Synthesis,spectral characterization,electrochemical properties and antimicrobial screening of sulfur containing acylferrocenes

Several known and eight new sulfur containing acylferrocenes of the general formula FcCO(CH₂)_nSR (where Fc = ferrocenyl, n = 1 or 2 and R = alkyl, 4-bromobenzyl or 2,6-dichlorobenzyl group) were synthesized in order to test their in vitro antimicrobial activity against 11 bacterial and three fungal/yeast strains. It has been shown that only four of the 14 ketones are completely inactive at the tested dose, while the activities of the other ones were noteworthy. All new compounds were well characterized by IR and NMR spectral data, and their electrochemical properties were investigated by cyclic voltammetry. The X-ray crystal structures of two representative ketones are also presented.     

Clar's sextet rule is a consequence of the sigma-electron framework

A number of condensed PAHs are examined to identify the underlying reasons governing empirical Clar's rule taking benzene as a limiting case. It is found that the so-called Clar's structures are the only minima on the MP2(fc) potential energy hypersurfaces, meaning that other conceivable valence isomers are nonexistent. The influence of the electron correlation energies to the stability of Clar's structures is substantial with predominating influence of the sigma-electrons. However, the contributions arising from the sigma- and pi-electron correlation energies are approximately the same, if Clar's structures are compared with some artificial pi-electron localized or graphite-like delocalized planar systems. Analysis of the Hartree-Fock (HF) energies provides a compelling evidence that the origin of stability of Clar's structures lies in a decrease of the positive T, V(ee) and V(nn) energy terms relative to some characteristic virtual "delocalized" or "localized" model geometries. Partitioning of the mixed and terms in the sigma- and pi-type contributions, by using the stockholder (SHR), equipartitioning (EQP) and standard pi (SPI) schemes, unequivocally shows that the driving force leading to Clar's structures are more favorable sigma-type interactions. All these conclusions hold for the archetypal benzene too, which could be considered as a limiting Clar system. Finally, the boundaries of Clar's hypothesis and some common misconceptions are briefly discussed. Perusal of the geometric parameters and pi-bond orders reveals that there are no benzene rings completely "vacant" or "fully occupied" by the pi-electrons, envisaged by Clar in his picture of condensed benzenoid compounds. Instead, there are six-membered rings with higher and lower total pi-electron density. The bond length anisotropy of the former rings is smaller. It is concluded that Clar's proposition is a useful rule of thumb providing qualitative information on the stability of the PAH systems, which in turn should not be overinterpreted.     

HPLC–DAD–FLD Determination of Veterinary Pharmaceuticals in Pharmaceutical Industry Wastewater with Precolumn Derivatization Using Fluorescamine

A simple and robust method suitable for routine analysis of pharmaceuticals from different classes in pharmaceutical industry wastewater samples is presented. Seven veterinary pharmaceuticals (antibiotics and anesthetic) were simultaneously isolated from a highly complex wastewater matrix. Target compounds were three sulfonamide antibiotics (sulfaguanidine, sulfadiazine, and sulfamethazine), three fluoroquinolone antibiotics (ciprofloxacin, enrofloxacin, norfloxacin), and one anesthetic, procaine. The investigated compounds were simultaneously pre-concentrated and cleaned up by solid-phase extraction using Strata-X extraction cartridges. The analysis was performed using liquid chromatography (LC) with diode array and fluorescence detectors connected in series to the chromatographic system. LC separation was performed on a C18 modified column (Phenomenex) with a gradient elution of mobile phase (0.1 % acetic acid in water and 0.1 % acetic acid in acetonitrile) in 25 min at 30 °C. Recoveries ranged from 86.9 to 110 % with relative standard deviations below 10.1 %. Method limits of quantification were in the range of 0.005–0.1 μg L^?1 depending on the fluorescence intensity after precolumn derivatization by fluorescamine.     

Performance evaluation of Mimetic Ligand™ B14-triazole-FractoAIMs adsorbents for the capture of human monoclonal immunoglobulin G from cell culture feed

The new affinity-type Mimetic Ligand™ B14 was coupled with a 1,2-diaminoethane spacer (2LP) and a [1,2,3]-triazole spacer (TRZ) to three different support media. In addition to the agarose-based PuraBead and the polymethacrylate-type Fractogel, three new polymeric support media were introduced, the FractoAIMs 1, 2, and 3 (FA1, FA2, and FA3). These new FA supports differ in pore size as well as density of epoxide groups. The immobilization of the B14-ligand onto an azide-group-modified surface was performed with a copper (I)-mediated Click reaction. The IgG capture performance was tested for various ligand–spacer support combinations using cell culture feed containing human immunoglobulin G₁ (hIgG₁). The most promising adsorbent, B14-TRZ-FA3, was further optimized by improving the surface chemistry through a triple endcapping concept employing an improved Click reaction protocol. This new technique enabled the most efficient deactivation of residual azide groups. In a direct comparison with a commercially available Protein A media, B14-TRZ-FA3 3× ec provided superior results at fast flow-rates and low bed-height. Dynamic binding capacities of 11.4 g/L for 10% breakthrough of hIgG₁, elution capacities of 16.0 g/L hIgG₁ and a recovery of 86% were achieved. The same results were obtained for a dialyzed and pre-purified feed solution, which is a clear indicator that triple-endcapped affinity support surfaces are practically inert to the non-specific binding of host cell proteins.     

