Polar Kerr rotation spectra in yttrium iron garnet and lithium ferrite: A comparative study

Polar Kerr rotation (PKR) spectra in the range 2.0–5.7 eV at 295 K of lithium ferrite and yttrium iron garnet (YIG) single crystals are reported. The spectra show more details and cover a more extended energy region than those published so far. The interpretation of the spectra is based on the assumptions that 1) PKR is an odd function of the sublattice magnetic moments 2) the origin of PKR in both compounds is of similar nature, the differences due to the different crystal structures (garnet and spinel) being less important. The calculated PKR sublattice components show some similarities in their energy dependences, the magnitude of the tetrahedral sublattice component being higher than that of the octahedral one. The components were used in the calculation of the PKR spectra in diamagnetically substituted yttrium iron garnet (J. Appl. Phys.49, 2212, 1978). The results correctly predict the trends observed experimentally.     

Synthesis,molecular docking and biological evaluation as HDAC inhibitors of cyclopeptide mimetics by a tandem three-component reaction and intramolecular [3+2] cycloaddition

Novel macrocyclic peptide mimetics have been synthesized by exploiting a three-component reaction and an azide–alkyne [3 + 2] cycloaddition. The prepared compounds were screened as HDAC inhibitors allowing us to identify a new compound with promising biological activity. In order to rationalize the biological results, computational studies have also been performed.     

Design,antihuman immunodeficiency activity and molecular docking studies of synthesized 2-aryl and 2-pyrimidinyl pyrrolidines

Molecular Diversity - A series of thirty-one new compounds were synthesized and evaluated for their anti-HIV-1 and cytotoxicity activity. Of these, twelve were found to be inhibitors of HIV...     

Design and synthesis of benzodiazepine-1,2,3-triazole hybrid derivatives as selective butyrylcholinesterase inhibitors

Molecular Diversity - A new series of compounds based on benzodiazepine-1,2,3-triazole were synthesized and evaluated as cholinesterase inhibitors by Ellman’s method. The compounds proved to...     

癌基因MDM2阻断剂的分子结构的NMR研究

根据P53-MDM2复合物晶体结构,设计合成了非肽类小分子作为MDM2的阻断剂.利用超导核磁共振波谱仪,测定了化合物的¹H谱、¹³C谱、¹H-¹H COSY谱、HMQC和HMBC谱,确定了化合物的结构,归属了化合物的¹H、¹³C化学位移,为筛选抗癌活性化合物提供了理论依据.     

Surface analysis of inhibitor films formed by imidazolines and amides on mild steel in an acidic environment

Imidazolines and amidic precursors were synthesized with good yields through an optimized process. These compounds were evaluated as corrosion inhibitors in an aqueous solution of 1.0 M HCl by gravimetric and polarization techniques. AISI 1018 carbon steel displayed a corrosion rate dependent on the molecular structure and concentration of inhibitor in the testing environment. Adsorption of inhibitors was found to follow the Langmuir's isotherm, this concept together with Gibbs’ free energy provided the basis to arrange corrosion inhibitors according to efficiency and stability. The surface analysis by AFM displayed that the damage on the metallic surface was considerably reduced in the presence of certain inhibitors. XPS determined the presence of a layer of inhibitor on the metal surface with protective properties.     

Application of computer assisted combinatorial chemistry in antivirial,antimalarial and anticancer agents design

