Synthesis, Mechanism Elucidation and Biological Insights of Tellurium(IV)-Containing Heterocycles.

Inspired by the synthetic and biological potential of organotellurium substances, a series of five- and six-membered ring organotelluranes containing a Te-O bond were synthesized and characterized. Theoretical calculations elucidated the mechanism for the oxidation-cyclization processes involved in the formation of the heterocycles, consistent with chlorine transfer to hydroxy telluride, followed by a cyclization step with simultaneous formation of the new Te-O bond and deprotonation of the OH group. Moreover, theoretical calculations also indicated anti-diastereoisomers to be major products for two chirality center-containing compounds. Antileishmanial assays against Leishmania amazonensis promastigotes disclosed 1,2λ4 -oxatellurane LQ50 (IC50 =4.1±1.0; SI=12), 1,2λ4 -oxatellurolane LQ04 (IC50 =7.0±1.3; SI=7) and 1,2λ4 -benzoxatellurole LQ56 (IC50 =5.7±0.3; SI=6) as more powerful and more selective compounds than the reference, being up to four times more active. A stability study supported by 125 Te NMR analyses showed that these heterocycles do not suffer structural modifications in aqueous-organic media or at temperatures up to 65 °C.

Competitive Reactivity of Tautomers in the Degradation of Organophosphates by Imidazole Derivatives.

The harmful impact caused by pesticides on human health and the environment necessitates the development of efficient degradation processes and control of prohibited stocks of such substances. Organophosphates (OPs) are among the most used agrochemicals in the world and their degradation can proceed through several possible pathways. Investigating the reactivity of OPs with nucleophilic species allows one to propose new and efficient catalyst scaffolds for use in detoxification. In light of the remarkable catalytic activity of imidazole (IMZ) at promoting dephosphorylation processes of OPs, the reactivity of 4(5)-hydroxymethylimidazole (HMZ) with diethyl-2,4-dinitrophenylphosphate (DEDNPP) and Paraoxon are evaluated by combining experimental and theoretical approaches. It is observed that HMZ is an efficient and regiospecific catalyst with reactivity modulated by competing tautomers. To propose an optimal IMZ-based catalyst, quantum chemical calculations were performed for monosubstituted 4(5)IMZ derivatives that might cleave DEDNPP. Both inductive effects and hydrogen bonding by the substituents are shown to influence barriers and mechanisms.

Puzzling Reaction of Imidazole with Methyl Parathion: P=S versus P=O Mechanistic Shift Dilemma in Organophosphates.

Organophosphates (OPs) constitute many toxic agrochemicals and warfare and can undergo a wide spectrum of mechanisms, some which are fairly unexplored. In this sense, concise mechanistic elucidation stands out as a strategic tool for achieving efficient detoxification and for monitoring processes. Particularly intriguing is the effect of substituting the oxygen atom of the phosphoryl moiety (P=O) in OPs with a sulfur atom to give the thio-derived OPs (i.e., OTPs, P=S). In general, imidazole (IMZ) reacts very efficiently with OPs by targeting the phosphorus atom, although herein we evidence a thio-driven shift with OTPs: IMZ undergoes unusual nucleophilic attack at the aliphatic carbon atom of methyl parathion. Alkylation of IMZ under mild conditions (aqueous weakly basic medium) is also novel and should be applicable to other novel IMZ-based architectures, and thereby, it can be a great ally for organic synthesis. Overall, a broader understanding of the mechanistic trend involved in such highly toxic agents is provided.

Synthesis, Antioxidant Activity and Cytotoxicity of N-Functionalized Organotellurides.

The use of antioxidants is the most effective means to protect the organism against cellular damage caused by oxidative stress. In this context, organotellurides have been described as promising antioxidant agents for decades. Herein, a series of N-functionalized organotellurium compounds has been tested as antioxidant and presented remarkable activities by three different in vitro chemical assays. They were able to reduce DPPH radical with IC50 values ranging from 5.08 to 19.20 µg mL-1, and some of them also reduced ABTS+ radical and TPTZ-Fe3+ complex in ABTS+ and FRAP assays, respectively. Initial structure-activity relationship discloses that the nature of N-substituent strongly influenced both activity and cytotoxicity of the studied compounds. Furthermore, radical scavenging activities of N-functionalized organotellurides have been compared with those of their selenilated congeners, demonstrating that the presence of tellurium atom has an essential role in antioxidant activity.

