A novel and efficient approach to new N3-substituted-6,8-diaminopurines

[Excerpt] Purine nucleobases are fundamental biochemicals in living organisms. They have been a valuable inspiration for drug design once they play several key roles in the cell.1 To the best of our knowledge, reported routes to 8-aminopurines are still scarce due to the difficulty in introducing amino groups in this position of the purine ring. Here we report a novel, inexpensive and facile synthetic method to generate N3,N6-disubstituted-6,8-diaminopurines. In our research group, a number of substituted purines have been obtained from a common imidazole precursor, the 5-amino-4-cyanoformimidoyl imidazole 1. Recently, a comprehensive study on the reactivity of imidazoles 1 with nucleophiles under acidic conditions led us to develop experimental methods to incorporate primary amines into the cyanoformimidoyl group.2 (...)

A new and efficient synthesis of benzoimidazopurine derivatives

[Excerpt] Purine nucleobases are essential biomolecules in living organisms. Playing several key roles in the cell, they have been a significant inspiration for drug design.1 Benzimidazole nucleus is an important pharmacophore in the development of molecules with pharmaceutical or biological interest. Benzimidazoles have been reported to display significant pharmacological activities such as antiulcer, antifungal, antiparkinson, anticancer and antibiotic.2 Fused structures incorporating these two scaffolds might be important for medicinal chemistry and, to the best of our knowledge, there are no reports of these systems in the literature. In particular, benzo[4,5]imidazo[2,1]purines seem to be novel and must be important target molecules in the heterocyclic synthesis. (...)

The synthesis of novel 5-aminoimidazoles derivatives with anticancer activity

[Excerpt] The imidazole nucleus is present in a significant number of biomolecules and the inclusion of this moiety in organic scaffolds is considered an important synthetic strategy in drug discovery.[1] 5-Aminoimidazoles are interesting building blocks in medicinal chemistry since they are key components in many bioactive molecules and their derivatives showed a wide pharmacological potential as anticancer drugs.[1] The hydrazones constitute an important class of biological active drug molecules due to their wide range of pharmacological properties that include antitumoral activities.[2] Amidrazone derivatives could be considered very promising in the perspective of new drug discovery, because they are very effective as building blocks to obtain various heterocycles.[2,3] The α-hydrazononitriles are a special case of compounds belonging to the family of hydrazones that is less common in the literature, but has a great interest due to their pharmacological applications.[4] (...)

Electrosynthesis of heterocyclic compounds by radical cyclization in environmentally friendly media

We investigated the reductive intramolecular cyclization of bromopropargyl ethers derivatives, catalyzed by electrogenerated (1,4,8,11-tetramethyl-1,4,8,11-tetraaza-cyclotetradecane)nickel(I), [Ni(tmc)]+ as the catalysts in N,N,N-trimethyl-N-(2- hydroxyethyl)ammonium bis(trifluoromethylsulfonyl)imide,[N1 1 1 2(OH)][NTf2] and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C2mim][NTf2] by cyclic voltammetry and controlled-potential electrolysis. The results show that the reaction leads to the formation of the expected cyclic compounds, which are important intermediates in the synthesis of natural products with possible biological activities.

Search for flavour-changing neutral current top quark decays t → Hq in pp collisions at √s=8 TeV with the ATLAS detector

A search for flavour-changing neutral current decays of a top quark to an uptype quark (q = u, c) and the Standard Model Higgs boson, where the Higgs boson decays to bb¯¯, is presented. The analysis searches for top quark pair events in which one top quark decays to Wb, with the W boson decaying leptonically, and the other top quark decays to Hq. The search is based on pp collisions at s√=8 TeV recorded in 2012 with the ATLAS detector at the CERN Large Hadron Collider and uses an integrated luminosity of 20.3 fb−1. Data are analysed in the lepton-plus-jets final state, characterised by an isolated electron or muon and at least four jets. The search exploits the high multiplicity of b-quark jets characteristic of signal events, and employs a likelihood discriminant that uses the kinematic differences between the signal and the background, which is dominated by tt¯→WbWb decays. No significant excess of events above the background expectation is found, and observed (expected) 95% CL upper limits of 0.56% (0.42%) and 0.61% (0.64%) are derived for the t → Hc and t → Hu branching ratios respectively. The combination of this search with other ATLAS searches in the H → γγ and H → WW *, ττ decay modes significantly improves the sensitivity, yielding observed (expected) 95% CL upper limits on the t → Hc and t → Hu branching ratios of 0.46% (0.25%) and 0.45% (0.29%) respectively. The corresponding combined observed (expected) upper limits on the |λ tcH | and |λ tuH | couplings are 0.13 (0.10) and 0.13 (0.10) respectively. These are the most restrictive direct bounds on tqH interactions measured so far.

