1—芳酰基—3—（4—苯磺酰胺）硫脲类化合物的合成

以无水丙酮作溶剂，由芳酰基异硫氰酸酯与左侧胺反应合成了一系列新的１－芳酰基－３－（４－苯磺酰胺）硫脲。     

(3-苄基-4-芳酰基-1,2,4-三唑-5-基)(5-本基-1,3,4-噁二唑-2-基)硫醚的合成

通过3-苄基-4-芳酰基-1,2,4-三唑-5-巯基负离子在2-甲磺酰基-5-苯基-1,3,4-噁二唑环2-位上的亲核取代反应,制得13个新的(3-苄基-4-芳酰基-1,2,4-三唑-5-基)(5-苯基-1,3,4-噁二唑-2-基)硫醚衍生物.经元素分析、IR、~1H NMR和MS裂解碎片分析确认结构.初步观察了它们在0.01％浓度时对大肠杆菌繁殖的抑制作用.     

2-芳基戊二酸酯的合成

在K2CO3-TEBA相转移催化体系中,4位或2位含有—NO2的苯磺酰基乙酸酯与α,β-不饱和酯发生加成-重排反应,制得2-芳基戊二酸酯,其收率较高(73%～87%)。研究了反应物-芳磺酰基乙酸酯苯环上取代基对加成-重排反应的影响,发现只有当芳环上4位或2位有硝基时,在K2CO3-TEBA相转移催化体系中,芳磺酰基乙酸酯与α,β-不饱和酯反应才可发生加成-重排反应,生成2-芳基戊二酸酯,其机理可能是芳磺酰基乙酸酯与α,β-不饱和酯首先发生Michael加成反应,随后加成产物发生分子内的亲核取代,酸化后脱去SO2得2-芳基戊二酸酯。而当芳环上4位或2位含有给电子基团(如,甲基)或弱吸电子基团(如,氯)时,却只能发生正常的Michael加成反应,生成相应的2-芳磺酰基戊二酸酯。     

酰氨基硫脲及其相关杂环衍生物的研究(Ⅹ)——1-(4′-吡啶甲酰基)-4-芳酰胺基硫脲类化合物环化反应的研究

本文研究1-(4′-吡啶甲酰基)-4-芳酰胺基硫脲(Ⅰ)在碱催化条件下的环化反应。结果表明,当(Ⅰ)芳环连接吸电子基如硝基、卤素或推电子取代基如甲基和甲氧基等时,均环化为3-(4′-吡啶基)-4-芳酰基-1,2,4-三唑啉-5-硫酮(Ⅱ),通过质谱裂解碎片分析确定其结构,并初步评价部分化合物对结核菌的抑制作用。     

新型2-甲氧羰基-5-芳甲亚胺基苯磺酰胺的合成及其生物活性

在微波或超声波辅助下,2-甲氧羰基-5-氨基苯磺酰胺与取代苯甲醛反应合成了8个新型2-甲氧羰基-5-芳甲亚胺基苯磺酰胺(3a ～ 3h),其结构经1H NMR,MS及元素分析表征.生物活性测试结果表明,大部分3具有一定的杀菌活性,其中3b和3f在用量为500 mg·L-1时,对黄瓜菌核病的防治效果高于90％.     

4-芳氧乙(丙)酰氨基苯磺酰胺的合成与除草活性

芳氧羧酸;4-芳氧乙(丙)酰氨基苯磺酰胺的合成与除草活性     

新型吖啶-9-磺酰胺衍生物的合成及光谱学性质

在吖啶磺酰胺分子中引入杂环安替比林吸电性基团,合成了N-对甲基苯磺酰基-N-(4-安替比林)-10-甲基吖啶-9-磺酰胺三氟甲基磺酸鎓盐.最终产物与未甲基化的前体分别与模型化合物N-对甲基苯磺酰基-N-苯基-10-甲基吖啶-9-酰胺三氟甲基磺酸鎓盐及其前体的紫外-可见吸收光谱(UV)、荧光光谱(FL)进行比较.结果表明,引入杂环安替比林使吖啶磺酰胺的UV和FL谱发生了变化,尤其是FL谱的最大激发与发射峰的位置比相应的模型化合物大幅蓝移.最终产物及其前体的最大λex分别为268和274 nm; λem分别为321和327 nm.而模型化合物及前体最大λex分别为365和359 nm; λem分别为504和440 nm.H2O2引发的目标产物的化学发光(CL)在1.1 s完成;化学发光量子产率与模型化合物相当,是Luminol的化学发光效率的5.6倍.     

