3D amino-induced electroless plating: a powerful toolset for localized metallization on polymer substrates

The "3D amino-induced electroless plating" (3D-AIEP) process is an easy and cost-effective way to produce metallic patterns onto flexible polymer substrates with a micrometric resolution and based on the direct printing of the mask with a commercial printer. Its effectiveness is based on the covalent grafting onto substrates of a 3D polymer layer which presents the ability to entrap Pd species. Therefore, this activated Pd-loaded and 3D polymer layer acts both as a seed layer for electroless metal growth and as an interdigital layer for enhanced mechanical properties of the metallic patterns. Consequently, flexible and transparent poly(ethylene terephtalate) (PET) sheets were selectively metalized with nickel or copper patterns. The electrical properties of the obtained metallic patterns were also studied.     

Characterization of the volatile profile of Antarctic bacteria by using solid-phase microextraction-gas chromatography-mass spectrometry

Bacteria belonging to the Burkholderia cepacia complex (Bcc) are significant pathogens in Cystic Fibrosis (CF) patients and are resistant to a plethora of antibiotics. In this context, microorganisms from Antarctica are interesting because they produce antimicrobial compounds inhibiting the growth of other bacteria. This is particularly true for bacteria isolated from Antarctic sponges. The aim of this work was to characterize a set of Antarctic bacteria for their ability to produce new natural drugs that could be exploited in the control of infections in CF patients by Bcc bacteria. Hence, 11 bacterial strains allocated to different genera (e.g., Pseudoalteromonas, Arthrobacter and Psychrobacter) were tested for their ability to inhibit the growth of 21 Bcc strains and some other human pathogens. All these bacteria completely inhibited the growth of most, if not all, Bcc strains, suggesting a highly specific activity toward Bcc strains. Experimental evidences showed that the antimicrobial compounds are small volatile organic compounds, and are constitutively produced via an unknown pathway. The microbial volatile profile was obtained by SPME-GC-MS within the m/z interval of 40-450. Solid phase micro extraction technique affords the possibility to extract the volatile compounds in head space with a minimal sample perturbation. Principal component analysis and successive cluster discriminant analysis was applied to evaluate the relationships among the volatile organic compounds with the aim of classifying the microorganisms by their volatile profile. These data highlight the potentiality of Antarctic bacteria as novel sources of antibacterial substances to face Bcc infections in CF patients.     

Glycerol and derived solvents: new sustainable reaction media for organic synthesis

The rapid growth of the biodiesel industry has led to a large surplus of its major byproduct, i.e. glycerol, for which new applications need to be found. Research efforts in this area have focused mainly on the development of processes for converting glycerol into value-added chemicals and its reforming for hydrogen production, but recently, in line with the increasing interest in the use of alternative greener solvents, an innovative way to revalorize glycerol and some of its derivatives has seen the light, i.e. their use as environmentally friendly reaction media for synthetic organic chemistry. The aim of the present Feature Article is to provide a comprehensive overview on the developments reached in this field.     

A series of tripodal cysteine derivatives as water-soluble chelators that are highly selective for copper(I)

A series of tripodal ligands derived from nitrilotriacetic acid and extended by three converging, metal-binding, cysteine chains was synthesised. Their ability to bind soft metal ions thanks to their three thiolate functions was investigated by means of complementary analytical and spectroscopic methods. Three ligands that differ by the nature of the carbonyl group next to the coordinating thiolate functions were studied: L(1) (ester), L(2) (amide) and L(3) (carboxylate). The negatively charged derivative L(3), which bears three carboxylate functions close to the metal binding site, gives polynuclear copper(I) complexes of low stability. In contrast, the ester and amide derivatives L(1) and L(2) are efficient Cu(I) chelators with very high affinities, close to that reported for the metal-sequestering metallothioneins (log K≈19). Interestingly, these two ligands form mononuclear copper complexes with a unique MS(3) coordination in water solution. An intramolecular hydrogen-bond network involving the amide functions in the upper cavity of the tripodal ligands stabilises these mononuclear complexes and was evidenced by the very low chemical-shift temperature coefficient of the secondary amide protons. Moreover, L(1) and L(2) display large selectivities for the targeted metal ion that is, Cu(I), with respect to bioavailable Zn(II). Therefore the two sulfur-based tripods L(1) and L(2) are of potential interest for intracellular copper detoxication in vivo, without altering the homeostasis of the essential metal ion Zn(II).     

Design, synthesis and characterisation of guanosine-based amphiphiles

A small library of sugar-modified guanosine derivatives has been prepared, starting from a common intermediate, fully protected on the nucleobase. Insertion of myristoyl chains and of diverse hydrophilic groups, such as an oligoethylene glycol, an amino acid or a disaccharide chain, connected through in vivo reversible ester linkages, or of a charged functional group provided different examples of amphiphilic guanosine analogues, named G1-G7 herein. All of the sugar-modified derivatives were positive in the potassium picrate test, showing an ability to form G-tetrads. CD spectra demonstrated that, as dilute solutions in CHCl(3), distinctive G-quadruplex systems may be formed, with spatial organisations dependent upon the structural modifications. Two compounds, G1 and G2, proved to be good low-molecular-weight organogelators in polar organic solvents, such as methanol, ethanol and acetonitrile. Ion transportation experiments through phospholipid bilayers were carried out to evaluate their ability to mediate H(+) transportation, with G5 showing the highest activity within the investigated series. Moreover, G3 and G5 exhibited a significant cytotoxic profile against human MCF-7 cancer cells in in vitro bioassays.     

