Supplementary Observations on the Chemistry of the Alkaloids of Berberine Series. II. The Ultraviolet Absorption Spectra of Berberines and Related Compounds

The ultraviolet absorption spectra of berbines and ?-berbines consist of a single, weak and narrow band in which λ_max position dependeds on the kind of auxochrome group i. e., methylenedioxy-or dimethoxy group attached to 2–3 position. The effect of the auxochrome group at 11–12 position or 12–13 position is very small. The shape of the band of oxyberberine, oxy-?-berberine and oxyprotoberberine are similar, especially those of the latter two substances resemble closely. Comparing with isoquinoline, the bands (b), (c) and (d) of G-berberines and protoberberine are considered as characteristic of isoquinoline structure, while the band (a) in visible region is of berberinium structure, however, the absorption curve of ?-berberines does not show any characteristic of isoquinoline or berberinium structure.     

小檗碱与人免疫球蛋白在仿生膜中的相互作用

利用荧光光谱、圆二色谱(CD)和动态激光散射技术研究了小檗碱与人免疫球蛋白(HGG)在以双(2-乙基己酯)-磺酸基琥珀酸钠(AOT)/异辛烷/水微乳液为膜的模拟环境下的结合反应. 通过Scatchard方程分别计算了不同温度下的反应结合常数. CD光谱结果表明: 小檗碱与HGG键合改变了蛋白原有的构象. 同时由热力学结果可知, 小檗碱与HGG之间的相互作用主要以疏水作用为主, 同时存在静电作用力和氢键作用力. 动态激光散射结果进一步证明了药物与HGG在微乳液中的相互作用. 通过计算机模拟技术, 在不考虑环境影响的条件下从理论上探讨了HGG与小檗碱的结合区域和结合模式.     

Media Influence on the Enhancement of the Fluorescence of Berberine Hydrochloride

 Berberine hydrochloride is an alkaloid with little or no fluorescence in water. In sodium dodecylsulfate solutions, the fluorescence intensity of this compound is enhanced several folds by ion-pairing with the anion of the surfactant. The enhanced fluorescence intensity reaches a maximum at a surfactant concentration of 4·10⁻³ M and then decreases to a constant value at the critical micelle concentration and beyond. At concentrations near the maximum, a calibration sensitivity of 3.23·10⁶/M was obtained. In addition, a good linear dynamic range and a low limit of detection (4·10⁻⁵ and 1.5·10⁻⁷ M, respectively) were determined. This observation indicates that this surfactant medium could be effectively used in fluorometric trace analysis of berberine hydrochloride. It was also observed in this work that solvents of low dielectric constant tend to stabilize this compound and thereby enhance its fluorescence.     

Media Influence on the Enhancement of the Fluorescence of Berberine Hydrochloride

Summary.  Berberine hydrochloride is an alkaloid with little or no fluorescence in water. In sodium dodecylsulfate solutions, the fluorescence intensity of this compound is enhanced several folds by ion-pairing with the anion of the surfactant. The enhanced fluorescence intensity reaches a maximum at a surfactant concentration of 4·10⁻³ M and then decreases to a constant value at the critical micelle concentration and beyond. At concentrations near the maximum, a calibration sensitivity of 3.23·10⁶/M was obtained. In addition, a good linear dynamic range and a low limit of detection (4·10⁻⁵ and 1.5·10⁻⁷ M, respectively) were determined. This observation indicates that this surfactant medium could be effectively used in fluorometric trace analysis of berberine hydrochloride. It was also observed in this work that solvents of low dielectric constant tend to stabilize this compound and thereby enhance its fluorescence. Received November 26, 1999. Accepted (revised) January 13, 2000     

Berberine alkaloid as a sensitive fluorescent probe for bile salt aggregates

Effect of sodium cholate (NaC) bile salt on the absorption and fluorescence properties of berberine cation was studied in aqueous solution and water-cosolvent mixtures. The alteration of the fluorescent behavior with increasing NaC concentration showed an entirely different trend from that found previously in the presence of sodium dodecylsulfate. Binding to bile salt agglomerates led to significant fluorescence intensity enhancement, and the fluorescence lifetime of berberine proved to be highly sensitive to the structure and size of the aggregates. The dual exponential decay kinetics above 10 mM NaC concentration showed that the probe resided in two totally different binding sites. At 2-10 mM NaC concentrations, only primary aggregates were detected. The aggregate disrupting power of cosolvents decreased in the series of dimethylformamide, acetonitrile, formamide, and methanol. These compounds enhanced the water accessibility of berberine bound to aggregates and diminished the number of secondary aggregates.     

