The study of the lipophilicity of alpha-(4-phenylpiperazin-1-yl)-gamma-phthalimidobutyramides using chromatographic and computational methods

The lipophilicity of the series of alpha-(4-phenylpiperazin-1-yl)-gamma-phthalimido-butyramides (1-8) has been investigated. Several methods, like reversed-phase thin-layer chromatography and high-performance liquid chromatography using reversed-phase RP18 and IAM.DD2 columns, were applied to determine RMO, log k0 and log k(0IAM) factors. The RP-TLC investigations were performed in mixtures of acetone-water and acetonitrile-water. For RP-HPLC method mixtures of acetonitrile, water and 0.01% TFA were used as the mobile phases while for IAM.DD2 investigations mixtures of acetonitrile and water were applied. The partition coefficients of compounds (1-8) were also calculated with the Pallas and CAChe programs. All the obtained data, both from experimental methods and computational calculations, were compared and a suitable conclusion was reached.     

Structure, microstructure, and size dependent catalytic properties of nanostructured ruthenium dioxide

Nanostructured powders of ruthenium dioxide RuO₂ were synthesized via a sol gel route involving acidic solutions with pH varying between 0.4 and 4.5. The RuO₂ nanopowders were characterized by X-ray diffraction, scanning and transmission electron microscopy (SEM and TEM). Rietveld refinement of mean crystal structure was performed on RuO₂ nanopowders and crystallized standard RuO₂ sample. Crystallite sizes measured from X-ray diffraction profiles and TEM analysis varied in the range of 4-10 nm, with a minimum of crystallite dimension for pH=1.5. A good agreement between crystallite sizes calculated from Williamson Hall approach of X-ray data and from direct TEM observations was obtained. The tetragonal crystal cell parameter (a) and cell volumes of nanostructured samples were characterized by values greater than the values of standard RuO₂ sample. In addition, the [Ru-O₆] oxygen octahedrons of rutile structure also depended on crystal size. Catalytic conversion of methane by these RuO₂ nanostructured catalysts was studied as a function of pH, catalytic interaction time, air methane composition, and catalysis temperature, by the way of Fourier transform infrared (FTIR) spectroscopy coupled to homemade catalytic cell. The catalytic efficiency defined as FTIR absorption band intensities I(CO₂) was maximum for sample prepared at pH=1.5, and mainly correlated to crystallite dimensions. No significant catalytic effect was observed from sintered RuO₂ samples.     

The Role of Singlet Oxygen in Photoreactivity and Phototoxicity of Curcumin

Curcumin is a plant-derived yellow-orange compound widely used as a spice, dye and food additive. It is also believed to have therapeutic effects against different disorders. On the other hand, there are data showing its phototoxicity against bacteria, fungi and various mammalian cells. Since the mechanism of its phototoxic action is not fully understood, we investigated here the phototoxic potential of curcumin in liposomal model membranes and in HaCaT cells. First, detection of singlet oxygen (¹O₂) luminescence proved that curcumin generates ¹O₂ upon blue light irradiation in organic solvent and in liposomes. Then, HPLC-EC(Hg) measurements revealed that liposomal and cellular cholesterol is oxidized by ¹O₂ photogenerated by curcumin. Enrichment of liposome membranes with curcumin significantly increased the oxygen photo-consumption rate compared to the control liposomes as determined by EPR oximetry. Cytotoxicity measurements, mitochondrial membrane potential analyses and protein hydroperoxides detection confirmed strong phototoxic effects of curcumin in irradiated HaCaT cells. These data show that since curcumin is advertised as a valuable dietary supplement, or a component of cosmetics for topical use, caution should be recommended especially when skin is exposed to light.     

Photophysical characterization of imidazolium-substituted Pd(II), In(III), and Zn(II) porphyrins as photosensitizers for photodynamic therapy

The photophysical properties of four imidazolium-substituted metalloporphyrins have been assessed to gain insights into the relative efficacy of the compounds for photodynamic therapy (PDT). A set of zinc(II), palladium(II), and chloro-indium(III) porphyrins all bear a net positive charge owing to the diethylimidazolium unit; one zinc chelate bears a negative charge owing to a bis(sulfobutyl)imidazolium unit. The photophysical properties of the cationic and anionic zinc porphyrins are very similar to one another in organic solvents, phosphate-buffered saline, and in the presence of bovine serum albumin. The properties of the zinc and palladium porphyrins bearing charged peripheral groups are generally similar to those of neutral analogs in organic solvents. The palladium porphyrin shows an essentially quantitative yield (≥0.99) of the triplet excited state compared to the zinc porphyrins (0.9), and all are quantitatively quenched (at the diffusion limit) by molecular oxygen in air-saturated fluid solution. If the rate constant and yield of quenching of the triplet excited state by energy or electron transfer to molecular oxygen is the same in the cellular environment as in solution, then these processes combined with the triplet yield contribute only a factor of 1.3 to the higher PDT activity of analogous palladium versus zinc porphyrins, which is much smaller than what is observed. Therefore, other factors such as transient reduction of the excited porphyrin or delivery to the target site must predominantly underlie the difference in PDT efficacy of these sensitizers.     

