药物构效关系研究与药物设计中常用计算机软件

分子力学、量子化学和分子图形学是研究有机药物分子电子特性、空间性质及其与受体相互作用的有力工具。现扼要介绍国内外较常用的量子化学和分子力学及分子图形学有关计算机程序的应用特性。     

Photodynamic therapy of tumours: value of quantum chemical procedures for characterization of new drugs. Prediction of the electronic structure of zinc(II) phthalocyanine with special emphasis on triplet state excitation energies

Zinc(II) phthalocyanine is the active component of the liposomal formulation CGP 55847 which showed a high activity in photodynamic therapy in a variety of animal tumours. The photophysical properties of zinc(II) phthalocyanine have been studied in detail and compared to those of Photofrin, the only sensitizing agent approved so far for phase III/IV clinical trials. Since the efficacy of photodynamic therapy intrinsically depends on the spectroscopic features of the sensitizer, quantum chemical methods have proven to be an efficient means for optimizing chemical structures. As will be shown, a simple modification of the time-honoured INDO model of Pople allows a prediction of the singlet and triplet state properties of molecules of the size of zinc(II) phthalocyanine with an rms error of ≤ 1000 cm⁻¹.     

苯并恶唑类化合物的研究——Ⅰ.化合物的合成及光物理性能

合成了四种结构类型的苯并恶唑化合物共15个:测试了它们的红外吸收光谱,以及它们在DMF中的紫外吸收、荧光发射和激光发射光谱。苯基取代物的荧光量子产率在0.64～0.66,无激光性能。其余的化合物荧光量子产率都大于0.70,在最大吸收波长下的激光转换效率为2.5～5.9%。     

An algorithm for the automated quantitation of metabolites in in vitro NMR signals.

The quantitation of metabolite concentrations from in vitro NMR spectra is hampered by the sensitivity of peak positions to experimental conditions. The quantitation methods currently available are generally labor intensive and cannot readily be automated. Here, an algorithm is presented for the automatic time domain analysis of high-resolution NMR spectra. The TARQUIN algorithm uses a set of basis functions obtained by quantum mechanical simulation using predetermined parameters. Each basis function is optimized by subdividing it into a set of signals from magnetically equivalent spins and varying the simulated chemical shifts of each of these groups to match the signal undergoing analysis. A novel approach to the standard multidimensional minimization problem is introduced based on evaluating the fit resulting from different permutations of possible chemical shifts, obtained from one-dimensional searches. Results are presented from the analysis of (1)H proton magic angle spinning spectra of cell lines illustrating the robustness of the method in a typical application. Simulation was used to investigate the biggest peak shifts that can be tolerated.     

生物功能化半导体量子点对活细胞内蛋白质分子可视化的研究进展

半导体量子点(或称半导体纳米微晶体)具有独特的光谱特性和良好的光化学稳定性。通过改变量子点的材料或粒径大小可在同一波长光激发下获得从紫外到近红外(或从蓝色到红色)波长范围内任意点的发射光谱。随着近年来生物亲和性功能化纳米技术的发展,为半导体量子点用于多通道、高通量对活细胞内蛋白质分子直接观察研究这一国际未解决的难题提供了可能。概述了生物功能化半导体量子点在活细胞生理条件对蛋白质分子进行可视化研究的最新进展,评价了其作为荧光探针对活细胞蛋白质分子进行实时动态研究的发展前景。     

量子共振对肿瘤患者维生素C和微量元素硒的研究

目的 :研究恶性肿瘤患者体内维生素C和微量元素硒的水平。方法 :对临床上已确诊为恶性肿瘤患者用量子共振同康信息检测仪检测其体内的维生素C和微量元素硒。结果 :肿瘤患者严重缺乏维生素C和微量元素硒。结论 :肿瘤患者与正常人群相比 ,体内严重缺乏维生素C和微量元素硒。     

Development of a fluorescence-linked immunoassay based on quantum dots for fenvalerate

