Electrophilic Properties Research Articles

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines.

Oxoisoaporphine alkaloids are conveniently prepared via direct ring metalation of alkoxy-substituted isoquinolines at C-1, followed by reaction with iodine. Subsequent Suzuki cross-coupling of the resulting 1-iodoisoquinolines to methyl 2-(isoquinolin-1-yl)benzoates and intramolecular acylation of the corresponding carboxylic acids with Eaton’s reagent afforded five alkaloids of the oxoisoaporphine type. The yield of the cyclization step strongly depends on the electrophilic properties of ring B. An alternative cyclization protocol via directed remote metalation of ester and amide intermediates was investigated thoroughly, but found to be not feasible. Two of the alkaloids showed strong cytotoxicity against the HL-60 tumor cell line.

Ring-expanded iridium and rhodium N-heterocyclic carbene complexes: a comparative DFT study of heterocycle ring size and metal center diversity

A new series of ring-expanded six- and seven-membered N-heterocyclic carbene precursors (re-NHCs) and their transition metal complexes were synthesized. The basic properties of the synthesized materials were investigated by density functional theory (DFT). The six- and seven-membered re-NHCs were synthesized in good yield via reaction of the corresponding alkyldibromides or alkyldiiodides with N,N′-bis-(2-phenylbenzene)formamidine in the presence of K2CO3 under aerobic conditions. Complexes, represented by the formula [ML1,2(COD)Cl] (where M = Ir or Rh and L is a ring-expanded N-heterocyclic carbene ligand), were synthesized in the presence of the corresponding free carbene and iridium or rhodium metal precursors in tetrahydrofuran. All new re-NHC complexes were characterized by different analytical techniques, including NMR spectroscopy, X-ray diffraction, UV spectroscopy and elemental analysis. According to molecular electrostatic potential calculations, the electrophilic properties of the complexes were aligned, from highest to lowest, as Ir-6-DiPh, Rh-6-DiPh and Ir-7-DiPh. The HOMO, LUMO and energy gaps of the complexes were calculated by DFT. On the basis of the DFT analysis, it can be predicted that Rh-6-DiPh is the most stable complex and Ir-7-DiPh is more reactive than Ir-6-DiPh.

Curcumin Protects Skin against UVB-Induced Cytotoxicity via the Keap1-Nrf2 Pathway: The Use of a Microemulsion Delivery System.

Curcumin was found to be beneficial in treating several skin pathologies and diseases, providing antioxidant protection due to its reducing properties and its electrophilic properties (the ability to activate the Nrf2 pathway and induce phase II cytoprotective enzymes). Nevertheless, clinical applications of curcumin are being hampered by its insufficient solubility, chemical instability, and poor absorption, leading to low efficacy in preventing skin pathologies. These limitations can be overcome by using a nanotechnology-based delivery system. Here, we elucidated the possibility of using curcumin encapsulated in a microemulsion preserving its unique chemical structure. We also examined whether curcumin microemulsion would reduce UVB-induced toxicity in skin. A significant curcumin concentration was found in the human skin dermis following topical application of a curcumin microemulsion. Moreover, curcumin microemulsion enhanced the reduction of UV-induced cytotoxicity in epidermal cells, paving the way for other incorporated electrophiles in encapsulated form protecting skin against stress-related diseases.

A Computational Study of Structure and Reactivity of N-Substitued-4-Piperidones Curcumin Analogues and Their Radical Anions.

In this work, a computational study of a series of N-substitued-4-piperidones curcumin analogues is presented. The molecular structure of the neutral molecules and their radical anions, as well as their reactivity, are investigated. N-substituents include methyl and benzyl groups, while substituents on the aromatic rings cover electron-donor and electron-acceptor groups. Substitutions at the nitrogen atom do not significantly affect the geometry and frontier molecular orbitals (FMO) energies of these molecules. On the other hand, substituents on the aromatic rings modify the distribution of FMO. In addition, they influence the capability of these molecules to attach an additional electron, which was studied through adiabatic (AEA) and vertical electron affinities (VEA), as well as vertical detachment energy (VDE). To study electrophilic properties of these structures, local reactivity indices, such as Fukui (f+) and Parr (P+) functions, were calculated, and show the influence of the aromatic rings substituents on the reactivity of α,β-unsaturated ketones towards nucleophilic attack. This study has potential implications for the design of curcumin analogues based on a 4-piperidone core with desired reactivity.

