石房蛤毒素(STX)衍生物的电子结构与毒性-结构关系研究

本文对十个石房蛤毒素(Saxitoxin,STX)衍生物进行了量子化学(INDO)计算,得到了多种电子结构信息。据此研究了它们的电子结构特征,确定了它们的活性部位。通过构效关系研究,发现某些电子结构指数与毒性之间存在较好的相关关系。这些结果为讨论该类化合物的作用机理、与受体之间的相互作用及进一步的分子设计提供了有价值的信息。     

4-取代Fentanyl类化合物电子结构及构效关系研究

本文对十一个4-取代Fentanyl类化合物进行了量子化学(INDO)计算, 研究了它们的电子结构及构效关系. 结果表明, 这些化合物同其他Fentanyl类化合物在主要活性部位和电子结构趋势上基本相同. 酰胺氧原子是最重要的负电中心, 哌啶氮原子在季铵化后发挥正电中心作用. 4-取代基的极性基团可能以电荷转移作用或氢键接受体形式与受体极性部位结合, 并能影响其他活性部位电子密度. 另外, 4-取代基的立体因素与疏水因素同生物活性相关.     

短裸甲藻毒素(Brevetoxins)的电子结构与构效关系研究

对短裸甲藻毒素衍生物进行了电子结构研究和构象分析,确定了它们的活性部位,探讨了作用方式,讨论了它们的结构-活性关系及受体的相互作用,解释了衍生物之间活性差异的原因。研究结果表明,分子骨架中段环上的烯键,A环及R烯键对活性有重要影响,分子骨架的折曲程度对活性也有较大影响。     

Synthesis, cytotoxic effect, and structure-activity relationship of Pd(II) complexes with coumarin derivatives

We report the influence of the substituent at the N atom of the ligands on the synthesis, biological activity, and stability of Pd(II) complexes of the general formula PdL(2). The compounds adopt a cis or trans configuration with respect to the substituent at the nitrogen atom. Sterically hindered substituents promote the formation of trans isomers, whereas when the nitrogen atom is unsubstituted, cis isomers are formed. The compounds were characterized by elemental analysis, infrared and 1H NMR spectroscopies, and electrospray mass spectrometry. The complexes were also studied using X-ray diffraction and computational DFT methods. Both complexes cis-3a and trans-3c exhibit square-planar geometries around the Pd(II) atom. The cytotoxic effects of these complexes were examined on two human leukemia cell lines, HL-60 and NALM-6. Pd complex cis-3a showed significant cytotoxic activity. The effects exhibited by this complex were comparable to those reported for carboplatin. Loigand 2a was not cytotoxic. Computational analysis carried out at the PB/B3LYP/LACVP**//mPW1PW91/LanL2DZ level showed excellent correlation between the energy difference of the cis and trans isomers and the cytotoxic activity, rendering computations a useful predictive tool for the design of new drugs.     

A study of the electronic spectrum of halogen derivatives of ethylene

The spectra of tetrachloroethylene, monofluoroethylene, gem-, cis- and trans-difluoroethylene and trifluoroethylene were studied in the region 150–250 nm in the gas, solid and Kr matrix. The valence character of the π å π^* transition in the various compounds was verified and the Rydberg transitions were identified. The lowest energy band in the fluoroethylene was found to be a Rydberg transition. The vibronic structure of the π å π^* transition in tetrachloroethylene indicates that the excited state geometry is planar. The existence of a π å σ^* transition at lower energy than the π å π^* transition was verified for cis-difluoroethylene and trifluoroethylene.     

A comparative QSAR study using Wiener, Szeged, and molecular connectivity indices

In this study we have investigated the relative correlation potential of Wiener (W), Szeged (Sz), and molecular connectivity indices (0chiR, 1chiR and 2chiR) in developing quantitative structure-activity relationships, QSAR; log P values of benzoic acid and its nuclear-substituted derivatives were used for this purpose. The statistical analyses for univariate and multivariate correlations had indicated that both W and Sz are closely related to the connectivity indices (mchiR) and that the W, the Sz, and the 1chiR indices have similar modeling potentials. 1chiR gives slightly better results than both W and Sz. Other connectivity indices 0chiR and 2chiR correlate poorly with log P.     

