本征值方法在抗氧化剂定量构效关系研究中的应用

Antioxidants are of great interest because of their involvement in many important biological and industrial processes. It is meaningful to study their structure-antioxidant activity relationship (SAAR) and design novel, efficient and low-toxicity antioxidant. In this paper, Eigen Value Analysis (EVA), a 3-dimensional quantitative structure activity relationship (3-D QSAR) method, was employed to study antioxidant SAAR. Significant relational models were obtained with all the PLS cross-validate qcv^2 values being larger than 0.5, meaning that the models have sound predictive power. Compared with other QSAR methods, EVA possesses several advantages, especially that it does not need alignment. It should be believed that EVA will be an efficient approach to SAAR.     

DFT‐based QSAR study and molecular design of AHMA derivatives as potent anticancer agents

A quantitative structure–activity relationship (QSAR) of 3‐(9‐acridinylamino)‐5‐hydroxymethylaniline (AHMA) derivatives and their alkylcarbamates as potent anticancer agents has been studied using density functional theory (DFT), molecular mechanics (MM+), and statistical methods. In the best established QSAR equation, the energy (E_NL) of the next lowest unoccupied molecular orbital (NLUMO) and the net charges (Q_FR) of the first atom of the substituent R, as well as the steric parameter (MR₂) of subsituent R₂ are the main independent factors contributing to the anticancer activity of the compounds. A new scheme determining outliers by “leave‐one‐out” (LOO) cross‐validation coefficient (q) was suggested and successfully used. The fitting correlation coefficient (R²) and the “LOO” cross‐validation coefficient (q²) values for the training set of 25 compounds are 0.881 and 0.829, respectively. The predicted activities of 5 compounds in the test set using this QSAR model are in good agreement with their experimental values, indicating that this model has excellent predictive ability. Based on the established QSAR equation, 10 new compounds with rather high anticancer activity much greater than that of 34 compounds have been designed and await experimental verification. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Aggregation of poly(1,3‐cyclohexadiene): Effects of molecular weight and polymer chain structure

The aggregation of poly(1,3‐cyclohexadiene) (PCHD), obtained by anionic polymerization with alkyllithium/amine systems, was examined using size exclusion chromatography (SEC) and size exclusion chromatography coupled with a multiangle laser light scattering photometer (SEC‐MALS). The PCHD polymer chain has a structure consisting of a main chain formed by 1,2‐addition (the 1,2‐CHD unit) and 1,4‐addition (the 1,4‐CHD unit). Mild stirring with relatively low temperature in the polymerization reaction forms an aggregation of PCHD. The molecular weight and molar ratio of 1,2‐CHD/1,4‐CHD units in the polymer chain strongly influence the aggregation of PCHD. In a high molecular weight PCHD, containing ～50% 1,2‐CHD units, an aggregation of the polymer was observed in tetrahydrofuran (THF) solution at room temperature. This aggregation of PCHD was soluble in 1,2,4‐trichlorobenzene (TCBz) and could be separated into each polymer molecule. In contrast, a polymer chain with a high content of 1,4‐CHD units having a relatively low cis‐stereospecificity was easily soluble in THF and TCBz without aggregating. A long polymer chain structure with a high content of 1,2‐CHD units is considered to be the reason for the generation of strong intermolecular forces contributing to the aggregation of PCHD with the solvophobic interactions. The degree of aggregation could be controlled by the conditions of the PCHD polymer solution. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 1442–1452, 2006     

An alignment‐free methodology for modelling field‐based 3D‐structure activity relationships using inductive logic programming

Traditional 3D‐quantitative structure–activity relationship (QSAR)/structure–activity relationship (SAR) methodologies are sensitive to the quality of an alignment step which is required to make molecular structures comparable. Even though many methods have been proposed to solve this problem, they often result in a loss of model interpretability. The requirement of alignment is a restriction imposed by traditional regression methods due to their failure to represent relations between data objects directly. Inductive logic programming (ILP) is a class of machine‐learning methods able to describe relational data directly. We propose a new methodology which is aimed at using the richness in molecular interaction fields (MIFs) without being restricted by any alignment procedure. A set of MIFs is computed and further compressed by finding their minima corresponding to the sites of strongest interaction between a molecule and the applied test probe. ILP uses these minima to build easily interpretable rules about activity expressed as pharmacophore rules in the powerful language of first‐order logic. We use a set of previously published inhibitors of factor Xa of the benzamidine family to discuss the problems, requirements and advantages of the new methodology. Copyright © 2007 John Wiley & Sons, Ltd.     

Retention Prediction System of O‐Aryl,O‐(1‐methylthioethylidene‐amino)phosphates on RP‐HPLC

Using factor analysis and stepwise linear regression methods, two parameters – CMR and ECCR – were selected from eight solute‐related structure parameters as the most retention‐influencing parameters. The relationships between the retention data (k ´) and the two structure parameters were established for 13 O‐aryl,O‐(1‐methylthioethylideneamino)phosphate compounds under a wide range of experimental conditions. The retention data (k ´) of another seven compounds with similar structures were predicted using these QSRR equations. Good agreement was obtained between the experimental k ´ values and predicted ones.     

Structural Characterization and Toxicity Prediction of Some Organic Compounds

A new molecular structural characterization(MSC)method called molecular vertexes correlative index(MVCI)was constructed in this paper.The index was used to describe the structures of 45 compounds and a quantitative structure-activity relationship(QSAR)model of toxicity(–lgEC50)was obtained through multiple linear regression(MLR)and stepwise multiple regression(SMR).The correlation coefficient(R)of the model was 0.912,and the standard deviation(SD)of the model was 0.525.The estimation stability and prediction ability of the model were strictly analyzed by both internal and external validations.The Leave-One-Out(LOO)Cross-Validation(CV)correlation coefficient(RCV)was 0.816 and the standard deviation(SDCV)was 0.739,respectively.For the external validation,the correlation coefficient(Rtest)was 0.905 and the standard deviation(SDtest)was 0.520,respectively.The results showed that the index was superior in molecular structural representation.The stability and predictability of the model were good.     