Combinatorial chemistry and technologies have been developed to a stage where synthetic schemes are available for generation of a large variety of organic molecules. The innovative concept of combinatorial design assumes that screening of a large and diverse library of compounds will increase the probability of finding an active analogue among the compounds tested. Since the rate at which libraries are screened for activity currently constitutes a limitation to the use of combinatorial technologies, it is important to be selective about the number of compounds to be synthesized. Early experience with combinatorial chemistry indicated that chemical diversity alone did not result in a significant increase in the number of generated lead compounds. Emphasis has therefore been increasingly put on the use of computer assisted combinatorial chemical techniques. Computational methods are valuable in the design of virtual libraries of molecular models. Selection strategies based on computed physicochemical properties of the models or of a target compound are introduced to reduce the time and costs of library synthesis and screening. In addition, computational structure-based library focusing methods can be used to perform in silico screening of the activity of Compounds against a target receptor by docking the ligands into the receptor model. Three case studies are discussed dealing with the design of targeted combinatorial libraries of inhibitors of HIV-1 protease, P. falciparum plasmepsin and human urokinase as potential antivirial, antimalarial and anti-cancer drugs. These illustrate library focusing strategies.     

Synthesis, structure, and biological activity of novel (oxdi/tri)azoles derivatives containing 1,2,3-thiadiazole or methyl moiety

To develop novel inhibitors of ketol-acid reductoisomerase, a series of (oxdi/tri)azoles derivatives was synthesized and characterized by (1)H NMR, MS, elemental analyses, and crystallography. According to the biological activities of these compounds obtained both in vivo and in vitro, compound 4-cyclopropyl-3-((4-fluorobenzyl)thio)-5-methyl-4H-1,2,4-triazole showed excellent KARI inhibitory activity (100% at 100?μg?mL?(-1) in vitro). In addition, most of the title compounds exhibited good herbicidal activity against Brassica campestris in vivo.     

Design, synthesis and biological evaluation of indolizine derivatives as HIV-1 VIF–ElonginC interaction inhibitors

The HIV-1 viral infectivity factor (VIF) protein is essential for viral replication. VIF recruits cellular ElonginB/C-Cullin5 E3 ubiquitin ligase to target the host antiviral protein APOBEC3G (A3G) for proteasomal degradation. Thus, the A3G-Vif–E3 complex represents an attractive target for the development of novel anti-HIV drugs. In this study, we describe the design and synthesis of indolizine derivatives as VIF inhibitors targeting the VIF–ElonginC interaction. Many of the synthesized compounds exhibited obvious inhibition activities of VIF-mediated A3G degradation, and 5 compounds showed improvement of activity compared to the known VIF inhibitor VEC-5 (1) with IC $_{50 }$ values about 20 $\upmu $ M. The findings described here will be useful for the development of more potent VIF inhibitors.     

含高碳糖片断的氨基醇及水解产物的波谱分析

利用C10高碳糖合成了具有潜在生物活性的含有高碳糖结构片断的氨基醇,检测了该氨基醇及其水解产物的¹H、¹³C NMR图谱,确证了该类化合物的结构,通过¹H-¹H COSY,HMQC,HMBC等2D NMR 技术对其水解产物的¹H和¹³C NMR数据进行了全归属和较详细的解析.     

Theoretical study of GSK−3<Emphasis Type="Italic">α</Emphasis>: neural networks QSAR studies for the design of new inhibitors using 2D descriptors

Glycogen synthase kinase-3 (GSK-3) targets encompass proteins implicated in AD and neurological disorders. The functions of GSK-3 and its implication in various human diseases have triggered an active search for potent and selective GSK-3 inhibitors. In this sense, QSAR could play an important role in studying these GSK-3 inhibitors. For this reason, we developed QSAR models for GSK−3α, linear discriminant analysis (LDA), and artificial neural networks (ANNs) from nearly 50,000 cases with more than 700 different GSK−3α inhibitors obtained from ChEMBL database server; in total we used more than 20,000 different molecules to develop the QSAR models. The model correctly classified 237 out of 275 active compounds (86.2%) and 14,870 out of 15,970 non-active compounds (93.2%) in the training series. The overall training performance was 93.0%. Validation of the model was carried out using an external predicting series. In these series, the model classified correctly 458 out of 549 (83.4%) compounds and 29,637 out of 31,927 non-active compounds (83.4%). The overall predictability performance was 92.7%. In this study, we propose three types of non-linear ANN as alternative to already existing models, such as LDA. Linear neural network: LNN: 236:236-1-1:1 which had an overall training performance of 96% proved to be the best model. In addition, we did a study of the different fragments of the molecules of the database to see which fragments had more influence in the activity. This can help design new inhibitors of GSK−3α. This study reports the attempts to calculate, within a unified framework probabilities of GSK−3α inhibitors against different molecules found in the literature.     