表面增强拉曼光谱研究小檗碱与DNA的相互作用

用表面增强拉曼光谱研究了小檗碱（BER）与小牛胸腺DNA（ct DNA)的相互作用,并对重要谱峰进行了归属。在Ag胶体系中,小檗碱分子的拉曼信号增强显著,表明小檗碱阳离子键合到银胶粒子的表面。加入ct NA之后,小檗碱分子的大部分SERS带的强度进一步增加,而仅有少数几个带的信号强度趋于消失,可能是小檗碱分子的异喹啉部分键合到DNA的小沟槽,小檗碱与DNA的相互作用模式主要是通过静电力及疏水相互作用,吸收光谱表明,Ag胶体系的存在并未改变小檗碱分子与DNA的相互作用模式。     

The Oxidizing Properties of the Third Transition Series Hexafluorides and Related Compounds

Some of the transition metal hexafluorides demonstrate an astonishing oxidizing power. In particular may be mentioned PtF₆, which is capable of oxidizing molecular oxygen or xenon, a process requiring an electron affinity, E(PtF₆), > ?156 kcal·mole^?1. From a comparative study of all of the hexafluorides of the third transition series the electron affinity is seen to increase regularly in the sequence WF₆ < ReF₆ < OsF₆ < IrF₆ < PtF₆. The increase in E with unit increase in atomic number of M appears to be ≈ ?20 kcal·mole^?1. On the other hand the ability of the hexafluorides to accept F^? decreases along this series. This effect enables IrF₆ to be more effective than PtF₆ in the generation of nitrogen oxide trifluoride, ONF₃, by the oxidative fluorination of nitrosyl fluoride, ONF. Both PtF₆ and IrF₆ interact spontaneously with ONF or O₂NF to generate fluorine, at or below room temperature. The decrease in F^? -acceptor ability along the series, which stands in sharp contrast to the increase in electron affinity, suggests that ligand crowding increases sharply across the series from WF₆ to PtF₆. This accords with the observed decrease in molecular volume along the series, both in the hexafluorides and in the MF₆^? salts. It is clear from this comparison that the species IrF₆ and PtF₆ are close to a minimum volume for this series. The oxide pentafluorides ReOF₅ and OsOF₅ are similar in oxidizing ability to their respective hexafluorides but are poorer F^? acceptors. Evidently the ligand crowding in MOF₅ molecules is greater than in MF₆.     

高选择性端粒G-四链体稳定性配体:9-O-多胺取代小檗碱衍生物的合成及活性评价

设计合成了3个多胺取代的小檗碱衍生物5a~5c, 并利用圆二色(CD)光谱、 荧光共振能量转移(FRET)熔点实验、 荧光光谱和聚合酶链反应(PCR)终止实验等手段研究了小檗碱衍生物5a~5c与端粒DNA的相互作用. 结果表明, 小檗碱衍生物5a~5c可以诱导端粒DNA序列形成反平行结构G-四链体, 显著地提高了端粒G-四链体的稳定性, 有效地抑制了端粒的扩增; 而与双链DNA的相互作用则很小, 是高选择性的端粒G-四链体配体.     

Electrochemical Oxidation of Berberine and of Its Oxidation Products at a Glassy Carbon Electrode

The electrochemical behavior of berberine, an isoquinoline plant alkaloid with a wide spectrum of physiological effects, was studied at a glassy carbon electrode using cyclic, differential pulse and square‐wave voltammetry. The oxidation of berberine is a quasireversible, diffusion‐controlled process and occurred in a cascade mechanism with the formation of several oxidation products. The diffusion coefficient of berberine was calculated from cyclic voltammetry studies to be D=1.69×10^?6 cm² s^?1. The oxidation process of berberine is also pH dependent and the number of electrons and protons transferred was determined using differential pulse voltammetry. The formation of several oxidation products that adsorbed at the glassy carbon electrode surface was observed and their electrochemical behavior characterized. A mechanism for the oxidation of berberine at a glassy carbon electrode was proposed.     

