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Colour changes of cultural heritage objects can be related with degradation of materials, thus a proper colour monitoring system can be used to detect conservation problems. With this purpose, a monitoring methodology for cultural heritage preventive conservation based on tailored colour reference charts and image analysis is proposed. Reference colour charts have been designed and tested for use in museums. Charts containing 64 colour patches have been printed using high-stability inks on 4 different substrates: Acid-free paper SkyLight, Acid-free paper covered with a propylene film, FOREX® and GlassPack. The stability has been studied by accelerated ageing in an UV chamber, and the harmlessness of the materials by Oddy Test. The final selection of material, laminated paper, is a balance between the colour change upon ageing and the performance in the Oddy Test. Using this material and the proposed design, colour change of copper and silver coupons has been assessed using images that are adjusted and calibrated by an adaptive calibration framework employing a given set of reference colours which homogenises the visual information in the supplied images. Thus, regardless of the camera of origin, any processed picture will deliver reliable information of the state of the colour in the metal surfaces at the moment it was taken. Results demonstrate the adequacy of the approach and the design for colour calibration, so these charts can be used to monitor colour change of sensitive materials ¿metal coupons¿ using photographs. As colour change of reference metals is a consequence of corrosion by environmental factors this may be used as a measure of air quality in museum environments. This methodology can be used to design a low-cost preventive conservation tool, where colour change of metal coupons ¿or other reference materials¿ can be followed through image analysis of pictures taken periodically by conservators or visitors, introducing citizen science in the conservation strategy., The final testing of the methodology is being possible thanks to the Museo Nacional de Ciencia y Tecnología (MUNCYT) and the Faculty of Chemistry of the Universidad Complutense de Madrid, that have allowed us to display the reference charts in their scientific collections. Authors also acknowledge the support of TechnoHeritage network and the CSIC Authors also acknowledge the support of TechnoHeritage network and the CSIC Interdisciplinary Thematic Platform-OPEN HERITAGE: RESEARCH AND SOCIETY (PTI-PAIS). Thanks are due also to Dr. Elena Mesa, for her suggestions and support, and Ignacio García, from Once34, for his generous collaboration for the printing of the charts. We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI), and Digital.CSIC for their help with the dataset deposit. This work has been funded by Comunidad de Madrid, European Regional Development Fund and European Social Fund, project MIPAC-CM (Y2018/NMT-4913); and Ministerio de Ciencia, Innovación y Universidades, project COMPACT (HAR2017-89911-R) and grant PRE2018-086667.

Hidradenitis suppurativa (HS) can affect children, and ultrasound has been proven to be useful in diagnosis and staging. The sonographic characteristics of HS in children have not been reported. We studied color Doppler ultrasound images of children (≤15 years old; n = 12) with clinically and sonographically positive criteria for HS. Sonographic scoring of hidradenitis suppurativa (SOS-HS) was used to stage the cases sonographically. Subclinical pseudocysts were found in 92% of the cases, fluid collections in 83%, and fistulous tracts in 58%. Retained hair tracts in the fluid collections and fistulous tracts were present in 100% of patients; 67% of cases were SOS-HS stage II. In 92% of cases, management was modified after the ultrasound examination. In conclusion, ultrasound can be a reliable and safe imaging tool to support diagnosis and staging and may help in the noninvasive monitoring of treatment in children.

La demodicosis es una patología cutánea crónica caracteriza-da por lesiones eritemato-maculares pruriginosas, cuyo agente causal son ácaros foliculares del género Demodex. Presenta un abanico amplio y polimorfo de manifestaciones clínicas, donde la sospecha clínica se presentará frente a una erupción facial crónica persistente o recurrente, resistente a terapia conven-cional y de distribución asimétrica. El diagnóstico definitio es difícil, y requiere un cuadro clínico compatible y la presencia de alta densidad de Demodex.El siguiente documento hace una revisión de conceptos con respecto a la patogenia, clínica, diagnóstico y tratamiento de esta entidad.

