Polyanionic N-donor ligands as chelating agents in transition metal complexes: synthesis, structural characterization and antiviral properties against HIV

We describe here the synthesis and characterization of new sulfonated and carboxylated-containing N-donor ligands [Na(4)(edts)]·4H(2)O (2), [Na(2)(dmeddp)]·2H(2)O (3) and [Na(4)(edtp)]·H(2)O (4) (edts = ethylene-diamine- N,N,N',N'-tetraethylenesulfonate ion; dmeddp = dimethyl-ethylene-diamine-N,N,N',N'-tetra-3-propionate ion; edtp = ethylene-diamine-N,N,N',N'-tetra-3-propionate ion) and their corresponding metal (Ni, Co, Cu and Zn) complexes. Mainly, UV-Vis and a computer aided analysis of the EPR spectra provided information on the geometry and structure of the complexes in solution. Some of the metal complexes inhibit HIV replication when treating both pre- and post-infected PBMC cells, and hustle the inhibitory effect compared to the metal salts alone.     

High relaxivity supramolecular adducts between human-liver fatty-acid-binding protein and amphiphilic Gd(III) complexes: structural basis for the design of intracellular targeting MRI probes

Gadolinium complexes linked to an apolar fragment are known to be efficiently internalized into various cell types, including hepatocytes. Two lipid-functionalized gadolinium chelates have been investigated for the targeting of the human liver fatty acid binding protein (hL-FABP) as a means of increasing the sensitivity and specificity of intracellular-directed MRI probes. hL-FABP, the most abundant cytosolic lipid binding protein in hepatocytes, displays the ability to interact with multiple ligands involved in lipid signaling and is believed to be an obligate carrier to escort lipidic drugs across the cell. The interaction modes of a fatty acid and a bile acid based gadolinium complex with hL-FABP have been characterized by relaxometric and NMR experiments in solution with close-to-physiological protein concentrations. We have introduced the analysis of paramagnetic-induced protein NMR signal intensity changes as a quantitative tool for the determination of binding stoichiometry and of precise metal-ion-center positioning in protein-ligand supramolecular adducts. A few additional NMR-derived restraints were then sufficient to locate the ligand molecules in the protein binding sites by using a rapid data-driven docking method. Relaxometric and (13)C NMR competition experiments with oleate and the gadolinium complexes revealed the formation of heterotypic adducts, which indicates that the amphiphilic compounds may co-exist in the protein cavity with physiological ligands. The differences in adduct formation between fatty acid and bile acid based complexes provide the basis for an improved molecular design of intracellular targeted probes.     

Interaction of cisplatin with human superoxide dismutase

cis-Diamminedichloroplatinum(II) (cisplatin) is able to interact with human superoxide dismutase (hSOD1) in the disulfide oxidized apo form with a dissociation constant of 37 ± 3 μM through binding cysteine 111 (Cys111) located at the edge of the subunit interface. It also binds to Cu(2)-Zn(2) and Zn(2)-Zn(2) forms of hSOD1. Cisplatin inhibits aggregation of demetalated oxidized hSOD1, and it is further able to dissolve and monomerize oxidized hSOD1 oligomers in vitro and in cell, thus indicating its potential as a leading compound for amyotrophic lateral sclerosis.     

Study of the nucleophilic behaviour of N-phenylbenzamidine towards 1,2-diaza-1,3-dienes: domino reactions for imidazole scaffolds

Depending on the nature of the solvent, alcohol or DMF, N-phenylbenzamidine shows different nucleophilic behaviour towards the conjugated azo–ene system of 1,2-diaza-1,3-dienes. In alcohol it reacts as a nucleophile through the N-phenyl imino nitrogen affording spiro pyrroloimidazoles and 1,3-diphenyl-1H-imidazoles. In DMF, by contrast, it behaves as nucleophile mainly by means of the imino amidino nitrogen providing 2-phenylimidazole derivatives by loss of the aniline molecule.     

Acute‐phase proteins investigation based on lectins affinity capture prior to 2‐DE separation: Application to serum from multiple sclerosis patients

Plasma acute‐phase proteins (APPs) glyco‐isoforms are important biomarkers of inflammatory processes such as those occurring in multiple sclerosis (MS). Specific analysis of these proteins is often hampered by sample biochemical complexity. The aim of our study was to set up a method to accurately visualize, identify and quantify APPs glyco‐isoforms in human serum. An enrichment strategy based on affinity chromatography using the carbohydrate‐binding proteins concanavalin A (ConA) and erythrina cristagalli lectin (ECL) was applied to pooled serum samples from 15 patients and 9 healthy individuals. Image analysis of 2‐DE detected 30 spots with a fold change higher than 1.5. A total of 14 were statistically significant (p value<0.05): 7 up‐regulated and 7 down‐regulated in MS samples. ESI LC‐Nanospray IT mass spectrometry analysis confirmed that all of them were APPs isoforms supporting the idea that the accurate analysis of differential glycosylation profiles in these biomarkers is instrumental to distinguish between MS patients and healthy subjects. Additionally, overlaps in ConA/ECL maps protein patterns suggest how the used lectins are able to bind sugars harbored by the same oligosaccharide structure. Among identified proteins, the presence of complex and/or hybrid type N‐linked sugar structures is well known. Performing galectin‐3 binding and Western blotting, we were able to demonstrate a correlation between hybrid type glyco‐isoforms of β‐haptoglobin and MS. In conclusion, although the patho‐physiological role of the identified species still remains unclear and further validations are needed, these findings may have a relevant impact on disease‐specific marker identification approaches.     

Divisorial prime ideals of int(D) when D is a krull-type domain

Let Dbe a domain with quotient field K. The ring of integer-valued polynomials over Dis Int (D):={f? K[X];f(4D) ? D}.We describe the divisorial prime ideals of Int(D) when Dis a domain of Krull-type and, in particular, when Dis also a d-ring.     

Micro-X-Ray Fluorescence and the Old Masters Non-destructive in situ characterisation of the varnish of historical Low Countries stringed musical instruments

In recent years, a growing attention has been addressed to the study of the varnish from early musical instruments. The surfaces of nine historical Low Countries stringed musical instruments from the collection of the “Musical Instruments Museum” in Brussels were non-destructively analysed by in situ micro-X-Ray Fluorescence spectroscopy in dispersive mode. It was found that the main pigments dispersed in the varnish were iron- and manganese-based earths. The presence of a chromium-based pigment in one of the analysed instruments makes it appreciably different from the others. Other findings were discussed and compared with previously published results. The collection of such information plays a relevant role in the recovery of the applied formulations that is an interesting issue for conservators, luthiers and art historians.     

Assessment of misorientation in metallic and semiconducting nanowires using precession electron diffraction

Precession electron diffraction (PED) allows for diffraction pattern collection under quasi-kinematical conditions. The combination of PED with fast electron diffraction acquisition and pattern matching software techniques is used for the high magnification ultra-fast mapping of variable crystal orientations and phases, similarly to what is achieved with the Electron Backscattered Diffraction technique in Scanning Electron Microscopes at lower magnifications and longer acquisition times. Here we report, for the first time, the application of this PED-based orientation mapping technique to both metallic and semiconducting nanowires.