芳香异羟肟酸二烃基锡配合物的合成、表征及其抗癌活性的研究

合成了９个Ｒ_２ＳｎＬ_２型（Ｒ＝乙基、正丁基和苯基；ＨＬ＝苯甲酰异羟肟酸，对羟基苯甲酰异羟肟酸和水杨酰异羟肟酸）和６个［Ｒ_２ＳｎＬ］_２Ｏ型（Ｒ＝乙基、正丁基；ＨＬ同上）二烃基锡新配合物。测定了它们的分子量、红外光谱和核磁共振谱，着重研究了这些配合物的体外抗癌活性。结果表明，这二类配合物对人白血病ＨＬ－６０，艾氏腹水和Ｓ－１８０癌细胞有很好的抑制能力。初步探讨了结构－抗癌活性间的关系。     

芳香异羟肟酸二烃基锡配事物的合成,表征及其抗癌活性的研究

合成了９个Ｒ２ＳｎＬ２型（Ｒ＝乙基，正丁基和苯基；ＨＬ＝苯甲酰异羟肟酸，对羟基苯甲酰异羟肟酸和水杨酰异羟肟酸）和６个（Ｒ２ＳｎＬ）２Ｏ型（Ｒ＝乙基，正丁基，ＨＬ同上）二烃基锡新配合物，测定了它们的分子量，红外光谱和核磁共振谱，着重研究了这些配合物的体外抗癌活性，结果表明，这二类配合物对人白血病ＨＬ－６０，艾氏腹水和Ｓ－１８０癌细胞具有很好的抑制能力，初步探讨了结构－抗癌活性间的关系。     

2-(2''-吡啶基)-6-甲苯并噻唑及其二氯有机锡(IV)络合物的结构与抗肿瘤活性

二氯有机锡(IV)含双氮配体络合物具有抗肿瘤活性. 本文报道了2-(2'-吡啶基)-6-甲苯并噻唑及其二氯二乙基合锡(IV)反应产物的谱学表征、晶体结构和抗癌活性筛选的主要结果.     

N-(ω-三丁基锡甲氧基聚乙氧基)邻苯甲酰磺酰亚胺的合成及其光化学反应

烷基二醇与三丁基锡碘甲烷反应得到三丁基锡甲氧基烷基醇(2);2与邻苯甲酰磺酰亚胺反应得到N-(ω-三丁基锡甲氧基聚乙氧基)邻苯甲酰磺酰亚胺(3);3在光诱导下发生单电子转移,经分子间自由基偶合合成了新化合物1,4-二(2-邻苯甲酰磺酰亚胺基乙氧基)丁烷(7).2,3和7的结构经1H NMR,13C NMR及MS表征.     

三齿配体杂环五配位有机锡化合物的合成与生物活性

邻氨基苯酚与邻羟基芳香醛(酮)反应,合成了4个三齿Schiff碱配体(2a,2d,2g和2j),2分别与二苄基二氯化锡,二苯基二氯化锡,二正丁基二氯化锡反应合成了12个未见文献报道的三齿配体杂环五配位有机锡配合物(3a~3l),其结构经1HNMR,IR和元素分析确证。体外抗菌和抗癌活性测试结果表明,3b,3c,3f,3i和3k具有较强的抑菌活性;3c和3l具有较好的抗癌活性。     

1-烃基-5-取代氨基-4-吡唑(N-取代)甲酰胺的合成及生物活性研究

本文采用吡唑并[3,4-d]-1,3-噁嗪-6-酮衍生物(Ⅰ)与伯胺反应,合成了1-烃基-5-取代苯甲酰胺基-4-吡唑(N-取代)甲酰胺(Ⅱ);由LiAlH₄,对Ⅱ分子中2个酰胺基的选择性还原合成了1-烃基-5-取代氨基-4-吡唑(N-取代)甲酰胺(Ⅲ).共合成新化合物23个,通过¹HNMR、¹³CNMR、MS、IR等证明了它们的化学结构,初步生物活性测定表明化合物Ⅱ具有一定的抗癌活性和农药活性。     

