环方铂立体异构体与小牛胸腺DNA作用的研究

研究了环方铂三种立体异构体（ＳＳ,ＲＳ和ＲＲ）与小牛胸腺ＤＮＡ的作用。差示扫描量热法（ＤＳＣ）测得的数据显示出三种经合物与ＤＮＡ作用的结果分别使其熔融温度下降了０．６,１．４和２．２Ｋ,有无ＤＮＡ存在时三种化合物及方酸。的＾１３Ｃ核磁共振谱表明,当三种化合物ＤＮＡ作用时,先释放出方酸根生成水铂,而后再与ＤＮＡ结合。综述上述实验结果,对三种化合物与ＤＮＡ的作用强度、方式及机理进行了讨论。     

二甲基亚砜及一些含氮环化合物与DNA的作用

通过实验探索了将既不溶于水又不能生成可溶性盐的一些含氮稠环化合物溶于二甲基亚砜（DMSO）水溶液中与小牛胸腺DNA作用的途径．溶解实验证明了DMSO及其水溶液对此类化合物极强的溶解性能，DMSO与小牛胸腺作用的紫外光谱（298 K）、圆二色谱（298 K）、~(31)P核磁谱（323 K）和摩尔焓变（298 K）数据均表明：在pH＝7.0的水溶液中，当DMSO浓度小于0．15 mol·L~(-1)时，其与DNA无作用．溶于DMsO水溶液中的八种含氮稠环化合物与小牛胸腺DNA作用的紫外光谱（298 K）、圆二色谱（298 K）和摩尔焓变（298 K）实验结果显示出两种化合物对DNA有较强的嵌插作用．通过对实验结果的分析，本文对具有相同含氮稠环骨架的化合物与DNA嵌播作用的规律和化合物本身微观结构的关系进行了讨论．     

[Co(tp)2(Me3-en)]ClO4手性配位氮的翻转动力学研究

用高效液相色谱（HPLC）法测定了水溶液中碱催化下异构体－（差向立体异构体）：Δ（S）∧（R）和Δ（R）∧（S）－[Co(tp)2(Me3-en)]ClO4（tp:2-羟基－2,4,6－环庚三烯－1－酮负离子;Me3-en:N,N,N'-三甲基乙二胺）手性配位氮的翻转（差向立体异构体）速率常数kep(34.0 ℃）,研究结果发现,碱催化下手性配位氮的翻转作用具有二级反应动力学方程：v=kep[配合物][OH^-],[Co(tp)2(Me3-en)]ClO4的kep值比[Co(tp)2(Me3-en)]ClO4的kep值大一个数量级,Δ（R）∧（S）-异构体比Δ（S）∧（R）－异构体具有更大的手性配位氮翻转速率。     

草酸根·(1R, 2R-环己二胺)合铂(Ⅱ)的质谱和热分析研究

铂配合物是目前最为广泛使用的抗肿瘤药物。自１９６５年Ｒｏｓｅｎｂｅｒｇ等人发现顺铂具有强烈抑制大肠杆菌细胞分裂的作用后［１］,对抗癌药物的研究和开发已成为生物无机化学的重要领域之一［２－４］。迄今为止,现已有四个铂配合物获准临床使用,其中之一就是草酸根·（１Ｒ,２Ｒ一环己二胺）合铂（Ⅱ）,它是由四氯合铂酸钾与反式－１, ２环己二胺的光学异构体作用,然后与草酸反应而制得的。为了深入研究该药物的物理性质,我们采用几种质谱方法和热分析仪对该化合物的分解机制和热稳定性进行了研究,探讨了分解的可能途径。１…     

8-羟基喹啉衍生化β-环糊精键合硅胶液相色谱固定相的合成与评价

β－环糊精键合硅胶经对甲苯磺酰化后, 与８－羟基喹啉反应得到８－羟基喹啉衍生化β－环糊精键合硅胶固定相（ＱＣＤＳ）． 采用元素分析、热分析及固体核磁波谱对键合固定相进行表征． 考察了ＱＣＤＳ对位置异构体、丹磺酰化氨基酸异构体、苯丙酸类药物和核苷等的分离性能．     