Plasma nitrogenation of polymer surfaces with a new type of combinatorial plasma‐printing reactor

A new method for combinatorial area‐selective polymer modification or deposition using DBD‐type plasmas at atmospheric pressure (“plasma‐printing”) is presented. Thereby a gradient of two gases perpendicular to the flow direction is established by triangular‐shaped overlapping gas inlets. Design of this reactor allows generation of spot arrays with controlled gradients of physicochemical surface properties which is first applied by investigating the influence of H2 admixtures to N2‐plasma‐treatment of polymers. Formation of functional groups is quantitatively characterized by ATR FT‐IR with preceding chemical derivatization using nucleophilic and electrophilic chemicals. It is shown that treatments using high gas flow velocities are more efficient than treatments with low gas speed. Also it is shown that direct plasma treatment leads to polymer surfaces with nucleophilic and electrophilic properties and that H2 content influences formation of both types of functionalities.

Modification of Tau by 8-Nitroguanosine 3′,5′-Cyclic Monophosphate (8-Nitro-cGMP): EFFECTS OF NITRIC OXIDE-LINKED CHEMICAL MODIFICATION ON TAU AGGREGATION

Neurofibrillar tangles caused by intracellular hyperphosphorylated tau inclusion and extracellular amyloid β peptide deposition are hallmarks of Alzheimer's disease. Tau contains one or two cysteine residues in three or four repeats of the microtubule binding region following alternative splicing of exon 10, and formation of intermolecular cysteine disulfide bonds accelerates tau aggregation. 8-Nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP) acts as a novel second messenger of nitric oxide (NO) by covalently binding cGMP to cysteine residues by electrophilic properties, a process termed protein S-guanylation. Here we studied S-guanylation of tau and its effects on tau aggregation. 8-Nitro-cGMP exposure induced S-guanylation of tau both in vitro and in tau-overexpressed HEK293T cells. S-guanylated tau inhibited heparin-induced tau aggregation in a thioflavin T assay. Atomic force microscopy observations indicated that S-guanylated tau could not form tau granules and fibrils. Further biochemical analyses showed that S-guanylated tau was inhibited at the step of tau oligomer formation. In P301L tau-expressing Neuro2A cells, 8-nitro-cGMP treatment significantly reduced the amount of sarcosyl-insoluble tau. NO-linked chemical modification on cysteine residues of tau could block tau aggregation, and therefore, increasing 8-nitro-cGMP levels in the brain could become a potential therapeutic strategy for Alzheimer's disease.

Ozonation in water treatment: the generation, basic properties of ozone and its practical application

AbstractThe widespread applications of ozone technologies are established on the basis of large-scale manufacture of ozone generator and chemical reactivity of ozone. It is hence necessary to summarize the principles of ozone generation and to analyze the physicochemical properties of ozone, which are of fundamental significance to indicate its technical developments and practical applications. This review presents a summary concerning ozone generation mechanisms, the physicochemical properties of ozone, as well as the applications of ozone in water treatment. Ozone can be produced by phosphorus contact, silent discharge, photochemical reactions, and electrochemical reactions, principally proceeding by the reaction of oxygen atom with oxygen molecule. There are side reactions to the generation of ozone, however, which are responsible for ozone depletion including thermal decomposition and quenching reactions by reactive species. The solubility of ozone in water is much higher than that of oxygen, suggesting that it may be reliably applied in water and wastewater treatment. Based on the resonance structures of ozone, one oxygen atom in ozone molecule is electron-deficient displaying electrophilic property, whereas one oxygen atom is electron-rich holding nucleophilic property. The superior chemical reactivity of ozone can also be indirectly revealed by radical-mediated reactions initiated from homogenous and heterogeneous catalytic decomposition of ozone. Owing to the reliable generation of ozone and its robust reactive properties, it is worthy to thoroughly elaborate the applications of ozone reaction in drinking water disinfection and pre- or post-treatment of industrial wastewater including cyanide wastewater, coking wastewater, dyeing wastewater, and municipal wastewater. The structural characteristics of ozone reactors and energy requirement of applied technologies are evaluated. In addition, future directions concerning the development of ozone generation, ozone reactivity, and industrial wastewater ozonation have been proposed.