利用Ugi反应合成2-{N-(3-三氟甲基苯基)-[3-(三氟甲基)苯甲酰、2-(取代苯氧)丙酰、2-(4,6-二甲氧基-嘧啶-2-氧基)苯甲酰]-氨基}-取代苯乙酰环己胺及其除草活性评价

为了寻找新型高活性的除草剂先导化合物,采用活性亚结构连接法,利用Ugi反应将3-三氟甲基苯甲酰基、2-(取代苯氧)丙酰基和2-(4,6-二甲氧基嘧啶-2-氧基)苯甲酰基等除草活性结构片段与3-三氟甲基苯基引入到同一分子中,合成了一系列2-{N-(3-三氟甲基苯基)-[3-(三氟甲基)苯甲酰、2-(取代苯氧)丙酰、2-(4,6-二甲氧基嘧啶-2-氧基)苯甲酰]-氨基}-取代苯乙酰环己胺3a~3i,采用IR,1H NMR,EI-MS和元素分析对其结构进行了表征.初步的除草活性测试结果表明:部分化合物在100 mg/L浓度下对油菜显示出中等至良好的除草活性.温室盆栽测试结果显示部分化合物在1.5kg/ha剂量下,在苗前处理时对油菜、反枝苋、稗草和马唐具有良好的除草活性.     

新型苯环5-(取代)苯甲酰胺基苯磺酰脲类化合物的比较定量构效关系研究

采用比较分子力场分析(CoMFA)方法, 对26个新型苯环5-(取代)苯甲酰胺基苯磺酰脲类化合物的除草活性进行了三维定量构效关系(3D-QSAR)研究, 建立了三维定量构效关系CoMFA模型(R²=0.948, F=91.364, SE=0.141). 结果表明, 此类磺酰脲类化合物的除草活性与苯环5位取代基的立体结构和电场性质密切相关. 根据CoMFA模型的立体场和静电场三维等值线图不仅直观地解释了结构与活性的关系, 而且为进一步设计高活性的目标化合物提供理论依据.     

新型双大环二正丁基锡羧酸酯的合成、晶体结构及生物活性

在乙醇钠催化下, 将3-(1,2亚丙二硫基)亚甲基-2,4-二羰基戊烷与2-羰基苯氧乙酸进行缩合反应, 获得了柔性二元酸配体1[4-(1,2-亚丙二硫基)亚甲基-3,5-二羰基-1,6-庚二烯-1,7-二(2-羰基苯)氧乙酸(LH2)]. 再将配体1与二正丁基氧化锡进行脱水反应, 获得新型二正丁基锡羧酸酯配合物2. 采用元素分析、1H NMR、 IR及晶体结构测定等手段对配体1和配合物2进行了结构表征, 配合物2是以菱形环Sn2O2为中心对称的二聚体结构, 中心菱形环通过氧原子与2个环外锡原子相连. 每个羧基分别与环内锡和环外锡原子配位, 形成2个对称的六元环, 3个环呈梯形排列, 将整个分子分割成2个对称的二十二元大环. 初步研究了其杀菌活性和抗癌活性.     

含有脲桥结构的双酰肼衍生物的合成和杀虫活性研究

经2,6-二氟苯甲酰基异氰酸酯(或异氰酸苯酯)与N-叔丁基-N-取代苯甲酰肼(或苯环上含有氨基的双酰肼化合物)反应得到一系列含有脲桥结构的双酰肼类化合物, 生测结果表明部分目标化合物具有好的杀幼虫活性. 例如, 化合物IIa和IIe, 药剂浓度为0.02%, 杀幼虫活性分别为95%和100%.     