1,2-二硫方酸的气相酸性和芳香性

在ＲＨＦ／６－３１１Ｇ、ＲＨＦ／６－３１１＋Ｇ　和Ｂ３ＬＹＰ／６－３１１＋Ｇ　水平,优化得到１,２－二硫方酸（３,４．二羟基－３－环丁烯－１,２－二硫酮）三种平面构象异构体的平衡几何构型．进一步用ＭＰＺ（ｆｕｌｌ）／６－３１１＋Ｇ　、／／ＲＨＦ／６－３１１＋Ｇ　方法计算三种异构体的单点能量,发现ＺＺ型异构体是能量最低构象,且ＺＺ和ＺＥ型能量非常接近．用优化的最稳定构象ＺＺ型异构体,在ＲＨＦ／６－３１１Ｇ　／／ＲＨＦ／６－３１１Ｇ　、ＲＨＦ／６．３１１＋Ｇ　／／ＲＨＦ／６－３１１＋Ｇ　、ＭＰＺ（ｆｕｌｌ）／６．３１１＋Ｇ　／／ＲＨＦ／６－３１１＋Ｇ　和Ｂ３ＬＹＰ／６－３１１＋Ｇ　斤Ｂ３ＬＹＰ／６－３１１＋Ｇ　水平,计算其气相酸性（△Ｇ＿２９８）,并用同键反应方法在同样水平计算其芳香性稳定化能．用基团加和法（ｇｒｏｕｐｉｎｃｒｅｍｅｎｔａｐｐｒｏａｃｈ）在ＲＨＦ／６．３１１＋Ｇ　／／ＲＨＦ／６－３１１＋Ｇ　和Ｂ３ＬＹＰ／６－３１１＋Ｇ　／／Ｂ３ＬＴｈ／６－３１１＋Ｇ　水平计算其磁化率增量（　）．计算结果指出,标题化合物的键长发生了平均化,芳香性稳定化能和磁化率增量均为负值,表明它具有芳香性,实现了标题化合物芳香     

含苯氧基萘并萘醌和偶氮苯双变色基化合物的合成和性质

通过６－氯－５，１２－萘并萘醌与４－羟基偶氮苯及其衍生物的反应合成了３种含苯氧基萘并萘醌和偶氮苯光致变色基的双变色基化合物，６－［４－（苯偶氮基）苯氧基］－５，１２－萘并萘醌（５），６－［４－（ｐ－乙氧基苯偶氮基）苯氧基］－５，１２－萘并萘醌（６）和６－［４－（ｐ－硝基苯偶氮基）苯氧基］－５，１２－萘并萘醌（７）．这些化合物的苯氧基萘并萘醌变色基的ＵＶ诱导光致变色性较弱；基于氨与苯氧基萘并萘醌ａｎａ显色体的不可逆反应，化合物５和６ＤＭＳＯ溶液在３６５ｎｍ紫外光辐照光稳态（ＰＳＳ）下的ａｎａ醌式摩尔分数估计分别为２２％和１７％．这些结果说明，苯偶氮基对苯氧基萘并萘醌变色基的光致变色性质有着极强的影响．另一方面，与４－羟基偶氮苯母体不同，这些双变色基化合物在ＤＭＳＯ中偶氮苯变色基的顺式异构体是相对稳定的     

新型St—Co—DMAEMA共聚物的合成与表征

本文研究了苯乙烯（St，M1）与N、N－二甲胺基甲基丙烯酸乙酯（MAEMA，M2）以AIBN为引发剂，在丁酮溶液中的共聚合反应。用元素分析法测定了共聚物的组成，同时分别用FR法、YBR法和K－T法对单体竞聚率进行估价。结果表明三种计算方法得到的单体竞聚率基本一致，结果分别为r1＝0．510，r2＝0．716（FR法）；r1＝0．512，r2＝0．720（YBR法）；r1＝0．505，r2＝0．697（K－T法）。     

多氯代吩噁嗪热力学性质的密度泛函理论研究

在B3LYP/6-31G*水平上对135个多氯代吩噁嗪(PCPXs)系列化合物进行了全优化和振动分析计算, 得到各分子在298.15 K, 1.013×105 Pa标准状态下的热力学性质. 设计等键反应, 计算了PCPXs系列化合物的标准生成热(Δf )和标准生成自由能(Δf ), 研究了这些参数与氯原子的取代位置及取代数目(NPCS)之间的关系, 结果表明: 熵( )、Δf , Δf 与NPCS之间有很强的相关性. 根据异构体标准生成自由能的相对大小, 从理论上求得异构体的相对稳定性. 以Gaussian 03程序的输出文件为基础, 采用统计热力学程序计算了PCPXs化合物在200 K至1800 K的摩尔恒压热容(Cp,m), 并用最小二乘法求得Cp,m与温度之间的相关方程, 发现Cp,m与T, T－1和T－2之间有着很好的相关性.     