Analysis of events with b-jets and a pair of leptons of the same charge in pp collisions at √s=8 TeV with the ATLAS detector

An analysis is presented of events containing jets including at least one b-tagged jet, sizeable missing transverse momentum, and at least two leptons including a pair of the same electric charge, with the scalar sum of the jet and lepton transverse momenta being large. A data sample with an integrated luminosity of 20.3 fb−1 of pp collisions at s√=8 TeV recorded by the ATLAS detector at the Large Hadron Collider is used. Standard Model processes rarely produce these final states, but there are several models of physics beyond the Standard Model that predict an enhanced rate of production of such events; the ones considered here are production of vector-like quarks, enhanced four-top-quark production, pair production of chiral b′-quarks, and production of two positively charged top quarks. Eleven signal regions are defined; subsets of these regions are combined when searching for each class of models. In the three signal regions primarily sensitive to positively charged top quark pair production, the data yield is consistent with the background expectation. There are more data events than expected from background in the set of eight signal regions defined for searching for vector-like quarks and chiral b′-quarks, but the significance of the discrepancy is less than two standard deviations. The discrepancy reaches 2.5 standard deviations in the set of five signal regions defined for searching for four-top-quark production. The results are used to set 95% CL limits on various models.

Measurement of the t(t)over-barW and t(t)over-barZ production cross sections in pp collisions at root s=8 TeV with the ATLAS detector

The production cross sections of top-quark pairs in association with massive vector bosons have been measured using data from pp collisions at s√=8 TeV. The dataset corresponds to an integrated luminosity of 20.3 fb−1 collected by the ATLAS detector in 2012 at the LHC. Final states with two, three or four leptons are considered. A fit to the data considering the tt¯W and tt¯Z processes simultaneously yields a significance of 5.0σ (4.2σ) over the background-only hypothesis for tt¯W (tt¯Z) production. The measured cross sections are σtt¯W=369+100−91 fb and σtt¯Z=176+58−52 fb. The background-only hypothesis with neither tt¯W nor tt¯Z production is excluded at 7.1σ. All measurements are consistent with next-to-leading-order calculations for the tt¯W and tt¯Z processes.

A search for t(t)over-bar resonances using lepton-plus-jets events in proton-proton collisions at root s=8 TeV with the ATLAS detector

A search for new particles that decay into top quark pairs is reported. The search is performed with the ATLAS experiment at the LHC using an integrated luminosity of 20.3 fb−1 of proton-proton collision data collected at a centre-of-mass energy of s√=8 TeV. The lepton-plus-jets final state is used, where the top pair decays to W+bW−b¯¯, with one W boson decaying leptonically and the other hadronically. The invariant mass spectrum of top quark pairs is examined for local excesses or deficits that are inconsistent with the Standard Model predictions. No evidence for a top quark pair resonance is found, and 95% confidence-level limits on the production rate are determined for massive states in benchmark models. The upper limits on the cross-section times branching ratio of a narrow Z′ boson decaying to top pairs range from 4.2 pb to 0.03 pb for resonance masses from 0.4 TeV to 3.0 TeV. A narrow leptophobic topcolour Z′ boson with mass below 1.8 TeV is excluded. Upper limits are set on the cross-section times branching ratio for a broad colour-octet resonance with Γ/m = 15% decaying to tt¯. These range from 4.8 pb to 0.03 pb for masses from 0.4 TeV to 3.0 TeV. A Kaluza-Klein excitation of the gluon in a Randall-Sundrum model is excluded for masses below 2.2 TeV.

Summary of the searches for squarks and gluinos using root s=8 TeV pp collisions with the ATLAS experiment at the LHC

A summary is presented of ATLAS searches for gluinos and first- and second-generation squarks in final states containing jets and missing transverse momentum, with or without leptons or b-jets, in the s√=8 TeV data set collected at the Large Hadron Collider in 2012. This paper reports the results of new interpretations and statistical combinations of previously published analyses, as well as a new analysis. Since no significant excess of events over the Standard Model expectation is observed, the data are used to set limits in a variety of models. In all the considered simplified models that assume R-parity conservation, the limit on the gluino mass exceeds 1150 GeV at 95% confidence level, for an LSP mass smaller than 100 GeV. Furthermore, exclusion limits are set for left-handed squarks in a phenomenological MSSM model, a minimal Supergravity/Constrained MSSM model, R-parity-violation scenarios, a minimal gauge-mediated supersymmetry breaking model, a natural gauge mediation model, a non-universal Higgs mass model with gaugino mediation and a minimal model of universal extra dimensions.