The glutathione-coated CdTe quantum dots (QDs) were synthesized in a paper. After purification, the QDs were coupled with monoclonal antibody to fight against fenvalerate. The conjugates had the same emission wavelength as that of QDs. The excitation wavelength and emission wavelength of the conjugates were determined to obtain the highest signal-to-noise ratio. After the antibody concentration optimization, the fluorescence-linked immunoassay method was developed. The method used the QDs as the signal to quantify the fenvalerate. Compared with the enzyme-linked immunosorbent assay (ELISA), it saved more than 1 h and decreased the false-positive rate using the specified emission wavelength of QDs. The 50% inhibitory concentration (IC₅₀) of the method was 0.28 µg mL^?1. The detection limit was 25 ng mL^?1 and the linear range was 60 ng mL^?1–3.83 µg mL^?1. Via preliminary application, fenvalerate residues in spiked samples were determined. The recovery of fenvalerate in water samples ranged from 84.5% to 96.2% and that in vegetables ranged from 72.5% to 125.7%. It was a rapid detection of the fenvalerate residue in environment and vegetables.     

Cavity cooling of an optically levitated submicron particle

The coupling of a levitated submicron particle and an optical cavity field promises access to a unique parameter regime both for macroscopic quantum experiments and for high-precision force sensing. We report a demonstration of such controlled interactions by cavity cooling the center-of-mass motion of an optically trapped submicron particle. This paves the way for a light–matter interface that can enable room-temperature quantum experiments with mesoscopic mechanical systems.     

Effects of Asymmetric Quantum Wells on the Structural and Optical Properties of InGaN-Based Light-Emitting Diodes

A metalorganic vapor phase epitaxy-grown InGaN/GaN multiple-quantum-well (MQW) with three graded-thickness wells (the first-grown well had the greatest width) near the n-GaN was used as the active layer of an LED. For LEDs with an asymmetric quantum well (AQW), high-resolution X-ray diffraction and transmission electron microscopic reveal that the modified MQWs with a reasonable crystalline quality were coherently strained on the underlying GaN epilayers without any relaxation. In addition, the slight increase of indium segregation in the LED with an AQW may be attributed to variations in indium contents experienced during epitaxial growth of the wide well-containing MQWs. By preventing the energetic electrons from accumulating at the topmost quantum well nearest the p-GaN, the presence of light intensity roll-off in the LED with an AQW is shifted to higher currents and the corresponding maximum light output power is increased with a ratio 7.9% higher than that of normal LEDs. Finally, similar emission wavelengths were observed in the electroluminescence spectra of both LEDs, suggesting that light emitted mostly from the top quantum wells (near the p-GaN) while the emissions from the AQW region were insignificant.     

Nuclear spin singlet states as a contrast mechanism for NMR spectroscopy

Nuclear magnetic resonance (NMR) spectra of complex chemical mixtures often contain unresolved or hidden spectral components, especially when strong background signals overlap weaker peaks. In this article we demonstrate a quantum filter utilizing nuclear spin singlet states, which allows undesired NMR spectral background to be removed and target spectral peaks to be uncovered. The quantum filter is implemented by creating a nuclear spin singlet state with spin quantum numbers j = 0, m_z = 0 in a target molecule, applying a continuous RF field to both preserve the singlet state and saturate the magnetization of undesired molecules and then mapping the target molecule singlet state back into an NMR observable state so that its spectrum can be read out unambiguously. The preparation of the target singlet state can be carefully controlled with pulse sequence parameters, so that spectral contrast can be achieved between molecules with very similar structures. We name this NMR contrast mechanism ‘Suppression of Undesired Chemicals using Contrast‐Enhancing Singlet States’ (SUCCESS) and we demonstrate it in vitro for three target molecules relevant to neuroscience: aspartate, threonine and glutamine. Copyright © 2013 John Wiley & Sons, Ltd.