A Nexus between Theory and Experiment: Non-Empirical Quantum Mechanical Computational Methodology Applied to Cucurbit[n]uril⋅Guest Binding Interactions

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• 作者：Jiří ; Hostaš ; Dr. David Sigwalt ; Marina Šekutor ; Haresh Ajani ; Dr. Matú ; š Dubecký ; Prof. Jan Řezá ; č ; Dr. Peter Y. Zavalij ; Dr. Liping Cao ; Christian Wohlschlager ; Prof. Kata Mlinarić-Majerski ; Prof. Lyle Isaacs ; Prof. Robert Glaser and Prof. Pavel Hobza
• 刊名：Chemistry - A European Journal
• 出版年：2016
• 出版时间：November 21, 2016
• 年：2016
• 卷：22
• 期：48
• 页码：17226-17238
• 全文大小：2078K
• ISSN：1521-3765

文摘

A training set of eleven X-ray structures determined for biomimetic complexes between cucurbit[n]uril (CB[7 or 8]) hosts and adamantane-/diamantane ammonium/aminium guests were studied with DFT-D3 quantum mechanical computational methods to afford ΔG_calcd binding energies. A novel feature of this work is that the fidelity of the BLYP-D3/def2-TZVPP choice of DFT functional was proven by comparison with more accurate methods. For the first time, the CB[n]⋅guest complex binding energy subcomponents [for example, ΔE_dispersion, ΔE_{electrostatic}, ΔG_solvation, binding entropy (−TΔS), and induced fit E_{deformation(host)}, E_{deformation(guest)}] were calculated. Only a few weeks of computation time per complex were required by using this protocol. The deformation (stiffness) and solvation properties (with emphasis on cavity desolvation) of cucurbit[n]uril (n=5, 6, 7, 8) isolated host molecules were also explored by means of the DFT-D3 method. A high ρ²=0.84 correlation coefficient between ΔG_exptl and ΔG_calcd was achieved without any scaling of the calculated terms (at 298 K). This linear dependence was utilized for ΔG_calcd predictions of new complexes. The nature of binding, including the role of high energy water molecules, was also studied. The utility of introduction of tethered [-(CH₂)_nNH₃]⁺ amino loops attached to N,N-dimethyl-adamantane-1-amine and N,N,N′,N′-tetramethyl diamantane-4,9-diamine skeletons (both from an experimental and a theoretical perspective) is presented here as a promising tool for the achievement of new ultra-high binding guests to CB[7] hosts. Predictions of not yet measured equilibrium constants are presented herein.