过渡金属L丙氨酸席夫碱配合物的合成及其抗O_2~(.-)性能

合成了Ｌ－丙氨酸缩邻香草醛席夫碱及其过渡金属Ｃｕ（Ⅱ）、Ｃｏ（Ⅱ）、Ｎｉ（Ⅱ）、Ｚｎ（Ⅱ）、Ｃｄ（Ⅱ）和Ｆｅ（Ⅲ）等的配合物．通过元素分析、摩尔电导、红外光谱、电子光谱、热分析及顺磁共振波谱等手段对它们进行了表征，并探讨了它们对Ｏ·－２的清除作用     

The supramolecular isomerism based on argentophilic interactions: the construction of helical chains with defined right-handed and left-handed helicity

The reactions of racemic and enantiopure macrocyclic compounds [Ni(alpha-rac-L)](ClO(4))(2) (containing equal amounts of SS and RR enantiomers), [Ni(alpha-SS-L)](ClO(4))(2), and [Ni(alpha-RR-L)](ClO(4))(2) with K[Ag(CN)(2)] in acetonitrile/water afford three 1D helical chains of {[Ni(f-rac-L)][Ag(CN)(2)](2)}(n) (1), {[Ni(f-SS-L)](2)[Ag(CN)(2)](4)}(n) (Delta-2), and {[Ni(f-RR-L)](2)[Ag(CN)(2)](4)}(n) (Lambda-2); one dimer of [Ni(f-rac-L)][Ag(CN)(2)](2) (3); and one trimer of [Ni(f-rac-L)Ag(CN)(2)](3).(ClO(4))(3) (4) (L = 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane). Compounds 1, Delta-2, Lambda-2, and 3, which are supramolecular isomers, are constructed via argentophilic interactions. In 1, [Ni(f-RR-L)][Ag(CN)(2)](2) enantiomers alternately connect with [Ni(f-SS-L)][Ag(CN)(2)](2) enantiomers through intermolecular argentophilic interactions to form a 1D meso-helical chain, and the 1D chains are further connected through the interchain hydrogen bonds to generate a 2D network. When chiral [Ni(alpha-SS-L)](ClO(4))(2) and [Ni(alpha-RR-L)](ClO(4))(2) were used as building blocks, two supramolecular stereoisomers of Delta-2 and Lambda-2 were obtained, which show the motif of homochiral right-handed and left-handed helical chains, respectively, and the 1D homochiral helical chains are linked by the interchain hydrogen bonds to form a 3D structure. In 3, a pair of enantiomers of [Ni(f-RR-L)][Ag(CN)(2)](2) and [Ni(f-SS-L)][Ag(CN)(2)](2) connect with each other through intermolecular argentophilic interactions to form a dimer. The reaction of [Ni(alpha-rac-L)](ClO(4))(2) with K[Ag(CN)(2)] in acetonitrile gives a trimer of 4; each trimer is chiral with unsymmetrical RR, RR, and SS, or RR, SS, and SS configurations. The homochiral nature of Delta-2 and Lambda-2 was confirmed by the results of solid circular dichroism spectra measurements. The solid samples of 1-4 show strong fluorescent emissions at room temperature.     

Chlorobenzylidine-herring sperm DNA interaction: binding mode and thermodynamic studies

The interaction of chlorobenzylidine with herring sperm DNA has been investigated by fluorescence, absorption, DNA melting experiment and differential scanning calorimetry (DSC). When bound to DNA, chlorobenzylidine shows hypochromism and red shift in absorption spectra, fluorescence quenching and polarization increasing in fluorescence spectra and increasing in DNA melting temperature. These spectral characteristics strongly support intercalation of chlorobenzylidine into herring sperm DNA. Scatchard plots constructed from fluorescence titration data give a binding constant of 3.2 x 10(4) M(-1) and a binding site size of six base pairs per bound drug molecule. The intercalative interaction is exothermic with a van't Hoff enthalpy of -30.6 kJ mol(-1). This result is obtained from DSC experiment. In addition, DeltaG degrees =-28.5 kJ mol(-1), and DeltaS degrees =-7.1 J mol(-1) K(-1). These results show that the binding of chlorobenzylidine to herring sperm DNA is exothermic.     

