槲皮素与尿嘧啶和胸腺嘧啶氢键的结合位点

深入理解药物分子和核酸碱基间的相互作用机制对合理设计研发新型高效药物有重要意义. 本文运用密度泛函理论B3LYP方法对核酸碱基尿嘧啶和胸腺嘧啶与药物分子槲皮素间的氢键相互作用位点进行了研究. 使用B3LYP/6-31G(d)方法优化得到了30个稳定的氢键复合物结构, 使用B3LYP/6-311++G(3df,2p)方法计算了这些复合物的结合能. 研究结果表明, 槲皮素可以使用5个不同的结合位点与尿嘧啶或胸腺嘧啶形成氢键复合物, 尿嘧啶或胸腺嘧啶可以使用3个不同的结合位点与槲皮素形成氢键复合物. 当槲皮素的结合位点固定时, 槲皮素与尿嘧啶的位点u1或胸腺嘧啶的位点t1形成的氢键作用最强, 与位点u2或位点t2形成的氢键强度最弱; 当尿嘧啶或胸腺嘧啶的作用位点固定时, 二者与槲皮素的位点qu1 形成的氢键作用最强, 与位点qu5 作用强度次之, 与位点qu3的作用强度最弱. 分子中原子(AIM)和自然键轨道(NBO)分析计算结果表明, 轨道作用在氢键中起重要作用.     

FUNCTIONALIZED β-CYCLODEXTRIN POLYMERS FOR THE SORPTION OF BILE SALTS

Poly(β-cyclodextrin) (PCD) resins were prepared by a crosslinking reaction of β-cyclodextrin with different amounts of epichlorhydrin. Some hydroxyl groups of these polymers were functionalized with alkyl quaternary ammonium groups. The polymers were tested for their ability to bind several bile salts (including the sodium salts of cholic acid, glycocholic acid, and chenodeoxycholic acid), individually and competitively, from phosphate buffer solutions. In all cases, the aminated PCD resin had a higher binding capacity for bile salts. The binding of chenodeoxycholate by the resins was much more effective than that of cholate and its conjugate, which indicates the importance of the host cavity size relative to that of the guest molecules. The degree of hydrophobicity of bile acids also plays a role in their binding by PCD resins. The variable temperature studies indicate that the electrostatic interactions become weaker at higher temperatures while the hydrophobic interactions are not as much affected.     

The Host-Guest Chemistry of Proflavine with Cucurbit[6,7,8]urils

The binding of the polyaromatic guest, 3,6-diaminoacridine (Proflavine) to cucurbit[n]uril (CB[n]) where n = 6, 7 and 8 has been studied by fluorescence spectrophotometry and binding constants determined using a least squares fitting method. Titration of CB[8] into a solution of Proflavine results in a 95% decrease in fluorescence up to a CB[8] to Proflavine ratio of 2:1. From the induced fluorescence spectra a binding constant of 1.9 × 10⁷ M^? 1 was determined. When Proflavine is titrated into a solution of CB[8] a similar binding constant is calculated (1.3 × 10⁷ M^? 1). Titration of CB[6] into a solution of Proflavine yields a decrease in fluorescence of 18–20%, but no binding is observed beyond what is seen within experimental error. Finally, titration of CB[7] into a solution of Proflavine results in an increase in fluorescence (32%) and a blue-shift of the emission wavelength from 509 nm to 485 nm. From the induced fluorescence spectra a binding constant of 1.65 × 10⁷ M^? 1 was determined. From ¹H NMR it appears that the decrease in fluorescence for Proflavine with CB[6] and CB[8] is due to collisional quenching, whereas the increase in fluorescence with CB[7] may be due to rotational restriction.     

抑制剂G4G与HIV-1蛋白酶作用模式的结合自由能计算研究

本文采用分子动力学模拟和结合自由能计算研究了抑制剂G4G与HIV-1蛋白酶的作用机制。研究结果表明范德华作用主导了抑制剂G4G与HIV-1蛋白酶的结合。基于残基的自由能计算表明残基Gly49、Ile50、Val82、Ile84、Gly27′、Ala28′、Ile50′和Ile84′与G4G产生了较强的相互作用,同时研究也表明CH-π,CH-O相互作用和氢键是其主要的作用形式。该研究能为以HIV-1蛋白酶为靶标的抗艾滋病药物设计提供理论上的指导。     

取代基对腺嘌呤与胸腺嘧啶氢键复合物体系结合能的影响简

优化得到了17个取代胸腺嘧啶与腺嘌呤形成的氢键复合物的结构,并计算了这些复合物的结合能,探讨了胸腺嘧啶上不同取代基对结合能的影响. 结果表明,CF3取代的胸腺嘧啶与腺嘌呤间的结合能大于胸腺嘧啶与腺嘌呤间的结合能,这可能是屈氟尿苷具有阻止病毒及肿瘤扩散功能的原因所在. SO3H,CN和NO2取代的胸腺嘧啶与腺嘌呤间具有更大的结合能,表明这3个基团取代的胸腺嘧啶也可能具有潜在的抗肿瘤作用. 分子中原子理论与自然键轨道分析表明,在所有体系中,氢键N—H…N最强,N—H…O=C次之,C—H…O=C最弱,轨道作用在氢键作用中占有重要地位.     

