Generation of thiyl radicals by the photolysis of 5-iodo-4-thiouridine

The photochemistry of 2',3',5'-tri-O-acetyl-5-iodo-4-thiouridine (3) in deoxygenated 1:1 CH(3)CN-H(2)O pH 5.8 (phosphate buffer) solution has been studied by means of steady-state and nanosecond laser flash photolysis methods. Under steady-state irradiation (lambda > or = 334 nm), the stable photoproducts were iodide ion, 2',3',5'-tri-O-acetyl-4-thiouridine (4), and two disulfides. The disulfides were the symmetrical bis-(2',3',5'-tri-O-acetyl-5-iodo-4-thiouridine) (5) and unsymmetrical 6, which contains both 4-thiouridine and 5-iodo-4-thiouridine residues. The formation of the dehalogenated photoproduct suggests that C(5)-I bond cleavage is a primary photochemical step. Attempts to scavenge the resulting C(5)-centered radical by suitable addends, bis-(N-alpha-acetyl)cystine-bis-N-ethylamide or benzene, were unsuccessful. Analysis of the photoproducts formed under these conditions showed that the S-atom is the reactive center. The photoproduct 4, obtained by irradiation of 3 in CD(3)CN-H(2)O, followed by reversed-phase HPLC isolation using nonlabeled eluents, did not contain deuterium. An analogous experiment performed in CH(3)CN-D(2)O gave deuterated product 4-d with 88% of the deuterium incorporated at C(5). Transient absorption observed upon laser excitation (lambda= 308 nm) of 3 was assigned to the 4-uridinylthiyl radical on the basis of the similarity of this spectrum with that obtained upon laser photolysis of the disulfide: bis-(2',3',5'-tri-O-acetyl-4-thiouridine) 14. On the basis of the results of steady-state and laser photolysis studies, a mechanism of the photochemical reaction of 3 is proposed. The key mechanistic step is a transformation of the C(5)-centered radical formed initially by C(5)-I bond cleavage into a long-lived S-centered radical via a 1,3-hydrogen shift. Theoretical calculations confirmed that the long-lived S-centered radical is the most stable radical derived from the 4-thiouracil residue.     

HPTLC-densitometric method of determination of oleanolic acid in the Lamii albi flos

HPTLC combined with densitometric method was used to determine the content of oleanolic acid in acetone extract from the Lamii albi flos L. The plant extract was separated on Si 60 HPTLC plates and determined with the use of two densitometric methods: measurement of fluorescence and absorbance. The content of oleanolic acid was statistically calculated. In a measurement of absorbance in 1 g of the dry Lamii albi flos L. 1458 microg of oleanolic acid was determined (0.147%). In a fluorescence method in 1 g of the plant material 1516 microg of oleanolic acid was determined (0.149%).     

Photochemical sources of organic acids. 2. Formation of C5-C9 carboxylic acids from alkene ozonolysis under dry and humid conditions

The dependence of organic acid generation by alkene ozonolysis on relative humidity, thermalized Criegee intermediate scavengers, and alkene structure is investigated. Carboxylic acids generated from the ozonolysis of 1-hexene, 1-octene, 1-decene, trans-3-octene, and 1-methylcyclohexene were analyzed as trimethylsilyl (TMS) derivatives. Experiments were performed under dry (relative humidity (RH) < 1%) and humid (RH = 65%) conditions with cyclohexane or n-butyl ether as an OH scavenger. Pentanoic acid is produced from 1-hexene and trans-3-octene with yields 8.5 +/- 2.6 and 5.0 +/- 1.5% under dry conditions and 5.1 +/- 1.5 and 2.8 +/- 0.8% under humid conditions, respectively. Heptanoic acid yields from 1-octene are 8.3 +/- 2.5 and 4.4 +/- 1.3% under dry and humid conditions, respectively. Ozonolysis of 1-methylcyclohexene produced six C5-C7 multifunctional carboxylic acids, with a total yield of 7%. Several other acids and aldehydes were also monitored and quantified. An additional set of experiments with added stabilized Criegee intermediate (SCI) scavengers was performed for 1-octene ozonolysis under dry conditions. The results indicate that SCIs and their reaction with water are minor contributors to acid formation in the atmosphere and suggest that many of the acids are formed directly.     