Spectroscopic studies of the interaction between pirimicarb and calf thymus DNA

The interaction between pirimicarb and calf thymus DNA in physiological buffer (pH 7.4) was investigated with the use of Neutral Red (NR) dye as a spectral probe by UV-vis absorption, fluorescence and circular dichroism (CD) spectroscopy, as well as viscosity measurements and DNA melting techniques. The results revealed that an intercalation binding should be the interaction mode of pirimicarb to DNA. CD spectra indicated that pirimicarb induced conformational changes of DNA. The binding constants of pirimicarb with DNA were obtained by the fluorescence quenching method. The thermodynamic parameters, enthalpy change (ΔHθ) and entropy change (ΔSθ) were calculated to be -52.13±2.04 kJ mol(-1) and -108.8±6.72 J mol(-1) K(-1) according to the van't Hoff equation, which suggested that hydrogen bonds and van der Waals forces might play a major role in the binding of pirimicarb to DNA. Further, the alternative least squares (ALS) method was applied to resolve a complex two-way array of the absorption spectra data, which provided simultaneously the concentration information for the three reaction components, pirimicarb, NR and DNA-NR. This ALS analysis indicated that the intercalation of pirimicarb into the DNA by substituting for NR in the DNA-NR complex.     

Spectroscopic identification of binding modes of anthracene probes and DNA sequence recognition

The binding properties of two anthracene derivatives with calf thymus DNA (CT DNA), poly(dA-dT), and poly(dG) x poly(dC) are reported. One contained bulky, cyclic cationic substituents at the 9 and 10 positions, and the other carried acylic, branched, cationic substituents. Binding of the probes to the DNA was examined by calorimetry, spectroscopy and helix melting studies. The cyclic derivative indicated exothermic binding, strong hypochromism, bathochromism, positive induced circular dichroism (CD, 300-400 nm), significant unwinding of the helix, large increases in the helix melting temperature, strong but negative linear dichroism (LD, 300-400 nm) and considerable stabilization of the helix. In contrast, the acyclic analog indicated thermoneutral binding, smaller hypochromism, no bathochromism, very weak induced CD, and no change in the helix melting temperature with any of the DNA polymers. A sharp distinction between the binding properties of the two probes is indicated, and both have intrinsic binding constants of approximately 10(6) M(-1) for the three polymers. However, when the ionic strength of the medium was lowered (10 mM NaCl), the absorption as well as CD spectral changes associated with the binding of the acyclic derivative corresponded with those of the cyclic derivative. The acyclic derivative showed large preference (10-fold) for poly(dG) x poly(dC) over poly(dA-dT), whereas the cyclic analog showed no preference. The characteristic spectroscopic signatures of the two distinct binding modes of these probes will be helpful in deciphering the interaction of other anthracene derivatives with DNA.     

The interactions of (-)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato)platinum(II) monohydrate (DWA2114R) and related compounds with deoxyribonucleic acid.

The interactions of a new antitumor platinum (Pt) complex, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +) platinum(II) monohydrate (DWA2114R, 2) and its related compounds, cis-diamminedichloroplatinum(II) (CDDP, 1), trans-diamminedichloroplatinum(II) (TDDP, 3), (+)-(S)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +) platinum(II) monohydrate (DWA2114S, 4), (R)-2-aminomethylpyrrolidinedichloroplatinum(II) (5) and cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA, 6), with calf-thymus deoxyribonucleic acid (DNA) and DNA nucleosides were investigated by ultraviolet (UV) and circular dichroism (CD) spectrometry. The UV spectra of the DNAs treated with these Pt complexes exhibited both bathochromic shift and hyperchromicity, showing a binding of Pt to the heterocyclic groups of these DNA as well as an alteration in the secondary structure of DNA. The reaction rates of the Pt complexes with DNA, however, differed from one another, and the order was CDDP, TDDP, 5 much greater than DWA2114R, S greater than CBDCA. The CD spectra of the DNAs treated with the Pt complexes, except TDDP, at a low Pt ratio (less than approximately (ca.) 0.1 of Pt bound to DNA/DNA base molar ratio) exhibited an increase of ellipticity at ca. 275 nm. The melting temperature of the DNAs treated with DWA2114R or CDDP were almost the same as the native DNA, while the melting temperature with TDDP was higher by 7-8 degrees C than that of the native DNA. All the Pt complexes reacted with 2'-deoxyguanosine (dG), 2'-deoxyadenosine and 2'-deoxycytidine, but none reacted with thymidine. The CD spectral change of the dG was largest. DWA2114R reacted faster with dG than other nucleosides.     