Microhydration effects on the structures and electrophilic properties of cytidine

Adiabatic electron affinities (AEAs) for cytidine hydrates with up to four water molecules.

Validation of Assays for Reactive Oxygen Species and Glutathione in Saccharomyces cerevisiae during Microgravity Simulation

ABSTRACT The effects of spaceflight on yeast have high concordance with agents that induce a very low intracellular redox state and induce a massive efflux of glutathione. These results raise important issues. Can the reduced redox state during spaceflight be reproduced and modulated in ground-based simulations? Will this allow definition of unique drug pathways as a low redox potential state mirrors the electrophilic properties of mitochondria where many drugs are metabolized? Unfortunately, assays for redox status and its major cellular determinant—glutathione—are diverse and often cell-type-specific. Currently, an accepted redox probe set for yeast studies is not available. This paper validates fluorescent probes for glutathione and reactive oxygen status in yeast to support mechanistic studies of microgravity and drug metabolism. The plethora of fluorescent reagents for reactive oxygen species and glutathione makes head-to-head comparisons of all the alternatives impractical. These reagents measure the physiological milieu of reactive oxygen species and diverse thiols, rather than specific individual molecules. We report that in yeast, monochlorobimane (mBCL) and 2’,7’-dichlorodihydrofluorescein diacetate (DC-FDA) are suitable for fluorometric and flow cytometry studies of glutathione and reactive oxygen species, respectively. Both dyes have low background fluorescence, predictable loading, good retention, and are not acutely toxic to Saccharomyces cerevisiae. Both dyes show concordance with other fluorescent and biochemical assays of reactive oxygen species.

Highly selective chemiluminescence detection of hydroxyl radical via increased π-electron densities of rhodamine B on montmorillonite matrix

The current chemiluminescence (CL) probes for hydroxyl radical (•OH) are poorly selective owing to a non-specific redox reaction. To the best of our knowledge, there have not been established on the CL probes for •OH using the strong electrophilicity of •OH. In this work, an ultrastrong CL emission is initiated by electrophilic attack of •OH towards rhodamine B (RhB) on the surface of montomorillonite (MMT). The improved CL emissions are attributed to the oriented H-type aggregation of RhB molecules on the surface of MMT by π–π stacking interactions, resulting in an increase in π-electron density of aromatic ring of RhB. The high π-electron density of benzene ring could facilitate the attack of electrophilic •OH towards RhB. In addition, a novel CL probe for •OH with high selectivity and high sensitivity has been established using the electrophilic properties of •OH rather than its common redox properties. The applicability of the proposed CL probe is evaluated by detecting •OH in untreated and gentamicin treated mouse fresh plasma samples. Our findings provide a new strategy to improve the selectivity of CL sensor of •OH.