none 20 si Crassiflorone is a natural product with anti-mycobacterial and anti-gonorrhoeal properties, isolated from the stem bark of the African ebony tree Diospyros crassiflora. We noticed that its pentacyclic core possesses structural resemblance to the quinone-coumarin hybrid 3, which we reported to exhibit a dual-targeted inhibitory profile towards Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR). Following this basic idea, we synthesized a small library of crassiflorone derivatives 15-23 and investigated their potential as anti-trypanosomatid agents. 19 is the only compound of the series showing a balanced dual profile at 10 μM (% inhibitionTbGAPDH= 64% and % inhibitionTcTR= 65%). In phenotypic assay, the most active compounds were 18 and 21, which at 5 μM inhibited Tb bloodstream-form growth by 29% and 38%, respectively. Notably, all the newly synthesized compounds at 10 μM did not affect viability and the status of mitochondria in human A549 and 786-O cell lines, respectively. However, further optimization that addresses metabolic liabilities including solubility, as well as cytochromes P450 (CYP1A2, CYP2C9, CYP2C19, and CYP2D6) inhibition, is required before this class of natural product-derived compounds can be further progressed. Uliassi, Elisa; Fiorani, Giulia; Krauth-Siegel, R. Luise; Bergamini, Christian; Fato, Romana; Bianchini, Giulia; Carlos Menéndez, J.; Molina, Maria Teresa; López-Montero, Eulogio; Falchi, Federico; Cavalli, Andrea; Gul, Sheraz; Kuzikov, Maria; Ellinger, Bernhard; Witt, Gesa; Moraes, Carolina B.; Freitas-Junior, Lucio H.; Borsari, Chiara; Costi, Maria Paola; Bolognesi, Maria Laura* Uliassi, Elisa; Fiorani, Giulia; Krauth-Siegel, R. Luise; Bergamini, Christian; Fato, Romana; Bianchini, Giulia; Carlos Menéndez, J.; Molina, Maria Teresa; López-Montero, Eulogio; Falchi, Federico; Cavalli, Andrea; Gul, Sheraz; Kuzikov, Maria; Ellinger, Bernhard; Witt, Gesa; Moraes, Carolina B.; Freitas-Junior, Lucio H.; Borsari, Chiara; Costi, Maria Paola; Bolognesi, Maria Laura*

Atmospheric plasma treated carbon fiber filaments (10 micrometer) were used as the base substrate in the design of a probe intended for use within intravascular access devices. The microfiber probe was further functionalized with a polyplumbagin layer through which the line pH could be determined voltammetrically and therein provide the potential for obtaining diagnostic information relating to bacterial colonization of the line. The redox processes attributed to the immobilized polymer are characterized and a methodology developed to enable the acquisition of a redox signal that is selective and sensitive to pH. The applicability of the composite probe was demonstrated through examining the direct response in whole blood., The authors thanks the Royal Society (London, JP100125)), Ministry of Science and Innovation (SAF-2009-10399), and the Engineering and Physical Sciences Research Council (EPSRC, U.K.) for supporting this work

Background: Current drugs available for the treatment of Chagas disease are fraught with several challenges including severe toxicity and limited efficacy. These factors coupled with the absence of effective drugs for treating the chronic stage of the disease have rendered the development of new drugs against Chagas disease a priority. Objective: This study screened several imidazole-based compounds for anti-Trypanosoma potential. Method: Using an in vitro experimental infection model, several imidazole-based compounds were screened for anti-proliferative effect on Trypanosoma cruzi epimastigotes. Additionally, all test compounds were evaluated for unspecific cytotoxicity on L929 murine fibroblasts. Benznidazole (BZN) served as reference drug. Results: All test compounds demonstrated interesting trypanocidal potential with IC values in the μM range (1< 1C 9.42). Conclusion: We provide evidence which implicate the imidazole-based compounds as potential prototypes for the development of anti-parasitic agents. Findings have far-reaching relevance to drug discovery efforts for trypanosomiasis.

The first examples of the direct arylation of benzo-fused 1,4-quinones by the dicationic Pd(II)-catalyzed addition of arylboronic acids are reported. The addition reaction is carried out under very mild conditions (dioxane-H2O, rt, open air atmosphere) and is tolerant of free OH groups. In addition, the reaction shows high regioselectivity when using nonsymmetrical quinones as starting materials., Projects UCM-BSCH GR58/08-910815 and CTQ2006-15279-C03-01 (both to A.G.C.), and SAF2006- 04698 (to M.T.M.), are gratefully acknowledged for financial support.

A small library of 2-phenoxy-1,4-naphthoquinone and 2-phenoxy-1,4-anthraquinone derivatives was initially developed to optimize the antitrypanosomatid profile of the multitarget hit compound B6 (1). The whole series was evaluated against the three most important human trypanosomatid pathogens (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania donovani), and two compounds (14 and 21) showed good activity, despite a concomitant mammalian cytotoxicity. Furthermore, a subset also inhibited the glycolytic TbGAPDH enzyme in vitro. In light of these results and aware of the antitumor properties of quinones, the anticancer potential of some selected derivatives was investigated. Intriguingly, the tested compounds displayed antitumor activity, while being less toxic against noncancerous cells. The observed cytotoxic potency was ascribed to a multitarget mechanism of action accounting for hGAPDH inhibition and mitochondrial toxicity. Overall, the development of further derivatives, able to finely modulate multiple pathways of cancer or parasite cell metabolism, might lead to more effective treatments against these devastating diseases. (Figure Presented)., This work was supported by the University of Bologna, MIUR (PRIN 201274BNKN_003), and a grant from Ministry of Science (MICINN, Spain) SAF2009-10399

