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The spread of infections from multi-resistant bacteria in hospitals around the world is raising at an alarming rate. With the increasing capacity of bacteria to develop resistance to traditional antibiotics that target a particular metabolic pathway inside the cell, the use of nanoparticles as therapeutic agents is gaining importance because of their ability to attack bacterial membranes without evoking resistance. We have synthesized the catanionic surfactants Coum12–Coum18, based on fluorescent lactose-derivative organic salts using low-cost starting materials. In water, they self-assemble spontaneously to form stable aggregates at a physiological pH. The antibacterial properties of Coum12–Coum18 were investigated towards multi-drug-resistant Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Compound Coum18 was found to have both a bacteriostatic and a bactericidal activity towards Gram-positive bacteria, although the values of both the MIC and MBC (32 μg mL−1) suggest only a topical use of the molecule. The valuable results that were found provide a challenging task for further investigation aimed at the development of this class of antibacterial drugs. In vitro fluorescence microscopy gave insight into the interaction between the aggregates and the cellular membranes on HeLa and CHO cells.

In this work, a multi-technical bulk and surface analytical approach was used to investigate the bioleaching of a pyrite and arsenopyrite flotation concentrate with a mixed microflora mainly consisting of Acidithiobacillus ferrooxidans. X-ray diffraction, X-ray photoelectron spectroscopy (XPS) and X-ray-induced Auger electron spectroscopy mineral surfaces investigations, along with inductively coupled plasma-atomic emission spectroscopy and carbon, hydrogen, nitrogen and sulphur determination (CHNS) analyses, were carried out prior and after bioleaching. The flotation concentrate was a mixture of pyrite (FeS(2)) and arsenopyrite (FeAsS); after bioleaching, 95% of the initial content of pyrite and 85% of arsenopyrite were dissolved. The chemical state of the main elements (Fe, As and S) at the surface of the bioreactor feed particles and of the residue after bioleaching was investigated by X-ray photoelectron and X-ray excited Auger electron spectroscopy. After bioleaching, no signals of iron, arsenic and sulphur originating from pyrite and arsenopyrite were detected, confirming a strong oxidation and the dissolution of the particles. On the surfaces of the mineral residue particles, elemental sulphur as reaction intermediate of the leaching process and precipitated secondary phases (Fe-OOH and jarosite), together with adsorbed arsenates, was detected. Evidence of microbial cells adhesion at mineral surfaces was also produced: carbon and nitrogen were revealed by CHNS, and nitrogen was also detected on the bioleached surfaces by XPS. This was attributed to the deposition, on the mineral surfaces, of the remnants of a bio-film consisting of an extra-cellular polymer layer that had favoured the bacterial action.

In this work, the microbe-mediated oxidative dissolution of enargite surfaces (Cu(3)AsS(4)) was studied on powdered samples exposed to 9K nutrient solution (pH 2.3) inoculated by Acidithiobacillus ferrooxidans initially adapted to arsenopyrite. These conditions simulate the acid mine environment. The redox potential of the inoculated solutions increased up to +0.72 V vs normal hydrogen electrode (NHE), indicating the increase of the Fe(3+) to Fe(2+) ratio, and correspondingly the pH decreased to values as low as 1.9. In the sterile 9K control, the redox potential and pH remained constant at +0.52 V NHE and 2.34, respectively. Solution analyses showed that in inoculated medium Cu and As dissolved stoichiometrically with a dissolution rate of about three to five times higher compared to the sterile control. For the first time, X-ray photoelectron spectroscopy (XPS) was carried out on the bioleached enargite powder with the aim of clarifying the role of the microorganisms in the dissolution process. XPS results provide evidence of the formation of a thin oxidized layer on the mineral surface. Nitrogen was also detected on the bioleached surfaces and was attributed to the presence of an extracellular polymer substance layer supporting a mechanism of bacteria attachment via the formation of a biofilm a few nanometers thick, commonly known as nanobiofilm.

