A new dithiolopyrrolone antibiotic triggered by a long fermentation of Saccharothrix algeriensis NRRL B-24137 in sorbic acid-amended medium.

Saccharothrix algeriensis NRRL B-24137 is an actinobacterium isolated from Algerian Saharan soil. It produces bioactive compounds belonging to the dithiolopyrrolone class of antibiotics, which are characterized by the possession of a unique pyrrolinonodithiole nucleus. Dithiolopyrrolones are known for their strong antibacterial and antifungal activities. This class of antibiotics generated great interest after the discovery of their anticancer properties. In this study, an antibiotic named PR11, produced after a long bacterial fermentation (11 days) in sorbic acid-containing culture broth, was characterized as a new dithiolopyrrolone derivative. After HPLC analysis and purification, the chemical structure of this antibiotic was determined by 1 H- and 13 C-nuclear magnetic resonance, mass and UV-visible data. PR11 was thus characterized as an iso-hexanoyl-pyrrothine, a novel dithiolopyrrolone derivative. The minimum inhibitory concentrations of the new induced antibiotic were determined against several pathogenic micro-organisms. A moderate to strong activity was noted against all Gram-positive bacteria, filamentous fungi and yeasts tested. SIGNIFICANCE AND IMPACT OF THE STUDY: Given the strong activities of dithiolopyrrolones against diverse prokaryotic and eukaryotic micro-organisms including potent selective-anticancer activity, the discovery of new-related derivatives draw continuous attention for therapeutic research. Depending on nature and concentration of added precursor, Saccharothrix algeriensis NRRL B-24137 produce several dithiolopyrrolone coumpounds. In this study, sorbic acid addition combined to long fermentation duration was shown to induce the biosynthesis of a novel dithiolopyrrolone derivative. After purification and full spectroscopic and spectrometric study, the compound was characterized as iso-hexanoyl-pyrrothine. In the future investigation for novel dithiolopyrrolone discovery, fermentation duration should be regarded as a key parameter as well.

Effective biosynthesis of benzoyl-pyrrothine dithiolopyrrolone antibiotic by cinnamic acid-precursor addition in culture of Saccharothrix algeriensis NRRL B-24137.

Dithiolopyrrolone antibiotics, produced by several micro-organisms, are known for their strong antimicrobial and antitumor activities. Among of this micro-organisms, Saccharothrix algeriensis NRRL B-24137, a rare actinobacterium, has the ability to produce several dithiolopyrrolones derivatives depending on precursors added in the culture medium. After 10 days of strain fermentation on semi-synthetic medium supplemented with cinnamic acid and HPLC purification, biosynthesis of benzoyl-pyrrothine dithiolopyrrolone was evidenced through complete spectroscopic (UV-visible and 1H and 13C NMR) and spectrometric (electron impact mass spectrum) analyses. The pure molecule showed appreciable minimum inhibitory concentration values against several Gram-positive bacteria and filamentous fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: Dithiolopyrrolone antibiotics, known for their strong antimicrobial activities, gained greater interest after the discovery of their antitumor properties. Depending on precursors added, Saccharothrix algeriensis NRRL B-24137 has the ability to produce several dithiolopyrrolones derivatives. Since biological activities of dithiolopyrrolones are related to their variable structure, discover of new natural analogues to be therapeutically explored remains a significant framework of research. In this study, a new dithiolopyrrolone derivative was purified from the fermentation broth of S. algeriensis NRRL B-24137. This new antibiotic, characterized as benzoyl-pyrrothine dithiolopyrrolone, was induced by adding cinnamic acid, as precursor, to a semi-synthetic medium.

A Novel Method for the Metallization of 3D Silicon Induced by Metastable Copper Nanoparticles.