Measurement of colour flow with the jet pull angle in t(t)over-bar events using the ATLAS detector at root s=8 TeV

The distribution and orientation of energy inside jets is predicted to be an experimental handle on colour connections between the hard--scatter quarks and gluons initiating the jets. This Letter presents a measurement of the distribution of one such variable, the jet pull angle. The pull angle is measured for jets produced in tt¯ events with one W boson decaying leptonically and the other decaying to jets using 20.3 fb−1 of data recorded with the ATLAS detector at a centre--of--mass energy of s√=8 TeV at the LHC. The jet pull angle distribution is corrected for detector resolution and acceptance effects and is compared to various models.

Search for metastable heavy charged particles with large ionisation energy loss in pp collisions at root s=8 TeV using the ATLAS experiment

Many extensions of the Standard Model predict the existence of charged heavy long-lived particles, such as R-hadrons or charginos. These particles, if produced at the Large Hadron Collider, should be moving non-relativistically and are therefore identifiable through the measurement of an anomalously large specific energy loss in the ATLAS pixel detector. Measuring heavy long-lived particles through their track parameters in the vicinity of the interaction vertex provides sensitivity to metastable particles with lifetimes from 0.6 ns to 30 ns. A search for such particles with the ATLAS detector at the Large Hadron Collider is presented, based on a data sample corresponding to an integrated luminosity of 18.4 fb−1 of pp collisions at s√ = 8 TeV. No significant deviation from the Standard Model background expectation is observed, and lifetime-dependent upper limits on R-hadrons and chargino production are set. Gluino R-hadrons with 10 ns lifetime and masses up to 1185 GeV are excluded at 95% confidence level, and so are charginos with 15 ns lifetime and masses up to 482 GeV.

Search for photonic signatures of gauge-mediated supersymmetry in 8 TeV pp collisions with the ATLAS detector

A search is presented for photonic signatures motivated by generalised models of gauge-mediated supersymmetry breaking. This search makes use of 20.3 fb−1 of proton-proton collision data at s√=8 TeV recorded by the ATLAS detector at the LHC, and explores models dominated by both strong and electroweak production of supersymmetric partner states. Four experimental signatures incorporating an isolated photon and significant missing transverse momentum are explored. These signatures include events with an additional photon, lepton, b-quark jet, or jet activity not associated with any specific underlying quark flavor. No significant excess of events is observed above the Standard Model prediction and model-dependent 95% confidence-level exclusion limits are set.

Search for Dark Matter in Events with Missing Transverse Momentum and a Higgs Boson Decaying to Two Photons in pp Collisions at root s=8 TeV with the ATLAS Detector

Results of a search for new phenomena in events with large missing transverse momentum and a Higgs boson decaying to two photons are reported. Data from proton--proton collisions at a center-of-mass energy of 8 TeV and corresponding to an integrated luminosity of 20.3 fb−1 have been collected with the ATLAS detector at the LHC. The observed data are well described by the expected Standard Model backgrounds. Upper limits on the cross section of events with large missing transverse momentum and a Higgs boson candidate are also placed. Exclusion limits are presented for models of physics beyond the Standard Model featuring dark-matter candidates.

The contribution of phenolic acids to the anti-inflammatory activity of mushrooms: Screening in phenolic extracts, individual parent molecules and synthesized glucuronated and methylated derivatives

In the present study, the ethanolic extracts of fourteen edible mushrooms were investigated for their anti-inflammatory potential in LPS (lipopolysaccharide) activated RAW 264.7 macrophages. Furthermore the extracts were chemically characterized in terms of phenolic acids and related compounds. The identified molecules (p-hydroxybenzoic, p-coumaric and cinnamic acids) and their glucuronated and methylated derivatives obtained by chemical synthesis were also evaluated for the same bioactivity, in order to establish structure-activity relationships and to comprehend the effects of in vivo metabolism reactions in the activity of the compounds. The extracts of Pleurotus ostreatus, Macrolepiota procera, Boletus impolitus and Agaricus bisporus revealed the strongest anti-inflammatory potential (EC50 values 96 ± 1 to 190 ± 6 µg/mL, and also the highest concentration of cinnamic acid (656 to 156 µg/g), which was also the individual compound with the highest anti-inflammatory activity. The derivatives of p-coumaric acid revealed the strongest properties, specially the derivative methylated in the carboxylic group (CoA-M1) that exhibited similar activity to the one showed by dexamethaxone used as anti-inflammatory standard; by contrast, the derivatives of p-hydroxybenzoic revealed the lowest inhibition of NO production. All in all, whereas the conjugation reactions change the chemical structure of phenolic acids and may increase or decrease their activity, the glucuronated and methylated derivatives of the studied compounds are still displaying anti-inflammatory activity.

Síntese de derivados de adenina e guanina

Tese de Doutoramento em Ciências (Especialidade em Química)