OP18 - Xanthohumol derivatives as mild mitochondrial uncouplers for treatment of metabolic syndrome

Xanthohumol (XN) is a prenylated flavonoid found in hops, beer, and in dietary supplements. There is substantial evidence in the literature that XN improves glucose and lipid metabolism of mammalian cells in vitro, but relatively little is currently known about the potential benefits/risks of chronic exposure to XN in vivo . Even less is known about the underlying mechanisms of action. Using Zucker fa/fa rats and diet-induced obese C57BL/6J mice as models of obesity and metabolic syndrome, we treated animals with XN at three dose levels 6-12 weeks (n=12-16/dose group). The XN-treated animals had significantly lower plasma glucose levels and smaller body weight gain compared to the control groups, while food intake was not affected by treatment. Using an untargeted metabolomics approach, we found a dose-dependent decrease of hepatic triglyceride content and metabolic products of dysfunctional lipid metabolism (medium-chain acylcarnitines, dicarboxy fatty acids, hydroperoxy and hydroxy fatty acids). Taken together, the results indicate that XN improves β-oxidation of fatty acids. Untargeted metabolomics analyses in combination with oxygen consumption measurements of mouse skeletal C2C12 muscle cells treated with XN revealed that it increased basal oxygen consumption and induced an adaptive stress response. Collectively, these findings are consistent with XN acting as a mild mitochondrial uncoupler of oxidative phosphorylation. Because XN has undesired electrophilic and pro-estrogenic properties, we prepared two hydrogenated derivatives of XN that lack electrophilicity and pro-estrogenicity. The derivatives were tested in the diet-induced obese C57BL/6J mice and in the C2C12 cells. They showed comparable activity as the parent XN but at lower doses and concentrations. These data suggest that hydrogenated XN derivatives are promising candidates for further development to treat metabolic syndrome.

Synthesis and chemical reactivity of α,β-unsaturated carbonyl fragments related to the marine natural product onchidal

Resurgence of drugs that covalently modify their target has led to an expansion in this therapeutic class with 39 covalent drugs currently approved as treatments for a wide range of clinical applications. Many of these drugs contain electrophilic fragments (Michael acceptors) that are common among several natural products including curcumin, herbimycin A, butein, kaempferol and zampanolide. We have previously examined the electrophilic properties of the dienone-containing alkaloids the discorabdins and the ketofuran containing halenaquinone. As part of our ongoing studies in this area, we recently initiated model studies on the covalent reactivity of the marine natural product onchidal. The reactivity of α,β-unsaturated aldehydes and masked 1,4-dialdehydes were examined utilising model thiol- and amine- based nucleophiles such as 1-pentanethiol and 1-pentylamine. To model potential reactions with cellular protein targets, the reactivity of these compounds towards lysozyme were studied. The synthetic strategy taken towards model compounds and biological studies undertaken on these compounds will be presented.

Hemoglobin adducts as biomarkers of human exposure to selected xenobiotics

In the living and working environments more and more new substances of anthropogenic origin exerting toxic properties appear. Simultaneously, the evaluation of human exposure is assessed. For many years adducts of hemoglobin (Hb) have been useful markers of the exposure of humans to various xenobiotics. These adducts are also termed biologically effective dose biomarkers. This paper focuses on a review of literature, mainly from the years 2010-2014, which refers to the hemoglobin adducts of toxic compounds with electrophilic properties. In the interactions of xenobiotics with hemoglobin, groups such as thiol, amino, carboxyl and hydroxyl of this hemoprotein are involved. These combinations occur most often in the reaction of xenobiotics with an N-terminal amino group of valine in Hb, imidazole nitrogen of histidine and cysteine sulfhydryl β93. Hb adducts are characterized by high availability, a long period of occurrence (up to 120 days) in the circulatory system, and high durability, and they have contact with all cells of the body. The measurement of hemoglobin adducts can be potentially used in the assessment of exposure to many xenobiotics such as acrylamide; substances present in tobacco smoke, e.g. benzo(α)pyrene and benzanthracene, ethylene oxide, aryl amines; and substances used on a large scale in industry such as glycidol and naphthalene and its derivatives. Recently the possibility of determination of hemoglobin adducts with estrogen metabolites has been postulated as indicators informing about heightened risk of breast cancer. Protein adducts are used as an alternative to DNA adducts for different classes of electrophilic substances.