The interaction of the substituted 1,4-anthraquinones with purple membranes (PM) is studied by the fluorescence and electric light scattering techniques. Substituted 1,4-anthraquinones are shown to quench bacteriorhodopsin tryptophan fluorescence. The quenching efficiency of 1,4-anthraquinone derivatives is smaller than that of 1,4-anthraquinone. It is the smallest at di-substituted 1,4-anthraquinones (R9=OCOCH 3 and R3=Cl or Br). The type of the halogen atom as substituent does not affect the quenching efficiency of di-substituted 1,4-anthraquinones (R9=OH or OCOCH 3 and R3=Cl or Br). The quenching efficiency depends on the position of the Cl atom for di-substituted 1,4-anthraquinone derivatives (R9=OH and R3=Cl or R9=OH and R10=Cl). 9-Hydroxy-1,4-anthraquinones induce decrease in purple membrane charge asymmetry distribution whereas mono-substituted 1,4-anthraquinones containing R9=OCH 3 or R9=OCOCH 3 induce increase in the membrane charge asymmetry. The membrane electric polarizability, related to the structure and dynamics of the electric double layer, decreases in the presence of 1,4-anthraquinone derivatives, the greatest effect being observed for the 9-hydroxy-1,4-anthraquinones. The energy transfer and the quenching of bR tryptophan fluorescence from 9-hydroxy-1,4-anthraquinones correlate with the variation of the surface electric properties of PM in the presence of relatively low concentrations of substituted 1,4-anthraquinones.

The effect of substituted 1,4-anthraquinones on the photochemical activity and chlorophyll fluorescence of thylakoid membranes was examined. Both the fluorescence and the photochemical activity depend on the 1,4-anthraquinone substituent. Stronger quinone-induced quenching of the chlorophyll fluorescence than quinone-induced changes in the activity of photosystem II is observed. The type (Cl or Br) and the position (Cl) of the chalogen atom strongly influence the degree of inhibition of PSII electron transport and the quenching of chlorophyll fluorescence. The data suggest that the quenching of chlorophyll fluorescence is due rather to the interaction of the 1,4-anthraquinones and chlorophyll molecules than to an indirect effect caused by stimulation of the photochemistry.

Several kynurenine analogues were synthesized and tested as inhibitors of the enzymes kynurenine hydroxylase and/or kynureninase with the aim of identifying new compounds able to inhibit the synthesis of quinolinic acid (an endogenous excitotoxin) and to increase that of kynurenic acid, an endogenous antagonist of ionotropic glutamate receptors. Among these analogues, we selected m-nitrobenzoylalanine (mNBA) as an inhibitor of kynurenine hydroxylase and o-methoxybenzoylalanine (oMBA) as an inhibitor of kynureninase. When administered to rats, mNBA was more potent than oMBA in increasing the content of kynurenine and of kynurenic acid in the brain, blood, liver, and kidney. This confirms that hydroxylation is the main pathway of kynurenine metabolism. Both mNBA and oMBA (50-400 mg/kg i.p.) increased the concentration of kynurenate in hippocampal extracellular spaces (as measured with a microdialysis technique) and, when simultaneously injected, their effects were additive. This biochemical effect was associated with a decrease in locomotor activity in rats and with a protection of audiogenic convulsions in DBA/2 mice. In conclusion, the results of the present experiments indicate the possibility of increasing the neosynthesis of kynurenic acid by inhibiting the enzymes that metabolize kynurenine to 3-hydroxykynurenine or to anthranilic acid. The increased synthesis of kynurenate is associated with behavioral effects such as sedation and protection from seizures, which suggests a functional antagonism of the excitatory amino acid receptors.

Ground and excited state deprotonation and protonation p K a values of anthraquinones with amino, hydroxy and chloro substituents were determined by means of spectrophotometric titrations and Forster cycle calculations. In the mixed amino-hydroxy 9,10-anthraquinones a second stage of deprotonation and protonation was not registered, and only when the primary amino function is attached to an electron-withdrawing group (–COCH 2 Cl) a second ionization takes place. Acidity of the hydroxy-1,4-anthraquinones in the ground state is about 2.5 p K a− units higher than that of the related 9,10-anthraquinones. The determined values of p K a+ of protonation are within the limits of −4.46 up to −8.39. The calculated values of the excited state of deprotonation are in the range 1.15–2.57, while the excited state values for protonation vary from 0.91 to 2.57 correspondingly. It was concluded that a proton transfer in the excited state is possible for all the investigated compounds.