The development of efficient copper deposition processes in high-aspect-ratio silicon structures is still a key technological issue for the microelectronic industry. We describe here a new process for the deposition of copper thin films in three-dimensional (3D) structures induced by the decomposition of a copper amidinate precursor in solution under a moderate H2 pressure. The reduction of a metal precursor under soft conditions (3 bar, 110 °C) affords the preparation of a high-purity, conformal metallic layer. We unveil a novel deposition mechanism driven by colloidal copper nanoparticles (NPs) in solution that behave as a reservoir of metastable metallic NPs that eventually condense as a solid film on all immersed surfaces. The film growth process is characterized by time-resolved analyses of the NPs in the colloidal state (nuclear magnetic resonance NMR and UV-vis spectra) and of the NPs and metallic layer on substrates (transmission electron microscopy TEM, and scanning electron microscopy SEM). Major deposition stages of this process are proposed and the conformal metallization of 3D silicon substrates is successfully achieved. This method is transposable to other metallic layers such as silver or nickel.

Zwitterionic amidinates as effective ligands for platinum nanoparticle hydrogenation catalysts.

Ligand control of metal nanoparticles (MNPs) is rapidly gaining importance as ligands can stabilize the MNPs and regulate their catalytic properties. Herein we report the first example of Pt NPs ligated by imidazolium-amidinate ligands that bind strongly through the amidinate anion to the platinum surface atoms. The binding was established by 15N NMR spectroscopy, a precedent for nitrogen ligands on MNPs, and XPS. Both monodentate and bidentate coordination modes were found. DFT showed a high bonding energy of up to -48 kcal mol-1 for bidentate bonding to two adjacent metal atoms, which decreased to -28 ± 4 kcal mol-1 for monodentate bonding in the absence of impediments by other ligands. While the surface is densely covered with ligands, both IR and 13C MAS NMR spectra proved the adsorption of CO on the surface and thus the availability of sites for catalysis. A particle size dependent Knight shift was observed in the 13C MAS NMR spectra for the atoms that coordinate to the surface, but for small particles, ∼1.2 nm, it almost vanished, as theory for MNPs predicts; this had not been experimentally verified before. The Pt NPs were found to be catalysts for the hydrogenation of ketones and a notable ligand effect was observed in the hydrogenation of electron-poor carbonyl groups. The catalytic activity is influenced by remote electron donor/acceptor groups introduced in the aryl-N-substituents of the amidinates; p-anisyl groups on the ligand gave catalysts several times faster the ligand containing p-chlorophenyl groups.

Thermoresponsive gold nanoshell@mesoporous silica nano-assemblies: an XPS/NMR survey.

This work provides a detailed study on the physico-chemical characterization of a mechanized silver-gold alloy@mesoporous silica shell/pseudorotaxane nano-assembly using two main complementary techniques: XPS and NMR (liquid- and solid-state). The pseudorotaxane nanovalve is composed of a stalk (N-(6-aminohexyl)-aminomethyltriethoxysilane)/macrocycle (cucurbit[6]uril (CB6)) complex anchored to the silica shell leading to a silica/nanovalve hybrid organic-inorganic interface that has been fully characterized. The stalk introduction in the silica network was clearly demonstrated by XPS measurements, with the Si 2p peak shifting to lower energy after grafting, and through the analysis of the C 1s and N 1s core peaks, which indicated the presence of CB6 on the nanoparticle surface. For the first time, the complex formation on nanoparticles was proved by high speed (1)H MAS NMR experiments. However, these solid state NMR analyses have shown that the majority of the stalk does not interact with the CB6 macrocycle when formulated in powder after removing the solvent. This can be related to the large number of possible organizations and interactions between the stalk, the CB6 and the silica surface. These results highlight the importance of using a combination of adapted and complementary highly sensitive surface and volume characterization techniques to design tailor-made hybrid hierarchical structured nano-assemblies with controlled and efficient properties for potential biological purposes.

Three bonding modes of bis(2-picolyl)phenylphosphine at iron: isolation of a dinuclear iron complex featuring dearomatized pyridine moieties.