Photon beams produced by a cobalt-60 Unit and a 6 MV linear accelerator equipped with stereotactic collimators were used to investigate some dosimetric properties of a radioluminescent dosimeter based on a Ce-doped optical fibre. The stability of the signal with increasing the irradiation time, enabled a reliable and real-time measurement of the dose rate. The methods, recently developed, of optical coupling, light collection and signal processing allowed to achieve a satisfactory signal to noise ratio, a good reproducibility and a linear dose-response. The punctual dimension of the doped fibre diameter was exploited in the characterization of stereotactic fields, providing results in agreement with those obtained using a micro-ionization chamber. © 2008 Elsevier Ltd. All rights reserved.

Phosphorescence emitted by a new dosimetric system based on a SiO2 optical fibre doped with Ce3+ ions was investigated. The defects in the matrix that, acting as electron traps, originate the phosphorescence signal were studied by means of thermally stimulated luminescence in the temperature interval 313-533 K. A continuous trap distribution with activation energies extending from 0.8 to 1.5 eV was observed. On the basis of these findings, the temperature dependence of the shape of isothermal phosphorescence decay was analysed and the corresponding spectrum was compared with that of radioluminescence. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

A novel series of 1-[2-(diarylmethoxy)ethyl]-2-methyl-5-nitroimidazole (DAMNI) analogues were synthesized and tested in cell-based assays and in enzyme assays against HIV-1 recombinant reverse transcriptase (RT). Preparation of the new derivatives was performed by reacting the appropriate benzhydrols or the corresponding bromides with 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole or the 3-hydroxypropyl homologue. Several compounds showed anti-HIV-1 activity in the submicromolar range. Structure-activity relationship studies suggested that meta substitution at one phenyl ring of the diarylmethane moiety strongly influences the antiviral activity. The 3,5-disubstitution at the same phenyl ring led to less potent derivatives. Molecular modeling and docking studies within the RT non-nucleoside binding site confirmed that DAMNIs, similar to other NNRTIs such as TNK-651 and delavirdine (BHAP U90152), assume a butterfly-like conformation that appears to be halfway between that of classical NNRTIs, such as nevirapine, HEPT, TBZ, TIBO, and DABOs, and the conformation of BHAPs. In particular, the diphenylmethane moiety mimics the wings whereas the 1-(2-methyl-5-nitroimidazolyl)ethane portion resembles the BHAP 5-methanesulfonamidoindole-2-carbonylpiperazine portion.

The synthesis and in vitro anti human immunodeficiency virus (HIV) and anti-hepatitis B virus (HBV) activities of some unnatural β- l -nucleoside enantiomers related to the anti-HIV compound 2′,3′-dideoxy-3′-fluoro-5-chlorouridine (β- d -3′Fdd5ClU) are reported. In contrast to β- d -3′Fdd5ClU, β- l -3′Fdd5ClU and the other l -congeners were devoid of significant anti-HIV effects, but β- l -2′,3′-dideoxy-5-chlorocytidine (β- l -dd5ClC) and β- l -2′,3′-dideoxy-3′-fluoro-cytidine (β- l -3′FddC) showed a distinct anti-HBV activity. Three mononucleoside phosphotriester derivatives with S -pivaloyl-2-thioethyl ( t- BuSATE) groups as biolabile phosphate protective groups were also synthesized. The bis( t -BuSATE) derivative of β- d -3′Fdd5ClU retained anti-HIV activity in thymidine kinase deficient (TK − ) CEM cells.

