Vuai Said A H, Sahini Mtabazi G, Onoka Isaac, Kiruri Lucy W, Shadrack Daniel M
Department of Chemistry, College of Natural and Mathematical Sciences, University of Dodoma P. O. Box 338 Dodoma Tanzania.
Department of Chemistry, Kenyatta University P. O. Box 43844-00100 Nairobi Kenya.
RSC Adv. 2021 Oct 7;11(52):33136-33147. doi: 10.1039/d1ra05358b. eCollection 2021 Oct 4.
The beneficial medicinal effects of niclosamide have been reported to be hampered by poor aqueous solubility and so a higher concentration dosage is required. In this work, we have studied the aggregation properties of niclosamide in water by varying the number of monomers. We have employed all-atom classical molecular dynamics simulation in order to explore such properties. The equilibrium structure exists in an aggregated state with structural rearrangements of the stacking units. Niclosamide monomers tend to form clusters in an orderly manner and tend to aggregate in parallel and antiparallel orientations of the phenyl rings as the monomers are increased in number from 4 to 9. Upon increasing the size from 9 to 14, and from 49 to 150, a considerable dominance of the metastable parallel arrangement is observed, resulting in the formation of a closely packed cluster with hydrophobic contacts. The metastable conformation self-arranges to a T-shape before forming a stable planar antiparallel displaced conformation. The aggregated π-π parallel and cation-π antiparallel clusters in water exist in a β-conformer. We further observed that formation of a stable cluster aggregate entails the formation of an intermediate metastable cluster that disperses in solution forming a large stable cluster. We also discovered that movement of the water is faster in less aggregated clusters and as the cluster size increases, the mobility rate becomes much slower.
据报道，氯硝柳胺的有益药用效果受到其较差的水溶性的阻碍，因此需要更高浓度的剂量。在这项工作中，我们通过改变单体数量研究了氯硝柳胺在水中的聚集特性。我们采用全原子经典分子动力学模拟来探索这些特性。平衡结构以聚集状态存在，堆积单元有结构重排。随着单体数量从4增加到9，氯硝柳胺单体倾向于有序形成簇，并倾向于以苯环的平行和反平行取向聚集。当尺寸从9增加到14，以及从49增加到150时，观察到亚稳平行排列有相当大的优势，导致形成具有疏水接触的紧密堆积簇。亚稳构象在形成稳定的平面反平行位移构象之前会自我排列成T形。水中聚集的π-π平行和阳离子-π反平行簇以β-构象存在。我们进一步观察到，稳定簇聚集体的形成需要形成一个中间亚稳簇，该亚稳簇分散在溶液中形成一个大的稳定簇。我们还发现，在聚集程度较低的簇中，水的移动更快，随着簇尺寸的增加，迁移率变得更慢。