The plant allelochemical, quinizarin (1,4-dihydroxy-9,10-anthraquinone), and five anthraquinones that were synthesized from quinizarin, namely, 1,4-anthraquinone; 2-hydroxy-1,4-anthraquinone; 2-methoxy-1,4-anthraquinone; 9-hydroxy-1,4-anthraquinone; and 9-methoxy-1,4-anthraquinone, were assessed as to their effects on the essential, P450-dependent ecdysone 20-monooxygenase system of the insect model Manduca sexta (tobacco hornworm). This steroid hydroxylase converts the arthropod molting hormone, ecdysone, to the physiologically required 20-hydroxyecdysone form. M. sexta fifth larval instar midgut homogenates were incubated with increasing concentrations (10-8 to 10-3 M) of each of the six anthraquinones followed by ecdysone 20-monooxygenase assessments using a radioenzymological assay. Four of the five anthraquinones exhibited I50's of about 4×10-6 to 6×10-2 M. The most effective inhibitors were 2-methoxy-1,4-anthraquinone and 1,4-anthraquinone followed by 9-hydroxy-1,4 anthraquinone and 9-methoxy-1,4-anthraquinone. At lower concentrations the latter anthraquinone stimulated E20M activity. Quinizarin was less inhibitory and 2-hydroxy-1,4-anthraquinone was essentially without effect. Significantly, these studies make evident for the first time that anthraquinones can affect insect E20M activity, and thus insect endocrine regulation and development, and that a relationship between anthraquinone structure and effectiveness is apparent. These studies represent the first demonstrations of anthraquinones affecting any steroid hydroxylase system.

Objectives The purpose of this study was to assess the sonographic morphology of the clinical and subclinical pathology of facial acne vulgaris. Methods We studied patients with facial acne vulgaris diagnosed by certified dermatologists, and using a standardized protocol for sonographic examinations, we sequentially described the sonographic pathomorphologic characteristics. Lesions of particular interest to the referring clinician were also analyzed separately. Additionally, acne involvement was staged clinically and sonographically (SOS-Acne) using morphologic definitions of the relevant lesions and predefined scoring systems for gradation of the severity of acne lesions. Results A total of 245 acne lesions in 20 consecutive patients were studied. Sonographic abnormalities consisted of pseudocysts, folliculitis, fistulas, and calcinosis. Most conditions were subclinical and mostly due to lesion extensions deep into the dermis and hypodermis (52% of pseudocysts and 68% of fistulas). The statistical concordance between acne severity scores assigned by two separate clinicians was strong (κ = 0.8020), but the corresponding sonographic scores generally showed more severe and clinically occult involvement. Conclusions Facial acne vulgaris often involves deeper tissues, beyond the reach of the spatially restricted clinical examination; these subclinical conditions can be detected and defined with sonography. Additionally, acne vulgaris is amenable to sonographic scoring.

Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT ICR) has revealed the existence of the P4Li+ ion as a stable species in the gas phase. High-level ab initio calculations show that P4...

The highly branched ester rac-1 has been prepared. It exists in the form of a conglomerate (m.p. 90–92 °C) in which the two enantiomers are present in separate crystal lattices, as indicated by the melting point diagram. Both enantiomers of 1 have been isolated by crystallization [m.p. 112–114 °C, [α]D22 = +24.4 ± 0.7 (c = 0.45, Et2O), –25.4 ± 0.8 (c = 0.44, Et2O)]; mechanical manipulation of the conglomerate provided samples enriched in one or the other enantiomer and subsequent recrystallization of these partially resolved samples furnished the isolated enantiomers. The high value of the enthalpy of fusion of enantiomers 1 (ΔHfenant = 8.8 ± 1.4 kcal mol–1) and the moderate value of the corresponding entropy (ΔSfenant = 23 ± 4 cal K–1 mol–1), both derived from the melting point diagram, are ascribed to the relative compactness of the highly branched molecule and to its reduced conformational flexibility, respectively. Ester rac-1 has been serendipitously obtained in the form of a racemic compound (m.p. 82–84 °C) by crystallization of the racemate. The racemic compound transforms into the conglomerate at 70 °C. This transformation may be regarded as a spontaneous optical resolution occurring in the solid crystalline state.

The standard molar energy of combustion of pentacyclo[5.4.0.02,6.03,10.05,9]undecane-8,11-dione has been determined by using a static bomb calorimeter. The vapour pressure of the compound was measured in the intervalT = 325.64 K toT = 340.97 K by the Knudsen-effusion technique. Enthalpy of fusion and enthalpy of transition measurements were carried out by differential scanning calorimetry (d.s.c.). From the experimental results of this work, the standard enthalpies of combustion, sublimation, and formation in the crystalline and gaseous state at the temperature 298.15 K have been derived for pentacyclo[5.4.0.02,6.03,10.05,9] undecane-8,11-dione: ΔfHmo(cr) = −(206.2 ± 3.2) kJ · mol−1, ΔsubHmo = (92.6 ± 1) kJ· mol−1, ΔfHmo(g) = −(113.6 ± 3.4) kJ− mol−1. Strain energy due to the presence of the two carbonyl groups in the molecule is estimated by three different methods with consistent results.