The synthesis and biological activity of selenophenfurin (5-beta-D-ribofuranosylselenophene-3-carboxamide, 1), the selenophene analogue of selenazofurin, are described. Glycosylation of ethyl selenophene-3-carboxylate (6) under stannic chloride-catalyzed conditions gave 2- and 5-glycosylated regioisomers, as a mixture of alpha- and beta-anomers, and the beta-2,5-diglycosylated derivative. Deprotected ethyl 5-beta-D-ribofuranosylselenophene-3-carboxylate (12 beta) was converted into selenophenfurin by ammonolysis. The structure of 12 beta was determined by 1H- and 13C-NMR, crystallographic, and computational studies. Selenophenfurin proved to be antiproliferative against a number of leukemia, lymphoma, and solid tumor cell lines at concentrations similar to those of selenazofurin but was more potent than the thiophene and thiazole analogues thiophenfurin and tiazofurin. Incubation of K562 cells with selenophenfurin resulted in inhibition of IMP dehydrogenase (IMPDH) (76%) and an increase in IMP pools (14.5-fold) with a concurrent decrease in GTP levels (58%). The results obtained confirm the hypothesis that the presence of heteroatoms such as S or Se in the heterocycle in position 2 with respect to the glycosidic bond is essential for both cytotoxicity and IMP dehydrogenase inhibitory activity in this type of C-nucleosides.

The decomposition pathways and kinetics in various biological media and the in vitro anti-HIV-1 and anti-HIV-2 activities of four derivatives of the 5'-mononucleotide of isoddA incorporating carboxylate esterase-labile transient phosphate protecting groups are reported and compared: namely, two mononucleoside aryl phosphoramidate derivatives 1a,b and two mononucleoside phosphotriester derivatives incorporating two S-acyl-2-thioethyl groups 2a,b. All four compounds show better antiviral activity, compared to the parent nucleoside analog isoddA. The results highlight that both types of compounds act as pronucleotides, i.e. they exert their antiviral effect via intracellular delivery of the 5'-mononucleotide of isoddA. The results may give insights for the design of new more efficient pronucleotides.

Different particulate solids such as glass powder, various types of activated carbon and bentonite suspended in Thiobacillus ferrooxidans cultures produce very different effects on the oxidizing activity of the microorganism. The atmospheric oxygen uptake by Thiobacillus ferrooxidans in Warburg respirometer flasks containing 9K medium with ferrous sulfate as energy source and suspended bentonite is 2.8 times that in the absence of solids. The dissolution rate of pure pyrite in 250 cm 3 shake flasks containing 9K medium and bentonite is considerably enhanced over that where the only solid phase is pyrite. Conversely, the oxidizing ability of the microorganism seems to be inhibited by all the activated carbons tested. The effect of ground glass seems to be related to its particle size distribution. Implications for the bioleaching of sulfide ores and coal pyrite are discussed in the light of current knowledge on the adsorption of Thiobacillus ferrooxidans cells on solid surfaces.

The synthesis and the in vitro anti-HIV-1 activity of novel pyrrolo annulated benzothiadiazepine acetic acids and some related derivatives are reported. The new compounds share chemical features with pyrrolo[1,2-d][1,4]benzodiazepin-6-one 1 and Ro 5-3335 pyrrylbenzodiazepinone 4, two inhibitors of HIV-replication at the level of reverse transcriptase (RT) and transcriptional transactivation by Tat, respectively. Two derivatives, namely methyl 10,11-dihydropyrrolo[1,2-b][1,2,5]benzothiadiazepine-11-acetic-5,5 -dioxide (5a) and 1,12b-dihydro-2H-azeto[2,1-d]pyrrolo[1,2-b][1,2,5]benzoth iadiazepin-2-one 8,8-dioxide (7a), were found to exhibit a significant, although not very potent, activity against human immunodeficiency virus Type 1 (HIV-1).

Molecular modeling analysis of compounds belonging to the recently published series of dihydro-alkoxy-benzyl-oxopyrimidines (DABOs), such as S-DABOs and DATNOs, gave support to the design of new 2, 6-disubstituted benzyl-DABO derivatives as highly potent and specific inhibitors of the HIV-1 reverse transcriptase (RT). To follow up on the novel DABO derivatives, we decided to investigate the effect of electron-withdrawing substituents in the benzyl unit of the S-DABO skeleton versus their anti-HIV-1 activity. Such chemical modifications impacted the inhibitory activity, especially when two halogen units were introduced at positions 2 and 6 in the phenyl portion of the benzyl group bound to C-6 of the pyrimidine ring. Various 5-alkyl-2-(alkyl(or cycloalkyl)thio)-6-(2, 6-dichloro(or 2,6-difluoro)phenylmethyl)-3, 4-dihydropyrimidin-4(3H)-ones were then synthesized and tested as anti-HIV-1 agents in both cell-based and enzyme (recombinant reverse transcriptase, rRT) assays. Among the various mono- and disubstituted phenyl derivatives, the most potent were those containing a 6-(2,6-difluorophenylmethyl) substituent (F-DABOs), which showed EC50's ranging between 40 and 90 nM and selectivity indexes up to >/=5000. An excellent correlation was found between EC50 and IC50 values which confirmed that these compounds act as inhibitors of the HIV-1 RT. The structure-activity relationships of the newly synthesized pyrimidinones are presented herein.