N-[5-(1-邻(对)氯苯氧乙基)-1,3,4-噻二唑-2-基]-N'-芳酰基硫脲的合成与生物活性

为了寻找高活性的杂环农药,通过2-氨基-5-(1-邻氯苯氧乙基)-1,3,4-噻二唑和2-氨基-5-(1-对氯苯氧乙基)-1,3,4-噻二唑与芳酰基异硫氰酸酯反应,合成了26种新的芳酰基硫脲.采用核磁共振氢谱、红外光谱及元素分析确证了它们的结构.初步的生物活性测定试验表明,部分目标化合物表现出良好的植物生长调节活性,其中3c,3d,3e,4b和4c具有优良的生长素活性.     

新型去氢枞酸基磺酰胺类化合物的合成及其生物活性

去氢枞酸与SOCl2反应制得去氢枞酸酰氯(2);芳磺酰氯与乙二胺经N-酰化反应制得N-芳磺酰基乙二胺(4a~4k);在DMAP催化下,2分别与4a~4k经N-酰化反应合成了11个新型的去氢枞酸基磺酰胺类化合物(5a~5k),其结构经1H NMR,13C NMR,IR和ESI-MS表征。生物活性测试结果表明,在用药量为50μg·mL-1时,5a~5k对黄瓜枯萎病菌、苹果轮纹病菌、番茄早疫病菌、花生褐斑病菌和小麦赤霉病菌有一定的抑菌活性,其中去氢枞酸基间甲基苯磺酰胺(5c)对番茄早疫病菌的杀菌活性最佳,抑制率为73.6%;在用药量为100μg·mL-1时,大部分化合物对油菜的胚根生长有一定抑制作用,其中去氢枞酸基对甲氧基苯磺酰胺(5d)的抑菌活性最佳,抑菌率为57.1%。     

1-[5-(α-萘)-2H-四唑-2-乙酰基]-4-芳酰基胺基硫脲和3-[5-(α-萘)-2H-四唑-2-亚甲基]-4-芳酰基-1,2,4-三唑啉-5-硫酮的合成

本文通过5-(α-萘)-2H-四唑-2-乙酰肼(Ⅰ)与芳酰基异硫氰酸酯缩合制得16种新的1-[5-(α-萘)-2H-四唑-2-乙酰基]-4-芳酰基胺基硫脲(Ⅱ),(Ⅲ)在碱性催化条件下环化为3-[5-(α-萘)-2H-四唑-2-亚甲基]-4-芳酰基-1,2,4-三唑啉-5-硫酮(Ⅲ),化合物的结构经元素分析,IR、~1H NMR和MS鉴定,对化合物(Ⅲ)的质谱裂解进行分析,解释了化合物(Ⅱ)的环化方向,经初步筛选,发现个别化合物对小麦胚芽生长有促进作用。     

2-芳酰氨基-5-(5-苄基四唑-2-亚甲基)-1,3,4-噻二唑的合成

1,3,4噻二唑环类衍生物具有抗菌,杀虫,除草,调节植物生长,消炎止疼等广泛的生理活性。本文在浓硫酸催化下将1-(5-苄基四唑-2-乙酰基)-4-芳酰基氨基硫脲(1)环化为2-芳酰氨基-5-(5-芳基四唑-2-亚甲基-1,3,4-噻二(2)。2 的结构经元素分析、红外、核磁振波谱以及质谱方法确定。     

Quantitation and differentiation of bioparticles based on the measurements of light-scattering signals with a common spectrofluorometer

By simultaneously scanning both the excitation and emission monochromators of a common spectrofluorometer with same starting excitation and emission wavelength (namely, Deltalambda = 0), we obtained synchronous light scattering (SLS) signals that related to Rayleigh and Mie scatterings. It was found that the SLS signals could be applied for quantitation and differentiation of model bioparticles such as Saccharomyces cerevisiae, Schizosaccharomyces pombe, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Bacillus thuringiensis and Bacillus megaterium. In PBS buffer, these model bioparticles could form colloidal suspensions or dispersions of sizes ranging from hundreds of nanometers to tens of micrometers, giving SLS signals with the intensity being proportional to the amount of bioparticles in the range from 1.7 x 10 (5) to 1.7 x 10 (9) CFU/mL. A further finding is that polarized synchronous light scattering (PSLS) signals of I 0 degrees -30 degrees against I 0 degrees -0 degrees , which could be obtained by introducing polarizing sheets accessory of the spectrofluorometer, and the derivative synchronous light scattering (DrSLS) signals, which could be obtained directly with the extension function of the spectrofluorometer, offer differentiation information of bioparticles connected with their size, shape, refractive indexes, and inner structure. Refractive indexes of spherical bacteria were then calculated based on light scattering signals.     

