Bahamonde-Padilla Víctor Eduardo, López-Cascales José Javier, Araya-Maturana Ramiro, Martínez-Cifuentes Maximiliano, Weiss López Boris Enrique
Universidad de Chile, Facultad de Ciencias, Departamento de Química, Casilla 653, Santiago (Chile); Universidad Politécnica de Cartagena, Grupo de Bioinformatica y Macromoléculas (BioMac), Area de Química Física, Aulario II, Campus de Alfonso XIII, 30203 Cartagena, Murcia (Spain).
Chemphyschem. 2014 May 19;15(7):1422-31. doi: 10.1002/cphc.201301146. Epub 2014 Apr 8.
A detailed description of the distribution, interaction, and dynamics of molecules with biological activity dissolved in a hydrophobic bilayer, a simple model of a biological membrane, provides valuable information for a better understanding of drug functioning, which can be very useful in drug design. Here we present an (2)H NMR and molecular dynamics study on the insertion, distribution, interactions, and thermodynamics of two biologically active molecules, 9,10-dihydroxy-4,4-dimethyl-1,4,5,8-tetrahydroanthracen-1-one (HQ), with anticancer activity, and 4,4-dimethyl-1,4,5,8,9,10-hexahydroanthracen-1,9,10-trione (Q) a fungicide, dissolved in a nematic discotic lyotropic liquid crystal (ndllc) composed of sodium dodecylsulphate (SDS), decanol (DecOH) and Na2 SO4 in water. (2)H NMR quadrupole splittings (ΔνQ ) and longitudinal relaxation times (T1) from HQ-d6, Q-d4, DecOH-α-d2, partially deuterated water, and SDS-d25 were measured and several molecular dynamics trajectories were also calculated. In particular, ΔG, ΔH, and ΔS profiles for the process of both molecules crossing the bilayer were estimated. It was evidenced that the insertion of both molecules into the aggregate is a spontaneous process, and the molecules are mainly distributed in the internal side of the interface. Addition of HQ or Q decreased the mobility of all aggregate components, but this effect was more pronounced for HQ. The rotational correlation time of Q allowed an estimate of 5.3 cP for the microviscosity inside the ndllc aggregate, in the order of previously measured values in similar environments. Both guest molecules display similar free-energy profiles for the process of crossing the bilayer, with a calculated barrier height of 25 and 36 kJ mol(-1) for HQ and Q, respectively.
对溶解于疏水双层（生物膜的简单模型）中的具有生物活性的分子的分布、相互作用及动力学进行详细描述，可为更好地理解药物功能提供有价值的信息，这在药物设计中非常有用。在此，我们展示了一项关于两种生物活性分子——具有抗癌活性的9,10 - 二羟基 - 4,4 - 二甲基 - 1,4,5,8 - 四氢蒽 - 1 - 酮（HQ）和作为杀菌剂的4,4 - 二甲基 - 1,4,5,8,9,10 - 六氢蒽 - 1,9,10 - 三酮（Q）——在由十二烷基硫酸钠（SDS）、癸醇（DecOH）和Na₂SO₄在水中组成的向列型盘状溶致液晶（ndllc）中的插入、分布、相互作用及热力学的（²H）核磁共振和分子动力学研究。测量了来自HQ - d₆、Q - d₄、DecOH - α - d₂、部分氘代水和SDS - d₂₅的（²H）核磁共振四极分裂（ΔνQ）和纵向弛豫时间（T₁），并计算了几条分子动力学轨迹。特别地，估计了两种分子穿过双层过程的ΔG、ΔH和ΔS曲线。结果表明，两种分子插入聚集体是一个自发过程，且分子主要分布在界面内侧。添加HQ或Q降低了所有聚集体组分的流动性，但这种效应对于HQ更为明显。Q的旋转相关时间使得能够估计ndllc聚集体内部的微粘度为5.3 cP，与之前在类似环境中测量的值处于同一量级。两种客体分子在穿过双层过程中显示出相似的自由能曲线，HQ和Q的计算势垒高度分别为25和36 kJ·mol⁻¹。