Preparation,antitumor activity in mice,pharmacokinetics and tissue distribution in rats of di‐n‐butyl‐di‐(4‐chlorobenzohydroxamato)tin(IV) liposome

Di‐n‐butyl‐di‐(4‐chlorobenzohydroxamato)tin(IV) (DBDCT) is an antitumor compound with high activity and relatively low bioavailability. In order to improve the pharmacokinetic characteristics and raise its therapeutic index, a liposome of DBDCT (DBDCT‐L) was prepared for the first time. A study of the pharmacokinetics and tissue distribution after intravenous administration of DBDCT‐L compared with free DBDCT to rats was investigated. DBDCT‐L showed a slower clearance, increased half‐time and a larger AUC value than those of free DBDCT, which demonstrated that DBDCT‐L could significantly alter the tissue distribution pattern of DBDCT in rats. The highest concentration distribution for DBDCT‐L was detected in liver, which may be associated with the enhanced antitumor activity in vivo against hepatocellular carcinoma H₂₂ and possible target release of the compound. Acute toxicity assay showed that the LD₅₀ value of DBDCT‐L was higher than that of free DBDCT. Further in vivo antitumor test showed that DBDCT‐L displayed higher antitumor activity against the hepatocellular carcinoma H₂₂ than free DBDCT, indicating that the liposome could prolong the action time of DBDCT in the system circulation, change its distribution in rats, reduce acute toxicity and finally increase antitumor activity. Copyright © 2014 John Wiley & Sons, Ltd.     

A molecular electrostatic potential bond critical point model for atomic and group electronegativities

A consistent set of atomic electronegativities of main block and d-block transition elements has been obtained from the position and value of the molecular electrostatic potential bond critical point of the C-E bond of a methyl-element-hydride system, H(3)C-EH(n) (E is an element and n = 0, 1, 2, 3, 4, and 5 depending on the position of E in the periodic table). The new scale shows very good agreement with the popular electronegativity scales such as Pauling, Allen, Allred-Rochow, Mulliken, and Sanderson scales of electronegativity, especially for the main block elements. The present scale of electronegativity for transition elements is expected to be more accurate than the previously derived values because of a more consistent approach. Further, the same approach has led to the evaluation of group electronegativities when the hydrogens of E are replaced by other substituent groups. These group electronegativity values are found to correlate well with Inamoto and Mullay scales.     

Investigation of transition metal-imido bonding in M(NBut)2(dpma)

A complete series down group 6 of the formula M(NBu(t))(2)(dpma) has been synthesized, where dpma is N,N-di(pyrrolyl-alpha-methyl)-N-methylamine. A fourth complex, Mo(NAr)(2)(dpma) (4), was also prepared, where Ar is 2,6-diisopropylphenyl. All four of these complexes display geometries in the solid state best described as square pyramidal with one imido ligand occupying the axial position and the other an equatorial site. In all cases, the axial imido ligand has a significantly smaller M-N(imido)-C bond angle with respect to the equatorial multiple-bond substituent. From the (1)H, (13)C, and (14)N NMR spectra, the axial (bent) imido appears to be more electron-rich than the equatorial and linear imido, with the differences becoming less pronounced down the column. The angular deformation energies for the axial imido ligands were studied by DFT in order to discern if and to what extent imido bond angles were important energetically. The electronic energies associated with straightening the axial imido ligand, while holding the remainder of the molecule at the ground-state geometry, for the Cr, Mo, and W derivatives were calculated as 4.5, 2.7, and 2.0 kcal/mol, respectively. A straight-line plot is found for deformation energies versus estimated electronegativity of the group 6 metals in the +6 oxidation state. The study suggests that the electronic differences between metal imido ligands of different angles are quite small; however, the effects may be more pronounced for metal centers with higher electronegativity, e.g. Cr(VI) with electron-withdrawing ligands.     

