Does alpha-fluorination affect the structural trans-influence and kinetic trans-effect of an alkyl ligand? Molecular structures of Pd(TMEDA)(CH(3))(R(F)) and a kinetic study of the trans to cis isomerization of Pt(TMEDA)(CH(3))(2)I(R(F)) [R(F) = CF(2)CF(3), CFHCF(3), CH(2)CF(3)

Reaction of Pd(TMEDA)(CH(3))(2) [TMEDA = tetramethylethylenediamine] with fluoroalkyl iodides R(F)I affords a series of square planar Pd(II) complexes Pd(TMEDA)(CH(3))(R(F)) [R(F) = CF(2)CF(3) (9), CFHCF(3) (10), CH(2)CF(3) (11)], presumably by oxidative addition followed by reductive elimination of CH(3)I. The solid-state structures of each compound have been determined by single crystal X-ray diffraction studies, allowing the effect of increasing alpha-fluorination on the structural trans-influence of alkyl ligands to be examined. In these compounds there is no significant difference observed in the trans-influence of the three fluorinated alkyl ligands toward the trans-N atom, although a significant cis-influence on the neighboring methyl ligand is apparent. Oxidative addition of the same series of fluoroalkyl ligands to the corresponding Pt(TMEDA)(CH(3))(2) affords octahedral Pt(IV) complexes trans-Pt(TMEDA)(CH(3))(2)(R(F))I [R(F) = CF(2)CF(3) (12), CFHCF(3) (13), CH(2)CF(3) (14)] as the kinetic products. In each case, subsequent isomerization to the corresponding all cis-isomers is observed; in the case of 13, the stereocenter at the alpha-carbon results in two diastereomeric cis-isomers, which are formed at different rates. The molecular structures of 13 and its more stable all cis-isomer 16b have been crystallographically determined. Kinetic studies of the trans-cis isomerization reactions show the mechanism to involve a polar transition state, presumably involving iodide dissociation, followed by rearrangement of the cation, and iodide recombination. High dielectric solvents increase the rate, but solvent coordinating ability has no effect. Dissolved salts (LiI, LiOTf) show normal accelerative salt effects, with no inhibition in the case of added iodide, consistent with the formation of an intimate ion pair intermediate. The kinetic parameters show that the trans-effects of fluoroalkyl ligands in these compounds follow the order expected from the relative sigma-donor properties of the ligands, with CF(2)CF(3) < CFHCF(3) < CH(2)CF(3).     

The synthesis of new weakly coordinating diborate anions: anion stability as a function of linker structure and steric bulk

The successive addition of KCN and Ph3CCl to B(C6F4-C6F5-2)3 (PBB) affords triphenylmethyl salts of the [NC-PBB]- anion. By contrast, the analogous reaction with sodium dicyanamide followed by treatment with Ph(3)CCl leads to the zwitterionic aminoborane H2NB(C12F9)2C12F8, via nucleophilic attack on an o-F atom, together with CPh3[F-PBB]. Whereas treatment of [NC-PBB]- with either PBB or B(C6F5)3 fails to give isolable cyano-bridged diborates, the reaction of Me3SiNC-B(C6F5)3 with PBB in the presence of Ph3CCl affords [Ph3C][PBB-NC-B(C6F5)3]. Due to steric hindrance this anion is prone to borane dissociation. The longer linking group N(CN)2- gives the very voluminous anions [N[CNB(C6F5)3]2]- and [N(CN-PBB)2]-. A comparison of propylene polymerisations with rac-Me2Si(Ind)2ZrMe2 activated with the various boranes or trityl borates gives an anion-dependent activity sequence, in the order [NC-PBB]- < [MeB(C6F5)3]- < [MePBB]- approximately [PBB-NCB(C6F5)3]- approximately [N[CNB(C6F5)3]2]- < [F-PBB]-< [B(C6F5)4]- < [N(CN-PBB)2]-. The anion [N(CN-PBB)2]- gives a catalyst productivity about 2500 times higher than that of [NC-PBB]- and exceeds that of [B(C6F5)4]- based catalysts. The van der Waals volumes and surface areas of the anions have been calculated and provide a rationale for the observed reactivity trends in polymerisation reactions.     