中药黄连有效成分盐酸小檗碱与牛血清白蛋白的相互作用

从天然中药材黄连中提取分离并精制得到盐酸小檗碱(BC),采用UV光谱和荧光光谱(FS)研究其与牛血清白蛋白(BSA)的相互作用,解释了BC导致BSA的荧光发射光谱峰裂分的现象,其二重峰分别归属于色氨酸及酪氨酸残基.结果表明,静态猝灭和非辐射能量转移是导致BC对BSA荧光猝灭的两大原因,BC与BSA的表观结合常数K_A为8.66×10⁴L/mol(30℃)和8.72×10⁴L/mol(37℃),BC在BSA分子上的结合位点数为(3.1±0.2).BC与BSA分子中荧光性氨基酸残基之间的距离为3.75nm(30℃)和3.62nm(37℃),表明BC的部分片段能够插入BSA分子内部.热力学函数计算结果表明,该作用过程是一个熵增加、Gibbs自由能降低的自发超分子作用过程,并由此推断BC与BSA之间以疏水相互作用为主.     

小檗碱衍生物合成及生理活性研究进展

小檗碱是一种季铵型异喹啉生物碱,主要存在于毛茛科、芸香科和小檗科等植物中,具有多种药理功能.近年来,大量小檗碱衍生物的合成,极大提高了小檗碱的生理活性及拓展了小檗碱的应用范围.文章重点综述了小檗碱及其衍生物的生物及化学合成,简述了其生理活性,并对新型小檗碱衍生物合成的设计方向作了展望.     

Study on the Interactions of Ruthenium(III), Rhodium(III) and Palladium(II) Ions with DNA

Fluorescence, absorption and circular dichroism spectra have been used in the interactions of ruthenium(III), rhodium(III) and palladium(II) ions with DNA with berberine as a probe (berberine, Scheme 1). The results are as follows: ruthenium(III) and rhodium(III) ions show different effects from that of the palladium(II) ion on the fluorescence spectra characteristics of berberine-DNA system. Quenching fluorescence is seen with palladium(II) ion addition, whereas increasing fluorescence is observed for ruthenium(III) and rhodium(III) ions. The addition of ruthenium(III), rhodium(III) and palladium(II) ions causes the increasing absorption of the DNA solution. The addition of ruthenium(III), rhodium(III) and palladium(II) ions to the DNA solution also causes the circular dichroism spectra to change. The above results suggest that different metal ions exhibit different affinity when binding to DNA, which could correlate well with the ions’ charge, structure and the ability to coordinate. There is a comparison between Pt(IV) and Pd(II) ions on the fluorescence of the berberine-DNA system.     

光谱法研究盐酸小檗碱与DNA的相互作用

采用荧光和紫外(UV)光谱等手段,研究了中药有效成分小檗碱(Ber)与脱氧核糖核酸(DNA)的键合作用。结果发现,小檗碱能插入到DNA双螺旋碱基对之间的空腔中,使小檗碱在eλm=530 nm处较弱的荧光强度显著提高;酸度显著影响其相互之间的作用;随着DNA浓度的增大,Ber的荧光强度增大,显示了很好的光敏性能。偏振、荧光猝灭实验等也进一步表明:Ber与DNA的作用方式主要是嵌插结合;离子强度的大小会影响Ber与DNA之间的作用。在pH=3.0适宜酸度条件下,建立了以Ber为探针定量测定DNA的分析方法。方法线性范围为0~5.2×10-5mol/L,精密度(RSD)为2.7%(n=7),检出限为1.43×10-7mol/L。     

Isostructural and Nonisostructural Compounds in Series of Halogenated Organic Crystal Substances. Structure of Hal-Aggregates

The local characteristics and the form of intermolecular Hal aggregates (assemblies of contacting halogen atoms of neighboring molecules), existing in haloorganic crystal substances differing only in the nature of Hal atoms, are compared. Twenty three series of halogenated hydrocarbons involving 57 crystal structures are considered. Pronounced specifics of Hal-aggregates has been established for compounds with low and medium halogen contents. It is found that k(Hal) (coordination number of the Hal atom with respect to the neighboring Hal atoms) generally increases in the series F–Cl–Br–I; for constant k(Hal), <> = i - 2R_Hal> nearly always decreases (r_i is the distance from the Hal atom in question to one of the k nearest Hal atoms, and R _Hal is the van der Waals radius).     