Infrared Absorption,Nuclear Magnetic Resonance and Electronic Spectra of N-Hydroxyureas and Carbamates

During the course of investigating the anticancer activities of new compounds, we have synthesized a series of novel cyclic N-hydroxyurea derivatives and several carbamate intermediates^1–3. Infrared absorption, nuclear magnetic resonance, and electronic absorption spectra were examined in order to confirm the identities and to study the molecular structure of these compounds.     

De novo design of N-(pyridin-4-ylmethyl)aniline derivatives as KDR inhibitors: 3D-QSAR, molecular fragment replacement, protein-ligand interaction fingerprint, and ADMET prediction

Vascular endothelial growth factor (VEGF) and its receptor tyrosine kinase VEGFR-2 or kinase insert domain receptor (KDR) have been identified as promising targets for novel anticancer agents. To achieve new potent inhibitors of KDR, we conducted molecular fragment replacement (MFR) studies for the understanding of 3D-QSAR modeling and the docking investigation of arylphthalazines and 2-((1H-Azol-1-yl)methyl)-N-arylbenzamides-based KDR inhibitors. Two favorable 3D-QSAR models (CoMFA with q ², 0.671; r ², 0.969; CoMSIA with q ², 0.608; r ², 0.936) have been developed to predict the biological activity of new compounds. The new molecular database generated by MFR was virtually screened using Glide (docking) and further evaluated with CoMFA prediction, protein?Cligand interaction fingerprint (PLIF) and ADMET analysis. 44 N-(pyridin-4-ylmethyl)aniline derivatives as novel potential KDR inhibitors were finally obtained. In this paper, the work flow developed could be applied to de novo drug design and virtual screening potential KDR inhibitors, and use hit compounds to further optimize and design new potential KDR inhibitors.     

The organic luminophores hetarylsubstituted naphthalic anhydride,naphthalimide and naphthoylenebenzimidazole

On the basis of naphthalic and 1,4,5-naphthalenetricarboxilic acids the colour gamma of organic luminophores was synthesized (λ_max in toluene 425–600 nm). The new luminophores are 4-hetarylsubstituted naphthalic anhydride, N-phenylnaphthalimide and 1,8-naphthoylene-1', 2'-benzimidazole, containing heterocyclic radicals: 2-phenyloxazolyl-5, 5-phenyloxazolyl-2, 2-phenyl-(1,3,4-oxadiazolyl)-5, 1,5-diphenylpirazolyl-3, 1,5-diphenylpirazolenyl-3, benzoxazolyl-2, benzimidazolyl-2, or benzthiazolyl-2. The synthesized compounds have an intense fluorescence in organic solvents and polymers and most of them show a strong luminescence in crystals. The relation between structure and luminescence of the synthesized compounds was investigated.     

1-苄基-3-酰胺基-4-取代苯基-2-吖丁啶酮系列化合物的360兆核磁共振氢谱

本文报告八种新合成的1-苄基-3-酰胺基-4-取代苯基-2-吖丁啶酮(即β-内酰胺单环卫生物)的360兆核磁共振氢谱。本系列化合物均未见诸文献。利用偶合常数签定了β-内酰胺环的立体构型,并对整个系列的图谱进行了较详细的解析,证明所合成的化合物均为顺式构型的β-内酰胺单环卫生物。利用80兆核磁共振仪测定,未能获得必要的信息。     

Investigations of the inhibition of copper corrosion in nitric acid solutions by ketene dithioacetal derivatives