Biohydrometallurgical solubilization cannotyet compete with conventional pyrometallurgical processes for recovering metals from sulphide concentrates, though the benefits deriving from its being much more environmentally friendly make it extremely attractive. Up to now, the main reason has been the relatively large size of the bioreactors and consequently the higher investment and power costs per unit mass of metal recovered compared to conventional processing. Bioreactor size is directly related to the biosolubilization process kinetics that, in turn, depend upon the suitability of the bioreactor to the process and on the prevailing biochemical conditions in the system. The Biorotor — the first reactor purpose built to match biohydrometallurgical requirements and developed by the authors - yields much faster biosolubilization kinetics than conventional bioreactors. It has been demonstrated that sulphur and iron biooxidation kinetics can be further enhanced, even in conventional bioreactors, by adding to the mineral suspension small amounts of substances capable of removing at least part of the metabolites. One of such substances is bentonite, a clay mineral that is already used as a scavenger in some commercial processes. Ferrous sulphate kinetics at least one order of magnitude higher than those reported in the literature can easily be obtained in the biorotor when the reaction takes place in the presence of bentonite.The concentration of oxidizable solids is more of a performance-limiting factor for conventional reactors than for the Biorotor and less harmful when bentonite is present in the solids suspension. Tests have been carried out in two identical Pachuca tanks operated in parallel using pure pyrite in concentrations increasing from 4.78% to 20.58% through 13.35%, one (No.I) containing a pyrite suspension and the other (No. 2) the same suspension admixed with bentonite. The ratio of pyrite solubilization rates in Pachuca No. 2 to those in Pachuca No. 1 increased almost linearly with increasing pyrite concentration. For 30% solids in Biorotor, without bentonite, the iron solubilization rate was 561 mgAdm 3 Ah -1 . Testing of Biorotor performance with bentonite confirmed the results obtained in the Pachuca, although less pronouncedly.

(R)- And (S)-8-aza-9(-)[2-(phosphonomethoxy)propyl]guanine [(R)-and (S)-8-aza-PMPG] were synthesized and tested in vitro for anti-human immunodeficiency virus (HIV) activity. The synthesis of the above compounds and of (R)-9(-)[2-(phosphonomethoxy)propyl]guanine [(R)-PMPG] was carried out through the alkylation of 8-azaguanine or guanine with (R)- and (S)-2-O(-)[(diisopropylphosphono)methyl]-1-O-(tolylsulfonyl) -1,2-propanediol followed by deprotection of the phosphonic moiety. A different, even more convenient synthesis of (R)-8-aza-PMPG starting from 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone and (R)(-)[2(-)[(diisopropylphosphono)-methoxy]propyl]amine is also reported. Both (R)-8-aza-PMPG and (R)-PMPG demonstrated anti-HIV activity in the MTT assay with EC50 values of 12 and 4.5 microM, respectively. The corresponding S enantiomers were found to be less potent. When evaluated in combination with AZT, ddI, or DABO 603, (R)-8-aza-PMPG gave additive, additive, and synergistic anti-HIV-1 effects, respectively.