Design,Synthesis, Antifungal Activities and SARs of (R)‐2‐Aryl‐4,5‐dihydrothiazole‐4‐carboxylic Acid Derivatives

Based on the structure of natural product 2‐aryl‐4,5‐dihydrothiazole‐4‐carboxylic acid, a series of novel (R)‐2‐aryl‐4,5‐dihydrothiazole‐4‐carboxylic acid derivatives were designed and synthesized. Their structures were characterized by ¹H NMR, ¹³C NMR and HRMS. The single crystal structure of compound 9b was determined by X‐ray diffraction analysis. The antifungal activities were evaluated for the first time. The bioassay results indicated that most compounds exhibited moderate to good antifungal activities. The antifungal activities of compound 13a (against Cercospora arachidicola Hori), 13d (against Alternaria solani), and 16e (against Cercospora arachidicola Hori) were 61.9%, 67.3% and 61.9%, respectively, which are higher than those of the commercial fungicides chlorothalonil and carbendazim. Moreover, compound 13d exhibited excellent antifungal activities against 7 kinds of the fungi tested (66.7%, 77.3%, 63.0%, 87.9%, 70.0%, 70.0% and 80.0% at 50 µg?mL). Therefore, 13d can be used as a new lead structure for the development of antifungal agents.     

N-(4-甲基苯甲酰氨基) N’-[5-(2-三氟甲基苯基)-2-呋喃甲酰硫脲的合成、晶体结构测定与生物活性测定

本文首次合成标题化合物N-(4-甲基苯甲酰氨基)-N’-[5-(2-三氟甲基苯基)-2-呋喃甲酰硫脲。化合物(C21H16F3N3O3S, Mr = 447.43)单晶经测定为单斜晶体,空间群为P -1。在晶体中,存在一些分子内和分子间的相互作用,分子间还有C—H···π 的相互作用,这可能导致晶体更稳定的原因。目标产物的结构经IR, H NMR和元素分析测定确证。初步生物活性测试表明,部分化合物对棉花枯萎病、黄瓜灰霉病、苹果轮纹病和棉花炭疽病有较好的选择性杀菌活性;部分目标化合物有较好的除草活性。     

Binding conformations,QSAR, and molecular design of Alkene‐3‐quinolinecarbonitriles as Src inhibitors

A theoretical study on binding orientations and quantitative structure–activity relationship (QSAR) of a novel series of alkene‐3‐quinolinecarbonitriles acting as Src inhibitors has been carried out by using the docking study and three‐dimensional QSAR (3D‐QSAR) analyses. The appropriate binding orientations and conformations of these compounds interacting with Src kinase were revealed by the docking studies, and the established 3D‐QSAR models show significant statistical quality and satisfactory predictive ability, with high R² values and q² values: comparative molecular field analysis (CoMFA) model (q² = 0.748, R² = 0.972), comparative molecular similarity indices analysis (CoMSIA) model (q² = 0.731, R² = 0.987). The systemic external validation indicated that both CoMFA and CoMSIA models possessed high predictive powers with $ R{^2}_{\!\!\!\rm pred} $ values of 0.818 and 0.892, $ {r^2}_{\!\!\!\rm m} $ values of 0.879 and 0.886, $ {r^2}_{\!\!\!\rm m(LOO)} $ values of 0.874 and 0.874, $ r^2_{\rm m(overall)} $ values of 0.879 and 0.885, respectively. Several key structural features of the compounds responsible for inhibitory activity were discussed in detail. Based on these structural factors, eight new compounds with quite higher predicted Src‐inhibitory activities have been designed and presented. We hope these theoretical results can offer some valuable references for the pharmaceutical molecular design as well as the action mechanism analysis. © 2012 Wiley Periodicals, Inc.     

Control of molecular aggregation in symmetrically substituted π‐conjugated bulky poly(p‐phenylenevinylene)s and their copolymers

A new series of symmetrically substituted bulky PPV‐copolymers based on poly(bis‐2,5‐(2‐ethylhexyloxy)‐1,4‐phenylenevinylene) ( BEH‐PPV ) bearing tricyclodecane (TCD) pendants were synthesized to study the effect of chain aggregation in the π‐conjugated polymer backbone. The composition of the copolymers was varied up to 100 mol % and the structures of the copolymer were confirmed by NMR and FTIR. The molecular weights of the copolymers were obtained as M_w = 11,500–1,78,800 depending on the TCD‐incorporation in BEH‐PPV. The origin of the π‐aggregation was investigated using mixture of solvents (polar or nonpolar) or temperature as external stimuli. Absorption, photoluminescence, and time‐resolved fluorescence decay techniques were employed as tools to trace molecular aggregation in solution and solid state. The TCD‐substituted bulky copolymers showed almost twice the enhancement in photoluminescence compared with that of BEH‐PPV . Solvent‐induced aggregation studies of copolymers revealed the existence of strong molecular aggregation in BEH‐PPV compared with that of bulky copolymers. Variable temperature studies further evidence for the reversibility of molecular aggregation on heating/cooling cycles and showed isosbetic points with respect to free and aggregated polymer chains. Time‐resolved fluorescent studies confirmed the existence of free and aggregated π‐conjugated species with a life time of 0.1 to 1.0 ns. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2631–2646, 2009