A free energy calculation study of the effect of H-->F substitution on binding affinity in ligand-antibody interactions

Changes in binding affinity to catalytic antibody 6D9 of chloramphenicol phosphonate derivatives (CPDs) containing H or F were investigated by performing free energy calculations based on molecular dynamics simulations. We calculated the binding free energy, enthalpy, and entropy changes (DeltaDeltaG, DeltaDeltaH, and -TDeltaDeltaS) attributable to H-->F substitution by comparing results for CPDs containing a trifluoroacetylamino group (CPD-F) or an acetylamino group (CPD-H). The calculated DeltaDeltaG, DeltaDeltaH, and -TDeltaDeltaS values were -2.9, -6.3, and 3.5 kcal mol(-1) and close to experimental values observed for a series of similar ligands, chloramphenicol phosphonates with F and H (-1.4, -3.5, and 2.1 kcal mol(-1)). Therefore, CPD-F binds more strongly to 6D9 than does CPD-H. To clarify the origin of the large difference in DeltaDeltaG, we apportioned the calculated values of DeltaDeltaG and DeltaG for the associated and dissociated states into contributions from various atomic interactions. We found that the H-->F substitution increased the binding affinity mainly by decreasing the hydration free energy and not by increasing favorable interactions with the antibody. The decreased hydration free energy of the ligand was mainly due to unfavorable coulombic interactions between the trifluoroacetylamino group and solvent waters, which increased the free energy of the dissociated state (by about 3.7 kcal mol(-1)). Also, the trifluoroacetylamino group slightly increased the free energy level of the associated state (about 0.8 kcal mol(-1)) because favorable van der Waals interactions compensated for unfavorable coulombic interactions with antibody atoms. In addition, the enthalpy and entropy changes, DeltaDeltaH and -TDeltaDeltaS (computationally -6.3 and 3.5 kcal mol(-1)), originated mainly from a decrease in hydration free energy in the dissociated state. The CPD-F and CPD-H ligands had substantially different structures in the dissociated and complexed states.     

A new approach to 6-deoxy-D-allofuranose- and 6-deoxy-L-talofuranose derivatives from 1,2:5,6-di-O-isopropylidene α-D-glucofuranose

3-O-Acetyl-1,2-O-isopropylidene--D-allofuranose (2 b) was prepared from 1,2:5,6-di-O-isopropylidene--D-allofuranose (1 b). Treatment of2 b with triphenylphosphine-diethyl azodicarboxylate afforded regio- and stereospecifically the 5,6-epoxy--D-allo derivative (3). The other diastereomeric compound, 5,6-epoxy-1,2-O-isopropylidene--L-talofuranose (6) was also prepared stereoselectively from2 b via the intermediates5 a and5 b. The epoxy sugars3 and6 were converted with lithium aluminum hydride to the corresponding 6-deoxy-1,2-O-isopropylidene--D-allofuranose (4 a) and --L-talofuranose (7 a) derivatives. Hydrolysis of4 a and7 a afforded 6-deoxy-D-allose and 6-deoxy-L-talose, respectively. The corresponding 3,5-di-O-acetyl- (4 b and7 b) and the 3,5-O-(tetraisopropyldisiloxane-1,3-diyl) derivatives (4 c and7 c) are also described. Selective removal of the isopropylidene group and subsequent acetylation offers a convenient route to prepare sugar derivatives containing furanose ring, like8 b, as a suitable precursor for nucleoside analogs.Herrn Prof. Dr.K. Komarek mit den besten Wünschen zum 60. Geburtstag gewidmet.     

Second derivative spectrophotometric method for simultaneous determination of cobalt, nickel and iron using 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol

A simple, sensitive and rapid derivative spectrophotometric method using 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (5-Br-PADAP) has been developed for simultaneous determination of Co(II), Ni(II) and Fe(II) which have very similar chemical behavior and appear together in many real samples. The complexes of all these metal ions with 5-Br-PADAP were formed immediately at pH 7.0 ammonium acetate buffered solution and were stable for at least 24 h. Second derivative spectra were selected for evaluation, because working wavelength determination was more precise and spectral overlap was less than in the ordinary and first derivative spectra. Three wavelengths at which the complexes exhibit extremum ²D values for Co(II), Ni(II) and Fe(II) were selected as analytical wavelengths, i.e., 640, 600 and 740 nm, respectively. Calibration curves drawn with zero-to-peak values at mentioned wavelengths were linear between 80 and 2000 ng ml⁻¹ for each metal ion. Concentrations of Co(II) and Ni(II) were calculated from the total ²D values and the sum of the linear equations for these three cations at 640 and 600 nm, after Fe(II) assay by making use of the ²D value at 740 nm. Limits of detection (LOD) for Co(II), Ni(II) and Fe(II) were 2.7, 13.9 and 3.0 ng ml⁻¹, respectively. The method has been applied to tool steel and heater resistance wire samples successfully.     

