Biolixivia??o de sulfetos secund?rios de cobre por micro?organismos mes?filos em diferentes reatores agitados.

Programa de P?s-Gradua??o em Engenharia de Materiais. Departamento de Engenharia Metal?rgica, Escola de Minas, Universidade Federal de Ouro Preto.A biolixivia??o de cobre a partir de sulfetos secund?rios, tais como a calcocita e a bornita, ? amplamente aplicada industrialmente em v?rios pa?ses do mundo. Isso ocorre porque esses sulfetos s?o facilmente oxidados pelo ?on Fe3+ produzido por microorganismos de biolixivia??o. No entanto, a biolixivia??o pode ser severamente impactada se o min?rio portar impurezas sol?veis que podem afetar o crescimento bacteriano. Este ? o caso do fluoreto, que existe como HF nas condi??es ?cidas aplicadas na biolixivia??o de metais b?sicos. Este ?ltimo pode atravessar membranas celulares e dissociar dentro da c?lula (por causa de seu pH neutro), reduzindo o crescimento bacteriano. Nesta disserta??o foi investigada a influ?ncia da concentra??o de fl?or sobre o crescimento de Acidithiobacillus ferrooxidans e revelou que 20 mg.L?1 F?total inibiram a biooxida??o do ?on Fe2+. Tal inibi??o foi superada por adi??o de sulfato de alum?nio ao meio de crescimento. Em seguida, foi estudada a biolixivia??o de um min?rio de cobre secund?rio portador de fl?or (contendo calcocita e bornita) pela cultura mes?fila. Os efeitos do pH bem como as concentra??es de Fe2+, Al3+ e Mg2+ na extra??o de cobre foram determinados, os experimentos foram realizados em frascos Erlenmeyer (250 mL) contendo 100 mL de solu??o e porcentagem de s?lidos a 5% (p/v) agitada a 150 min?1. A cin?tica de lixivia??o da amostra foi ligeiramente afetada pelo pH e concentra??es do ?on Fe2+, sendo que as maiores extra??es de cobre foram observadas para pH 1,6?1,8 e 5?10 g.L?1 Fe2+. As concentra??es de alum?nio (at? 5 g.L?1) melhoraram a cin?tica de extra??o do cobre ? medida que os ?ons fluoreto foram complexados pelo elemento e a extra??o final de cobre atingiu 75%. Al?m disso, propondo uma adapta??o ao programa de ensaios metal?rgicos visando uma futura aplica??o industrial de lixivia??o em pilhas, especificamente em sistemas agitados, a segunda parte da disserta??o buscou comparar o perfil de lixivia??o de tr?s diferentes reatores (frascos Erlenmeyer, garrafas rotativas e um biorreator agitado mecanicamente) durante a biolixivia??o de duas amostras de sulfetos secund?rios com diferentes teores de cobre e fl?or. Na aus?ncia de uma fonte externa de alum?nio, os ensaios em Erlenmeyer n?o mostraram qualquer aumento no potencial da solu??o, independentemente da amostra de min?rio estudada. Concentra??es de fl?or e alum?nio em torno de 300 mg.L?1 foram registradas neste reator e a raz?o Al/F em torno de 1 explicou o baixo potencial registrado. Por outro lado, nos ensaios em garrafa e biorreator, a amostra de min?rio com menor teor de cobre produziu alum?nio (530 mg.L?1) acima das concentra??es de fl?or (380 mg.L?1), de modo que esse maior ?ndice Al/F estimulou o crescimento bacteriano. Isto se justificou, pelo fato do potencial da solu??o ter atingido valores acima de 600 mV ao final do experimento, o que indicou o crescimento bacteriano nesses reatores. Quando o alum?nio foi adicionado ao meio de crescimento, o potencial da solu??o aumentou exponencialmente, indicando boa atividade de biolixivia??o e at? 97% de extra??o de cobre foi observada nos tr?s reatores, mas as garrafas rotativas apresentaram uma cin?tica de lixivia??o mais r?pida devido a altas popula??es bacterianas (> 108 c?lulas. mL?1) proporcionada por uma melhor aera??o da solu??o (6 mg.L?1 como a concentra??o de oxig?nio dissolvido).Copper bioleaching from secondary sulphides such as chalcocite and bornite is widely applied industrially in several countries worldwide. This is because these sulphides are easily oxidized by the ferric iron produced by bioleaching microorganisms. Notwithstanding, bioleaching can be severely hampered if the ore contains soluble impurities which can affect bacterial growth. This is the case of fluoride, which exists as HF in the acid conditions applied in the bioleaching of base metals. The latter can cross cell membranes and dissociate inside the cell (because of its neutral pH) reducing the bacterial growth. The current dissertation investigated initially the fluoride concentration which impaired the growth of At. ferrooxidans and revealed that 20 mg.L? 1 Ftot inhibited ferrous iron bio?oxidation. Such inhibition was overcome by aluminium sulphate supplementation to the growth medium. Subsequently the bioleaching of a fluoride?bearing secondary copper ore (containing chalcocite and bornite) by the mesophile culture was studied. The effects of pH as well as the concentrations of Fe2+, Al3+ and Mg2+ on copper extraction were determined in experiments were performed in Erlenmeyer flasks (250 mL) containing 100 mL of a 5% (w/v) pulp stirred at 150 min?1. The leaching kinetics of the sample was slightly affected by both pH and ferrous iron concentrations and the largest copper extractions were observed for pH 1.6?1.8 and 5? 10 g.L?1 Fe2+. Aluminium concentrations (up to 5 g.L?1) improved the copper extraction kinetics as fluoride ions were complexed by the element and the final copper extraction reached 75%. In addition, the metallurgical testwork proposed in feasibility studies for leaching projects comprise different type of reactor experiments such as rolling bottles whereas shaking flasks tests are of widespread use in academic research. Therefore the second part of the current dissertation sought to compare the leaching profile of three different reactors (Erlenmeyer flasks, rolling bottles and a mechanically stirred bioreactor) during bioleaching of two samples of the secondary sulphide ore with different copper and fluoride content. In the absence of an external aluminium source, the shaking flask experiments did not show any increase in the solution potential, regardless of the ore sample studied. Fluoride and aluminium concentrations around 300 mg.L?1 were recorded in this reactor and the Al/F ratio around 1 explained the low potential recorded. Conversely, the ore sample with the lower fluoride content produced aluminium (530 mg.L?1) above fluoride (380 mg.L?1) concentrations so that such higher Al/F ratio fostered bacterial growth. This justified the solution potential attaining values above 600 mV by the end of the experiment, which indicated bacterial growth in that reactor. When aluminium was added to the growth medium the solution potential increases exponentially indicating good bioleaching activity and up to 97% copper extraction was observed in the three reactors, but the rolling bottles depicted a faster leaching kinetics due to high bacterial populations (>108 cells.mL?1) provided by a better aeration of the solution (6 mg.L?1 as the dissolved oxygen concentration)