We have determined the gas-phase basicities of S6 and S8 by means of Fourier transform ion cyclotron resonance spectroscopy (FT-ICR): 167.8 and 187.1 kcal/mol, respectively. An ab initio investigation of the local minima of the S6H+ potential energy surface shows that the most stable protonated species corresponds to a distorted five-membered ring structure rather than to a six-membered ring species. When the final energy of the aforementioned protonated species is evaluated at the G2(SVP,MP2) level, the agreement with the experimental value is very good. A G2(MP2) survey of the S4 and S4H+ potential energy surfaces shows that the most stable neutral and protonated species present cis open-chain structures. The relative stabilities of the different species investigated are extremely sensitive to electron correlation effects. At the G2(MP2) level S4 is predicted to be slightly more basic than S6 in the gas phase. Some preliminary ab initio calculations on the most probable structures of S8H+ are also repo...

The molar single activity coefficients associated with propionate ion (Pr) have been determined at 25°C and ionic strengths comprised between 0.300 and 3.00 M, adjusted with NaClO4, as background electrolyte. The investigation was carried out potentiometrically by using a second class Hg/Hg2Pr2 electrode. It was found that the dependence of propionate activity coefficients as a function of ionic strength (I) can be assessed through the following empirical equation: log ypr = –0.185 J3/2 + 0.104 I2. Next, simple equations relating stoichiometric protonation constants of several monocarboxylates and formation constants associated with 1:1 complexes involving some bivalent cations and selected monocarboxylates, in aqueous solution, at 25°C, as a function of ionic strength were derived, allowing the interconversion of parameters from one ionic strength to another, up to I = 3.00 M. In addition, thermodynamic formation constants as well as parameters associated with activity coefficients of the comple...

A method based on ion exchange(IE)-atomic absorption spectrometry(AAS) coupled by flow techniques, allowing the determination of formation constants of, at least, the first species of complex systems, in aqueous solution, was developed. The IE-AAS coupling reduces significantly the number of experimental steps in comparison with IE batch methods, resulting in an important increase in analytical rate. The method is simple both from experimental and computational points of view, making possible its utilization by workers without special expertise in the field of complex equilibria in solution. On the other hand, taking into account mainly the amount of hollow cathode lamps available to date, the developed procedure may be applied, within certain limitations, to the study of many systems whose features prevent the use of traditional approaches.

The protonation constants of 4-methylbenzylidenepyruvate (4Me-BP) and 4-isopropylbenzylidenepyruvate (4IP-BP) as well as the stability constants of their binary 1:1 complexes with Cu(II), La(III), Pr(III), Sm(III), Eu(III), Yb(III), Sc(III) and Th(IV) have been determined spectrophotometricaily in aqueous solution at 25 °C and ionic strength 0.500 M, maintained with sodium perchlorate. For all metal ions considered, the stability changes move in the same direction as the p K a of the ligands. Linear free energy relationships, as applied to oxygen donor substances, suggest the -COCOO − moiety as the metal binding site of the ligands. The results are discussed mainly taking into account that benzylidenepyruvates, besides the α-keto canonical form, may display other forms in aqueous solution with changing pH and the possible occurrence of extra intra-ligand charge polarization, induced by metal ions.

4-Dimethylaminocinnamylidenepyruvic acid (H-DMCP)and its sodium salt (Na-DMCP) have been synthesized and characterized. The protonation constant of DMCP as well as the stability constants of its binary 1:1 complexes with trivalent lanthanides (except Pm), Yttrium(III), Scandium(III), Thorium(IV) and Uranium(VI) were determined in an aqueous medium at 25 °C and ionic strength 0.500 M. The mode of coordination of this ligand is discussed.

Background Naphthoquinones (NQs) are privileged structures in medicinal chemistry due to the biological effects associated with the induction of oxidative stress. The present study evaluated the activities of sixteen NQs derivatives on Trypanosoma cruzi. Results Fourteen NQs displayed higher activity against bloodstream trypomastigotes of T. cruzi than benznidazole. Further assays with NQ1, NQ8, NQ9 and NQ12 showed inhibition of the proliferation of axenic epimastigotes and intracelulluar amastigotes interiorized in macrophages and in heart muscle cells. NQ8 was the most active NQ against both proliferative forms of T. cruzi. In epimastigotes the four NQs induced mitochondrial swelling, vacuolization, and flagellar blebbing. The treatment with NQs also induced the appearance of large endoplasmic reticulum profiles surrounding different cellular structures and of myelin-like membranous contours, morphological characteristics of an autophagic process. At IC50 concentration, NQ8 totally disrupted the ΔΨm of about 20% of the parasites, suggesting the induction of a sub-population with metabolically inactive mitochondria. On the other hand, NQ1, NQ9 or NQ12 led only to a discrete decrease of TMRE + labeling at IC50 values. NQ8 led also to an increase in the percentage of parasites labeled with DHE, indicative of ROS production, possibly the cause of the observed mitochondrial swelling. The other three NQs behaved similarly to untreated controls. Conclusions NQ1, NQ8, NQ9 and NQ12 induce an autophagic phenotype in T. cruzi epimastigoted, as already observed with others NQs. The absence of oxidative stress in NQ1-, NQ9- and NQ12-treated parasites could be due to the existence of more than one mechanism of action involved in their trypanocidal activity, leaving ROS generation suppressed by the detoxification system of the parasite. The strong redox effect of NQ8 could be associated to the presence of the acetyl group in its structure facilitating quinone reduction, as previously demonstrated by electrochemical analysis. Further experiments using biochemical and molecular approaches are needed to better characterize ROS participation in the mechanism of action of these NQs.

