Reaction mechanism in the photochemistry of the antileukaemic agents 2-chloro- and 2-bromo-2'-deoxyadenosine, studied by nanosecond laser flash photolysis.

The reaction mechanism in the UV photochemistry of 2-chloro-2'-deoxyadenosine (Cladibrine) and 2-bromo-2'-deoxyadenosine in aqueous solution has been studied by laser photolysis at nanosecond time resolution. It is found that excitation at 266 nm wavelength produces heterolytic cleavage of the halogen-carbon bond by one-photon absorption and formation of the unstable 2-hydroxy tautomer of 2'-deoxyisoguanosine as predominant 'primary' product. The 2-hydroxy tautomer then transforms in 10(-6)-10(-5) s into the stable 2-oxo tautomer in an acid-base-catalysed reaction. A reaction mechanism is proposed and discussed in relation to previous UV low-intensity studies of these halogenodeoxyadenosines.     

Facile synthesis of benzimidazole bearing 2-pyridone derivatives as potential antimicrobial agents

A series of benzimidazole bearing 2-pyridones 5a-k were synthesized and assessed in vitro for their activity as antimicrobial agents using the conventional broth dilution method. The results of the antimicrobial study revealed that compounds 5b, 5c, Sj and 5k exhibited substantial antibacterial activity while compound 5d emerged as amore potent antifungal agent compared to the standard drugs chloramphenicol and ketoconazole, respectively. It was observed that the presence of inductively electron withdrawing groups remarkably enhance the antibacterial activity of the newly synthesized compounds. Cytotoxicity studies suggested that none of the tested compounds exhibited any significant cytotoxic effects.     

Laser photolysis of 2-phenylheptamethyltrisilane

Two transient absorptions have been detected in the 266 nm laser photolysis of 2-phenylheptamethyltrisilane in cyclohexane solution at room temperature, and their time evolution was recorded in the presence and absence of air and added trapping agents. The shorter-lived 440 nm transient (t1/2 < 20μs) is tentatively assigned to the silylene :SiMePh and the more persistent 380 nm transient to the disilene MePhSiSiMePh. The reactivity of this silylene is much lower than had been expected.     

Concepts in receptor optimization: targeting the RGD peptide

Synthetic receptors have a wide range of potential applications, but it has been difficult to design low molecular weight receptors that bind ligands with high, "proteinlike" affinities. This study uses novel computational methods to understand why it is hard to design a high-affinity receptor and to explore the limits of affinity, with the bioactive peptide RGD as a model ligand. The M2 modeling method is found to yield excellent agreement with experiment for a known RGD receptor and then is used to analyze a series of receptors generated in silico with a de novo design algorithm. Forces driving binding are found to be systematically opposed by proportionate repulsions due to desolvation and entropy. In particular, strong correlations are found between Coulombic attractions and the electrostatic desolvation penalty and between the mean energy change on binding and the cost in configurational entropy. These correlations help explain why it is hard to achieve high affinity. The change in surface area upon binding is found to correlate poorly with affinity within this series. Measures of receptor efficiency are formulated that summarize how effectively a receptor uses surface area, total energy, and Coulombic energy to achieve affinity. Analysis of the computed efficiencies suggests that a low molecular weight receptor can achieve proteinlike affinity. It is also found that macrocyclization of a receptor can, unexpectedly, increase the entropy cost of binding because the macrocyclic structure further restricts ligand motion.     

Medium-scale ligand-affinity purification of two soluble forms of human interleukin-2 receptor

Recombinant technology has facilitated the production of two soluble forms of human interleukin-2 receptor (IL-2R) in Chinese hamster ovary cells. We have developed a ligand-affinity method for the medium-scale purification of these two IL-2Rs, based on the biochemical interactions between the matrix-bound ligand (interleukin-2) and its soluble receptor. The affinity-purified IL-2R is further purified by anion-exchange chromatography followed by gel filtration. This method has provided enough highly pure IL-2R for structure and function studies and for use in practical applications such as high-flux drug screening assays and the receptor-affinity purification of human recombinant interleukin-2.     

Spectral and kinetic parameters of transient species in the photolysis of naphthylmethylideneiminospironaphthopyran by excitation at different wavelengths: Nano- and femtosecond laser photolysis

Intramolecular processes occurring in a photobifunctional compound (PBC) comprising the spironaphthopyran and hydroxyazomethine moieties have been studied in methanol solutions by femtosecond laser photolysis using light with wavelengths of 340 and 490 nm. At the excitation wavelength of 490 nm, the cis-trans photoisomerization in the azomethine moiety occurs in the S₁ state. In the case of PBC photolysis with 340-nm light, the opening of the spiro bond of the spiropyran moiety (formation of the X form) also takes place during relaxation of the S_n state to the S₁ state followed by isomerization to the merocyanine form. The spectral and kinetic characteristics of different electronically excited have been were determined. The data have been compared with those of nanosecond laser photolysis.     

