Deogratias Geradius, Shadrack Daniel M, Munissi Joan J E, Kinunda Grace A, Jacob Fortunatus R, Mtei Regina P, Masalu Rose J, Mwakyula Issakwisa, Kiruri Lucy W, Nyandoro Stephen S
Chemistry Department, College of Natural and Applied Sciences, University of Dar es Salaam, P.O. Box 35061, Dar es Salaam, Tanzania.
Department of Chemistry, Faculty of Natural and Applied Sciences, St. John's University of Tanzania, P.O. Box 47, Dodoma, Tanzania.
J Mol Graph Model. 2022 Nov;116:108243. doi: 10.1016/j.jmgm.2022.108243. Epub 2022 Jun 23.
Luteolin is a flavonoid obtained from different plant species. It is known for its versatile biological activities. However, the beneficial effects of luteolin have been limited to small concentrations as a result of poor water solubility. This study aimed at investigating the hydrophobic interaction and hydration of luteolin towards the improvement of its solubility when used as a drug. We report the aggregation properties of luteolin in water by varying the number of monomers using atomistic molecular dynamics simulation. Results show that the equilibrium structure of luteolin occurs in an aggregated state with different structural arrangements. As the monomers size increase, the antiparallel flipped conformation dominates over T-shaped antiparallel, T-shaped parallel, and antiparallel conformations. The formation of intramolecular hydrogen bonding of 0.19 nm between the keto-enol groups results in hydrophobic characteristics. A larger cluster exhibits slow hydrogen bond dynamics for luteolin-luteolin than luteolin-water interaction. Water structure at large cluster size exhibited slow dynamics and low self-diffusion of luteolin. The existence of hydrophobic π-π and hydrogen bonds between luteolin molecules drives strong self-aggregation resulting in poor water solubility. Breakage of these established interactions would result in increased solubility of luteolin in water.
木犀草素是一种从不同植物物种中获得的黄酮类化合物。它以其多样的生物活性而闻名。然而，由于水溶性差，木犀草素的有益作用仅限于低浓度。本研究旨在研究木犀草素的疏水相互作用和水合作用，以改善其作为药物时的溶解度。我们通过使用原子分子动力学模拟改变单体数量来报告木犀草素在水中的聚集性质。结果表明，木犀草素的平衡结构以具有不同结构排列的聚集状态出现。随着单体尺寸的增加，反平行翻转构象比T形反平行、T形平行和反平行构象占主导地位。酮-烯醇基团之间0.19纳米的分子内氢键形成导致疏水特性。对于木犀草素-木犀草素相互作用，较大的聚集体表现出缓慢的氢键动力学，而木犀草素-水相互作用则不然。大聚集体尺寸下的水结构表现出缓慢的动力学和木犀草素的低自扩散。木犀草素分子之间存在疏水π-π和氢键，导致强烈的自聚集，从而导致水溶性差。这些已建立的相互作用的破坏将导致木犀草素在水中的溶解度增加。