Analysis of the Raman spectra of Ca(2+)-dipicolinic acid alone and in the bacterial spore core in both aqueous and dehydrated environments

The core of dormant bacterial spores suspended in water contains a large depot of dipicolinic acid (DPA) chelated with divalent cations, predominantly Ca(2+) (CaDPA), and surrounded by water molecules. Since the intensities of the vibration bands of CaDPA molecules depend significantly on the water content in the CaDPA's environment, the Raman spectra of CaDPA in spores may allow the determination of the spore core's hydration state. We have measured Raman spectra of single spores of three Bacillus species in different hydration states including the spores suspended in water, air-dried and vacuum-dried. As a comparison, we also measured the Raman spectra of CaDPA and DPA in different forms including in aqueous solution, and as amorphous powder and crystalline form. We also monitored changes in Raman spectra of an individual spore during dehydration under vacuum. The results indicated that (1) the state of CaDPA in the core of a spore suspended in water is close to an amorphous solid or a glassy state, but still mixed with water molecules; (2) the ratio of intensities of Raman bands at 1575 and 1017 cm(-1) (I(1575)/I(1017)) is sensitive to the water content in the CaDPA's environment; (3) variations in I(1575)/I(1017) are small (～4%) in a population of dormant Bacillus spores suspended in water; and (4) the I(1575)/I(1017) ratio increases significantly during dehydration under vacuum. Consequently, measurement of the I(1575)/I(1017) ratio of CaDPA in spores may allow a qualitative estimation of the degree of hydration of the bacterial spore's core.     

Synthesis,Crystal Structure and Antimicrobial Study of N,N,N''-Tris(3-aminopropyl)ethylenediamine Copper(Ⅱ) Diperchlorate

The title compound [Cu(C11H29N5)](ClO4)2 was synthesized and characterized by elemental analysis,IR and X-ray single-crystal diffraction.The compound crystallizes in the monoclinic system,space group P21/n with a = 9.405(2),b = 14.495(3),c = 14.715(3)(A),β = 90.262(3)°,V =2006.1(7)(A)3,Mr = 493.83,Z= 4,F(000) = 1028,Dc= 1.635 g/cm3,T= 298(2) K,μ = 1.403 mm-1 and λ = 0.71073(A).The structure was refined to R = 0.0508 and wR = 0.1250 for 2293 observed reflections with I ＞ 2σ(I).The Cu(Ⅱ)atom possesses a five-coordinate CuN5 environment which shows a slightly distorted square-pyramidal geometry.Antimicrobial activity study found that the complex is active against Salmonella species,Staphylococcus aureu,Bacillus pumilus and Bacillus coliforms.     

Synthesis,characterization and antibacterial activity of a curcumin–silver(I) complex

The current study reports the synthesis of a curcumin–silver(I) complex and its preliminary tests against four bacterial strains viz. Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Bacillus cereus using agar well diffusion method. The results were compared with curcumin by testing it in parallel with the sample. Curcumin showed zones of inhibition against all tested strains of bacteria. Among all bacterial strains, S. aureus was the most sensitive to curcumin with zone of inhibition of 12.2 mm. However, the curcumin–Ag(I) complex did not show the expected enhanced activity against all bacteria. This is perhaps due to the replacement of curcumin phenolic protons by silver ions which might have suppressed the antibacterial property of curcumin. The current research findings suggest that while synthesizing curcumin–metal complexes, the phenolic heads may either be left unaltered or need to be replaced by better substituents than hydroxy groups. Based on the current findings, biologically enhanced models have been provided as future recommendations.     

稠杂环化合物研究 i: 3-(4'-吡啶基)-6-芳基-均-三唑并[3,4-b]-1,3,4-噻二唑的合成及其抗菌性能

本文研究3-(4'-吡啶基)-4-氨基-5-巯基-1,2,4-三唑(1)与取代苯甲酸(2s-s)在氯化氧磷催化下的反应, 制得19种新的3-(4'-吡啶基)-6-芳基-均-三唑并[3,4-b]-1,3,4-噻二唑(3a-s), 确证了结构。初步观察了它们在约0.01%的浓度时, 对枯草杆菌, 大肠杆菌, 变形杆菌和金黄色葡萄球菌繁殖的抑制作用。     

SINGLE-STRAND BREAKS INDUCED IN BACILLUS SUBTILIS DNA BY ULTRAVIOLET LIGHT: ACTION SPECTRUM and PROPERTIES

Abstract— The induction of single-strand breaks (alkali-labile bonds plus frank breaks) in the DNA of Bacillus subtilis irradiated in vivo by monochromatic UV light at wavelengths from 254 to 434 nm was measured. The spectrum consists of a major far-UV (below 320 nm) component and a minor near-UV shoulder. A mutant deficient in DNA polymerase I accumulates breaks caused by near-UV (above 320 nm) wavelengths faster than the wild-type strain proficient in polymerase I. Measurable breaks in extracted DNA are induced at a higher frequency than those induced in vivo. Anoxia, glycerol, and diazobicyclo (2.2.2.) octane inhibit break formation in extracted DNA. Alkali-labile bonds induced by 365-nm UV radiation are largely (78%) covalent bond chain breaks, the remainder consists of true alkali-labile bonds, probably apurinic and apyrimidinic sites.     

