Synthesis and structure-activity relationship study of monotesone-A, an antifungal component of Monotes engleri

The synthesis of (+/-)-monotesone-A, an antifungal component of Monotes engleri, as well as its four structural analogues were accomplished starting from the corresponding MOM-protected phloracetophenone and benzaldehyde derivatives. Antifungal activities of the five flavanone derivatives were studied against Candida albicans (14053 and ATCC 10231), Candida inconspicua, Candida dubliniensis and Candida krusei.     

Application of a Data Reconciliation Method to the Stoichiometric Analysis of Fibrobacter succinogenes Growth

Fibrobacter succinogenes S85, a strictly anaerobic Gram-negative bacterium, was grown in continuous culture in a bioreactor at different dilution rates (0.02 to 0.092 h(-1)) on a fully synthetic culture medium with glucose as carbon source. Glucose and ammonium sulfate consumption, as well as biomass, succinate, acetate, formate, and carbohydrate production were regularly measured. The relevant biomass elemental compositions were established for each dilution rate. Robustness of the experimental information was checked by C and N mass balances estimation, which were satisfactory. A detailed overall stoichiometry analysis of the process, including all substrates and products of the culture, was proposed. Online and off-line parameters measured during the culture brought a large number of data which were weighted by their respective variance associated to the measured value. The material balance resulted in an overdetermined linear system of equations made of weighted relationships including experimental data, elemental balances (C, H, O, N, S, Na), and an additional constraint. The mass balances involved in stoichiometric equations were solved using data reconciliation and linear algebra methods to take into account error measurements. This methodology allowed to establish the overall stoichiometric equation for each dilution rate studied.     

Ring-opening metathesis polymerization-derived monolithic capillary columns for high-performance liquid chromatography. Downscaling and application in medical research

Monolithic capillary columns were prepared via ring-opening metathesis polymerization (ROMP) using norborn-2-ene (NBE) and 1, 4, 4a, 5, 8, 8a-hexahydro-1, 4, 5, 8-exo,endo-dimethanonaphthalene (DMN-H6) as monomers. The monolithic polymer was copolymerized with Grubbs-type initiator RuCl(2)(PCy(3))(2)(CHPh) and a suitable porogenic system within the confines of fused silica capillaries of different inner diameter (I.D.). The first part of the study focused on batch-to-batch reproducibility of ROMP-derived capillary monoliths. Capillary monoliths of 200 microm I.D. showed good reproducibility in terms of retention times, with relative standard deviations (RSD) of 1.9% for proteins and 2.2% for peptides. However, the separately synthesized capillary monoliths revealed pronounced variation in back pressure with RSD values of up to 31%. These variations were considerably reduced by cooling of the capillaries during polymerization. Using this optimized preparation procedure capillary monoliths of 100 and 50 microm I.D. were synthesized and the effects of scaling down the column I.D. on the morphology and on the reproducibility of the polymerization process were investigated. In the second part, the applicability of ROMP-derived capillary monoliths to a separation problem common in medical research was assessed. A 200 microm I.D. monolithic column demonstrated excellent separation behavior for insulin and various insulin analogs, showing equivalent separation performance to Vydac C4 and Zorbax C3-based stationary phases. Moreover, the high permeability of monoliths enabled chromatographic separations at higher flow rates, which shortened analysis time to about one third. For the analysis of insulin in human biofluid samples, enhanced sensitivity was achieved by using a 50 microm I.D. ROMP-derived monolith.     

Determination of phenols and chlorophenols as trimethylsilyl derivatives using gas chromatography-mass spectrometry

A rapid and simple method is described for the simultaneous determination of 6 phenols (phenol, o-, m-, p-cresol, catechol and resorcinol) and 19 chlorophenols (all mono-, di-, tri-, and tetrachlorophenol isomers and pentachlorophenol) present in aqueous samples. The method is based on derivatization with trimethylsilyl-N,N-dimethylcarbamate (TMSDMC). In contrast to other derivatization agents, TMSDMC instantaneously reacts with the phenolic compounds at room temperature and no further sample processing is necessary prior to instrumental analysis. The determination of the derivatives was performed by capillary gas chromatography-mass spectrometry (GC-MS). The stability of the most instable trimethylsilyl derivative (pentachlorophenol) was studied using different excess levels of the derivatization reagent. The derivatization method was tested on spiked water samples preconcentrated by solid phase extraction on Isolute ENV+ cartridge. The overall method gave detection limits of 0.01-0.25 microg/L for all compounds and < 0.05 microg/L for 17 of them.     