Chlorobenzylidine-calf thymus DNA interaction II: circular dichroism and nuclear magnetic resonance studies

The binding of chlorobenzylidine to calf thymus DNA has been studied in detail by means of circular dichroism (CD), nuclear magnetic resonance (1H NMR), viscosimetry and denaturation temperature (Tm). Chlorobenzylidine is found to intercalate between base pairs of DNA as evidence by: (1) induced circular dichroism; (2) broadened 1H NMR signals; (3) enhanced viscosity; and (4) increased denaturation temperature of the DNA helix. In addition, Scatchard plot from CD titration data gives a binding constant of 2.6 x 10(4) M(-1) and a binding site size of 4 base pairs at 25 degrees C. Matrix rank analysis shows that there are three main components contributing to the observed CD spectra. The nuclear magnetic resonance experiment shows that the planar aromatic ring of tetrahydroberberine group in chlorobenzylidine intercalates between the base pairs of DNA when chlorobenzylidine is bound to DNA.     

Resonance Raman spectroscopic study of nitrophorin 1, a nitric oxide-binding heme protein from Rhodnius prolixus, and its nitrosyl and cyano adducts.

The resonance Raman (RR) spectra of nitrophorin 1 (NP1) from the saliva of the blood-sucking insect Rhodnius prolixus, in the absence and presence of nitric oxide (NO) and in the presence of cyanide (CN(-)), have been studied. The NP1 displayed RR spectra characteristic of six-coordinate high-spin (6cHS) ferric heme at room temperature and six-coordinate low-spin heme (6cLS) at low temperature (77 K). NO and CN(-) each bind to Fe(III), both ligands forming 6cLS complexes with NP1. The Fe(III)-NO stretching and bending vibrational frequencies of nitrosyl NP1 were identified at 591 and 578 cm(-1), respectively, on the basis of 15NO isotope shifts. These frequencies are typical of Fe-NO ferric heme proteins, indicating that the NP1 nitrosyl adduct has typical bond strength. Thus, the small NO release rate displayed by NP1 must be due to other protein interactions. Room and cryogenic temperature (77 K) RR spectroscopy and 13C, 15N, and 13C15N isotope substitutions have been used to determine vibrational mode frequencies associated with the Fe(III)-CN(-) bond for the cyano adducts at 454, 443, 397, and 357 cm(-1). The results were analyzed by normal mode calculations to support the assignment of the modes and to assess the NO and CN(-) binding geometries. The observed isotope shifts for the cyano NP1 are smaller than expected and reveal vibrational coupling of Fe(III)-CN(-) modes with heme modes. We also find that the observed frequencies are consistent with the presence of a nearly linear Fe(III)CN(-) linkage (173 degrees ) coexisting with a population with a bent structure (155 degrees ).     

Do amorphous troglitazones prepared from two diastereomer-pairs have the same molecular mobility and crystallization rate at the surface?

The surface of amorphous compounds crystallizes faster compared to the bulk. This suggests that molecules at the surface have high molecular mobility. Crystallization behavior is affected by various factors including molecular weight and glass transition temperature (T(g)). In this study, we focus on troglitazone which is composed of diastereomers, RR/SS and RS/SR, as model compound, because each diastereomer has the same molecular weight and similar chemical structure. Troglitazone is isolated into each diastereomer, and both amorphous prepared from RR/SS and RS/SR showed similar T(g) (around 60°C). The surface relaxation of each amorphous troglitazone prepared from two diastereomers, RR/SS and RS/SR, was determined to compare surface molecular mobility, using inverse gas chromatography under dry conditions. As a result, amorphous prepared from RS/SR, showed the shorter surface relaxation time at 40°C (temperature below T(g)), which means it has higher molecular mobility than that from RR/SS at the surface although both have the same molecular weight and similar T(g). Microscopy analysis was conducted to observe the crstallization behavior at the surface of amorphous troglitazone in conditions of high temperature and humidity. Micrographs showed that crystallization area at the surface of amorphous prepared from RS/SR, which showed the shorter surface relaxation time, increased faster than that of the amorphous prepared from RR/SS. Although the reason for the difference in the surface relaxation time of each amorphous troglitazone could not be determined, factors such as the difference of configuration might affect the difference.