We have investigated the energetic, structural, and other physical-chemical properties (aromaticity, intrinsic strain, hydrogen bond interaction) of 1,4-anthraquinone (1), its better known isomer 9,10-anthraquinone (2) and the derivatives 9-hydroxy-1,4-anthraquinone (3) and 9-methoxy-1,4-anthraquinone (4). In particular, the standard enthalpy of formation in the gas phase at 298.15 K of 1,4-anthraquinone was determined Δ f Hm o (g, 1) = - 4 4.9 ± 5.7 kJ mol - 1 ]. Using isodesmic/homodesmotic reaction schemes, we have experimentally estimated: (i) the stabilization energy of 1 (162.2 ± 7.2 kJ mol-1) and 2 (193.2 ± 5.2 kJ mol -1), (ii) strength of intramolecular hydrogen bonding in 3 (HB = 79.8 ± 10.8 kJ mol-1), and (iii) additional strain energy due to peri-oxygen interaction in 4 (-34.2 ± 7.6 kJ mol-1). A computational study of these species, at the B3LYP/6-311++G(3df,2p) level, sheds light on structural, aromatic, intrinsic strain, or hydrogen bond effects and further confirmed the consistency of the experimental results. © 2013 Springer Science+Business Media New York.

The energy of combustion of cyclododecanone has been determined using a static bomb calorimeter. The vapour pressure of the compound was measured over a temperature interval of 18 K, by the Knudsen-effusion technique. Heat capacity measurements betweenT= 270 K andT= 328 K were also carried out by d.s.c. From the experimental results of this work, the following standard molar enthalpies of combustion, sublimation, and formation for cyclododecanone in the crystalline and gaseous state at the temperature,T= 298.15 K have been derived: ΔfHmo(cr) = -(442.5 ± 3.1) kJ·mol-1; ΔsubHmo= -(83.2 ± 0.3) kJ·mol-1; and ΔfHmo(g) = -(359.3 ± 3.1) kJ·mol-1., The support of the Spanish DGICYT under Project PB93-0289-CO2-02 is gratefully acknowledged.

A series of novel 2,4-disubstituted-7-methyl-1,1,3-trioxo-2H,4H-pyrazolo[4,5-e][1,2,4]thiadiazines (PTDs) was prepared starting from a ring of pyrazolo[4,5-e][1,2,4]thiadiazine nuclei with two different alkyl halides obtained by a facile one-pot reaction. The structures of all synthesized compounds were confirmed by 1H- and 13C-NMR, infrared spectra (IR), and mass spectra (MS) spectroscopic analysis. Anti-HIV activity was evaluated and none of the compounds were found to inhibit HIV replication in human T-lymphocyte (MT-4) cell culture. ispartof: Drug discoveries & therapeutics vol:5 issue:6 pages:279-85 ispartof: location:Japan status: published

BACE1 activity, inhibition of Aβ aggregation, and disaggregation of preformed Aβ fibrils constitute the three major targets in the development of small-molecule lipophilic new drugs for the treatment of Alzheimer's disease (AD). Quinones are widely distributed among natural products and possess relevant and varied biological activities including antitumor and antibiotic, inhibition of HIV-1 reverse transcriptase, antidiabetic, or COX-inhibition, among others. We report herein the interaction of several arylquinones and their derivatives with the amyloidogenic pathway of the amyloid precursor protein processing. Our studies put forward that these compounds are promising candidates in the development of new drugs which are effective simultaneously towards the three major targets of AD.