苯并噻二嗪吸电子基取代衍生物电子性质的理论研究

运用量子化学半经验方法对1，2，4-苯并噻二嗪-1，1二氧类化合物的8种取代衍生物进行了量子化学计算，从体系能量、几何构型、电子结构、前线分子轨道等几方面分析了吸电子基-CN，-NO2等取代后体系的电子性质变化规律．结果表明：随着取代基吸电子能力的增强，体系的活性增强，可为药物合成提供一定的理论指导．     

Revisiting the calculation of (13)C chemical shift tensors in cadmium acetate dihydrate with EIM and EIM/cluster methods

The chemical shift tensors of the acetate anions in cadmium acetate dihydrate are calculated using a cluster approach, the embedded ion method (EIM), and a combination of the two in the EIM/cluster method. The results of these calculations are compared with those completed on the isolated acetate anion and show the need for the inclusion of intermolecular interactions. The RMS difference between experiment and theory improves from over 60 ppm when the calculation is completed on an isolated anion, to below 10 ppm when interactions to nearby atoms are included. The best cluster model includes three cadmium acetate dihydrate and gives an RMS result of 4.4 ppm. The EIM method, which uses point charges to account for the intermolecular effects, achieves an RMS of 7.7 ppm on individual anions alone. A combination of the two, the EIM/cluster method, shows that the only necessary atom to explicitly add is the nearest cadmium; this addition results in an RMS of 4.1 ppm. These results are also discussed in terms of the computational cost of the different calculations.     

A comparative study of quantitative structure-activity relationship methods based on gallic acid derivatives

By using hologram quantitative structure-activity relationship (HQSAR) and comparative molecular field analysis (CoMFA) methods, the relationships between the structures of 49 gallic acid derivatives and their analgesic activity have been investigated to yield statistically reliable models with considerable predictive power. The best HQSAR model was generated using atoms, bond and connectivity as fragment distinction parameters and fragment size 5-7 from a hologram length of 307 with 3 components. High conventional r2 (r2 = 0.825) and cross-validation r2 (r2(cv) = 0.726) values were obtained. CoMFA analyses varying lattice size and location, grid spacing, probe charges and using, Tripos standard and Indicator force field were performed. The best model was developed with 4 components using sp3-hybridized carbon atom with +1.0 charge as probe, grid spacing (2 A), lattice offset (1.0, 3.0, -2.5). The CoMFA model showed a conventional correlation coefficient r2 of 0.889 and across-validation r2(cv) equals to 0.633. The robustness and predictive ability of the HQSAR and CoMFA models have been validated by means of an external test set. The results indicate that both models possess high statistical quality in the prediction of analgesic potency of novel gallic acid analogs.     

Protecting groups for glucuronic acid: application to the synthesis of new paclitaxel (taxol) derivatives

To prepare two new glucuronide conjugates, allyl ester and allyl carbonates were used as protecting groups of the glucuronic moiety. In this way, an aniline glycosyl carbamate spacer linked to the 2'-OH of paclitaxel was obtained. By using palladium chemistry, an efficient one-step removal of all the allyl groups at the end of the synthesis afforded the desired compounds in good yields.     

Structural and electronic characterization of nitrosyl(octaethylporphinato)iron(III) perchlorate derivatives

The synthesis and crystallographic characterization of the five-coordinate iron(III) porphyrinate complex [Fe(OEP)(NO)]ClO4 are reported. This [FeNO]6 complex has a nearly linear Fe-N-O group (angle = 173.19(13) degrees) with a small off-axis tilt of the Fe-N(NO) vector from the heme normal (angle = 4.6 degrees); the Fe-N(NO) distance is 1.6528(13) A and the iron is displaced 0.32 A out-of-plane. The complex forms a tight cofacial pi-pi dimer in the solid state. M?ssbauer spectra for this derivative as well as for a related crystalline form are measured both in zero applied magnetic field and in a 7 T applied field. Fits to the measurements made in applied magnetic field demonstrate that both crystalline forms of [Fe(OEP)(NO)]ClO4 have a diamagnetic ground state at 4.2 K. The observed isomer shifts (delta = 0.22-0.24 mm/s) are smaller than those typically observed for low-spin iron(III) porphyrinates. Analogous M?ssbauer measurements are also obtained for a six-coordinate derivative, [Fe(OEP)(Iz)(NO)]ClO4 (Iz = indazole). The observed isomer shift for this species is smaller still (delta = 0.02 mm/s). All derivatives show a strong temperature dependence of the isomer shift. The data emphasize the strongly covalent nature of the FeNO group. The M?ssbauer isomer shifts suggest formal oxidation states greater than +3 for iron, but the NO stretching frequencies are not consistent with such a large charge transfer to NO. Differences in the observed nitrosyl stretching frequencies of the two crystalline forms of [Fe(OEP)(NO)]ClO4 are discussed.     