As an approach to more extensive structural modifications of [(oxazolylphenoxy)alkyl]isoxazoles, we synthesized new compounds characterized by the replacement of the isoxazole nucleus with furan, pyrrole, and thiophene rings and by the presence of a ketocarbonyl group in the aliphatic chain connecting these pentatomic heterocycles to the 4-(4,5-dihydro-2-oxazolyl)phenoxy, 4-(ethoxycarbonyl)phenoxy, and 4-carboxyphenoxy moieties. Some pentamethylene derivatives were also prepared, and their antirhinovirus activity was compared to that of the corresponding ketomethylene derivatives. Syntheses were carried out by Friedel-Crafts acylation of the above pentatomic heterocycles and subsequent reaction of chloroalkyl ketones with the proper 4-substituted phenol. Reduction of the ketone function afforded the related polymethylene derivatives. The new compounds were tested for antirhinovirus activity and cytotoxicity in comparison with WIN 51711, used as reference drug. Inspection of the structure-activity relationships revealed that the thiophene ring and the carbonyl group are the structural components which to a large extent contribute to the positive biological profile in terms of both wideness of spectrum and low cytotoxicity. Among the various derivatives, compounds 8e,d showed in vitro the same potency of WIN 51711 but a cytotoxicity at least 10 times lower.

Some aza and deaza analogues of the anti-HIV agent 2',3'-dideoxy-3'-oxoadenosine (isoddA) (8-aza-, 8-aza-1-deaza, 8-aza-3-deaza-, 1-deaza-, and 3-deaza-isoddA) were synthesized and found inactive against HIV in vitro. The hypothesis that the inactivity of these isonucleosides might be due to their poor affinity for cellular nucleoside kinases was checked by the synthesis of a series of 5'-[bis(2,2,2-trichloroethyl) phosphate] triesters and 5'-phenyl phosphoramidate derivatives which, acting as membrane soluble prodrugs, could release the free phosphate form inside the cell. The 5'-(phenylmethoxy)alaninyl phosphate derived from 8-aza-isoddA was found active against HIV-1 and HIV-2 with a potency similar to that of isoddA, while the anti-HIV potency of 5'-(phenylmethoxy)alaninyl phosphate of isoddA proved remarkably higher than that of isoddA, in particular against HIV-2, being similar to that of AZT. Further evidence that 8-aza-isoddA could behave as anti-HIV agent, provided that it is activated as phosphate, was obtained by the synthesis of its 5'-triphosphate derivative, which proved to be an active inhibitor of HIV-1 recombinant reverse transcriptase.

The recent discovery of gold finely intergrown with the complex metal sulphides in the Tertiary volcanites of the Serrenti-Furtei district in central and southern Sardinia, prompted the investigation of gold extraction methods that are both economically viable and environmentally friendly. Here two types of integrated processes for gold extraction are compared: roasting plus cyanidation and bioleaching plus cyanidation. With the first process, overall gold recoveries as high as 85% are achieved, whereas with a variant of the second, total gold recovered does not exceed 77%. Both types of processes investigated are described in detail. The findings of the investigation suggest that the advantages offered by the biohydrometallurgical processes—especially from the environmental viewpoint—may compensate the lower gold recovery they yield.

With the aim of developing novel inhibitors of human immunodeficiency virus, various derivatives (10-17) related to 5H-pyrrolo[1,2-b] [1,2,5]benzothiadiazepine (PBTD) were prepared and tested in vitro. The title tricyclic derivatives were obtained by intramolecular cyclization of the open-chain intermediate arylpyrrylsulfones, followed by N-alkylation at position 10. Among test derivatives some 10-alkyl-5H-pyrrolo[1,2-b] [1,2,5]benzothiadiazepin-11(10H)-one-5,5-dioxides were found to exert potent and specific activity against HIV-1. In particular, 7-chloro derivatives 11i and j showed a potency comparable to that of nevirapine. However, when the chloro atom was shifted to the 8 position, the related products were scarcely active or totally inactive. Replacement of the pyrrole with pyrrolidine led to inactive products and the reduction of SO2 to S strongly diminished the antiviral potency. PBTD derivatives active in cell cultures were also inhibitory to the recombinant HIV-1 RT in enzyme assays, thus allowing the conclusion that PBTDs are a new class of non-nucleoside reverse transcriptase inhibitors (NNRTIs).