荧光光谱法研究蛋白质构象的电磁-温度协同效应

长期以来电磁生物效应受到人们普遍关注，近年来从各个角度进行了相关研究。电磁－温度协同效应是当前的热点。本研究通过电磁场及温度协同对蛋白质影响的研究，发现蛋白质在电磁场作用下的不可逆变性，而且这种变性也遵循Arrhenius规律，并进一步得出电磁－温度协同作用的蛋白质变性模型。本文从分子反应动力学的角度解释了电磁－温度协同效应，并对非热效应作了一定的探讨。     

1，4－二氟四苯基苯的合成、结构与构象

借助电子转移催化反应的方法，用电子给予体１，４－二锂四苯基丁二烯将惰性的三溴氟甲烷活化，并与之发生反应，产物１，４－二氟四苯基苯的结构经ＭＳ、ＮＭＲ和Ｘ射线单晶衍射确证，并以分子力学的方法对其进行了构象分析。     

Conformation control of bilatrienes by peptides: A survey

Summary A variety of bilipeptides has been synthesized and investigated by UV-VIS and CD spectroscopy to explore the conformational influence of peptide ligands on the covalently bound tetrapyrrol moiety. The results obtained are complemented by those reported previously. From the comprehensive data thus available several features of the peptidic chain regulating interactions with the bilatriene moiety have been elucidated. Accordingly, the presence of three amide linkages at the ligand is prerequiste for induction of pronounced conformational changes consisting either in a complete transition ofM intoP helical bilatriene species by inversion of all torsional angles, or in a stretching of the chromophore. The kind of conformational influence can be controlled by varying the position of the prolyl entity within a given peptide.Dedicated to Prof. Dr. Kurt Schaffner on occasion of his 60th birthday     

Structure-activity relationships of pyrethroid insecticides. Part 2. The use of molecular dynamics for conformation searching and average parameter calculation

Summary Molecular dynamics simulations have been performed on a number of conformationally flexible pyrethroid insecticides. The results indicate that molecular dynamics is a suitable tool for conformational searching of small molecules given suitable simulation parameters. The structures derived from the simulations are compared with the static conformation used in a previous study. Various physicochemical parameters have been calculated for a set of conformations selected from the simulations using multivariate analysis. The averaged values of the parameters over the selected set (and the factors derived from them) are compared with the single conformation values used in the previous study.     

Structural changes by sulfoxidation of phenothiazine drugs

Summary The side-chain conformations of psychoactive phenothiazine drugs in crystals are different from those of biologically inactive ring sulfoxide metabolites. This study examines the potential energies, molecular conformations and electrostatic potentials in chlorpromazine, levomepromazine (methotrimeprazine), their sulfoxide metabolites and methoxypromazine. The purpose of the study was to examine the significance of the different crystal conformations of active and inactive phenothiazine derivatives, and to determine why phenothiazine drugs lose most of their biological activity by sulfoxidation. Quantum mechanics and molecular mechanics calculations demonstrated that conformations with the side chain folded over the ring structure had lowest potential energy in vacuo, both in the drugs and in the sulfoxide metabolites. In the sulfoxides, side chain conformations corresponding to the crystal structure of chlorpromazine sulfoxide were characterized by stronger negative electrostatic potentials around the ring system than in the parent drugs. This may weaken the electrostatic interaction of sulfoxide metabolites with negatively charged domains in dopamine receptors, and cause the sulfoxides to be virtually inactive in dopamine receptor binding and related pharmacological tests.     

Biphenyl-tricarbonylchrom-komplexe, 9. Mitt.: Synthesen,chromatographische Enantiomerentrennung,Circulardichroismus und Chiralität von mono- und bis-(Tricarbonylchrom)-Komplexen di- und tetrasubstituierter sowie überbrückter Biphenyle

Chiral title compounds have been resolved by medium pressure liquid chromatography (MPLC) on triacetylcellulose in ethanol. Whereas a quantitative separation was achieved for16 and20, a recycling technique had to be applied to1,4,6,10 and15 leading to a 100% e.e. for1,6 and15 and to ca. 60% e.e. for4 and10.An unambiguous assignment of the chirality (+)-(R) _a -(S) _m for tricarbonylchromium-6,6-dimethyl-diphenicacid dimethylester (4) was deduced both from the photochemical decomplexation to (-)-5 with the known chirality (R) _a (whose e.e. was determined by MPLC on triacetylcellulose) and by comparison of the¹H-n.m.r. spectra of4 and5 thereby proving the structure 4 for the former.Other chiralities both for mono and bis(tricarbonylchromium)biphenyl complexes were established by chemical correlations and comparison of the CD spectra with those of key compounds.