[13991-08-7] C30H24P2 (MW 446.46) InChI = 1S/C30H24P2/c1-5-15-25(16-6-1)31(26-17-7-2-8-18-26)29-23-13-14-24-30(29)32(27-19-9-3-10-20-27)28-21-11-4-12-22-28/h1-24H InChIKey = NFRYVRNCDXULEX-UHFFFAOYSA-N (ligand for conjugate addition, conjugate reduction, cyclization, cross-coupling, carbonylation, and epoxidation reactions) Alternate Names: o-bis(diphenylphosphino)benzene, dppben, dppbenz, dppbe, dppBz, dppbz. Physical Data: mp 185–187°C,1 X-ray (triclinic system);2 1H-NMR: 7.39–7.17 (m, 20 H), 7.13–7.03 (m, 4 H) ppm;3 13C-NMR: 137.3, 134.1–134.0, 133.7, 129.0, 128.5–128.1 ppm.3 31P-NMR: −13.2 ppm;3 MS: 446, 369, 183.4 Solubility: sol in most organic solvents. Form Supplied in: white crystals; available from major chemical suppliers (Acros, Aldrich, Alfa Aesar, Strem Chemicals). Preparation: although commercially available at a moderate price, the reagent has been prepared by several methods. Typical methods use a o-dihalobenzenes that is converted into o-chlorophenyldiphenylphosphine.5 Changing to the bromo derivative increases the yield from 3% to 60%.1 Several alternatives and improvements have been reported over the years,6-9 but one of the best syntheses of the ligand was published by Stille (eq 1).3 (1) The synthesis starts with 2-bromoiodobenzene, which was phosphinated in 82% yield to afford 1. Sequential lithiation and further phosphination yielded dppben in 75% overall yield. This procedure has been applied to the preparation of ring-substituted phosphine ligands, which have been incorporated into silica gel for polymerization studies,10 and in homogeneous catalysis.11 Another concise synthesis of dppben takes advantage of a double displacement onto o-difluorobenzene with potassium diphenylphosphide in refluxing toluene affording dppben in 75% yield (eq 2).12 (2) Purification: commonly used as received, it can be recrystallized from several solvents (dichloromethane, ethanol–toluene, DMF). Commercial material can also be treated with potassium hydride followed by recrystallization (THF-pentane).13 Handling, Storage, and Precautions: the reagent is air stable and can be stored for a long time. However, diphenyl(trimethylsilyl)phosphine,3 used in one of the most efficient syntheses of dppben, has been reported as pyrophoric.14 Biological Activity: moderate cytotoxic activity of dppben and its gold(I) complexes against P388 leukemia cells and murine B16 melanoma cells in vitro.15

BACE1 activity, inhibition of Ab aggregation, and disaggregation of preformed Ab fibrils constitute the three major targets in the development of small-molecule lipophilic new drugs for the treatment of Alzheimer’s disease (AD). Quinones are widely distributed among natural products and possess relevant and varied biological activities including antitumor and antibiotic, inhibition of HIV-1 reverse transcriptase, antidiabetic, or COX-inhibition, among others. We report herein the interaction of several arylquinones and their derivatives with the amyloidogenic pathway of the amyloid precursor protein processing. Our studies put forward that these compounds are promising candidates in the development of new drugs which are effective simultaneously towards the three major targets of AD, Andrea Ortega (PhD fellow) thanks the government of Chile and the ‘Universidad Católica del Norte’ (Antofagasta, Chile) for a grant (MECESUP program, UCN0604). Projects CTQ2009-14124-C02-01, CTQ2010-16170 and SAF2009-10399 from the Spanish government are gratefully acknowledged for financial support

Mixed diesters, ω-amide and ω-thioesters are obtained from both N-Boc ethyl pyroglutamate and pyroaminoadipate under neutral or basic conditions. Under neutral conditions, the reaction is catalyzed by KCN and the use of Ultrasound speeds up the process. In basic conditions, reaction times are even shorter. In both cases, no transesterification of the α-ester was observed and the chirality of the α-amino acid was preserved.

The aim of this study is to find out whether several 1,4-naphthoquinones (1,4-NQ) can interact with the amyloidogenic pathway of the amyloid precursor protein processing, particularly targeting at β-secretase (BACE), as well as at β-amyloid peptide (Aβ) aggregation and disaggregating preformed Aβ fibrils. Compounds bearing hydroxyl groups at the quinoid (2) or benzenoid rings (5, 6) as well as some 2- and 3-aryl derivatives (11-15) showed BACE inhibitory activity, without effect on amyloid aggregation or disaggregation. The halogenated compounds 8 and 10 were selective for the inhibition of amyloid aggregation. On the other hand, 1,4-naphthoquinone (1), 6-hydroxy-1,4-naphthoquinone (4) and 2-(3,4-dichlorophenyl)-1,4-naphthoquinone (26) did not show any BACE inhibitory activity but were active on amyloid aggregation and disaggregation preformed Aβ fibrils. Juglone (5-hydroxy-1,4-naphthoquinone (3), and 3-(p-hydroxyphenyl)-5-methoxy-1,4-napththoquinone (19) were active on all the three targets. Therefore, we suggest that 1,4-NQ derivatives, specially 3 and 19, should be explored as possible drug candidates or lead compounds for the development of drugs to prevent amyloid aggregation and neurotoxicity in Alzheimer's disease.