Redox-controlled photosensitization of nanocrystalline titanium dioxide.

Photosensitization of nanocrystalline titanium dioxide materials has been achieved by chemisorption of the pentacyanothiamineferrate(II) complex, which offers a relatively high redox potential that determines the photoelectrochemical properties of the photosensitized TiO(2). The adsorbed pentacyanoferrate complex binds to TiO(2) through the cyanide bridge and forms a new surface complex characterized by a metal-to-metal charge-transfer transition (MMCT) (Fe(II)-->Ti(IV)). The photosensitization can be observed only at low potentials at which Fe(II) moieties are present. Photocurrent switching between anodic and cathodic can be induced by varying either the photoelectrode potential or the wavelength of the incident light. Simple molecular modeling-together with spectroscopic and electrochemical measurements-allows the elucidation of the mechanism of the observed photoelectrochemical behavior.     

Synthesis, photophysical studies and anticancer activity of a new halogenated water-soluble porphyrin

A water-soluble halogenated porphyrin, namely 5,10,15,20-tetrakis(2-chloro-3-sulfophenyl)porphyrin (TCPPSO(3)H), was prepared and evaluated as sensitizer for photodynamic therapy (PDT). Photophysical properties of TCPPSO(3)H, such as high photostability, long triplet lifetime and high singlet oxygen quantum yield suggest high effectiveness of this class of halogenated porphyrins in PDT. TCPPSO(3)H is non-toxic in the dark and causes a significant photodynamic effect examined against MCF7 (human breast carcinoma), SKMEL 188 (human melanoma) and S91(mouse melanoma) cell lines upon red light irradiation (cutoff < 600 nm) at low light doses. Time-dependent cellular uptake of TCPPSO(3)H reached plateau at 120 min and was the highest for S91, 20% lower for MCF7 and 70% lower for SKMEL 188. Our results show that this halogenated water-soluble porphyrin is an efficient photosensitizer and reveal the potential of this class of compounds as PDT agents.     

Structural analysis of poly[(R,S)-3-hydroxybutyrate-co-L-lactide] copolyesters by electrospray ionization ion trap mass spectrometry

Two random copolyesters of poly[(R,S)-3-hydroxybutyrate-co-L-lactide] (P[(R,S)-3HB-co-LA]), prepared by equimolar reaction of (R,S)-beta-butyrolactone with L-lactic acid and (R,S)-3-hydroxybutyric acid with L-lactide, respectively, were characterized by electrospray ionization ion trap mass spectrometry (ESI-ITMS). Detailed studies of these copolyesters were performed by means of collision-induced dissociation (CID). The molecular architecture of individual copolyester macromolecules, including chemical structures of their end groups (hydroxyl and carboxylate), were established on the basis of their ESI mass spectra. The influence of an intermolecular transesterification reaction on the microstructure of the copolyester synthesized by equimolar reaction of (R,S)-3-hydroxybutyric acid with L-lactide was observed. The mass spectra provided information on sequence distribution and indicated that, despite the synthetic pathway applied, random P[(R,S)-3HB-co-LA] copolyesters were formed predominantly. The arrangements of comonomer structural units along the copolyester chains were evaluated by the respective ESI-MS/MS fragmentation pathways.     

Synthesis of 2‐phosphoro‐1,2‐thiazetidine 1,1‐dioxide

The reactions of phosphorochloridites 5a–c with an equimolar amount of 1,2‐thiazetidine 1,1‐dioxide (2) or L(−)‐3‐carboethoxy‐1,2‐thiazetidine 1,1‐dioxide (7) in the presence of triethylamine, affords the N‐phosphitylated β‐sultams 6a–b and L(−)‐8a,c. Their oxidation by addition of oxygen, sulfur, or selenium results in formation of stable organophosphorus β‐sultams 10a–b, L(−)‐11a,c, 12a, 13a, L(−)‐14c, and L(−)‐15c. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 61–67, 1999     

Structure-Morphology-Antimicrobial and Antiviral Activity Relationship in Silver-Containing Nanocomposites Based on Polylactide