Computer-aided multichannel detection in high-performance liquid chromatography

Summary The development of a computer-aided rapid-scanning detector for HPLC based on the linear photodiode array UV-visible spectrophotometer is described. Chomatograms monitored at up to three wavelengths, with automatic capture of spectra for eluted peaks and post-run processing of spectral data to generate log₁₀ (A) spectra, second derivative and fourth derivative spectra, are described. Methods are reported for the analysis of forensic samples of diacetylmorphine (heroin) in the presence of the degradation products and potential contaminants caffeine, papaverine, 6-acetylcodeine, thebaine, 6-acetyl-morphine, procaine and morphine separated by HPLC. The novel use of second and higher derivative spectra for the qualitative characterisation of drugs and contaminants separated by HPLC is described.Presented at the 14th International Symposium on Chromatography London, September, 1982     

Synthesis and X-ray structural characterisation of the tetramethylene oxonium derivative of the hydrodecaborate anion. A versatile route for derivative chemistry of [B10H10]

The oxonium derivative P(C₆H₅)₄[2-B₁₀H₉O(CH₂)₄] (1) has been prepared from [B₁₀H₁₀]²⁻ by a solvent-addition reaction route, promoted by Et₂O · BF₃. Its structure has been confirmed by single crystal X-ray analysis. 1 is assumed to be a useful synthon for the derivative chemistry of [B₁₀H₁₀]²⁻. As an illustration, ring-opening reaction occurred in presence of the strong nucleophilic agent OH⁻, giving the monoanionic derivative [P(C₆H₅)₄]₂[2-B₁₀H₉O(CH₂)₄OH] (2).     

Organofluorine compounds and fluorinating agents

Starting with 1,2,4,6-tetra-O-acetyl-3-O-dodecyl-β-d-glucose (1), mixed alkyl-perfluoroalkyl substituted sugar derivatives with an anomeric perfluoroalkylthio group and an O-alkyl group in the 3 position were synthesized via 2,4,6-tri-O-acetyl-3-O-dodecyl-1-thio-β-d-glucose (4). The latter was S-perfluorohexylated with 1-iodoperfluorohexane in a dithionite initiated reaction yielding perfluorohexyl 2,4,6-tri-O-acetyl-3-O-dodecyl-1-thio-β-d-glucopyranoside (5). Experiments with the aim compound 5 completely to deacetylate ended in surprising results. Thus, methanolic methanolate solution produced the orthoester 7 as the result of α-fluoride replacement by methoxy groups as well as the methyl glucoside 8 as the result of a transglycosylation reaction. Alumina supported cesium fluoride cleaved regioselectively the two acetyl groups in the 4- and 6-position yielding perfluorohexyl 2-O-acetyl-3-O-dodecyl-1-thio-β-d-glucopyranoside (10). A complete deacetylation of 5 to amphiphile 11 succeeded only with methanolic tert-butanolate. However, the products 8 and 10 were likewise formed.     

应用扩展的重叠分辨率法优化液相色谱条件分离二茂铁类化合物

本文对优化液相色谱分离条件的重叠分辨率法进行了改进与扩展：首先利用全范围的二元线性梯度淋洗进行溶剂强度的优化，再通过重叠分辨率法进行了溶剂选择性的优化，并且建立了计算机系统，使此方法程序化。利用此方法建立了分离Ｎ－二茂铁甲酰基－Ｎ＇－芳基硫脲类衍生物的最佳流动相体系。     

Photovoltaic Characteristics of a Naphthylamine Derivative

Organic photovoltaic （OPV） cells were fabricated via vacuum vapor deposition with {4-[2-（3-di-cyanomethylidene-5,5-dimethylcyclohexenyl）vinyl]phenyl}di（1-naphthyl）amine （DNP-2CN） as the electron donor, and fullerene （C60） as the electron acceptor. A thin film （10 nm） of tris（8-quinolinolato）aluminum （Alq3） was adopted as the buffer layer. A device based on this DNP-2CN exhibited an open circuit voltage （Voc） of 370 mV, a short-circuit current density （Jsc） of 0.61 mAocm 2, and a white-light power conversion efficiency （ η） of 0.09% （AM1.5, 75 mW.cm^- 2）.     

Capillary electrochromatographic separation of enantiomers under aqueous mobile phases on a covalently bonded cellulose derivative chiral stationary phase

A chemically bonded cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phase (CSP) was prepared by a radical polymerization reaction. The prepared CSP was packed into fused-silica capillaries with inner diameter of 75 microm to perform enantiomer separations in CEC. The electrochromatographic behavior of the CSP was investigated. On the prepared CSP, high EOF could be generated under acidic mobile phases, which represented an advantage for the separation of acidic enantiomers. Several neutral, acidic, and basic enantiomers were resolved on the prepared CSP under aqueous mobile phases. The column efficiencies were between 20,000 and 100,000 plates/m, which were much higher than those of HPLC. In addition, it was observed that the separation of some enantiomers benefited from the adoption of THF as mobile phase modifier.     

四（2,4—二叔戊基苯氧基）酞菁铜（Ⅱ）的合成及其LB膜

合成了标题酞菁铜衍生物,并通过元素分析,高压液相色谱,紫外光谱,红外光谱,核磁共振谱,电镜,顺磁共振谱及质谱加以确认。该化合物在稀氯仿溶液和LB膜中各以单,双分子缔合的形式存在。Z型沉积形成的单层LB膜对氨气有很高的灵敏度和选择性。