Water PMF for predicting the properties of water molecules in protein binding site

Water is an important component in living systems and deserves better understanding in chemistry and biology. However, due to the difficulty of investigating the water functions in protein structures, it is usually ignored in computational modeling, especially in the field of computer‐aided drug design. Here, using the potential of mean forces (PMFs) approach, we constructed a water PMF (wPMF) based on 3946 non‐redundant high resolution crystal structures. The extracted wPMF potential was first used to investigate the structure pattern of water and analyze the residue hydrophilicity. Then, the relationship between wPMF score and the B factor value of crystal waters was studied. It was found that wPMF agrees well with some previously reported experimental observations. In addition, the wPMF score was also tested in parallel with 3D‐RISM to measure the ability of retrieving experimentally observed waters, and showed comparable performance but with much less computational cost. In the end, we proposed a grid‐based clustering scheme together with a distance weighted wPMF score to further extend wPMF to predict the potential hydration sites of protein structure. From the test, this approach can predict the hydration site at the accuracy about 80% when the calculated score lower than ?4.0. It also allows the assessment of whether or not a given water molecule should be targeted for displacement in ligand design. Overall, the wPMF presented here provides an optional solution to many water related computational modeling problems, some of which can be highly valuable as part of a rational drug design strategy. © 2012 Wiley Periodicals, Inc.     

Recovery performance and characteristics in shape memory effects of aliphatic polyether urethane

The analysis on the recovery performance and characteristics in shape memory effects is helpful for the optimal design and engineering applications of shape memory polymers and their composites. To investigate the relationships among recovery performance, material parameters, and loading conditions, by taking aliphatic polyether urethane as an example, the researchers simulate the shape memory behaviors numerically using a three‐dimensional viscoelastic model. The material parameters for this model are taken from stress relaxation tests, rather than dynamic mechanical analysis tests. Both the unconstrained and the constrained recovery behaviors during strain‐controlled shape memory processes are analyzed. The results reveal that the unconstrained recovery occurs at the same temperature regardless of the applied strain values. Another interesting result is that the shape recovery temperature in unconstrained recovery situations increases and the maximum recovery stress under constrained recovery conditions decreases with the increase of heating rates. Copyright © 2013 John Wiley & Sons, Ltd.     

嘧啶衍生物与人血清白蛋白的相互作用

在模拟生理条件下,运用荧光光谱、激光闪光光解(LFP)和分子对接等技术研究了8种具有抗肿瘤活性的嘧啶衍生物(PDs,其中PDs A 5-FU为成药,PDs B-H为实验室自制)与人血清白蛋白(HSA)的相互作用.利用Stern-Volmer方程和激光闪光光解技术分析了PDs对HSA的荧光猝灭机制,PDs A和B为静态猝灭,PDs G和H为动态猝灭.用双倒数曲线法得出5种PDs与HSA的结合常数Ka和结合位点数n,在测定条件下5种PDs与载体结合位点数均为1,且均以弱结合力结合,通过热力学参数ΔH,ΔS和ΔG推测出PDs B,C和E与HSA之间的作用力为静电作用力和疏水作用力,PDs A和D与HSA之间的作用力是氢键和范德华力,分子对接结果与其一致.根据F9rster非辐射能量转移理论(FRET)分析了HSA和PDs之间的结合距离(r),其结果均小于4 nm,符合能量转移理论.进一步利用同步荧光、三维荧光和圆二色光谱考察了PDs与HSA结合过程中HSA空间构象的变化,结果显示,仅PDs A和C对HSA的芳香族氨基酸周围的疏水性略有增强作用.体外实验结果表明,HSA可以作为优良的载体来运输和储存PDs A~E,这为嘧啶衍生物的后续研究提供了可参考的实验数据.     