Synthesis and novel structure-activity relationships of potent sansalvamide A derivatives

Synthesis of twelve Sansalvamide A derivatives and their SAR against colon cancer (HT-29).     

A total synthesis of (-)-hemiasterlin using N-Bts methodology.

A total synthesis of (-)-hemiasterlin has been accomplished in nine steps from 25(8) (>35% yield overall). An improved enantiocontrolled route to the tetramethyltryptophan subunit 32 was developed using an asymmetric Strecker synthesis (five steps, 50% yield from 25), and the dipeptide 22 was prepared in seven steps, 37% yield from valinol. The synthesis exploits the high reactivity of a Bts-protected amino acid chloride in the difficult peptide coupling of sterically hindered amino acid residues 18 and 20 to form 21 (70%, recrystallized) and also uses N-Bts intermediates for the high-yielding N-methylations of 14 and 31. In addition, the Bts-protected di-tert-butyl N-acylimidodicarbonate 33 is shown to undergo efficient coupling with 22 to form 34 (97% in the coupling step; 79% over the activation; coupling sequence from 32).     

A study of 8-mercaptoquinoline (thiooxine) and its derivatives

The absorption spectra of 5-fluoro-8-mercaptoquinoline in aqueous solutions at various pH values have been studied. The _max values of the 5-fluoro-8-mercaptoquinolinium ion and also of the 5-fluoro-8-mercaptoquinolate ion, and the apparent molar absorption coefficient of the hydrated form have been determined. In the hydrated form, a molecule of water is connected by hydrogen bonds both with the nitrogen and with the mercapto group. The presence of the fluorine atom in positions 5 of the molecule of the 8-mercaptoquinoline increases the acidic properties of the mercapto group and decreases the basic properties of the nitrogen, in comparison with those in 8-mercaptoquinoline. The dissociation constants of 5-fluoro-8-mercaptoquinoline are pK_SH=7.49 ± 0.02 (thermodynamic) and pK_NH= 1.97 ±0.02 (concentration). The isoelectric point is at pH 4.70.For part XXXVIII, see [4].     

A CASPT2 study of the electronic spectrum of hexacyanoosmate(III)

CASPT2 calculations reveal that the ligand field splitting parameter Delta(o) of [Os(CN)6]3- is much higher than previously proposed values of +/-38,000 cm(-1). In line with the expected increase down a transition-metal group, Delta(o) is found to be +/-55,000 cm(-1), excluding the possible appearance of ligand field transitions in the UV-vis spectrum. Instead, the calculations confirm that the observed spectrum arises from the three lowest symmetry-allowed ligand-to-metal charge-transfer (LMCT) excitations. Spin-orbit coupling in the ground state is found to be about 4350 cm(-1), leading to a spin-orbit coupling constant zeta of +/-2900 cm(-1). Spin-orbit coupling in the 2T(1u) LMCT states is found not to be negligible, contrary to previous belief.     

Structural and electronic factors controlling the refractive indices of the chalcogenides ZnQ and CdQ (Q = O, S, Se, Te)

On the basis of first-principles electronic band structure theory, we calculated the refractive indices of the zinc blende and wurtzite structures of the chalcogenides ZnQ and CdQ (Q = O, S, Se, Te) and analyzed their trends by calculating the total absorption power per unit formula. The calculated refractive indices are in good agreement with the available experimental data. The total absorption power per formula unit is found to allow one to distinguish the effect of the chromophore from that of the cell volume on the refractive indices of insulating inorganic compounds.