3D QSAR Studies on Benzyl Phenyl Ether Diamidine Derivatives with Antiprotozoal Activities

Human African trypanosomiasis (HAT) is a neglected tropical disease, and some drugs treating HAT have been used for even more than 60 years. Currently, a series of benzyl phenyl ether diamidine derivatives are discovered, which exhibit high antiprotozoal activities and low cytotoxicity, leading to good development prospects. The comparative molecular field analysis (CoMFA) and the comparative molecular similarity indices analysis (CoMSIA) are used to study the relationship between the structure and antiprotozoal activities. The established 3D QSAR model shows not only significant statistical quality, but also satisfies predictive ability: the best CoMFA model had r² = 0.958 and q² = 0.766, the best CoMSIA model had r² = 0.957 and q² = 0.812, the predictive ability of CoMFA and CoMSIA model were further confirmed by a test set which had 11 compounds, giving the correlation coefficient Q_ext² of 0.792, 0.873, respectively. The contour maps and contribution maps show important features that can improve the antiprotozoal activity: position 3 from substituent R4 should be a low electronegativity group, position 4 from substituent R₄ should have higher electronegativity, substituent R₂ should be selected to a low electronegativity and small bulk group. Together these results may offer some useful theoretical information in designing potential inhibitors.     

Polar effects and structural variation in 4-substituted 1-phenylbicyclo[2.2.2]octane derivatives: a quantum chemical study

The transmission of polar effects through the bicyclo[2.2.2]octane framework has been investigated by ascertaining how the geometry of a phenyl group at a bridgehead position is affected by a variable substituent at the opposite bridgehead position. We have determined the molecular structure of several Ph-C(CH(2)-CH(2))(3)C-X molecules (where X is a charged or dipolar substituent) from HF/6-31G and B3LYP/6-311++G molecular orbital calculations and have progressively replaced each of the three -CH(2)-CH(2)- bridges by a pair of hydrogen atoms. Thus the bicyclo[2.2.2]octane derivatives were changed first into cyclohexane derivatives in the boat conformation, then into n-butane derivatives in the anti-syn-anti conformation, and eventually into assemblies of two molecules, Ph-CH(3) and CH(3)-X, appropriately oriented and kept at a fixed distance. For each variable substituent the deformation of the benzene ring relative to X = H remains substantially the same even when the substituent and the phenyl group are no longer connected by covalent bonds. This provides unequivocal evidence that long-range polar effects in bicyclo[2.2.2]octane derivatives are actually field effects, being transmitted through space rather than through bonds. Varying the substituent X in a series of Ph-C(CH(2)-CH(2))(3)C-X molecules gives rise to geometrical variation (relative to X = H) not only in the benzene ring but also in the bicyclo[2.2.2]octane cage. The two deformations are poorly correlated. The rather small deformation of the benzene ring correlates well with traditional measures of long-range polar effects in bicyclo[2.2.2]octane derivatives, such as sigma(F) or sigma(I) values. The much larger deformation of the bicyclo[2.2.2]octane cage is controlled primarily by the electronegativity of X, similar to deformation of the benzene ring in Ph-X molecules. Thus the field and electronegativity effects of the substituent are well separated and can be studied simultaneously, as they act on different parts of the molecular skeleton.     

Influence of substituent groups at the 3‐position on the mass spectral fragmentation pathways of cephalosporins

The structural fragment ions of nine cephalosporins were studied by electrospray ionization quadrapole trap mass spectrometry (Q‐Trap MSⁿ) in positive mode. The influence of substituent groups in the 3‐position on fragmentation pathway B, an α‐cleavage between the C7? C8 single bond, coupled with a [2,4]‐trans‐Diels‐Alder cleavage simultaneously within the six‐membered heterocyclic ring, was also investigated. It was found that when the substituent groups were methyl, chloride, vinyl, or propenyl, fragmentations belonging to pathway B were detected; however, when the substituents were heteroatoms such as O, N, or S, pathway B fragmentation was not detected. This suggested that the [M–R₃]⁺ ion, which was produced by the bond cleavage within the substituent group at the 3‐position, had a key influence on fragmentation pathway B. This could be attributed to the strong electronegativity of the heteroatoms (O, N, S) that favors the production of the [M–R₃]⁺ ion. Moreover, having the positive charge of the [M–R₃]⁺ ion localized on the nitrogen atom in the 1‐position changed the electron density distribution of the heterocyclic structure, which prohibits a [2,4]‐reverse‐Diels‐Alder fragmentation and as a result fragmentation pathway B could not occur. The influence of the substituent group in the 3‐position was determined by the intensity ratio (e/d) of ions produced by fragmentation pathway A, a [2,2]‐trans‐Diels‐Alder cleavage within the quaternary lactam ring, including the breaking of the amide bond and the C6? C7 single bond (ion d), and fragmentation pathway B (ion e). The results indicate that the electronegativity of the substituent group was a key influencing factor of pathway B fragmentation intensity, because the intensity ratio (e/d) is higher for a chlorine atom, a vinyl, or a propenyl group than that of a methyl group. This study provided some theoretical basis for the identification of cephalosporin antibiotics and structural analysis of related substances in drugs. Copyright © 2010 John Wiley & Sons, Ltd.     