Pulsed CO2 laser photolysis of CF2Cl2

The pulsed infrared laser photolysis of CF₂Cl₂ yields primarily (more than 85%) the CF₂Cl free radical and atomic chlorine. Somewhat smaller amounts (less than 15%) of CF₂ and molecular chlorine are produced in a competing primary process. Depending on experimental conditions, e.g. pressure and intensity, secondary processes can occur that can obscure the primary chemistry. For example, at low intensity the CF₂Cl radical can thermally dissociate to yield CF₂ plus chlorine atoms while at high intensity the CF₂Cl radical can undergo reaction with chlorine atoms to yield CF₂ and molecular chlorine. Quantitative measurements can be made of the relative importance of the primary atomic or molecular chlorine elimination channels under conditions where secondary removal of CF₂Cl is entirely eliminated. Under these conditions, the relative importance of these two channels does not depend on the intensity of the laser or on the laser wavelength.The overall chemistry occurring in this complex system is evaluated in the absence as well as in the presence of atomic and free-radical scavengers using conventional end-product analysis techniques.     

Intercalation and photolysis of PbI2 crystals

It has been established that reductants sensitize the photolysis of PbI₂ but only commencing from a threshold concentration. An anisotropy is observed in the photodecomposition of single crystals in the presence of amines. It has been shown that intercalation competes with the sensitization of photolysis. An interpretation of the effect is proposed.Translated from Teoreticheskaya i Eksperimental'naya Khimiya, Vol. 21, No. 6, pp. 757–759, November–December, 1985.We thank L. A. Ageev, A. M. Gorbenko, V. S. Paivin, and K. V. Savchenko for assistance in the experiments.     

Vacuum ultraviolet photolysis of CClF2CH2Cl

Photolysis of CClF₂CH₂Cl was studied by 147 nm vacuum ultraviolet irradiation. In the presence of NO; CF₂CH₂, CF₂CHCl, and CClF₂CN were produced. These products represent three different reaction paths; the molecular dechlorination, molecular dehydrochlorination, and chlorine radical elimination reactions. The reactant pressure and the addition gas (He or NO) pressure effects upon the product yield were studied. © 1994 John Wiley & Sons, Inc.     

Pulsed CO2 laser photolysis of CF2Cl2

The pulsed infrared laser photolysis of CF₂Cl₂ yields primarily (more than 85%) the CF₂Cl free radical and atomic chlorine. Somewhat smaller amounts (less than 15%) of CF₂ and molecular chlorine are produced in a competing primary process. Depending on experimental conditions, e.g. pressure and intensity, secondary processes can occur that can obscure the primary chemistry. For example, at low intensity the CF₂Cl radical can thermally dissociate to yield CF₂ plus chlorine atoms while at high intensity the CF₂Cl radical can undergo reaction with chlorine atoms to yield CF₂ and molecular chlorine. Quantitative measurements can be made of the relative importance of the primary atomic or molecular chlorine elimination channels under conditions where secondary removal of CF₂Cl is entirely eliminated. Under these conditions, the relative importance of these two channels does not depend on the intensity of the laser or on the laser wavelength.The overall chemistry occurring in this complex system is evaluated in the absence as well as in the presence of atomic and free-radical scavengers using conventional end-product analysis techniques.     

Flash photolysis in Eu2+ doped NaCl

The luminescence of NaCl:Eu under flash-lamp and N₂-laser excitation has been studied. It has been found an anomalous non-exponential luminescence decay which follows a dependence I=I₀t^m with m=1 at low (90K) and room temperatures. The observed kinetics is consistent with a tunneling mechanism involving recombination of electrons and holes (V_k) at Eu sites.     

Microwave-assisted parallel synthesis of benzofuran-2-carboxamide derivatives bearing anti-inflammatory,analgesic and antipyretic agents

A series of benzofuran-2-carboxamides of biological and medicinal significance were synthesized by a microwave-assisted one-pot parallel approach via O-alkylation/Knoevenagel condensation. All the compounds were characterized and assayed for their in vivo anti-inflammatory, analgesic and antipyretic activities. The activity data of all compounds were listed and discussed in detail, among which some derivatives exhibited potent activities of particular interest.     

