Binding to DNA purine base and structure-activity relationship of a series of structurally related Ru(II) antitumor complexes: a theoretical study

The thermodynamics of the binding of a series of structurally related Ru(II) antitumor complexes, that is, alpha-[Ru(azpy)2Cl2] 1, beta-[Ru(azpy)2Cl2] 2, alpha-[Ru(azpy)(bpy)Cl2] 3, and cis-[Ru(bpy)2Cl2] 4 to DNA purine bases (gunine, adenine at N7 site) has been studied by using the DFT method. The binding of imine form of 9-methyladenine (9-MeAde) to the Ru(II) moiety in a didentate fashion via its N6 and N7 atoms was also considered. The geometrical structures of the DNA model base adducts were obtained at the B3LYP/(LanL2DZ + 6-31G(d)) level in vacuo. The following exact single-point energy calculations were performed at the B3LYP/(LanL2DZ(f)+6-311+G(2d, 2p)) level both in vacuo and in aqueous solution using the COSMO model. The bond dissociation enthalpies and free energies, reaction enthalpies and free energies both in the gas phase and in aqueous solution for all considered Ru(II)-DNA model base adducts were obtained from the computations. The calculated bond dissociation enthalpies and free energies allow us to build a binding affinity order for the considered Ru(II)-DNA model base adducts. The theoretical results show that the guanine N7 is a preferred site for this series of complexes and support such an experimental fact that alpha-[Ru(azpy)(bpy)(9-EtGua)H2O](2+) (3-(9-EtGua)) is isomerized to alpha'-[Ru(azpy)(bpy)(9-EtGua)H2O](2+) (3'-(9-EtGua)). On the basis of structural and thermodynamical characteristics, the possible structure-activity relationship was obtained, and the distinct difference in cytotoxicities of this series of structurally related antitumor complexes was explained theoretically.     

抗癌性钌配合物[HL][trans-RuⅢCl4L2](L=4H-1，2，4-triazole)水解机理的理论研究

采用密度泛函理论(DFT)方法,并结合导体极化连续模型(CPCM)研究了具有抗肿瘤活性的"Keppler型"钌配合物[Htrz][trans-RuⅢCl4(4H-1,2,4-triazole)2](1)的水解反应过程。首先,在B1B95/(LanL2DZ+6-31G(d))理论水平上对水解反应中各平衡构型在气相条件下的有关结构进行全几何优化及振动频率分析。然后,在更高的基组水平LanL2DZ(f)+6-311++G(3df,2dp)上对优化的结构进行单点能计算,并考虑溶剂效应。计算得到水解反应过程中相应的结构特征和详细的反应势能面。对于第一步水解,水溶液中配合物1的活化能垒为116.6 kJ.mol-1,比已经报道的配合物[ImH][trans-RuⅢCl4(Im)2](ICR)的活化能垒高得多,进一步证实了降低含氮杂环中N原子碱性,可增强配合物在水溶液中的稳定性的水解规律。对于第二步水解,如同已经研究的多数"Keppler型"抗肿瘤钌配合物一样,反应在热力学上优先生成顺式双水解产物。     

纳米氧化铁对铀(Ⅵ)吸附性能的研究

用可见分光光度法研究了新型吸附剂纳米氧化铁对水中铀的静态吸附行为,考察了溶液pH值、吸附时间、离子强度和铀初始浓度等对吸附率的影响.结果表明,溶液pH对吸附率的影响较明显,在pH为6时,吸附率达最大,吸附5min后达到吸附平衡,且吸附率达95%以上;随铀酰离子浓度的增加,吸附率呈下降趋势,而吸附容量逐渐上升;铀在纳米氧...     

2D/3D-QSAR Studies of [1,2,4]Triazolo[1,5-a]pridinylpyridine Derivatives as Potent Anticancer Agents

By using a combined method of density functional theory(DFT), molecular mechanics(MM2) and statistics for two-dimensional(2D), as well as the comparative molecular field analysis(Co MFA) and comparative molecular similarity index analysis(Co MSIA) methods for three-dimensional(3D), theoretical studies on 2D/3D quantitative structure-activity relationships(QSAR) of 22 novel compounds of [1,2,4]triazolo[1,5-a] pyridinylpyridines acting as PI3 K inhibitors against the human colon carcinoma cell line(HCT-116) have been performed. Both the 2D- and 3D-QSAR models established from the random 18 compounds in training set show significant statistical quality and satisfactory predictive ability(R2 = 0.821, q2 = 0.773 for 2D-QSAR, R2 = 0.966, q2 = 0.668 for Co MFA, R2 = 0.979, q2 = 0.753 for Co MSIA). The combined 2D- and 3D-QSAR studies suggest that the moderate-size, hydrophilic and electron-withdrawing group at R1 position, the bulky and hydrophobic group at R2 position, and the minor, hydrophobic, H-bond donor and electron-donating group at R3 position would enhance the anticancer activities. These obtained results help to insight into the action mechanism, and will serve as a basis for the design of new potent anticancer agents.     

抗癌性钌配合物[HL][trans-RuIIICl4L2](L=2-NH2-5-Me-STz)的水解机理

用量子化学密度泛函理论(DFT), 并结合导体极化连续模型(CPCM)研究了具有潜在抗肿瘤活性的“Keppler型”钌配合物trans-[RuIIICl4(2-NH2-5-Me-STz)2](1)的水解反应过程. 首先, 在UB3LYP/(LanL2DZ+6-31G(d))理论水平上对水解反应中各平衡构型在气相条件下的有关结构进行全几何优化及振动频率分析; 然后, 在更高的基组水平LanL2DZ(f)+6-311++G(3df,2dp)上对优化的结构进行单点能计算, 并考虑溶剂效应. 计算得到水解反应过程中相应的结构特征和详细的反应势能面. 对于第一步水解, 液相中配合物1的活化能垒为92.9 kJ·mol-1, 与已经报道的配合物trans-[RuIIICl4(2-NH2-Tz)2](2)的活化能垒(96.3 kJ·mol-1)相接近, 并与实验结果相符. 对于第二步水解, 反应在热力学上优先生成顺式双水解产物, 恰如顺铂的水解反应机理一样, 存在着所谓“顺式效应”, 即生成的顺式水解产物有利于其与生物分子靶标的键合, 因此, 顺式双水解产物在生物反应中有望成为重要的前体药物. 本文研究结果有助于深入理解抗癌性Ru(III)配合物与相关生物靶标的作用机理.     

辐射对流传热对不可逆太阳能Braysson热机性能的影响

建立高温端同时辐射对流传热、低温端对流传热的不可逆太阳能Braysson热机循环新模型,探索有限速率热传导和绝热过程不可逆性等对热机循环性能的影响,基于热力学分析方法,导出热机输出功率和效率的解析表达式,数值计算结果揭示了等压温比、内不可逆参量及与热传导系数和面积有关的匹配参量等对热机性能特性的影响,所得结论不仅能导出其它不可逆太阳能热机的优化性能.且可为太阳能热机的参数设计和性能评价提供新理论参考.