Electrochemical and solvatochromic study of cyclopalladated complexes

The electrochemistry and the optical absorption properties of a series of cyclopalladated complexes are reported. Variation of the cyclometallated ligand has been performed (azobenzene, 2-phenylpyridine and benzo[h]quinoline) as well as variation of the ancillary ligand (acetylacetone and hexafluoroacetylacetone). Results have confirmed that the LUMO energy levels of these complexes is mainly distributed on the cyclometallated ligand. High electronegativity of the fluorinated groups has a weak influence on the electrochemical and absorption properties of the complexes, except for the benzo[h]quinoline for which its planar and comparatively more aromatic character lead to a partial delocalisation of the LUMO energy level.     

Carbon-13 magnetic resonance: γ-anti substituent effects

γ-anti Substituent effects of the first row elements (CH₃, NH₂, OH, F) and the higher-row halogens on ¹³C chemical shifts are shown to have separate linear relationships with element electronegativity. The halogens generally show an increasing upfield shift with increasing electronegativity, but the response of the effect of the first-row elements to changing electronegativity is dependent upon the substitution pattern of the atoms involved. In molecules with the substituent at a bridgehead, increasing electronegativity causes increasing downfield shift of the γ-anti carbon, whereas in other systems which have the substituent at a secondary carbon, increasing electronegativity causes an increasing upfield shift. Examples are cited to show that the γ-anti effect of a hydroxyl group is more shielding (by about 2 ppm) when a 1,3-diaxial interaction between an α and a γ hydrogen is present, than when this interaction is removed by replacement of either of the hydrogens. This correlation is taken as evidence of this hydrogen-hydrogen interaction as one pathway for the transmission of the γ-anti substituent effects of first-row elements.     

Tuning the π-Accepting Properties of Mesoionic Carbenes: A Combined Computational and Experimental Study

Mesoionic imidazolylidenes are recognized as excellent electron-donating ligands in organometallic and main group chemistry. However, these carbene ligands typically show poor π-accepting properties. A computational analysis of 71 mesoionic imidazolylidenes that bear different aryl or heteroaryl substituents in C2 position was performed. The study has revealed that a diphenyltriazinyl (Dpt) substituent renders the corresponding carbene particularly π-acidic. The computational results could be corroborated experimentally. A mesoionic imidazolylidene with a Dpt substituent was found to be a better σ-donor and a better π-acceptor compared to an Arduengo-type N-heterocyclic carbene. To demonstrate the utility of the new carbene, the ligand was used to stabilize a low-valent paramagnetic tin compound.     

几种芴衍生物(有机材料增感剂)的13C核磁共振研究

利用FX-60Q脉冲付里叶变换核磁共振波谱仪(磁场强度为14093高斯,观察频率为15.04MH_z)测定了四种劳衍生物的非去偶谱、偏共振谱和质子完全去偶谱。借助于偏共振技术、质子噪声(宽带)去偶、取代基化学位移加合规则以及模式化合物比较,确定了各峰的化学位移和一键、二键及三键偶合常数。实验结果表明,用化学位移和偶合常数的值除帮助识别各峰的归属外,还能推断未知化合物的碳键状态及取代基电负性的大小,对鉴别化合物结构可提供有用的线索。