Theoretical analysis of core size effect in metalloporphyrins

Density functional theory has been applied to a series of unsubstituted planar metalloporphyrins (MPs) to elucidate how geometry and frequencies correlate with the metal-nitrogen distance, referred to as the core size. Different transition metals can invoke expansion or contraction of the porphyrin core due to electronic effects resulting from the amount of d-electron pairing as well as occupancy of the d(x(2)(-y(2))) orbital. A full vibrational analysis consisting of all in-plane and out-of-plane frequencies was carried out, and the resulting modes were plotted against core size for a linear analysis and grouped within symmetry blocks. The modes were separated according to planarity, and all modes with a large slope and best fit greater than 0.8 were considered sensitive to metal-nitrogen distances. All planar skeletal modes above 1450 cm(-1), including the pyrolle ring deformations, are found to be core-size sensitive. The most significant out-of-plane modes sensitive to core size are gamma(8) and gamma(9), which are infrared active and grouped within the A(2u) symmetry block. The present work also opens possible quantitative applications for the correlation of spectroscopic properties of MPs and heme proteins with actual structural parameters.     

AFM of biological complexes: What can we learn?

The term “biological complexes” broadly encompasses particles as diverse as multisubunit enzymes, viral capsids, transport cages, molecular nets, ribosomes, nucleosomes, biological membrane components and amyloids. The complexes represent a broad range of stability and composition. Atomic force microscopy offers a wealth of structural and functional data about such assemblies. For this review, we choose to comment on the significance of AFM to study various aspects of biology of selected non-membrane protein assemblies. Such particles are large enough to reveal many structural details under the AFM probe. Importantly, the specific advantages of the method allow for gathering dynamic information about their formation, stability or allosteric structural changes critical for their function. Some of them have already found their way to nanomedical or nanotechnological applications. Here we present examples of studies where the AFM provided pioneering information about the biology of complexes, and examples of studies where the simplicity of the method is used toward the development of potential diagnostic applications.     

One-pot organocatalytic domino Michael/alpha-alkylation reactions: direct catalytic enantioselective cyclopropanation and cyclopentanation reactions

The development of one-pot organocatalytic domino Michael/alpha-alkylation reactions between bromomalonates or bromoacetoacetate esters and alpha,beta-unsaturated aldehydes is presented. The chiral-amine-catalyzed reactions with bromomalonates as substrates give access to the corresponding 2-formylcyclopropane derivatives in high yields with excellent diastereoselectivity and up to 99 % ee. The catalytic domino Michael/alpha-alkylation reactions between 4-bromo-acetoacetate and enals provide a route for the synthesis of functionalized cyclopentanones in good to high yields with 93-99 % ee. The products from the organocatalytic reactions were also reduced with high diastereoselectivity to the corresponding cyclopropanols and cyclopentanols, respectively. Moreover, one-pot combinations of amine and heterocyclic carbene catalysis (AHCC) enabled the highly enantioselective synthesis of beta-malonate esters (91-97 % ee) from the reaction between bromomalonates and enals. The tandem catalysis included the catalytic domino reaction followed by catalytic in situ chemoselective ring-opening of the 2-formylcyclopropane intermediates.     

One-pot catalytic enantioselective domino nitro-michael/michael synthesis of cyclopentanes with four stereocenters

A highly enantioselective organocatalytic one-pot synthesis of nitro-, formyl-, and ester-functionalized cyclopentanes with four stereocenters is presented. The cyclopentanes were formed as a predominant diasteroisomer and isolated in high yields with 97-99 % ee.     

Self-assembled monolayer of alkanephosphoric acid on nanotextured Ti

Surface modification of titanium and its alloys is of great importance for their practical application as biomedical implants. We have studied and compared assembly of dodecylphosphoric acid on commercial polished and on nanostructured titanium disks. The latter were produced by chemical etching that created nanoscale pits of typical size of about 20 nm. Enhanced hydrophobicity and high molecular density were obtained after functionalization of the nanotextured substrate. Aging tests showed a lifetime of the organic films of about one month in phosphate buffer. The samples were characterized by means of infrared spectroscopy, contact angle measurements, ellipsometry, and atomic force and scanning tunneling microscopies.     

Antimicrobial properties of biosynthesized silver nanoparticles studied by flow cytometry and related techniques

This work reports the effect of silver bionanoparticles (Bio(AgNPs) synthesized by Actinobacteria CGG 11n on selected Gram (+) and Gram (–) bacteria. Flow cytometry, classical antibiogram method and fluorescent microscopy approach was used for evaluation of antimicrobial activity of Bio(AgNPs) and their combination with antibiotics. Furthermore, the performed research specified the capacity of flow cytometry method as an alternative to the standard ones and as a complementary method to electromigration techniques. The study showed antibacterial activity of both BioAgNPs and the combination of antibiotics/BioAgNPs against all the tested bacteria strains in comparison with a diffusion, dilution and bioautographic methods. The synergistic effect of antibiotics/BioAgNPs combination (e.g. kanamycin, ampicillin, neomycin and streptomycin) was found to be more notable against Pseudomonas aeruginosa representing a prototype of multi‐drug resistant “superbugs” for which effective therapeutic options are very limited.