СИНТЕЗ ТА ДОСЛІДЖЕННЯ АНТИОКСИДАНТНОЇ АКТИВНОСТІ ДЕЯКИХ ПОХІДНИХ НА ОСНОВІ 4-ІМІНОТІАЗОЛІДИН-2-ОНУ

<p class="BodyText2" align="center"><strong>Synthesis and antioxidant activity evaluation of </strong><strong>some novel derivatives based on 4-iminothiazolydine-2-one</strong></p><p align="center">T.I. Сhaban</p><p> </p><p align="center">Lviv, Danylo Halytsky Lviv National Medical University</p><p align="center"><strong> </strong></p><p class="a"><strong>Summary</strong>: Thiazolydine derivatives belong to the group of biologically active compounds which are widely used in modern medical chemistry. They were shown to posses the wide range of biological actions.</p><p>4-Imino-2-thiazolydones are relatively unexplored with regard to their preparation synthetic protocols and biological action spectrum in the modern organic and pharmaceutical chemistry as compared to their 2-imino derivatives. Thus the objective of the present work was to synthesize a series of novel 4-imino-2-thiazolydone derivatives as the potential drug-like molecules. </p><p>3-Aryl-thiazolydine-2,4-dions were firstly prepared using the common synthetic protocol and they were then subjected to thionation reaction with phosphorus pentasulfide leading to the appropriate 3-aryl-4-thioxo-thiazolydin-2-ones obtaining.</p><p>The above-mentioned derivatives were obtained under the conditions similar to that under which well-known 4-thioxo-thiazolydine-2-one (isorhodanine) synthesis was preceded. The synthetic potential of the synthesized compounds allowed 3-aryl-4-thioxo-thiazolydones treatment with 25 % ammonia aqueous solution leading to novel 3-aryl-4-imino-thiazolydine-2-one obtaining not mentioned in the scientific literature. The reaction proceeding was possible taking into account the advantage of thione group significant activity possessing in 3-aryl-4-thioxo-thiazolydine-2-ones as cyclic thioamides owing to stronger electrophilic properties of thiocarbonyl group carbon atom as compared with carbonyl group in C<sup>4</sup> position of 3-aryl-thiazolydine-2,4-diones, consequently. One of the proofs of synthesized compounds structure was their acidic hydrolysis with 3-aryl-thiazolydine-2,4-ones generation.</p><p>The presence of active methylene group in C<sup>5</sup> position of 3-phenyl-4-imino-thiazolydine-2-one thiazolydine ring provided an entry for aldol condencation carrying out with the respective 3-phenyl-4-imino-thiazolydine-2-one 5-aryliden derivatives generation. We discovered that the high yield of the product could be achieved by introducing the equimolar amounts of 3-phenyl-4-imino-thiazolydine-2-one and appropriate aromatic aldehydes using monoaminoethanol as a catalyst.</p><p>The next stage of our strategy included the core heterocycle further structural modification in its C<sup>5</sup> position. In particular the nitrosylation reaction with nitrous acid was proceeded. It was found that 3-phenyl-4-imino-thiazolydine-2-one could interact with nitrous acid obtained in its turn under sodium nitrite treatment with hydrochloric acid. Nitrosylation reaction allowed to achiev novel 5-isonitrozo-4-imino-3-phenyl-thiazolydine-2-one which was not mentioned in chemical literature. </p><p> The structures of the obtained compounds were confirmed by <sup>1</sup>H NMR spectroscopy and elemental analysis.</p><p>The antioxidant activity of the novel compounds was determined <em>in vitro</em> on basis of free radical scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. DPPH radical has found many applications due to its high stability in a methanolic solution and intense purple color. In its oxidized form, the DPPH radical has an absorbance maximum centered at a wavelength about 540 nm. The absorbance decreases when the radical is reduced by antioxidants. Its reduction affords 2,2-diphenyl-1-picrylhydrazine (DPPH-H), or the corresponding anion (DPPH<sup>–</sup>) in basic medium. The DPPH radical acts as a scavenger for other odd-electron species which afford para-substitution products at phenyl rings.</p><p>The pharmacology screening allowed to state that the synthesized compounds had been shown to possess the moderate antioxidant activity. So it may be concluded that the functionalization of 4-iminotiazolidyn-2-one by its N<sup>3</sup> and C<sup>5</sup> positions did not lead to the free-radical-scavenging activity enhancement. </p>