Improving selectivity preserving affinity: New piperidine-4-carboxamide derivatives as effective sigma-1-ligands

We report the design, synthesis and binding evaluation against \u3c31 and \u3c32 receptors of a series of new piperidine-4-carboxamide derivatives variously substituted on the amide nitrogen atom. Specifically, we assessed the effects exerted on \u3c3 receptor affinity by substituting the N-benzylcarboxamide group present on a series of compounds previously synthesized in our laboratory with different cyclic or linear moieties. The synthesized compounds 2a-o were tested to estimate their affinity and selectivity toward \u3c31 and \u3c32 receptors. Very high \u3c31 affinity (Ki\ua0=\ua03.7\ua0nM) and Ki\u3c32/Ki\u3c31 selectivity ratio (351) were found for the tetrahydroquinoline derivative 2k, featuring a 4-chlorobenzyl moiety linked to the piperidine nitrogen atom

Computer-assisted design, synthesis, binding and cytotoxicity assessments of new 1-(4-(aryl(methyl)amino)butyl)-heterocyclic sigma 1 ligands

In this work we applied a blend of computational and synthetic techniques with the aim to design, synthesize, and characterize new \u3c31 receptor (\u3c31R) ligands. Starting from the structure of previously reported, high-affinity benzoxazolone-based \u3c31 ligands, the threedimensional homology model of the \u3c31R was exploited for retrieving the molecular determinants to fulfill the optimal pharmacophore requirements. Accordingly, the benzoxazolone moiety was replaced by other heterocyclic scaffolds, the relevant conformational space in the \u3c31R binding cavity was explored, and the effect on \u3c31R binding affinity was ultimately assessed. Next, the compounds designed in silico were synthesized, and their affinity and selectivity toward \u3c31 and \u3c32 receptors were tested. Finally, a representative series of best \u3c31R binders were assayed for cytotoxic activity on the SH-SY5Y human neuroblastoma cell line. Specifically, the new 4-phenyloxazolidin-2-one derivatives 2b (i.e., (R)-2b and (S)-2b) emerged as potential leads for further development as \u3c31R agents, as they were found endowed with the highest \u3c31R affinity (Ki\u3c31 values in the range 0.95-9.3 nM), and showed minimal cytotoxic levels exhibited in the selected, cell-based test, in line with a \u3c31R agonist behavior

Biolixiviation of secondary copper sulphates by Acidithiobacillus ferrooxidans.