Ketene dithioacetal derivatives, namely 3-[bis(methylthio)methylene] pentane-2,4-dione (1), 3-(1,3-dithian-2-ylidene) pentane-2,4-dione (2) and 3-(1,3-dithiolan-2-ylidene) pentane-2,4-dione (3) were synthesized and their respective capacity to inhibit copper corrosion in 3 M HNO₃ was investigated by means of weight loss, potentiodynamic polarization, scanning electron microscopy (SEM) and energy dispersive X-ray fluorescence (XRF). The obtained results indicate that the addition of these compounds significantly decreases the corrosion rate. Potentiodynamic polarization studies clearly showed that the inhibition efficiency increases with increasing concentration of the investigated compounds at a fixed temperature, but decreases with increasing temperature. These results on the whole showed that the studied substances are good cathodic inhibitors for copper corrosion in nitric acid medium. SEM and energy dispersive X-ray (EDAX) examination of the copper surface revealed that these compounds prevented copper from corrosion by adsorption on its surface to form a protective film, which acts as a barrier to aggressive agents. The presence of these organic compounds adsorbed on the electrode surface was confirmed by XRF investigations.     

Electrochemical and quantum chemical studies of some Schiff bases on the corrosion of steel in H2SO4 solution

The efficiency, as steel-corrosion inhibitors in 0.1 M and 1 M H₂SO₄, of two Schiff bases, 2-{[(4-methoxyphenyl)imino]methyl}phenol and 1-{[(4-methoxyphenyl)imino]methyl}-2-naphthol, (abbreviated SB-1 and SB-2, respectively) was investigated by Tafel extrapolation and linear polarization methods. Corrosion parameters and adsorption isotherms were determined from current-potential curves. It was found that the percent inhibition efficiencies (η%) and surface coverage (θ) increase with an increases in the concentrations of inhibitors. The results showed that these compounds act as good corrosion inhibitors especially at high concentrations. The adsorption of used compounds on the steel surface obeys Langmuir's isotherm. Obvious correlation was found between corrosion inhibition efficiency and quantum chemical parameters obtained by B3LYP/6-31g(d) method. The obtained theoretical results have been compared with the experimental findings.     

以(NH_4)_2Ce(NO_3)_6氧化体系合成己二酰-1′,6′-双(4-卤偶氮苯)

以自制的己二酰-1′,6′-双(4-卤苯肼)化合物为原料,在室温条件下用(NH4)2Ce(NO3)6氧化体系氧化脱氢得3种己二酰-1′,6′-双(4-卤偶氮苯)化合物。产品的结构经元素分析、IR、1H NMR确证。产率在89%—93%之间。     

基于支持向量机、支持向量回归和分子对接的CYP450 1A2抑制剂的发现研究

支持向量机,支持向量回归和分子对接的计算方法已广泛应用于化合物的药理活性计算。为了提高计算的准确性和可靠性,拟以细胞色素P450酶1A2为研究载体,运用建立的联合SVM-SVR-Docking计算模型预测潜在的CYP1A2抑制剂。其中,建立的最优SVM定性模型训练集,内部测试集和外部测试集的准确率分别为99.432%,97.727%和91.667%。最优SVR定量模型训练集和测试集的R和MSE分别为0.763,0.013和0.753,0.056。实验表明两个模型具有较高的准确性和可靠性。通过对SVM和SVR模型结果的比较分析,发现连接性指数、分子构成描述符和官能团数目等分子描述符可能与CYP1A2抑制剂的辨识和活性预测密切相关。随后利用分子对接技术分析化合物与CYP1A2的结合构象及相互作用的稳定性。形成氢键相互作用的关键氨基酸包括THR124,ASP320;形成疏水相互作用的关键氨基酸包括ALA317和GLY316。所获得模型可用于天然产物化学成分中CYP1A2潜在抑制剂的活性计算及其介导的药物-药物相互作用预测提供理论指导,也为合理联合用药提供一定参考。共获得20个对CYP1A2具有潜在抑制活性的化合物。部分结果与文献结果相互印证,进一步说明了模型的准确性和联合计算策略的可靠性.