3‐(Pyridin‐4‐yl)acetylacetone: CdII and HgII compete for nitrogen coordination

3‐(Pyridin‐4‐yl)acetylacetone (HacacPy) acts as a pyridine‐type ligand towards Cd^II and Hg^II halides. With CdBr₂, the one‐dimensional polymer [Cd(μ‐Br)₂(HacacPy)Cd(μ‐Br)₂(HacacPy)₂]_∞ is obtained in which five‐ and six‐coordinated Cd^II cations alternate in the chain direction. Reaction of HacacPy with HgBr₂ results in [Hg(μ‐Br)Br(HacacPy)]_∞, a polymer in which each Hg^II centre is tetracoordinated. In both compounds, each metal(II) cation is N‐coordinated by at least one HacacPy ligand. Equimolar reaction between these Cd^II and Hg^II derivatives, either conducted in ethanol as solvent or via grinding in the solid state, leads to ligand redistribution and the formation of the well‐ordered bimetallic polymer catena‐poly[[bromidomercury(II)]‐μ‐bromido‐[aquabis[4‐hydroxy‐3‐(pyridin‐4‐yl)pent‐3‐en‐2‐one]cadmium(II)]‐di‐μ‐bromido], [CdHgBr₄(C₁₀H₁₁NO₂)₂(H₂O)]_n or [{HgBr}(μ‐Br){(HacacPy)₂Cd(H₂O)}(μ‐Br)₂]_∞. Hg^II and Cd^II cations alternate in the [100] direction. The HacacPy ligands do not bind to the Hg^II cations, which are tetracoordinated by three bridging and one terminal bromide ligand. The Cd^II centres adopt an only slightly distorted octahedral coordination. Three bromide ligands link them in a (2 + 1) pattern to neighbouring Hg^II atoms; two HacacPy ligands in a cis configuration, acting as N‐atom donors, and a terminal aqua ligand complete the coordination sphere. Classical O—H…Br hydrogen bonds stabilize the polymeric chain. O—H…O hydrogen bonds between aqua H atoms and the uncoordinated carbonyl group of an HacacPy ligand in a neighbouring strand in the c direction link the chains into layers in the (010) plane.     

A three‐dimensional cadmium coordination polymer based on 1,4‐bis(1,2,4‐triazol‐1‐yl)but‐2‐ene and benzene‐1,3,5‐tricarboxylic acid

The Cd^II three‐dimensional coordination poly[[[μ₄‐1,4‐bis(1,2,4‐triazol‐1‐yl)but‐2‐ene]bis(μ₃‐5‐carboxybenzene‐1,3‐dicarboxylato)dicadmium(II)] dihydrate], {[Cd₂(C₉H₄O₆)₂(C₈H₁₀N₆)]·2H₂O}_n , (I), has been synthesized by the hydrothermal reaction of Cd(NO₃)₂·4H₂O, benzene‐1,3,5‐tricarboxylic acid (1,3,5‐H₃BTC) and 1,4‐bis(1,2,4‐triazol‐1‐yl)but‐2‐ene (1,4‐btbe). The IR spectrum suggests the presence of protonated carboxylic acid, deprotonated carboxylate and triazolyl groups. The purity of the bulk sample was confirmed by elemental analysis and X‐ray powder diffraction. Single‐crystal X‐ray diffraction analysis reveals that the Cd^II ions adopt a five‐coordinated distorted trigonal–bipyramidal geometry, coordinated by three O atoms from three different 1,3,5‐HBTC²⁻ ligands and two N atoms from two different 1,4‐btbe ligands; the latter are situated on centres of inversion. The Cd^II centres are bridged by 1,3,5‐HBTC²⁻ and 1,4‐btbe ligands into an overall three‐dimensional framework. When the Cd^II centres and the tetradentate 1,4‐btbe ligands are regarded as nodes, the three‐dimensional topology can be simplified as a binodal 4,6‐connected network. Thermogravimetric analysis confirms the presence of lattice water in (I). Photoluminescence studies imply that the emission of (I) may be ascribed to intraligand fluorescence.     

A new two‐dimensional polymeric cadmium(II) complex containing dicyanamide bridging ligands

As part of an exploration of new coordination polymers, a cadmium‐dicyanamide complex, namely poly[benzyltriethylammonium [tri‐μ‐dicyanamido‐κ⁶N ¹:N⁵‐cadmium(II)]], {(C₁₃H₂₂N)[Cd(C₂N₃)₃]}_n , has been synthesized by the reaction of benzyltriethylammonium bromide, cadmium nitrate tetrahydrate and sodium dicyanamide in aqueous solution, and characterized by single‐crystal X‐ray diffraction at room temperature. In the crystal structure, each Cd^II cation is coordinated by six nitrile N atoms from six anionic dicyanamide (dca) ligands to furnish a slightly distorted octahedral geometry. Neighbouring Cd^II cations are linked by dicyanamide bridges to construct a two‐dimensional anionic layer coordination polymer. One amide N atom in the bridging dca ligand is disordered over two sites. The cations lie between the anionic frameworks and there are no hydrogen‐bond interactions between the cations and anions. The organic cations are not involved in the formation of the supramolecular network.     