Differentiation of strains from the Bacillus cereus group by RFLP‐PFGE genomic fingerprinting

Bacillus mycoides, Bacillus pseudomycoides, Bacillus weihenstephanensis, Bacillus anthracis, Bacillus thuringiensis, and Bacillus cereus belong to the B. cereus group. The last three species are characterized by different phenotype features and pathogenicity spectrum, but it has been shown that these species are genetically closely related. The macrorestriction analysis of the genomic DNA with the NotI enzyme was used to generate polymorphism of restriction profiles for 39 food‐borne isolates (B. cereus, B. mycoides) and seven reference strains (B. mycoides, B. thuringiensis, B. weihenstephanensis, and B. cereus). The PFGE method was applied to differentiate the examined strains of the B. cereus group. On the basis of the unweighted pair group method with the arithmetic mean method and Dice coefficient, the strains were divided into five clusters (types A–E), and the most numerous group was group A (25 strains). A total of 21 distinct pulsotypes were observed. The RFLP‐PFGE analysis was successfully used for the differentiation and characterization of B. cereus and B. mycoides strains isolated from different food products.     

CopAb, the second N-terminal soluble domain of Bacillus subtilis CopA, dominates the Cu(I)-binding properties of CopAab

The Cu(I)-detoxifying P-type ATPase CopA from Bacillus subtilis contains two N-terminal soluble domains, CopAa and CopAb, connected by a short linker. This arrangement is extremely common in prokaryotic Cu(I) transporters and is also found amongst the multiple soluble domains of eukaryotic homologues. Previous studies of a protein containing only these domains (CopAab) revealed complex Cu(I)-binding properties: both domains are able to bind Cu(I) extremely tightly and, at levels of Cu(I) > 1 per CopAab, the protein undergoes dimerisation, yielding a highly luminescent multi-Cu(I) bound species (Singleton and Le Brun, Dalton Trans., 2009, 688-696). To investigate this complex Cu(I)-binding behaviour and, in particular, to determine the contributions of the two domains to the overall behaviour of the N-terminal part, we generated and purified each domain in isolation. Here, we report studies of the second domain, CopAb. The protein was found to bind Cu(I) with an extremely high affinity (K = ~1 × 10(18) M(-1)) and remained as a monomer up to a level of 1 Cu(I) per protein. Above this level, the protein dimerised, generating a weakly luminescent species. Studies of the acid-base properties of the binding motif Cys residues revealed pK(a) values of < ~5 and ~6.3, adding further support to the proposal that high Cu(I)-affinity is correlated with low proton affinity. Exchange of Cu(I) between the protein and a high affinity chelator was found to occur rapidly via Cu(I)-mediated association, a process that is relevant to in vivo Cu(I) trafficking. Overall, the Cu(I)-binding properties of CopAb are very similar to those of the two-domain protein CopAab, indicating that this domain plays a dominant role in determining the binding properties of CopAab.     

Structure and dynamics of Cu(I) binding in copper chaperones Atox1 and CopZ: a computer simulation study

Copper chaperones deliver reduced copper (i.e., Cu(I)) to metal-binding domains of P-type ATPases in the cytoplasm of a range of organisms. Both chaperones and target domains have a ferredoxin-like fold and metal-binding motifs involving two Cys residues. Here, we investigated the Cu-binding geometry and structural dynamics of two homologous Cu(I) chaperones, Homo sapiens Atox1 and Bacillus subtilis CopZ, using a combination of quantum mechanical-molecular mechanics (QM-MM) and classical molecular dynamics (MD) methods. Our QM-MM optimized geometries for the holo- proteins suggested that Cu(I) in Atox1 favors a linear Cys(S)-Cu-Cys(S) arrangement but that this angle is close to 150 degrees in CopZ. Classical MD simulations suggest that both Atox1 and CopZ apo- forms have an increased conformational flexibility as compared to the respective holo- forms. This difference is most pronounced in CopZ and correlates with a lower in vitro thermal stability. Both average fluctuation (i.e., rmsd) and radius of gyration data demonstrate that the effects of Cu(I) coordination extend throughout the proteins. Distinct deviations between the two homologues were found in protein-solvent interactions, entropy of Cu(I) binding, and apo-protein Cys-Cys distance distributions. Our in silico results provide new insights into copper chaperone behavior with direct implications for copper transport mechanisms in vivo.