Pentakis(trifluoromethyl)phenyl, a sterically crowded and electron-withdrawing group: synthesis and acidity of pentakis(trifluoromethyl)benzene, -toluene, -phenol, and -aniline

A general route to functionalized pentakis(trifluoromethyl)phenyl (C6(CF3)5) derivatives, promising building blocks for designing novel stable carbenes, radical species, superacids, weakly coordinating anions and other practically and theoretically useful species, is presented. This pertrifluoromethylation route proceeds via conveniently pregenerated (trifluoromethyl)copper (CF3Cu) species in DMF, stabilized by addition of 1,3-dimethyl-2-imidazolidinone (DMI). These species react with hexaiodobenzene at ambient temperature to give the potassium pentakis(trifluoromethyl)phenoxide along with hexakis(trifluoromethyl)benzene and pentakis(trifluoromethyl)benzene in a combined yield of 80%. A possible reaction pathway explaining the formation of pentakis(trifluoromethyl)phenoxide is proposed. Pentakis(trifluoromethyl)phenol gives rise to easily functionalized pentakis(trifluoromethyl)chlorobenzene and pentakis(trifluoromethyl)aniline. Pertrifluoromethylation of pentaiodochlorobenzene and pentaiodotoluene allows straightforward access to pentakis(trifluoromethyl)chlorobenzene and pentakis(trifluoromethyl)toluene, respectively. XRD structures of several C6(CF3)5 derivatives were determined and compared with the calculated structures. Due to the steric crowding the aromatic rings in all C6(CF3)5 derivatives are significantly distorted. The gas-phase acidities (Delta Gacid) and pKa values in different solvents (acetonitrile (AN), DMSO, water) for the title compounds and a number of related compounds have been measured. The origin of the acidifying effect of the C6(CF3)5 group has been explored using the isodesmic reactions approach.     

A crossed beam and ab initio study of the reaction of atomic boron with ethylene

The reaction of atomic boron, B(2P), with the simplest alkene, C2H4, has been investigated under single collision conditions in crossed beam experiments with mass spectrometric detection. Our experimental data clearly showed that the atomic boron versus hydrogen exchange reaction led to molecule(s) of gross formula C2H3B via bound intermediate(s). According to the experimentally derived fraction of the available energy released as product translational energy, we propose that an important reaction pathways is the one leading to the borirene plus atomic hydrogen and/or the one leading to ethynylborane plus atomic hydrogen. The experimental results are accompanied by electronic structure calculations of the relevant potential energy surface and RRKM estimates of the product branching ratio. According to RRKM calculations, within the limit of complete energy randomization, the three isomers borirene, BH=C=CH2 and BH2-CCH, are all formed, with BH2-CCH being the dominant one. The discrepancies between the trend of the product translational energy distributions and the picture emerging from RRKM estimates are a symptom that a statistical treatment is not warranted for this system.     

A sparse matrix based full-configuration interaction algorithm

We present an algorithm related to the full-configuration interaction (FCI) method that makes complete use of the sparse nature of the coefficient vector representing the many-electron wave function in a determinantal basis. Main achievements of the presented sparse FCI (SFCI) algorithm are (i) development of an iteration procedure that avoids the storage of FCI size vectors; (ii) development of an efficient algorithm to evaluate the effect of the Hamiltonian when both the initial and the product vectors are sparse. As a result of point (i) large disk operations can be skipped which otherwise may be a bottleneck of the procedure. At point (ii) we progress by adopting the implementation of the linear transformation by Olsen et al. [J. Chem Phys. 89, 2185 (1988)] for the sparse case, getting the algorithm applicable to larger systems and faster at the same time. The error of a SFCI calculation depends only on the dropout thresholds for the sparse vectors, and can be tuned by controlling the amount of system memory passed to the procedure. The algorithm permits to perform FCI calculations on single node workstations for systems previously accessible only by supercomputers.     

Ion-induced nucleation in solution: promotion of solute nucleation in charged levitated droplets

We have investigated the nucleation and growth of sodium chloride in both single quiescent charged droplets and charged droplet populations that were levitated in an electrodynamic levitation trap (EDLT). In both cases, the magnitude of a droplet's net excess charge (ions(DNEC)) influenced NaCl nucleation and growth, albeit in different capacities. We have termed the phenomenon ion-induced nucleation in solution. For single quiescent levitated droplets, an increase in ions(DNEC) resulted in a significant promotion of NaCl nucleation, as determined by the number of crystals observed. For levitated droplet populations, a change in NaCl crystal habit, from regular cubic shapes to dome-shaped dendrites, was observed once a surface charge density threshold of -9 x 10(-4) e.nm(-2) was surpassed. Although promotion of NaCl nucleation was observed for droplet population experiments, this can be attributed in part to the increased rate of solvent evaporation observed for levitated droplet populations having a high net charge. Promotion of nucleation was also observed for two organic acids, 2,4,6-trihydroxyacetophenone monohydrate (THAP) and alpha-cyano-4-hydroxycinnamic acid (CHCA). These results are of direct relevance to processes that occur in both soft-ionization techniques for mass spectrometry and to a variety of industrial processes. To this end, we have demonstrated the use of ion-induced nucleation in solution to form ammonium nitrate particles from levitated droplets to be used in in vitro toxicology studies of ambient particle types.