Validation and application of modeling algorithms for the design of molecularly imprinted polymers

In the study, four different semiempirical algorithms, modified neglect of diatomic overlap, a reparameterization of Austin Model 1, complete neglect of differential overlap and typed neglect of differential overlap, have been applied for the energy optimization of template, monomer, and template‐monomer complexes of imprinted polymers. For phosmet‐, estrone‐, and metolcarb‐imprinted polymers, the binding energies of template‐monomer complexes were calculated and the docking configures were assessed in different molar ratio of template/monomer. It was found that two algorithms were not suitable for calculating the binding energy in template‐monomers complex system. For the other algorithms, the obtained optimum molar ratio of template and monomers were consistent with the experimental results. Therefore, two algorithms have been selected and applied for the preparation of enrofloxacin‐imprinted polymers. Meanwhile using a different molar ratio of template and monomer, we prepared imprinted polymers and nonimprinted polymers, and evaluated the adsorption to template. It was verified that the experimental results were in good agreement with the modeling results. As a result, the semiempirical algorithm had certain feasibility in designing the preparation of imprinted polymers.     

Novel analytical methods for characterising binding media and protective coatings in artworks

Since the first reported analytical studies and technical examinations of art and archaeological objects conducted in the late 18th century, analytical techniques and methods applied to the study of artworks have constantly grown. Among the materials composing the art object, organic compounds used as binding media or protective coatings have attracted the attention of the conservation profession given their noticeable ability for undergoing morphological and chemical changes on ageing. Thus, the aim of this paper is to review the most recent advances in the identification and determination of organic compounds present in art and art conservation materials. Immunofluorescence techniques have been proposed in recent decades as an alternative to the classical and simpler microchemical tests. Besides, a variety of instrumental techniques have also been improved in an attempt to enhance the sensitivity, repeatability and accuracy of the analytical results. Spectroscopic techniques, such as UV-vis, FTIR and Raman spectroscopy, have been coupled with light microscopes for these purposes. Synchrotron radiation FTIR microspectroscopy has also been successfully applied to the analysis of artworks. Mass spectrometry has also been increasingly used as a detector system coupled with a chromatographic device. Chromatographic methods have also improved in recent years. Paper and thin layer chromatographic techniques have been progressively replaced with gas chromatography (GC), pyrolysis-GC, high performance liquid chromatography and capillary electrophoresis. More complex proteomics hyphenated techniques, such as nano-liquid chromatography-nano-electrospray ionisation/collision quadrupole time-of-flight tandem mass spectrometry, have been recently applied to the identification and determination of proteinaceous binders. Microbeam analytical techniques have also been incorporated into the list of advanced instrumental techniques for art conservation purposes. Finally, a number of new instrumental techniques have been proposed as a suitable alternative to the conventional microscopy techniques for morphological studies.     

Specificity in the Cu interactions with prion protein fragments and related His-rich peptides from mammals to fishes

The prion proteins may play a critical role in copper homeostasis and the antioxidant activity in the brain. This review presents the state of art in the studies on Cu²⁺ prion systems. The proteins discussed are from different species from mammals to fishes. All proteins are His-rich and the research discussed clearly indicates the basic role of imidazole side chains and the adjacent amide nitrogen atoms in metal ion binding. Prions represent the family of proteins with new mode of Cu²⁺ binding which includes the amide nitrogen coordination. The multi-imidazole coordination is also likely and it can play a critical role in the antioxidant activity of the copper–prion complexes. The combination of the imidazole and amide nitrogen atoms to Cu²⁺ ions could also be relevant in histidine-rich peptide antibiotics including demegen. The impact of peptide sequence and His positions on copper binding ability is also discussed.     

Influence of phosphonium-based ionic liquid on the micellization behavior of surfactants system and potential application in paracetamol drug aggregation

The current study examines the effects of a phosphonium-based ionic liquid, trihexyltetra-decylphosphonium bis-(2,4,4-trimethyl pentyl)phosphinate [THTDPP], on the micellization properties of surfactants, namely sodium dodecyl sulfate (SDS) and Triton X-100 by using the stalagmometry, viscosity, colorimetric, and FTIR methods. The surface adsorption parameters, such as CMC, γ_CMC, Γ_max, A_min, π_CMC, and _pC₂₀, were determined using the stalagmometry method. The results show that with the addition of different weight percentages of [THTDPP], the CMC and γ_CMC values decreased considerably in the following order: water >0.5 wt% of IL > 0.7 wt% of IL > 1.0 wt% of IL. The A_min values decreased with an increase in the wt% of IL for Triton X-100, but for SDS, this value increased. The _pC₂₀ was observed to be greater in Triton X-100 compared to SDS. The ability of [THTDPP] to decrease the CMC was found to be greater in Triton X-100 compared to SDS. The relative viscosity was calculated, and the first observation was made at the pre-CMC stage, where the concentration of SDS+0.7 wt% IL was 4.0 mM. The second finding was made post-CMC at a concentration of 5.0 mM. Afterward, the relative viscosity graph grew slowly and gradually. The functional groups involved in the complexation between [THTDPP] and both surfactants were examined using FTIR spectroscopy. Additionally, the micellar solutions of surfactants + [THTDPP] were used to explore Paracetamol [PCM] aggregation. The findings from UV–vis spectroscopy show that Triton X-100 exhibits the highest binding affinity and has the most encouraging effect compared to SDS.