Capillary electrophoretic approach to screen for enzyme inhibitors in natural extracts

This paper demonstrates development of electrophoretically mediated micro analysis (EMMA), for screening protein tyrosine phosphatase (PTP) inhibitors in natural extracts. It is demonstrated that capillary electrophoresis (CE) separation of the substrate and the product allows for using the assay in an on-column format to monitor the reaction without typically used fluorogenic substrates. Michaelis-Menten kinetics parameters calculated based on the EMMA results (Km = 1.2-1.5 microM) were in a good agreement (Km = 1.0-1.5 microM) obtained using an off-line CE functional assay (CE FA). EMMA of PTP titrated with different concentrations of ligand demonstrated the peak-shift phenomenon normally seen in affinity capillary electrophoresis. This feature of EMMA gives an indication of the binding affinity of the ligand in addition to its functional activity, providing another dimension in characterization of the protein-inhibitor interaction. It was demonstrated that simultaneous screening of the primary PTP target and a secondary, counter target (PTP-C) using the EMMA format can be used to prioritize hits based on their specificity.     

Ab initio structures and stabilities of helide cations: (X = B-Ne, Al-Ar and n = 1-3)

The electronic structure and molecular properties of helides of the form (where , Al-Ar and ) were studied using the CCSD(T) method in conjunction with the series of correlation-consistent basis sets. The highest level of theory employed, the CCSD(T)_-FC/cc-pVQZ model, was used to elucidate trends in bond lengths, dissociation energies and harmonic frequencies. The more highly charged species were found to have shorter bond lengths than the singly charged species. The ground states of the helide cations were often those with longer bond lengths when compared with the excited state ions. Received: 11 May 1998 / Received in final form: 2 September 1998     

Synthesis of the antifungal beta-1,3-glucan synthase inhibitor CANCIDAS (caspofungin acetate) from pneumocandin B0

A novel three-step synthesis of the highly functionalized antifungal agent CANCIDAS (caspofungin acetate, 2) is described, starting from the natural product pneumocandin B0 (1). The highlights of the synthesis include a stereoselective formation of a phenylthioaminal, a remarkable chemoselective, high-yielding, one-step borane reduction of a primary amide, and a stereoselective substitution of the phenylthioaminal with ethylenediamine producing 2 in a 45% overall yield.     

The effect of catalysts on the decomposition of trisethylene diamine chromium(III) trichloride

Journal of Thermal Analysis and Calorimetry - The thermal decomposition of trisethylene diamine chromium(III) trichloride in an inert atmosphere has been shown to be catalysed by ammonium chloride...     

The chemistry of phosphole derivatives

Synthetic approaches to, and the chemistry of, phospholes, benzophospholes and dibenzophospholes are reviewed and particular attention is paid to the possible aromatic character of the phosphole ring. Systems containing the 2H- and 3H-phosph(V)ole nucleus are surveyed as are phosphole derivatives containing pentacovalent and six-coordinate phosphorus. Stereochemical considerations in the more complex phosphole derivatives are discussed.     

The thermal decomposition of alkaline earth formates

The thermal decomposition of alkaline earth formates has been studied. Experiments with single crystals, compacts and powders of strontium formate demonstrate that the method of sample presentation can affect the rate of decomposition.For anhydrous calcuim, strontium and barium formates, isothermal kinetic runs show that the decompositions follow the Erofeev law, In(l-α) = ktⁿ; the measured activation energies were 199.4, 228 and 270 kJ/mol respectively.     

Evaluation of models for the low temperature combustion of alkanes through interpretation of pressure-temperature ignition diagrams

The purpose of this paper is to show the application of global uncertainty analysis to comprehensive and reduced kinetic models as a tool to identify important thermochemical and reaction rate parameters as determinants of the conditions leading to autoignition. Propane oxidation is taken as the test case. The simulation of experimental investigations of the cool flames and two-stage ignitions, via the pressure-temperature ignition diagram, show that existing kinetic models for the low temperature combustion of propane at sub-atmospheric pressures reflect a greater reactivity than seems to be appropriate. That is, the models lead to a prediction of two-stage ignition at pressures somewhat lower and with ignition delays shorter than is found experimentally. The inconsistency between experiment and numerical simulation seems not to be an inherent problem of the qualitative structure of the models, but may derive from uncertainties in the parameters within the mechanism. By use of "brute force", Morris-one-at-a-time and Monte-Carlo simulations, we show that uncertainties in only a small number of parameters, and falling well within the errors that may reasonably be assigned, can shift the response appropriately. Moreover, it appears that in the low temperature combustion regime, thermochemistry is at least as, if not more, important than the reaction rates, yet usually receives less attention within sensitivity studies. In the present case, the main factors controlling the temperature reached in the first stage of two-stage ignition and the time to ignition appear to be connected with the thermochemistry of three specific hydroperoxyalkyl radicals and their derivatives. Other factors, such as heat and mass transport are also addressed, and their effects are mitigated to some extent by evaluation of initial and revised models against experimental data for ignition delay obtained under microgravity. The results highlight more general issues that pertain to the numerical simulation of the combustion of higher hydrocarbons and contribute to the development of the protocol necessary for testing kinetic models before they are ready for use in a predictive capacity.