k连通图可缩边导出子图的连通性

引进S1 3边形的概念 .证明了 ,对于k(k =3或 4)连通图G ,若G无S1 3边形 ,则 是 2连通的 ;另外也得到 ,设G是k(k≥ 2 )连通图 ,若对G的任一断片F ,有｜F｜ >[k/2 ]+ 1 ,则 是 2连通的 .从而改进并推广了N .Dean的结论 .     

On the validity of the counterpoise correction for the basis set superposition error including the fragment relaxation terms

It is demonstrated that relatively large geometrical changes make Emsley et al.'s assumption (J Am Chem Soc (1978) 100:3303) on the counterpoise correction for the basis set superposition error including the fragment relaxation terms unacceptable. Received: 23 September 1997 / Accepted: 31 October 1997     

Nonaqueous CE ESI‐IT‐MS analysis of Amaryllidaceae alkaloids

The Amaryllidaceae are widely distributed medical plants. Lycorine, lycoramine, lycoremine, and lycobetaine are the major active alkaloids in Amaryllidaceae plants. A nonaqueous CE ESI‐IT‐MS method for separation, identification, and quantification of the Amaryllidaceae alkaloids has been developed. The MS^1–3 behavior has been studied and the fragmentation pathways of main fragment ions have been proposed. The effects of several factors such as composition and concentration of buffer, applied voltage, composition, and flow rate of the sheath liquid, nebulizing gas pressure, flow rate, and temperature of drying gas were investigated. Under the optimal conditions, the linear concentration range of these compounds was wide with the correlation coefficient (R²) >0.99. RSDs of migration time and peak areas were <10%. The LODs were <240 ng/mL. The proposed method can be successfully applied to the determination of the related alkaloids in the Lycoris radiata roots.     

Atomic level analysis of biomolecules by the scanning atom probe

Utilizing the unique features of the scanning atom probe (SAP) the binding states of the biomolecules, leucine and methionine, are investigated at atomic level. The molecules are mass analyzed by detecting a single atom and/or clustering atoms field evaporated from a specimen surface. Since the field evaporation is a static process, the evaporated clustering atoms are closely related with the binding between atoms forming the molecules. For example, many thiophene radicals are detected when polythiophene is mass analyzed by the SAP. In the present study the specimens are prepared by immersing a micro cotton ball of single walled carbon nanotubes (SWCNT) in the leucine or methionine solution. The mass spectra obtained by analyzing the cotton balls exhibit singly and doubly ionized carbon ions of SWCNT and the characteristic fragments of the molecules, CH₃, CHCH₃, C₄H₇, CHNH₂ and COOH for leucine and CH₃, SCH₃, C₂H₄, C₄H₇, CHNH₂ and COOH for methionine.     

Bis-peri-dinaphtho-rylenes: Facile Synthesis via Radical-Mediated Coupling Reactions and their Distinctive Electronic Structures

Polycyclic aromatic hydrocarbons (PAHs) with a one-dimensional (1D), ribbon-like structure have the potential to serve as both model compounds for corresponding graphene nanoribbons (GNRs) and as materials for optoelectronics applications. However, synthesizing molecules of this type with extended π-conjugation presents a significant challenge. In this study, we present a straightforward synthetic method for a series of bis-peri-dinaphtho-rylene molecules, wherein the peri-positions of perylene, quaterrylene, and hexarylene are fused with naphtho-units. These molecules were efficiently synthesized primarily through intramolecular or intermolecular radical coupling of in situ generated organic radical species. Their structures were confirmed using X-ray crystallographic analysis, which also revealed a slightly bent geometry due to the incorporation of a cyclopentadiene ring at the bay regions of the rylene backbones. Bond lengh analysis and theoretical calculations indicate that their electronic structures resemble pyrenacenes more than quinoidal rylenes. That is, the aromatic sextets are predominantly localized along the long axis of the skeletones. As the chain length increases, these molecules exhibit enhanced electronic absorption with a bathochromic shift, and multiple amphoteric redox waves. This study introduces a novel synthetic approach for generating 1D extended PAHs and GNRs, along with their structure-dependent electronic properties.     

