McGrath Jacqueline M, Pluth Michael D
Department of Chemistry and Biochemistry, Materials Science Institute, University of Oregon , Eugene, Oregon 97403-1253, United States.
J Org Chem. 2014 Jan 17;79(2):711-9. doi: 10.1021/jo402500a. Epub 2014 Jan 7.
Synthetic barbiturate receptors have been utilized for many applications due to their high binding affinities for complementary guests. Although interest in this class of receptors spans from supramolecular to materials chemistry, the effects of receptor steric bulk and preorganization on guest binding affinity has not been studied systematically. To investigate the roles that steric bulk and preorganization play in guest binding, we prepared a series of 12 deconstructed Hamilton receptors with varying degrees of steric bulk and preorganization. Both diethylbarbital and 3-methyl-7-propylxanthine were investigated as guests for the synthetic receptors. The stoichiometry of guest binding was investigated using Job plots for each host-guest pair, and (1)H NMR titrations were performed to measure the guest binding affinities. To complement the solution-state studies, DFT calculations at the B3LYP/6-31+G(d,p) level of theory employing the IEF-PCM CHCl3 solvation model were also performed. Calculated guest binding energies correlated well with the experimental findings and provided additional insight into the factors influencing guest binding. Taken together, the results presented highlight the interplay between preorganization and steric interactions in establishing favorable interactions for self-assembled hydrogen-bonded systems.
由于合成巴比妥酸受体对互补客体具有高结合亲和力，已被用于许多应用。尽管对这类受体的研究兴趣涵盖了从超分子化学到材料化学的领域，但受体空间位阻和预组织对客体结合亲和力的影响尚未得到系统研究。为了研究空间位阻和预组织在客体结合中所起的作用，我们制备了一系列12种具有不同程度空间位阻和预组织的解构汉密尔顿受体。二乙巴比妥酸和3-甲基-7-丙基黄嘌呤均作为合成受体的客体进行了研究。使用乔布曲线（Job plots）对每对主客体进行了客体结合化学计量学研究，并进行了¹H NMR滴定以测量客体结合亲和力。为补充溶液状态研究，还采用IEF-PCM CHCl₃溶剂化模型在B3LYP/6-31+G(d,p)理论水平上进行了密度泛函理论（DFT）计算。计算得到的客体结合能与实验结果良好相关，并为影响客体结合的因素提供了额外的见解。综上所述，所呈现的结果突出了预组织和空间相互作用在为自组装氢键系统建立有利相互作用中的相互作用。