Neste trabalho, foi investigada a biolixivia??o de sulfetos secund?rios de cobre com Acidithiobacillus ferrooxidans. O efeito dos par?metros pH, concentra??o dos c?tions Fe2+, Al3+ e Mg2+, sob a extra??o de cobre foram avaliados. Os experimentos em frascos agitados mostraram elevadas recupera??es de cobre pr?ximas a 75%. A cin?tica de extra??o do metal foi afetada pelo pH e concentra??o de Fe2+ e os valores ideais foram 1,6-1,8 e 5-10 g.L-1, respectivamente. A adi??o de fontes externas de alum?nio (at? 5 g.L-1) favoreceu a biolixivia??o devido ? complexa??o do ?on fluoreto liberado durante a dissolu??o do mineral.This work investigated the bioleaching of secondary copper ores (chalcocite and bornite) by a mesophile culture comprised mostly of Acidithiobacillus ferrooxidans. O efeito dos par?metros pH, concentra??o dos c?tions Fe2+, Al3+ e Mg2+, sob a. Experiments were performed in Erlenmeyer flasks (250 mL) containing 100 mL of a 5% (w/v) pulp stirred at 150 min-1. The effects of pH, Fe2+, Al3+ and Mg2+ concentrations on copper extraction were determined. The leaching kinetics from the marginal ore was slightly affected by both pH and ferrous iron concentrations and the largest leaching rates were observed at pH 1,6-1,8 and 5-10 g.L-1 Fe2+. Aluminum concentrations (up to 5 g.L-1) improved the copper extraction kinetics as fluoride ions were complexed by the element and the final copper extraction reached 75%

Synthesis and receptor binding studies of some new arylcarboxamide derivatives as sigma-1 ligands

We describe here the synthesis and the binding interaction with simga1 and sigma2 receptors of a series of new arylcarboxamide derivatives variously substituted on the aromatic portions. Maintaining a partial scaffold of a series of compounds previously synthesized by us, we evaluate the effect of the substitution on sigma binding. The synthesized compounds have been tested to estimate their affinity and selectivity toward sigma1 and sigma2 receptors. Two out of 16 derivatives showed an interesting sigma1 affinity (21.2 and 13.6 nM - compounds 2m and 2p) and a good selectivity (Ki(sigma2) / Ki(sigma1) >140 and >40 respectively)

Additional file 2: Figure S1. of Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis

Comparative effect in hematologic toxicities of chemotherapy with bevacizumab versus chemotherapy alone. (PDF 503 kb

Substituted benzylaminoalkylindoles with preference for the \u3c32 binding site

In the attempt to develop new s ligands we synthesized a series of N-benzyl-3-[1-(4-fluorophenyl)-1H-indol-3-yl]-N-methylpropan-1-amines and N-benzyl-4-[1-(4-fluorophenyl)-1H-indol-3-yl]-N-methylbutan-1-amines variously substituted on the phenyl ring. The displacement percentages of [3H]-DTG and [3H]-(\ufe)-pentazocine determined in rat liver omogenates by these compounds at the fixed 100 nM concentration have been determined as a preliminary evaluation of their s1 and s2 affinity, respectively. The results suggested that the phenyl substituents may positively modulate, in comparison with the unsubstituted compound, the ability to displace [3H]-DTG from s2 sites, whereas the same phenyl substituents reduced the displacement percentages of [3H]-(\ufe)-pentazocine from s1 sites. Some of these compounds were selected for radioligand binding assays. Compounds with a butylene intermediate chain displayed the greatest binding affinity for s2 over s1 receptors. The butylene derivative with 2,4-dimethyl substitution on the phenyl ring showed the greatest s2 affinity (s2Ki \ubc 5.9 nM) and an appreciable s2 over s1 selectivity (s1Ki/s2Ki \ubc 22). The obtained results suggest that a butylene chain separating the indole moiety from variously substituted benzylamino groups may be required to their interaction with a hypothetical secondary s2 binding site