Investigation of Chemical Stability of Dihalogenated Organotelluranes in Organic-Aqueous Media: The Protagonism of Water.

The biological activity of tellurium compounds is closely related to the tellurium oxidation state or some of their structural features. Hypervalent dihalogenated organotelluranes 1-[butyl(dichloro)-λ4-tellanyl]-2-(methoxymethyl)benzene (1a) and 1-[butyl(dibromide)-λ4-tellanyl]-2-(methoxymethyl)benzene (1b) have been described as inhibitors of proteases (cysteine and threonine) and tyrosine phosphatases. However, poor attention has been given to their physicochemical properties. Here, a detailed investigation of the stability in water of these organotelluranes is reported using 125Te NMR analysis. Dihalogenated organotelluranes 1a and 1b were both stable in DMSO- d6 (from 25 to 75 °C), demonstrating their thermal stability. However, the addition of a phosphate buffer solution (pH 2-8) to 1a or 1b resulted in an immediate conversion to a new Te species, assumed to be the corresponding telluroxide. Similar behavior was observed in pure water, demonstrating the low chemical stability of these dihalogenated species in the presence of water. These results allow concluding that previous biological activity reported for dihalogenated organotelluranes 1a and 1b could be attributed to the corresponding derivatives from the reaction with water. In the same way as for AS-101, we demonstrated that organotelluranes 1a and 1b are not stable in aqueous solution. It suggests a proactive role of these organotelluranes in previously reported biological activity.

Reactivity of Imidazole Derivatives toward Phosphate Triester in DMSO/Water Mixtures: A Comprehensive Study on the Solvent Effect.

Many imidazole (IMZ) derivatives of pharmaceutical interest, which are potentially catalytic in dephosphorylation reactions, are soluble solely in mixtures of water and organic solvent. In order to understand these poorly explored reactions and properly compare them, a thorough study related to solvent effects for the analogous spontaneous reaction and with common IMZ derivatives is necessary, which is lacking in the literature. Herein, we report a quantitative solvent effect analysis in DMSO/water mixtures for (i) the hydrolysis reaction of diethyl 2,4-dinitrophenylphosphate (DEDNPP) and (ii) the nucleophilic reaction of IMZ and 1-methylimidazole (MEI) with DEDNPP. The solvent effect was fitted satisfactorily with multiple regression analysis, correlating the obtained second-order rate constants with solvent parameters such as acidity, basicity, and polarity/polarizability from Catalán's scale. The contribution of these parameters can be taken into account to elucidate the reactivity in these media. Interestingly, IMZ is more reactive than MEI in DMSO, compared to water alone, which is attributed to the availability of hydrogen-bond formation. Nuclear magnetic resonance spectroscopy ((1)H, (13)C, and (31)P), mass spectrometry, thermodynamic analysis, and density functional theory calculations were carried out to corroborate the proposed nucleophilic mechanism.

Biosynthesis and site of production of sex pheromone components of the cerambycid beetle, Hedypathes betulinus.

We determined the site of pheromone production tissues and a partial route for the biosynthesis of the sex pheromone in Hedypathes betulinus (Coleoptera: Cerambycidae: Lamiinae), Brazil's main green maté pest. Pheromone was found predominantly in the prothorax of males, suggesting that this is the region of production of pheromones in this insect. Scanning electron microscopy revealed small pores that may be associated with pheromone release in males; these pores also were observed in females. A deuterium-labeled putative precursor (geranyl acetone-D5) of the sex pheromone of H. betulinus was synthesized. When applied to the prothorax of males, label from the precursor was incorporated into the pheromone components, confirming that pheromone production occurs in the prothorax and that the pheromone components are biosynthesized from geranyl acetone.

4,4-Dimethyl-2-[3-nitro-2-phenyl-1-(phenyl-sulfan-yl)prop-yl]-4,5-dihydro-1,3-oxazole.

In the title compound, C(20)H(22)N(2)O(3)S, the oxazoline ring is planar (r.m.s. deviation = 0.045 Å) and forms dihedral angles of 47.24 (8) and 10.11 (8)° with the S- and C-bound phenyl rings, respectively. The nitro group lies to the same side of the mol-ecule as the oxazoline ring but is orientated so as not to inter-act with the ring. Linear supra-molecular chains along [010] are formed via C-H⋯O and C-H⋯S contacts. Chains are consolidated into a three-dimensional architecture by C-H⋯π and van der Waals inter-actions.