Herrn Prof. Dr.H. Tuppy mit besten Wünschen zum 60. Geburtstag gewidmet.     

Neurosteroid analogues: synthesis of 6-aza-allopregnanolone

An efficient synthesis of 6-azapregnane derivatives and their biological activity is described. The nitrogen was introduced into the B ring using Beckmann rearrangement of the (E)-oxime of 6-oxo-B-nor-5α-pregnane derivatives. The required 3α-hydroxyl was produced either by solvolysis of the corresponding 3β-mesyloxy group or by the Meerwein-Ponndorf-Verley reduction of the 3-oxo group; this reduction could be carried out selectively with an unprotected 3,20-dioxo derivative. The binding of the 6-aza-steroids to the γ-aminobutyric acid receptor (GABA_A) was measured using [³⁵S]-tert-butyl-bicyclo[2.2.2]phosphorothionate (TBPS) and [³H]flunitrazepam. The only analogue to be slightly active was that lacking any oxygen function in position 3.     

What crystals of small analogs are trying to tell us about cellulose structure

The molecular geometries from crystal structures of 23 small molecules such as cellobiose were reviewed and extrapolated to give model cellulose chains. Within a given model, all monosaccharide units and their linkages are identical so the models are regular helices. Despite fairly large ranges for the glycosidic linkage torsion angles and , 29° and 57°, respectively, there is little variation in the n and h parameters of the model helices. They are extended, with h values (the advance per residue along the helix axis) of 5.04–5.27 Å. Some models were slightly right-handed, with n values up to 2.12 residues per helix turn. Left-handed models were in the majority, and their n values were as large as –2.91. These results are consistent with known structures of cellulose and its derivatives. An exception comes from a heavily derivatized cellobiose molecule. It yields right-handed helices with n 4.5 and h 3 Å. Because one half turn of this helix reverses the direction of the chain in a compact region, the linkage geometry is a model for chain-folding. Other derivatives that are unable to form the O3O5 hydrogen bond gave left-handed helices. The puckering of the glucose rings was also surveyed. A number of rings in small molecule structures are puckered to a degree that is similar to the puckering determined for methyl cellotrioside, cellotetraose, cellulose I and cellulose II.     

溶液中N—乙酸基取代氮氧杂大环的构象及其配合物的NMR研究

用~1HNMR方法研究了溶液中大环化合物1,12-二氮杂-3,4:9,10-二本并-5,8-二氧杂环十五烷-N,N’-二乙酸盐的构象.NMR变温实验表明,在溶液中大环与Zn(Ⅱ)、Ni(Ⅱ)、Co(Ⅱ)的配合物环上醚氧不参与配位,其中Ni(Ⅱ)配合物为低自旋反磁性的平面四方形配位.     

Structural Studies of Transition Metal Compounds

A historical overview will be given on the structural studies on transition metal compounds and their interaction with other fields of coordination chemistry. About three decades have passed away since the structure and absolute configuration of tris(ethylenediamine)cobalt(III) complex ion were determined. At present accumulation of the structural data for isomers has enabled us to understand structural principles of chelate complexes in considerable detail. The energy minimization calculations can predict the detailed geometries of the complexes. Differences in thermodynamic properties between different conformers are well reproduced. Aspherical distribution of 3d electrons in transition metal complexes was detected for the first time in crystals of [Co(NH3)₆][Co(CN)₆] in 1973. Such an accurate electron density study provides important information on the d electrons placed in a ligand field. The high-spin and low-spin states can be distinguished unequivocally. In spite of a very small valence/total electron ratio, the asphericity of 4d and 5d electrons in a ligand field can be detected. The crystal structures of a series of dimeric copper(II) carboxylate adducts of the general formula [Cu(RCOO)₂L]₂ have been determined or redetermined as accurately as possible. The temperature dependent magnetic susceptibility of these crystals indicated that the isolated pairs of Cu(II) ions interact strongly through exchange forces. Molecular orbital calculations revealed that the electron population in the carbon atom of the bridging OCO group plays an important role in determining the strength of the spin superexchange interaction. In the crystals of some cobaloxime complexes, racemization of chiral groups bonded to Co proceeds on X-ray exposure without degradation of crystallinity. Several intermediate stages could be determined by X-ray analysis. Various reaction pathways were recognized and the reaction rate could be correlated with the atomic arrangement in the crystal.