Different Aspects of Single Wall Carbon Nanotube Functionalization by Aniline Adsorption; Quantum Mechanics/Molecular Mechanics Study

In this research, kinetics and mechanism of aniline adsorption on different single-walled carbon nanotubes (SWCNT) was investigated, using 2-layer ONIOM (Our own N-layered Integrated molecular Orbital and molecular Mechanics) method at the ONIOM (B3LYP/6-31G (d);UFF) level. Various orientations of aniline relative to the carbon nanotube surface were investigated. To investigate the adsorption of aniline, three models including open-ended (model 1), cap-ended (model 2) and 1-cap-ended (model 3) SWCNT have been modeled. Calculated activation energies of adsorption showed that model 2 has the lowest activation energy of 40.8 kcal.mol-1. Natural bond orbital and frontier molecular orbital analysis confirmed the charge transfer from the aniline to the SWCNT. Density of states analysis showed that Fermi level is shifted towards the positive values after aniline adsorption which confirmed the effective interactions between the aniline and the SWCNT. According to the quantum theory of atoms in molecules studies, new bonds formed between the SWCNT and aniline which possess a covalence nature. Finally, based on the quantum reactivity indices, new linear correlations between the chemical hardness, charge transfer and activation energy and the inverse relationship of the electrophilic property and chemical electronic potential in the functionalized carbon nanotubes were obtained. Wiberg bond index calculations show that this reaction is carried out through an asynchronous concerted mechanism. Asynchronicity value in the case of model 2 is higher than other models.

Smart tools and orthogonal click-like reactions onto small unilamellar vesicles

Click-based reactions were conducted at the surface of small unilamellar vesicles (SUVs) to provide onto-vesicle chemistry with efficient innovative ready-for-use tools. For that purpose, four amphiphilic molecules were designed to insert into bilayers while presenting a reactive functional head. In this manner, a dioleylglycero-ethoxy-ethoxy-ethoxy-ethanamine (DOG-PEG4-NH2) was chosen as a common platform while the reactive amine head was converted into several electrophilic functions. Thus, two dioleylglycerol-based cyclooctyne anchors were prepared: cyclooct-1-yn-3-glycolic acid-based anchor (DOG-COA) and 1-fluorocyclooct-2-ynecarboxylic acid-based anchor (DOG-FCOA). The last one differed from the first one in that a fluorine atom reinforces the electrophilic properties of the unsaturated bond. In addition, a third dioleylglycerol-based triphenylphosphine (DOG-PPh3) was synthesized for the first time. These three innovative amphiphilic anchors were designed to react with any azide-based biomolecule following copper-free Huisgen 1,4-cycloaddition and Staudinger ligation, respectively. A fourth anchor bearing a 3,4-dibromomaleimide ring (DOG-DBM) was also unprecedentedly synthesized, to be further substituted by two thiols. Model reactions conducted in solution with either model biotinyl azide or model biotinyl disulfide gave good to total conversions and excellent isolated yields. The four new anchors were inserted into SUVs whose formula is classically used in in vivo biology. Stability and surface overall electrostatic charge were in the expected range and constant over the study. Then, the functionalized liposomes were ligated to biotin-based reagents and the experimental conditions were finely tuned to optimize the conversion. The biotinyl liposomes were demonstrated functional and totally accessible in an affinity test based on biotin scaffold quantification. Finally, DOG-FCOA’s reactivity was confronted to that of DOG-DBM in a ‘one-pot’ orthogonal reaction. (Biotin-S)2 and TAMRA-N3 (tetramethylcarboxyrhodamine azide) were successively conjugated to the liposome suspension in a successful manner. These data implement and reinforce the interest of bioorthogonal click-like reactions onto lipid nanoparticles.