Identification and characterization of new Fusarium masked mycotoxins,T2 and HT2 glycosyl derivatives,in naturally contaminated wheat and oats by liquid chromatography–high‐resolution mass spectrometry

The presence of glucoside derivatives of T‐2 and HT‐2 toxins (type A trichothecene mycotoxins) in naturally contaminated wheat and oats is reported for the first time. The use of advanced high‐resolution mass spectrometry based on Orbitrap technology allowed to obtain molecular structure details by measuring exact masses of main characteristic fragments, with mass accuracy lower than 2.8 ppm (absolute value). A monoglucoside derivative of T‐2 toxin and two monoglucoside derivatives of HT‐2 toxin were identified and characterized. The analysis of their fragmentation patterns provided evidence for glucosylation at C‐3 position for T‐2 toxin and at C‐3 or C‐4 position for HT‐2 toxin. A screening for the presence of these new masked forms of mycotoxins was carried out on a set of naturally contaminated wheat and oats samples. On the basis of peak area ratio between glucoside derivatives and free T‐2 and HT‐2 toxins, the presence of glucoside derivatives was more likely in wheat than in oats samples. The present work confirms the widespread occurrence of trichothecene glucosides in cereal grains naturally contaminated with the relevant unconjugated toxins, thus suggesting the importance of developing suitable analytical methods for their detection. Besides toxicity studies, tracking down these new masked forms of trichothecenes along the food/feed chain would enable to collect information on their relevance in human/animal exposure to mycotoxin risk. Copyright © 2012 John Wiley & Sons, Ltd.     

Spectroscopic characterization of the key catalytic intermediate Ni-C in the O2-tolerant [NiFe] hydrogenase I from Aquifex aeolicus: evidence of a weakly bound hydride

Ni-C in the O(2)-tolerant hydrogenase I from Aquifex aeolicus binds a hydride weaker than that in O(2)-sensitive hydrogenases. This is in line with the enhanced light-sensitivity of Ni-C, greater lability of the hydride complex and increased catalytic redox potentials relevant to bio-H(2) oxidation.     

Femtomolar Ln(III) affinity in peptide-based ligands containing unnatural chelating amino acids

The incorporation of unnatural chelating amino acids in short peptide sequences leads to lanthanide-binding peptides with a higher stability than sequences built exclusively from natural residues. In particular, the hexadentate peptide P(22), which incorporates two unnatural amino acids Ada(2) with aminodiacetate chelating arms, showed picomolar affinity for Tb(3+). To design peptides with higher denticity, expected to show higher affinity for Ln(3+), we synthesized the novel unnatural amino acid Ed3a(2) which carries an ethylenediamine triacetate side-chain and affords a pentadentate coordination site. The synthesis of the derivative Fmoc-Ed3a(2)(tBu)(3)-OH, with appropriate protecting groups for direct use in the solid phase peptide synthesis (Fmoc strategy), is described. The two high denticity peptides P(HD2) (Ac-Trp-Ed3a(2)-Pro-Gly-Ada(2)-Gly-NH(2)) and P(HD5) (Ac-Trp-Ada(2)-Pro-Gly-Ed3a(2)-Gly-NH(2)) led to octadentate Tb(3+) complexes with femtomolar stability in water. The position of the high denticity amino acid Ed3a(2) in the hexapeptide sequence appears to be critical for the control of the metal complex speciation. Whereas P(HD5) promotes the formation of polymetallic species in excess of Ln(3+), P(HD2) forms exclusively the mononuclear complex. The octadentate coordination of Tb(3+) by both P(HD) leads to total dehydration of the metal ion in the mononuclear complexes with long luminescence lifetimes (>2 ms). Hence, we demonstrated that unnatural amino acids carrying polyaminocarboxylate side-chains are interesting building blocks to design high affinity Ln-binding peptides. In particular the novel peptide P(HD2) forms a unique octadentate Tb(3+) complex with femtomolar stability in water and an improvement of the luminescence properties with respect to the trisaquo TbP(22) complex by a factor of 4.     

Chelation therapy in Wilson's disease: from D-penicillamine to the design of selective bioinspired intracellular Cu(I) chelators

Wilson's disease is an orphan disease due to copper homeostasis dysfunction. Mutations of the ATP7B gene induces an impaired functioning of a Cu-ATPase, impaired Cu detoxification in the liver and copper overload in the body. Indeed, even though copper is an essential element, which is used as cofactor by many enzymes playing vital roles, it becomes toxic when in excess as it promotes cytotoxic reactions leading to oxidative stress. In this perspective, human copper homeostasis is first described in order to explain the mechanisms promoting copper overload in Wilson's disease. We will see that the liver is the main organ for copper distribution and detoxification in the body. Nowadays this disease is treated life-long by systemic chelation therapy, which is not satisfactory in many cases. Therefore the design of more selective and efficient drugs is of great interest. A strategy to design more specific chelators to treat localized copper accumulation in the liver will then be presented. In particular we will show how bioinorganic chemistry may help in the design of such novel chelators by taking inspiration from the biological copper cell transporters.