Green synthesis of silver-containing nanocomposites based on polylactide (PLA) was carried out in two ways. With the use of green tea extract, Ag⁺ ions were reduced to silver nanoparticles with their subsequent introduction into the PLA (mechanical method) and Ag⁺ ions were reduced in the polymer matrix of PLA-AgPalmitate (PLA-AgPalm) (in situ method). Structure, morphology and thermophysical properties of nanocomposites PLA-Ag were studied by FTIR spectroscopy, wide-angle X-ray scattering (WAXS), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) methods. The antimicrobial, antiviral, and cytotoxic properties were studied as well. It was found that the mechanical method provides the average size of silver nanoparticles in the PLA of about 16 nm, while in the formation of samples by the in situ method their average size was 3.7 nm. The strong influence of smaller silver nanoparticles (3.7 nm) on the properties of nanocomposites was revealed, as with increasing nanosilver concentration the heat resistance and glass transition temperature of the samples decreases, while the influence of larger particles (16 nm) on these parameters was not detected. It was shown that silver-containing nanocomposites formed in situ demonstrate antimicrobial activity against gram-positive bacterium S. aureus, gram-negative bacteria E. coli, P. aeruginosa, and the fungal pathogen of C. albicans, and the activity of the samples increases with increasing nanoparticle concentration. Silver-containing nanocomposites formed by the mechanical method have not shown antimicrobial activity. The relative antiviral activity of nanocomposites obtained by two methods against influenza A virus, and adenovirus serotype 2 was also revealed. The obtained nanocomposites were not-cytotoxic, and they did not inhibit the viability of MDCK or Hep-2 cell cultures.     

Chemical Synthesis of Oligoribonucleotide (ASL of tRNALys T. brucei) Containing a Recently Discovered Cyclic Form of 2-Methylthio-N6-threonylcarbamoyladenosine (ms2ct6A)

The synthesis of the protected form of 2-methylthio-N⁶-threonylcarbamoyl adenosine ( ms²t⁶A) was developed starting from adenosine or guanosine by using the optimized carbamate method and, for the first time, an isocyanate route. The hypermodified nucleoside was subsequently transformed into the protected ms²t⁶A -phosphoramidite monomer and used in a large-scale synthesis of the precursor 17nt ms²t⁶A -oligonucleotide (the anticodon stem and loop fragment of tRNA^Lys from T. brucei). Finally, stereochemically secure ms²t⁶A → ms²ct⁶A cyclization at the oligonucleotide level efficiently afforded a tRNA fragment bearing the ms²ct⁶A unit. The applied post-synthetic approach provides two sequentially homologous ms²t⁶A - and ms²ct⁶A -oligonucleotides that are suitable for further comparative structure–activity relationship studies.     

Bioactive Compounds Obtained from Polish “Marynka” Hop Variety Using Efficient Two-Step Supercritical Fluid Extraction and Comparison of Their Antibacterial,Cytotoxic, and Anti-Proliferative Activities In Vitro

Given the health-beneficial properties of compounds from hop, there is still a growing trend towards developing successful extraction methods with the highest yield and also receiving the products with high added value. The aim of this study was to develop efficient extraction method for isolation of bioactive compounds from the Polish “Marynka” hop variety. The modified two-step supercritical fluid extraction allowed to obtain two hop samples, namely crude extract (E1), composed of α-acids, β-acids, and terpene derivatives, as well as pure xanthohumol with higher yield than that of other available methods. The post-extraction residues (R1) were re-extracted in order to obtain extract E2 enriched in xanthohumol. Then, both samples were subjected to investigation of their antibacterial (anti-acne, anti-caries), cytotoxic, and anti-proliferative activities in vitro. It was demonstrated that extract (E1) possessed more beneficial biological properties than xanthohumol. It exhibited not only better antibacterial activity against Gram-positive bacteria strains (MIC, MBC) but also possessed a higher synergistic effect with commercial antibiotics when compared to xanthohumol. Moreover, cell culture experiments revealed that crude extract neither inhibited viability nor divisions of normal skin fibroblasts as strongly as xanthohumol. In turn, calculated selectivity indexes showed that the crude extract had from slightly to significantly better selective anti-proliferative activity towards cancer cells in comparison with xanthohumol.