Department of Chemistry & Earth Sciences, College of Arts & Science, Qatar University, Doha, P.O. Box 2713, State of Qatar.
Department of Chemistry & Earth Sciences, College of Arts & Science, Qatar University, Doha, P.O. Box 2713, State of Qatar.
Spectrochim Acta A Mol Biomol Spectrosc. 2019 May 5;214:531-536. doi: 10.1016/j.saa.2019.02.030. Epub 2019 Feb 21.
In this work, the supramolecular host-guest interaction of the prodrug Olsalazine (OLZ) and β-Cyclodextrin (β-CD) was examined experimentally and computationally. Experimentally, employing the UV-Vis spectroscopic method in aqueous media at various pH's, results obtained using the Benesi-Hilderbrand approach demonstrated that OLZ can form supramolecular inclusion complex with β-CD with stoichiometric ratio of 1:1. Furthermore, these results revealed that the formation of OLZ: β-CD complexes exhibited insignificant pH dependency in the range 5-8 with an average binding constant (K) of approximately 1×10M. Computationally, geometry optimization of 1:1 OLZ: β-CD complexes was performed employing the ONIOM (DFT((ωB97XB)/6-31+G(d)),SQM(PM3)) approach. Obtained results demonstrated that OLZ: β-CD complex is stabilized by the formation of intermolecular hydrogen bonds with an average length of approximately 1.8Å. Additionally, the stability of OLZ: β-CD complex was demonstrated employing ADMP molecular dynamic simulations over a timeframe of 500fs. The molecularity of the supramolecular host-guest interaction between OLZ and β-CD is presented and interpreted in the essence of TD-DFT and molecular orbitals analyses.
在这项工作中，我们通过实验和计算研究了前药奥沙拉嗪（OLZ）和β-环糊精（β-CD）的超分子主体-客体相互作用。实验方面，在不同 pH 值的水介质中采用紫外-可见光谱法，根据 Benesi-Hilderbrand 方法得到的结果表明，OLZ 可以与 β-CD 形成 1:1 的超分子包络物。此外，这些结果表明，OLZ:β-CD 配合物的形成在 pH 5-8 范围内几乎没有依赖性，平均结合常数（K）约为 1×10M。在计算方面，采用 ONIOM（DFT((ωB97XB)/6-31+G(d)),SQM(PM3))方法对 1:1 OLZ:β-CD 配合物进行了几何优化。得到的结果表明，OLZ:β-CD 配合物通过形成平均长度约为 1.8Å的分子间氢键而稳定。此外，通过在 500fs 的时间范围内进行 ADMP 分子动力学模拟，证明了 OLZ:β-CD 配合物的稳定性。通过 TD-DFT 和分子轨道分析，提出并解释了 OLZ 和 β-CD 之间超分子主体-客体相互作用的分子特性。