Composition and antimicrobial activity of Seseli montanum subsp. tommasinii essential oil

The essential oil isolated from Seseli montanum L. subsp. tommasinii Reich. f. was analyzed by GC/MS and the most abundant components were beta-pinene (30.2%), germacrene D (10.1%), sabinene (8.0%), alpha-pinene (7.2%) and limonene (6.6%). The antimicrobial effect of the essential oil was evaluated against four bacterial and four fungal species among which were food contaminants, spoilage fungi, and plant, fungal and animal pathogens. The oil possessed moderate to strong antimicrobial activity.     

Ruthenacarborane and Quinoline: A Promising Combination for the Treatment of Brain Tumors

Gliomas and glioblastomas are very aggressive forms of brain tumors, prone to the development of a multitude of resistance mechanisms to therapeutic treatments, including cytoprotective autophagy. In this work, we investigated the role and mechanism of action of the combination of a ruthenacarborane derivative with 8-hydroxyquinoline (8-HQ), linked via an ester bond (complex 2), in rat astrocytoma C6 and human glioma U251 cells, in comparison with the two compounds alone, i.e., the free carboxylic acid (complex 1) and 8-HQ, and their non-covalent combination ([1 + 8-HQ], in 1:1 molar ratio). We found that only complex 2 was able to significantly affect cellular viability in glioma U251 cells (IC₅₀ 11.4 μM) via inhibition of the autophagic machinery, most likely acting at the early stages of the autophagic cascade. Contrary to 8-HQ alone, complex 2 was also able to impair cellular viability under conditions of glucose deprivation. We thus suggest different mechanisms of action of ruthenacarborane complex 2 than purely organic quinoline-based drugs, making complex 2 a very attractive candidate for evading the known resistances of brain tumors to chloroquine-based therapies.     

Sucrose ester-based biocompatible microemulsions as vehicles for aceclofenac as a model drug: formulation approach using D-optimal mixture design

We assessed the functionality of sucrose esters (sucrose laurate, myristate, palmitate, and stearate), relatively innocuous nonionic surfactants, in formulation of biocompatible microemulsions. The putative influence of surfactant structure on the extension of microemulsion region was explored through the construction of the pseudo-ternary phase diagrams for the isopropyl myristate/sucrose ester-isopropyl alcohol/water system, using the titration method and mixture experimental approach. Minor changes in surfactant tail length strongly affected the microemulsion area boundaries. D-optimal mixture design proved to be highly applicable in detecting the microemulsion regions. Examination of conductivity, rheology, and thermal behavior of the selected sucrose laurate and sucrose myristate-based microemulsions, upon dilution with water, indicated existence of percolation threshold and suggested the phase inversion from water-in-oil to oil-in-water via a bicontinuous structure. Atomic force micrographs confirmed the suggested type of microemulsions and were valuable in further exploring their inner structure. The solubilization capacity of aceclofenac as a model drug has decreased as the water volume fraction in microemulsion increased. High surfactant concentration and the measured solubility of aceclofenac in microemulsion components suggested that the interfacial film may mostly contribute to aceclofenac solubilization.     

Comparison of Metallothionein Detection by Using Brdicka Reaction and Enzyme‐Linked Immunosorbent Assay Employing Chicken Yolk Antibodies

In this study, two methods for metallothioneins (MT) determination in a biological sample were compared. Particularly, twenty five human and nine pig blood serum samples and liver and kidney samples from thirty five carps (Cyprinus carpio) were analyzed by enzyme‐linked immunosorbent assay and differential pulse voltammetry Brdicka's reaction. The results obtained by these two methods were in good agreement. For commercially available MT standard the correlation coefficient between the single concentrations signal height was 0.99. In biological samples the correlation coefficients were 0.90 for fish liver and kidney samples, 0.91 for pig blood serum and 0.93 for human blood serum.     

Über die Konstitution der synthetischen und durch Äthanolyse aus dem Holz isolierbaren Ketole vom Typus des Oxy-propio-guajacons

Ohne ZusammenfassungAn die Redaktion der Berichte der dtsch. chem. Ges. am. 11. Dezember 1944 eingesandt, kam diese Arbeit infolge der Kriegsereignisse nicht mehr zum Druck.