Diacetal Ditellurides as Highly Active and Selective Antiparasitic Agents toward Leishmania amazonensis.

Leishmaniasis is a neglected tropical disease and a public health concern in at least 98 countries, affecting mainly the poorest populations. Pharmaceuticals and chemotherapies available for leishmaniasis treatment have several limitations, which clearly justify the efforts to find new potential antileishmanial drugs. In this context, antiprotozoal activities toward different Leishmania species have been reported for hypervalent tellurium compounds, which motivated us to investigate, for the first time, the leishmanicidal properties of some nonhypervalent diaryl ditellurides. Thus, this work describes in vitro activity against Leishmania amazonensis and the cytotoxicities of diaryl ditellurides. Ditelluride LQ7 revealed a strong leishmanicidal activity on promastigotes and amastigotes at submicromolar levels (IC50 = 0.9 ± 0.1 and 0.5 ± 0.1 µmol L-1, respectively) and presented selectivity indexes greater than those of reference drug miltefosine. This preliminary study suggests that diaryl ditellurides may be promising scaffolds for the development of new agents for leishmaniasis treatment.

Facile room temperature synthesis of large graphene sheets from simple molecules.

The largest graphene sample obtained through a chemical reaction under ambient conditions (temperature and pressure), using simple molecules such as benzene or n-hexane as precursors, is reported. Starting from a heterogeneous reaction between solid iron chloride and the molecular precursor (benzene and n-hexane) at a water/oil interface, graphene sheets with micrometric lateral size are obtained as a film deposited at the liquid/liquid (L/L) interface. The pathway involving the cyclization and aromatization of n-hexane to benzene at the L/L interface, and the sequence of conversion of benzene to biphenyl and biphenyl to condensed rings (which originates the graphene structures) was followed by different characterization techniques and a mechanistic proposal is presented. Finally, we demonstrate that this route can be extended for the synthesis of N-doped graphene, using pyridine as the molecular precursor.

Males Are Attracted by Female Traps: A New Perspective for Management of Diabrotica speciosa (Germar) (Coleoptera: Chrysomelidae) Using Sexual Pheromone / Machos são Atraídos por Armadilhas com Fêmeas: Uma Nova Perspectiva para Manejo de Diabrotica speciosa (Germar) (Coleoptera: Chrysomelidae) Usando Feromônio Sexual

As respostas de Diabrotica speciosa (Germar) para armadilhas com adultos foram estudadas como sugestão da produção de feromônio. Inicialmente, um ensaio para estabelecer a altura adequada para colocação de armadilhas para capturar D. speciosa foi conduzido em campo de feijão. Armadilhas colocadas a 0,25 m de altura capturaram cerca de 3,5 vezes mais adultos do que a 0,5; 0,75 e 1,0 m. As respostas para fêmeas e machos virgens de duas idades (mais novos = 24 a 72h e mais velhos = 72 a 120h após emergência de adultos), fêmeas e machos copulados foram avaliadas em campo de feijão consorciado com café, Coffea arabica L. Armadilhas com fêmeas virgens capturaram cerca de 22 (mais jovens) e 13 vezes (mais velhas) mais adultos machos do que as testemunhas (armadilhas sem insetos). Capturas foram cerca de 70 por cento mais efetivas usando fêmeas mais jovens. Nenhum dos outros tratamentos aumentou as capturas nas armadilhas. Os resultados indicam que há um feromônio sexual produzido por fêmeas em D. speciosa.

The field responses of Diabrotica speciosa (Germar) to traps baited with adults were studied as an suggestion of the pheromone production. Firstly, an assay to settle a suitable height placement to capture D. speciosa was carried out in common beans, Phaseolus vulgaris L., field. Traps placed at 0.25-m height captured ca. 3.5 times more beetles than 0.5, 0.75 and 1.0-m traps. The responses to virgin females and males of two ages (younger = 24 to 72h and older = 72 to 120h after adult emergence), mated females and males were assessed in common bean interplanted among coffee, Coffea arabica L., field. Virgin females baited traps captured ca. 22 times (younger) and 13 times (older females) more male beetles than control traps. Captures were ca. 70 percent more effective using younger females. None of the other treatments improved trap attraction. These results strongly indicated that there is a female-produced sexual pheromone in D. speciosa.