1 5FU-βCD络合物，所述一个放置5FU的互变异构体酮垂直于宿主腔和形成N-H···ö _CD和CO···ħ  ö _CD与羟基形成氢键βCD的较小边缘的稳定性最高（E _int＝ -195kJ / mol）。有趣的是，与βCD宿主腔的内部疏水部分没有相互作用。βCD较小边缘的分子间氢键强度与5FU-水和5FU-甲醇簇中的强度相当，可作为表征非共价相互作用的模型系统。在一些研究过的主客体系统中，内部系统比外部系统更稳定。我们的结果表明，考虑DFT中的分散相互作用对于5FU-βCD配合物的结构，相互作用和稳定性的可靠建模至关重要。这项研究对于理解5FU与固态βCD的相互作用至关重要，另外还提出了5FU-βCD复合物与5FU溶剂化之间存在平衡。