氯金酸-小檗碱离子缔合物体系的共振瑞利散射光谱研究及其分析应用

在pH＝2.0的HCl-NaOAc缓冲溶液中, 小檗碱阳离子与氯金酸根阴离子由于静电引力和疏水作用力形成离子缔合物时, 将引起溶液共振瑞利散射(RRS)显著增强, 并产生新的RRS光谱, 其最大RRS波长位于370 nm, 另在277 nm也有一个较强的RRS峰. 在1.83×10^－8～5.0×10^－6 mol/L范围内小檗碱浓度与散射强度(ΔI)成正比; 反应有很高的灵敏度, 对小檗碱的检出限(3σ/K)为1.83×10^－8 mol/L (7.5 ng/mL). 研究了共振瑞利散射光谱测定小檗碱的影响因素, 考察了共存物质的影响, 实验表明该方法有良好的选择性. 基于小檗碱与氯金酸反应产物的RRS光谱, 发展了一种高灵敏、简便、快速测定小檗碱的新方法, 用于中成药和中药饮片样品的测定, 结果满意. 本文还对反应机理进行了初步的探讨.     

Small molecule-biopolymer interactions: Ultraviolet-visible and fluorescence spectroscopy and chemometrics

Interactions between small molecules with biopolymers e.g. the bovine serum albumin (BSA protein), are important, and significant information is recorded in the UV-vis and fluorescence spectra of their reaction mixtures. The extraction of this information is difficult conventionally and principally because there is significant overlapping of the spectra of the three analytes in the mixture. The interaction of berberine chloride (BC) and the BSA protein provides an interesting example of such complex systems. UV-vis and fluorescence spectra of BC and BSA mixtures were investigated in pH 7.4 Tris-HCl buffer at 37 °C. Two sample series were measured by each technique: (1) [BSA] was kept constant and the [BC] was varied and (2) [BC] was kept constant and the [BSA] was varied. This produced four spectral data matrices, which were combined into one expanded spectral matrix. This was processed by the multivariate curve resolution-alternating least squares method (MCR-ALS). The results produced: (1) the extracted pure BC, BSA and the BC-BSA complex spectra from the measured heavily overlapping composite responses, (2) the concentration profiles of BC, BSA and the BC-BSA complex, which are difficult to obtain by conventional means, and (3) estimates of the number of binding sites of BC.     

Dependence of Fluorescence Properties of Compounds from Psoralen,Angelicin, and Carbazole Series on the Character of Their Terminal Substituents

Absorption, luminescence excitation and emission spectra of nine compounds from 4,8,4'-trimethylpsoralen, 4,4'-dimethylangelicin, and 1,2,3,4-tetrahydrocarbazole series with various terminal substituents were studied in water and 2-propanol. Proceeding from the data obtained in the present and also some previous studies we have formulated the main rules concerning a general mechanism of changes in the fluorescence characteristics of DNA-specific dyes depending on their chemical structure, substrate properties, and measurement medium.     

Alkaloids ofThalictrum sachalinense. V

Summary Glaucine, N-methylnantenine, thalrugosine, magnoflorine, berberine, and the unidentified bases (II) and (III) have been obtained from the roots and rhizomes ofThalictrum sachalinense. The main alkaloid in the combined bases of the roots and rhizomes was magnoflorine.Intitute of the Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. Pacific Ocean Institute of Bioorganic Chemistry, Far Eastern Scientific Center of the Academy of Sciences of the USSR, Vladivostok. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 594–597, September–October, 1978.     

Enantioselective Oxidative Aerobic Dealkylation of N‐Ethyl Benzylisoquinolines by Employing the Berberine Bridge Enzyme

N‐Dealkylation methods are well described for organic chemistry and the reaction is known in nature and drug metabolism; however, to our knowledge, enantioselective N‐dealkylation has not been yet reported. In this study, exclusively the (S)‐enantiomers of racemic N‐ethyl tertiary amines (1‐benzyl‐N‐ethyl‐1,2,3,4‐tetrahydroisoquinolines) were dealkylated to give the corresponding secondary (S)‐amines in an enantioselective fashion at the expense of molecular oxygen. The reaction is catalyzed by the berberine bridge enzyme, which is known for C? C bond formation. The dealkylation was demonstrated on a 100 mg scale and gave optically pure dealkylated products (ee>99 %).