The coordination ability of the bis(2-picolyl)phenylphosphine (NPN) compound has been probed toward the iron precursor [Fe{N(SiMe3)2}2]. By a careful control of the experimental conditions we were able to isolate and characterize three complexes displaying different coordination modes of the NPN ligand as revealed in particular by X-ray diffraction, and multinuclear solution and solid state NMR analyses. It is shown that NPN can be used as a proton-responsive ligand with enough flexibility to allow the formation of the dinuclear complex [Fe{P(CH2(C5H4N))(CH(C5H4N))}(N(SiMe3)2)]2 with two NPN ligands spanning the two metal centres.

Photocontrol of luminescent inorganic nanocrystals via an organic molecular switch.

A photo-controlled and quasi-reversible switch of the luminescence of hexadecylamine-coated ZnO nanocrystals (ZnO@HDA Ncs) is operated via a molecular photoswitch (dithienylethene, DTE). The interaction between the DTE switch and the ZnO@HDA Ncs is thoroughly investigated using NMR spectroscopy techniques, including DOSY and NOESY, showing that the DTE switch is weakly adsorbed at the surface of the Ncs through the formation of hydrogen bonds with HDA. Steady state and time-resolved luminescence quenching experiments show a complex behavior, related to the spatial distribution of the emitting defects in the Ncs. Analysis of the data using models previously developed for Ncs supports static quenching. Both isomeric forms (open or closed) of the DTE switch quench the emission of Ncs, the efficiency being more than ten times higher for the closed isomer. The mechanism of quenching is discussed and we show that quenching occurs mainly through resonant energy transfer for the closed isomer and through electron transfer for the open one. The HDA layer mediates the quenching efficiency as only defects located near the surface are quenched.

Taxonomy, purification and chemical characterization of four bioactive compounds from new Streptomyces sp. TN256 strain.

A new actinomycete strain designated TN256, producing antimicrobial activity against pathogenic bacteria and fungi, was isolated from a Tunisian Saharan soil. Morphological and chemical studies indicated that strain TN256 belonged to the genus Streptomyces. Analysis of the 16S rDNA sequence of strain TN256 showed a similarity level ranging between 99.79 and 97.8% within Streptomyces microflavus DSM 40331(T) and Streptomyces griseorubiginosus DSM 40469(T) respectively. The comparison of its physiological characteristics showed significant differences with the nearest species. Combined analysis of the 16 S rRNA gene sequences (FN687758), fatty acids profile, and results of physiological and biochemical tests indicated that there were genotypic and phenotypic differentiations of that isolate from other Streptomyces species neighbours. These date strongly suggest that strain TN256 represents a novel species with the type strain Streptomyces TN256 (=CTM50228(T)). Experimental validation by DNA-DNA hybridization would be required for conclusive confirmation. Four active products (1-4) were isolated from the culture broth of Streptomyces TN256 using various separation and purification steps and procedures. 1: N-[2-(1H-indol-3-yl)-2 oxo-ethyl] acetamide 'alkaloid' derivative; 2: di-(2-ethylhexyl) phthalate, a phthalate derivative; 3: 1-Nonadecene and 4: Cyclo (L: -Pro-L: -Tyr) a diketopiperazine 'DKP' derivative. The chemical structure of these four active compounds was established on the basis of spectroscopic studies NMR and by comparing with data from the literature. According to our biological studies, we showed in this work that the pure compounds (1-4) possess antibacterial and antifungal activities.

Guanine oxidation: NMR characterization of a dehydro-guanidinohydantoin residue generated by a 2e-oxidation of d(GpT).

The Mn-TMPyP/KHSO(5) system was used to oxidize guanine contained within a dinucleoside monophosphate d(GpT). To identify the guanine oxidation product having a mass with 4 amu above the mass of guanine itself, this relatively unstable compound was reduced to a more stable one. The ESI/MS and NMR data allowed us to propose a dehydro-guanidinohydantoin structure for the (G+4) guanine oxidation product.

Solution conformation of an abasic DNA undecamer duplex d(CGCACXCACGC) x d(GCGTGTGTGCG): the unpaired thymine stacks inside the helix.