The gas phase acidity and basicity of 2,2,2-trifluoroethanethiol (TFET), i.e., the standard Gibbs energy changes for the following two reactions have been determined by means of Fourier transform i...

1 Introduction 2 Energetics and Structure of Thiocarbonyl Compounds.Their Influence on Reactivity and Physical Properties 3 Syntheses 4 Chemical Properties of Thiocarbonyl Compounds 5 Coordination Chemistry 6 Acknowledgments Keywords: thiocarbonyl group; energetics and thiocarbonyl compound structure; photoelectron spectroscopy (PES); addition reactions to alkynes and alkenes; cycloreversion reactions; reductive C,S cleavage; desulfurization reactions; coordination chemistry

The NHC-catalyzed conjugate hydroacylation of 1,4-naphthoquinones allows for the synthesis of monoacylated 1,4-dihydroxynaphthalene derivatives. These targets, difficult to prepare selectively by standard protocols, represent important intermediates in the elaboration of highly substituted 1,4-naphthoquinone derivatives, which constitute relevant pharmaceutical scaffolds. High regioselectivity has been observed in the hydroacylation reaction when starting from nonsymmetrical quinones.

The first examples of the direct arylation of benzo-fused 1,4-quinones by the dicationic Pd(II)-catalyzed addition of arylboronic acids are reported. The addition reaction is carried out under very mild conditions (dioxane−H2O, rt, open air atmosphere) and is tolerant of free OH groups. In addition, the reaction shows high regioselectivity when using nonsymmetrical quinones as starting materials.

The NHC-catalyzed conjugate hydroacylation of 1,4-naphthoquinones allows for the synthesis of monoacylated 1,4-dihydroxynaphthalene derivatives. These targets, difficult to prepare selectively by standard protocols, represent important intermediates in the elaboration of highly substituted 1,4-naphthoquinone derivatives, which constitute relevant pharmaceutical scaffolds. High regioselectivity has been observed in the hydroacylation reaction when starting from nonsymmetrical quinones., Projects UCM-BSCH GR58/08-910815 and CTQ2006-15279-C03-01 (both to A.G.C), and SAF2006-04698 (to M.T.M.), are gratefully acknowledged for financial support.

Larvicidal (against Aedes aegypti Linnaeus, 1762) and molluscicidal (against Biomphalaria glabrata Say,1818) activities of several natural and synthetic naphthoquinoneswere measured, with significant results. The best larvicidal compound is 3-bromojuglone, while the better molluscicides are 2-bromo- and 3- bromo-5-acetoxy-1,4-naphthoquinones together with the 3-bromo-5-methoxy derivative. The present results reinforce the potential use of substituted hydroxyquinones, their salts and halogenated quinones as very promising compounds against 4th instar larves of Aedes aegypti, the vector of dengue and against adult snail of Biomphalaria glabrata., This work was supported by CNPq, RHAE/CNPq, Ministério da Saúde/Programa Dengue, CAPES and FAPEAL (Fundac¸ ão de Apoio à Pesquisa do Estado de Alagoas, Maceió, Al. Brazil), IMSEAR, BNB, RENORBIO, IM-INOFAR/CNPq, CSIC-CNPq (2005 BR0046, to M.T.M and M.O.F.G), DGICYT ((Spain, grants BQU2003- 00813 and SAF2006-04698 to M.T.M.), CSIC (for a I3P contract to E.L.-M.)

A series of novel 2,4-disubstituted 7-methyl-1,1,3-trioxo-2,4-dihydro-pyrazolo[4,5-e] [1,2,4]thiadiazines (PTDs) was synthesized, structurally confirmed by spectral analysis, and evaluated for their anti-HIV activities by inhibition of HIV-induced cytopathogenicity in MT-4 cell culture. The results showed that some compounds exhibited inhibitory activity specifically against HIV-2 replication. The most active HIV-2 inhibitor was compound 7i (R1 = benzyl, R2 = 4-t-butyl-benzyl) with an EC50 value of 18.7 microM and SI=15, which may provide a useful lead for further molecular optimization.

A series of novel 2,4-disubstituted 7-methyl-1,1,3-trioxo-2,4-dihydro-pyrazolo[4,5-e] [1,2,4]thiadiazines (PTDs) was synthesized, structurally confirmed by spectral analysis, and evaluated for their anti-HIV activities by inhibition of HIV-induced cytopathogenicity in MT-4 cell culture. The results showed that some compounds exhibited inhibitory activity specifically against HIV-2 replication. The most active HIV-2 inhibitor was compound 7i (R1 = benzyl, R2 = 4-t-butyl-benzyl) with an EC50 value of 18.7 microM and SI=15, which may provide a useful lead for further molecular optimization.