Three‐dimensional printed magnetophoretic system for the continuous flow separation of avian influenza H5N1 viruses

As a result of the low concentration of avian influenza viruses in samples for routine screening, the separation and concentration of these viruses are vital for their sensitive detection. We present a novel three‐dimensional printed magnetophoretic system for the continuous flow separation of the viruses using aptamer‐modified magnetic nanoparticles, a magnetophoretic chip, a magnetic field, and a fluidic controller. The magnetic field was designed based on finite element magnetic simulation and developed using neodymium magnets with a maximum intensity of 0.65 T and a gradient of 32 T/m for dragging the nanoparticle–virus complexes. The magnetophoretic chip was designed by SOLIDWORKS and fabricated by a three‐dimensional printer with a magnetophoretic channel for the continuous flow separation of the viruses using phosphate‐buffered saline as carrier flow. The fluidic controller was developed using a microcontroller and peristaltic pumps to inject the carrier flow and the viruses. The trajectory of the virus–nanoparticle complexes was simulated using COMSOL for optimization of the carrier flow and the magnetic field, respectively. The results showed that the H5N1 viruses could be captured, separated, and concentrated using the proposed magnetophoretic system with the separation efficiency up to 88% in a continuous flow separation time of 2 min for a sample volume of 200 μL.     

Anti‐inflammatory bioactive equivalence of combinatorial components β‐carboline alkaloids identified in Arenaria kansuensis by two‐dimensional chromatography and solid‐phase extraction coupled with liquid–liquid extraction enrichment technology

Bioactive equivalent combinatorial components play a critical role in herbal medicines. However, how to discover and enrich them efficiently is a question for herbal pharmaceuticals researchers. In our work, a novel two‐dimensional reversed‐phase/hydrophilic interaction high‐performance liquid chromatography method was established to perform real‐time components trapping and combining for preparation and isolation of coeluting components. Arenaria kansuensis was taken as an example, and solid‐phase extraction coupled with liquid–liquid extraction as a simple and efficient method for enriching trace components, reversed phase column coupled with hydrophilic interaction liquid chromatography XAmide column as two‐dimensional chromatography technology for isolation and preparation of coeluting constituents, enzyme‐linked immune‐sorbent assay as bio‐guided assay, and anti‐inflammatory bioactivity evaluation for bioactive constituents. A combination of 12 β‐carboline alkaloids was identified as anti‐inflammatory bioactive equivalent combinatorial components from A. kansuensis , which accounts for 1.9% w/w of original A. kansuensis . This work answers the key question of which are real anti‐inflammatory components from A. kansuensis and provides a fast and efficient approach for discovering and enriching trace β‐carboline alkaloids from herbal medicines for the first time. More importantly, the discovery of bioactive equivalent combinatorial components could improve the quality control of herbal products and inspire a herbal medicine based on combinatorial therapeutics.     

Comprehensive two‐dimensional PC‐3 prostate cancer cell membrane chromatography for screening anti‐tumor components from Radix Sophorae flavescentis

Radix Sophorae flavescentis is generally used for the treatment of different stages of prostate cancer in China. It has ideal effects when combined with surgical treatment and chemotherapy. However, its active components are still ambiguous. We devised a comprehensive two‐dimensional PC‐3 prostate cancer cell membrane chromatography system for screening anti‐prostate cancer components in Radix Sophorae flavescentis . Gefitinib and dexamethasone were chosen as positive and negative drugs respectively for validation and optimization the selectivity and suitability of the comprehensive two‐dimensional chromatographic system. Five compounds, sophocarpine, matrine, oxymatrine, oxysophocarpine, and xanthohumol were found to have significant retention behaviors on the PC‐3 cell membrane chromatography and were unambiguously identified by time‐of‐flight mass spectrometry. Cell proliferation and apoptosis assays confirmed that all five compounds had anti‐prostate cancer effects. Matrine and xanthohumol had good inhibitory effects, with half maximal inhibitory concentration values of 0.893 and 0.137 mg/mL, respectively. Our comprehensive two‐dimensional PC‐3 prostate cancer cell membrane chromatographic system promotes the efficient recognition and rapid analysis of drug candidates, and it will be practical for the discovery of prostate cancer drugs from complex traditional Chinese medicines.     

Efficient separation of high‐purity compounds from Oxytropis falcata using two‐dimensional preparative chromatography

The separation of high‐purity compounds from traditional Tibetan medicines plays an important role in investigating their bioactivity. Nevertheless, it is often quite difficult to isolate compounds with high purity because of the complexity of traditional Tibetan medicines. In this work, an offline two‐dimensional reversed‐phase preparative method was successfully developed for the separation of high‐purity compounds from Oxytropis falcata . Based on the analysis results, an ODS C18 prep column was used for first‐dimensional preparation, and 14.8 g of the crude sample was separated into five fractions with a recovery of 74.6%. Then, an XAqua C18 prep column was used to isolate high‐purity compounds in the second‐dimensional preparation because its separation selectivity is different with the ODS C18 stationary phase. As a result, eight compounds in the crude sample were isolated in more than 98% purity. This is the first report of trans‐cinnamic acid ( 1 ) and trifolirhizin ( 2 ) from Oxytropis falcata . This method has the potential to be an efficient separation method of high‐purity compounds from Oxytropis falcata and it shows great promise for the separation of high‐purity compounds from complex samples.