Regioselectivity in ligand substitution reactions on diiron complexes governed by nucleophilic and electrophilic ligand properties.

The discovery of a diiron organometallic site in nature within the diiron hydrogenase, [FeFe]-H2ase, active site has prompted revisits of the classic organometallic chemistry involving the Fe-Fe bond and bridging ligands, particularly of the (μ-SCH2XCH2S)[Fe(CO)3]2 and (μ-SCH2XCH2S)[Fe(CO)2L]2 (X = CH2, NH; L = PMe3, CN(-), and NHC's (NHC = N-heterocyclic carbene)), derived from CO/L exchange reactions. Through the synergy of synthetic chemistry and density functional theory computations, the regioselectivity of nucleophilic (PMe3 or CN(-)) and electrophilic (nitrosonium, NO(+)) ligand substitution on the diiron dithiolate framework of the (μ-pdt)[Fe(CO)2NHC][Fe(CO)3] complex (pdt = propanedithiolate) reveals the electron density shifts in the diiron core of such complexes that mimic the [FeFe]-H2ase active site. While CO substitution by PMe3, followed by reaction with NO(+), produces (μ-pdt)(μ-CO)[Fe(NHC)(NO)][Fe(CO)2PMe3](+), the alternate order of reagent addition produces the structural isomer (μ-pdt)[Fe(NHC)(NO)PMe3][Fe(CO)3](+), illustrating how the nucleophile and electrophile choose the electron-poor metal and the electron-rich metal, respectively. Theoretical explorations of simpler analogues, (μ-pdt)[Fe(CO)2CN][Fe(CO)3](-), (μ-pdt)[Fe(CO)3]2, and (μ-pdt)[Fe(CO)2NO][Fe(CO)3](+), provide an explanation for the role that the electron-rich iron moiety plays in inducing the rotation of the electron-poor iron moiety to produce a bridging CO ligand, a key factor in stabilizing the electron-rich iron moiety and for support of the rotated structure as found in the enzyme active site.

Ambiphilic properties of SF5CF2CF2Br derived perfluorinated radical in addition reactions across carbon-carbon double bonds.

The extraordinary properties of the pentafluorosulfanyl (SF5) group attract attention of organic chemists. While numerous SF5-substituted compounds have been synthesized, the direct introduction of SF5(CF2)n moieties has remained almost unexplored. Our investigations revealed the ambiphilic character of the SF5CF2CF2 radical. Addition reactions to electron-rich or electron-deficient alkenes profit either from its electrophilic or nucleophilic properties. Thus, the readily available SF5CF2CF2Br proved to be a promising and versatile building block for the introduction of this perfluorinated moiety.

A novel 1,8-naphthalimide derivative with an open space for an anion: unique fluorescence behaviour depending on the binding anion's electrophilic properties.

We have designed a novel 1,8-naphthalimide derivative with an open space for an anion. Computational calculation has predicted that the space could trap various anion species and photo-induced charge transfer depending on the anion's electrophilic properties. Indeed, the fluorescence behaviour of the 1,8-naphthalimide derivative complexes with each anion is consistent with the computational prediction.

A new target for squamous cell skin cancer?

Prostaglandins (PGs) derived from arachidonic acid of cell membrane are synthesized by PG G/H synthase (cyclooxygenase; COX-1/-2) and signal as autocrine/paracrine lipids (1, 2). Similar to other tissues, COX-1 is constitutively expressed in keratinocytes of normal epidermis, whereas COX-2 expression is more variable and regulated (3, 4). COX-2 is induced for example by cytokines and growth factors; accumulated prostaglandins from COX-2 regulate pain, inflammation, and cancers (2, 3). In the case of cancer, increased levels of PGs disrupt differentiation and thus contribute to the sensitization of cells to carcinogens and ensuing hyperplasia (5, 6). Therefore, the inhibition of COX-2 activity with aspirin like compounds has been suggested as a potent chemo-preventive therapy to suppress tumor development, not just in skin but particularly for gastrointestinal cancers (2, 7).