The three-dimensional structural analysis of DNA undecamer 5'd(C1G2C3A4C5X6C7A8C9G10C11)3', 3'd(G22C21G20T19G18T17G16T15G14C13G12)5' duplex in which the X residue is a modified abasic site [3-hydroxy-2-(hydroxymethyl)tetrahydrofuran] has been performed using NOESY, DQFCOSY, TOCSY, and 31P-1H HSQC-TOCSY spectra in relation with molecular dynamics simulations. A total of 249 distances and 224 dihedral angles were used for construction. The optimal distances were calculated using the complete relaxation matrix method from hybrid matrices which were built with the experimental NOE intensities and additional data derived from either standard A- or B-DNA. Six independent refined structures starting from canonical A- and B-DNA were determined on the basis of the NMR data, and all converged to a single family with average rms deviations below 0.6 A and final NOE Rx factors of 0.055 +/- 0.03. A satisfactory agreement was obtained between measured NOE intensities and those resulting from full relaxation matrix calculations. A single intrahelical form of right-handed DNA duplex is observed; the aromatic base of residue T17 opposite the abasic site is stacked inside the helix. No clear correlation was detected between the C5 and C7 residues, excluding their proximity and the looping out of the abasic site. The abasic site induces a kink of about 30 degrees in the DNA duplex. This kink allows the formation of a bifurcated hydrogen bond between the amino protons of C5 and the O4 oxygen of T17. A detailed analysis of the final structures and their comparison with previous studies of abasic site lesions are described.

NMR and molecular modeling studies of the interaction of artificial AP lyases with a DNA duplex containing an apurinic abasic site model.

Tailor-made molecules, DTAc and ATAc, that incorporate a nucleic base (adenine or 2,6-diaminopurine) linked by a diamino chain to an intercalator (9-amino-6-chloro-2-methoxyacridine) selectively recognize and efficiently cleave abasic sites in DNA via a beta-elimination reaction. The three-dimensional structure of the complexes of DTAc and ATAc bound to a DNA undecamer, the 5'd(C1G2C3A4C5X6C7A8C9G10C11)3' x 3'd(G22C21G20T19G18T17G16T15G14C13G12)5' duplex in which the X residue is a stable abasic site [3-hydroxy-2-(hydroxymethyl)tetrahydrofuran], has been studied by combined NMR-energy minimization methods. Analysis of the NMR spectra reveals that DTAc and ATAc interact with a very similar fashion and form two different complexes with DNA, present in a ratio of 70/30 (+/-10). In both complexes, the acridine ring intercalates exclusively between the C3 x G20 and A4 x T19 base pairs, the linker is located in the minor groove, and the base moiety docks in the abasic site. The principal difference between the major and the minor complexes consists of a 180 degrees rotation of the acridine ring around the Acr-C-N bond within the same intercalation site. Molecular modeling studies with few intermolecular ligand-DNA restraints were used to investigate the geometry of the base pair formed between the diaminopurine of DTAc and the T17 ring. The most energetically favored complex has the 2,6-diaminopurine of DTAc base paired with the T17 ring in a Hoogsteen conformation. The models DTAc and ATAc are also discussed as nuclease mimics and cleaving agents at abasic sites.

Molecular modelling study of DNA-Troeger's bases interactions.

The two enantiomeric forms: 1R,5R (R) and 1S,5S (S) of the Troeger's base analog, 9,19-methano-9,10,19,20-tetrahydrodiacridino-[b,f]-[1,5]- diazocine which possess a C2 axis of symmetry, are susceptible to interact differently with DNA. This paper reports the results of molecular modelling calculations on B DNA-Troeger's base complexes. Two interaction modes have been examined: intercalation and binding in the grooves. Into the limits of accuracy of such a kind of calculations, some tendencies seem to appear. In the intercalation mode, the R and S enantiomers exhibit a selectivity for alternating dinucleotidic sequences and the minor groove is enantioselective for S. Binding in the major groove is selective for S with G-C sequences, and in the minor groove the stereoselectivity appears for R with A-T sequences. The S-(dG-dC)5.(dG-dC)5 complex in the major groove seems to be the most favoured.