Analysis and use of fragment-occurrence data in similarity-based virtual screening

Current systems for similarity-based virtual screening use similarity measures in which all the fragments in a fingerprint contribute equally to the calculation of structural similarity. This paper discusses the weighting of fragments on the basis of their frequencies of occurrence in molecules. Extensive experiments with sets of active molecules from the MDL Drug Data Report and the World of Molecular Bioactivity databases, using fingerprints encoding Tripos holograms, Pipeline Pilot ECFC_4 circular substructures and Sunset Molecular keys, demonstrate clearly that frequency-based screening is generally more effective than conventional, unweighted screening. The results suggest that standardising the raw occurrence frequencies by taking the square root of the frequencies will maximise the effectiveness of virtual screening. An upper-bound analysis shows the complex interactions that can take place between representations, weighting schemes and similarity coefficients when similarity measures are computed, and provides a rationalisation of the relative performance of the various weighting schemes.     

The multiple roles of computational chemistry in fragment-based drug design

Fragment-based drug discovery (FBDD) represents a change in strategy from the screening of molecules with higher molecular weights and physical properties more akin to fully drug-like compounds, to the screening of smaller, less complex molecules. This is because it has been recognised that fragment hit molecules can be efficiently grown and optimised into leads, particularly after the binding mode to the target protein has been first determined by 3D structural elucidation, e.g. by NMR or X-ray crystallography. Several studies have shown that medicinal chemistry optimisation of an already drug-like hit or lead compound can result in a final compound with too high molecular weight and lipophilicity. The evolution of a lower molecular weight fragment hit therefore represents an attractive alternative approach to optimisation as it allows better control of compound properties. Computational chemistry can play an important role both prior to a fragment screen, in producing a target focussed fragment library, and post-screening in the evolution of a drug-like molecule from a fragment hit, both with and without the available fragment-target co-complex structure. We will review many of the current developments in the area and illustrate with some recent examples from successful FBDD discovery projects that we have conducted.     

Lessons for fragment library design: analysis of output from multiple screening campaigns

Over the past 8 years, we have developed, refined and applied a fragment based discovery approach to a range of protein targets. Here we report computational analyses of various aspects of our fragment library and the results obtained for fragment screening. We reinforce the finding of others that the experimentally observed hit rate for screening fragments can be related to a computationally defined druggability index for the target. In general, the physicochemical properties of the fragment hits display the same profile as the library, as is expected for a truly diverse library which probes the relevant chemical space. An analysis of the fragment hits against various protein classes has shown that the physicochemical properties of the fragments are complementary to the properties of the target binding site. The effectiveness of some fragments appears to be achieved by an appropriate mix of pharmacophore features and enhanced aromaticity, with hydrophobic interactions playing an important role. The analysis emphasizes that it is possible to identify small fragments that are specific for different binding sites. To conclude, we discuss how the results could inform further development and improvement of our fragment library. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

环戊二烯分子内π电子的离域是失稳定的--分子内π和σ轨道分离法

为环戊二烯分子中非平面片断的片断轨道的建立提供了一个新的方法和计算程序 .分子内的Morokuma作用能的计算表明 ,“π电子的离域是失稳定的”与“离域的π体系是失稳定的”是两个完全不同的概念 .π电子离域的结构效应完全取决于 σ体系对离域的作用 .在环戊二烯分子中 ,π电子的离域和离域的π体系均是失稳定的 .在苯分子中 ,π电子的离域是失稳定的 ,它的离域π体系也是失稳定的 .但在 D6 h中 ,离域 π体系是“较小失稳定”的 .应该强调 π与 σ电子间空间作用对分子性能的重大影响 ,以改变经典有机结构理论重 π轻 σ电子效应的研究模式