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首页> 外文期刊>RSC Advances >Membrane partition of bis-(3-hydroxy-4-pyridinonato) zinc(ii) complexes revealed by molecular dynamics simulations
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Membrane partition of bis-(3-hydroxy-4-pyridinonato) zinc(ii) complexes revealed by molecular dynamics simulations

机译：分子动力学模拟揭示双（3-羟基-4-吡啶并萘）锌（ii）配合物的膜分配

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摘要

The class of 3-hydroxy-4-pyridinone ligands is widely known and valuable for biomedical and pharmaceutical purposes. Their chelating properties towards biologically-relevant transition metal ions highlight their potential biomedical utility. A set of 3-hydroxy-4-pyridinone Zn( II ) complexes at different concentrations was studied for their ability to interact with lipid phases. We employed umbrella sampling simulations to attain the potential-of-mean force for a set of ligands and one Zn( II ) complex, as these permeated a 1,2-dimyristoyl- sn -glycero-3-phosphocholine (DMPC) hydrated bilayer system. In addition, we used conventional molecular dynamics simulations to study the behavior of various Zn( II ) complexes in hydrated bilayer systems. This work discusses: (i) the partition of 3-hydroxy-4-pyridinone ligands to bilayer phases; (ii) self-aggregation in crowded environments of Zn( II ) complexes; and (iii) possible mechanisms for the membrane translocation of Zn( II ) complexes. We observed distinct interactions for the studied complexes, and distinct membrane partition coefficients ( K _(mem) ) depending on the considered ligand. The more hydrophobic ligand, 1-hexyl-3-hydroxy-2-methyl-4(1 H )-pyridinone, partitioned more favorably to lipid phases (at least two orders of magnitude higher K _(mem) when compared to the other ligands), and the corresponding Zn( II ) complex was also prone to self-aggregation when an increased concentration of the complex was employed. We also observed that the inclusion of a coordinated water molecule in the parameterization of the Zn( II ) coordination sphere, as proposed in the available crystallographic structure of the complex, decreased the partition coefficient and membrane permeability for the tested complex.
机译：3-羟基-4-吡啶酮配体的种类是众所周知的，对于生物医学和药学目的是有价值的。它们对生物相关的过渡金属离子的螯合性能突出了其潜在的生物医学用途。研究了一组不同浓度的3-羟基-4-吡啶酮Zn（II）配合物与脂质相相互作用的能力。我们采用了伞式采样模拟来获得一组配体和一个Zn（II）配合物的平均势能，因为它们渗透了1,2-二肉豆蔻酰基-锡-甘油-3-磷酸胆碱（DMPC）水合双层系统。此外，我们使用常规的分子动力学模拟来研究水合双层系统中各种Zn（II）配合物的行为。这项工作讨论：（i）3-羟基-4-吡啶酮配体分配到双层相; （ii）在拥挤的Zn（II）配合物环境中自聚集; （iii）Zn（II）配合物膜易位的可能机制。我们观察到复杂的相互作用的研究复合物和不同的膜分配系数（K _（mem）），取决于所考虑的配体。疏水性更高的配体1-己基-3-羟基-2-甲基-4（1 H）-吡啶酮更易分配到脂质相（与其他配体相比，K _（mem）高至少两个数量级），当使用浓度较高的配合物时，相应的Zn（II）配合物也易于自聚集。我们还观察到，如配合物的可用晶体学结构中所建议的那样，在Zn（II）配位球的参数化中包含配位水分子降低了测试配合物的分配系数和膜渗透性。

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