The gas phase photolysis of CHFCl2

The photolysis of CHFCl₂ at 300 K has been investigated at 213.9, 163.3 and 147 nm. Methane, Br₂, HBr and HCl were added as free radical interceptors in order to unravel the primary photodecomposition processes. Analysis of the data shows that at 213.9 and 163.3 nm the photodissociative process

occurs with a quantum yield of 0.9 – 1.0, giving stable CHFCl radicals. At shorter wavelengths the quantum yield of CHFCl shows a drastic decrease with concurrent appearances of species such as CFCl, CHF and CF. The laboratory experiments indicate that CF is mainly formed via the dissociative process

The CF radicals react with CH₃ to yield C₂H₂ (CF + CH₃ → C₂H₂ + HF) while the CHF species insert readily into HCl to yield CH₂FCl. In the presence of Br₂, CF and CHF undergo reactions which result in the formation of CFBr₃ and CHFBr₂ respectively.     

Human beta-defensin 2 is induced by interleukin-1beta in the corneal epithelial cells

Mammalian epithelia produce the various antimicrobial peptides against the bacterial or viral infection, thereby acting as the active immune modulators in the innate immunity. In this study, we examined the effects of the various proinflammatory cytokines or LPS on cell viability and antimicrobial beta-defensin gene expressions in human corneal epithelial cells. Results showed that the cytokines or LPS did not exert severe cytotoxic effects on the cells, and that beta-defensin 1 was constitutively expressed, while beta-defensin 2 was specifically induced by IL-1beta, supporting the idea that these cytokines or LPS involve the defense mechanism in the cornea. Furthermore, the reporter and gel shift assay to define the induction mechanism of beta-defensin 2 by IL-1beta demonstrated that the most proximal NF-kappaB site on the promoter region of beta-defensin 2 was not critical for the process. Data obtained from the normal or patients with the varying ocular diseases showed that our in vitro results were relevant in the clinical settings. Our results clearly demonstrated that beta-defensin 1 and 2 are important antimicrobial peptides in the corneal tissues, and that the mechanistic induction process of beta-defensin 2 by IL-1beta is not solely dependent on proximal NF-kappaB site activation, thus suggesting that the long distal portion of the promoter is needed for the full responsiveness toward IL-1beta.     

On the photolysis of 1-Phenyl-2-hydroxy-2-methyl-propanone-1 in the presence of methylmethacrylate,styrene, and acrylonitrile: Laser flash photolysis studies

1-Phenyl-2-hydroxy-2-methyl-propanone-1 (I) has been irradiated in argonsaturated benzene solution containing various amounts of styrene (St), methyl-methacrylate (MMA) or acrylonitrile (AN) with 25 ns flashes of 347 nm light. The aim of this work was to elucidate the kinetics of (a) the reactions of monomers with the triplets of (I) and (b) the reaction of initiator fragment radicals with monomers. Upon applying the optical absorption detection method the rate constants (in l mol⁻¹ s⁻¹) of the reaction of triplets of I with the three monomers were determined as 7 × 10⁹ (St), 8 × 10⁶ (MMA) and 1 × 10⁷ (AN). Therefore, (I) is not appropriate for photocuring coating formulations on the basis of styrene. Radicals stemming from the α-scission of (I¹) react with the monomers with the following rate constants (in l mol⁻¹ s⁻¹): 4·7 ×10⁵ (St), 6·3 × 10⁵ (MMA) and 1·6 × 10⁶ (AN).     

Mechanism of the long wavelength photolysis of CS2 vapor

It is proposed that in the long wavelength (λ ≥ 290 nm) photolysis of CS₂ vapor the observed CS and S₂ are produced in the reaction sequence:      

Furocoumarins photolysis products induce differentiation of human erythroid cells

Psoralens, also known as furocoumarins, are a well-known class of photosensitizers largely used in the therapy of various skin disease. In this study we have evaluated the effects of crude pre-irradiated solutions of furocoumarins derivatives on (a) erythroid differentiation and apoptosis of human leukemic K562 cells and (b) hemoglobin synthesis in cultures of human erythroid progenitors derived from the peripheral blood. To prove the activity of a mixture of photoproducts generated by UVA irradiation of the three psoralen derivatives 5-methoxypsoralen (5-MOP) 8-methoxypsoralen (8-MOP), and angelicin (ANG), we employed the human leukemic K562 cell line and the two-phase liquid culture procedure for growing erythroid progenitors. The results obtained demonstrate that pre-irradiated solutions of psoralen derivatives significantly induce erythroid differentiation of K562 cells irrespective of the type of derivative used, suggesting that the active photoproduct(s) share a common structure. Interestingly, solutions of psoralens irradiated in anaerobic conditions do not exhibits erythroid inducing ability, indicating that the effect is mostly due to photooxidized psoralen products. In erythroid precursor cells, psoralens photolysis products stimulates at low concentrations an increase of hemoglobin A and hemoglobin F. Altogether, these data suggest that photoproducts of psoralen warrant further evaluation as potential therapeutic drugs in beta-thalassaemia and sickle cell anaemia.