Unveiling the Hidden Therapeutic Potential of Carnosine,a Molecule with a Multimodal Mechanism of Action: A Position Paper

Carnosine (β-alanyl-L-histidine) is a naturally occurring endogenous dipeptide and an over-the-counter food supplement with a well-demonstrated multimodal mechanism of action that includes the detoxification of reactive oxygen and nitrogen species, the down-regulation of the production of pro-inflammatory mediators, the inhibition of aberrant protein formation, and the modulation of cells in the peripheral (macrophages) and brain (microglia) immune systems. Since its discovery more than 100 years ago, a plethora of in vivo preclinical studies have been carried out; however, there is still substantial heterogeneity regarding the route of administration, the dosage, the duration of the treatment, and the animal model selected, underlining the urgent need for “coordinated/aligned” preclinical studies laying the foundations for well-defined future clinical trials. The main aim of the present position paper is to critically and concisely consider these key points and open a discussion on the possible “alignment” for future studies, with the goal of validating the full therapeutic potential of this intriguing molecule.     

Monitoring of Spirulina Flakes and Powders from Italian Companies

Microalgae and microalgae-derived compounds have great potential as supplements in the human diet and as a source of bioactive products with health benefits. Spirulina (Arthrospira platensis (Nordstedt) Gomont, or Spirulina platensis) belongs to the class of cyanobacteria and has been studied for its numerous health benefits, which include anti-inflammatory properties, among others. This work was aimed at comparing some spirulina products available on the Italian market. The commercial products here analyzed consisted of spirulina cultivated and processed with different approaches. Single-component spirulina products in powder and flake form, free of any type of excipient produced from four different companies operating in the sector, have been analyzed. The macro- and micromorphological examination, and the content of pigments, phycobiliproteins, phenols, and proteins have shown differences regarding the morphology and chemical composition, especially for those classes of particularly unstable compounds such as chlorophylls and carotenoids, suggesting a great influence of both culture conditions and processing methods.     

GO-SWCNT Buckypapers as an Enhanced Technology for Water Decontamination from Lead

Water decontamination is an important challenge resulting from the incorrect disposal of heavy metal waste into the environment. Among the different available techniques (e.g., filtration, coagulation, precipitation, and ion-exchange), adsorption is considered the cheapest and most effective procedure for the removal of water pollutants. In the last years, several materials have been tested for the removal of heavy metals from water, including metal-organic frameworks (MOFs), single-walled carbon nanotubes (SWCNTs), and graphene oxide (GO). Nevertheless, their powder consistency, which makes the recovery and reuse after adsorption difficult, is the main drawback for these materials. More recently, SWCNT buckypapers (SWCNT BPs) have been proposed as self-standing porous membranes for filtration and adsorption processes. In this paper, the adsorption capacity and selectivity of Pb²⁺ (both from neat solutions and in the presence of other interferents) by SWCNT BPs were evaluated as a function of the increasing amount of GO used in their preparation (GO-SWCNT buckypapers). The highest adsorption capacity, 479 ± 25 mg g⁻¹, achieved for GO-SWCNT buckypapers with 75 wt.% of graphene oxide confirmed the effective application of such materials for cheap and fast water decontamination from lead.     

Copper Binding and Oligomerization Studies of the Metal Resistance Determinant CrdA from Helicobacter pylori

Within this research, the CrdA protein from Helicobacter pylori (HpCrdA), a putative copper-binding protein important for the survival of bacterium, was biophysically characterized in a solution, and its binding affinity toward copper was experimentally determined. Incubation of HpCrdA with Cu(II) ions favors the formation of the monomeric species in the solution. The modeled HpCrdA structure shows a conserved methionine-rich region, a potential binding site for Cu(I), as in the structures of similar copper-binding proteins, CopC and PcoC, from Pseudomonas syringae and from Escherichia coli, respectively. Within the conserved amino acid motif, HpCrdA contains two additional methionines and two glutamic acid residues (MMXEMPGMXXMXEM) in comparison to CopC and PcoC but lacks the canonical Cu(II) binding site (two His) since the sequence has no His residues. The methionine-rich site is in a flexible loop and can adopt different geometries for the two copper oxidation states. It could bind copper in both oxidation states (I and II), but with different binding affinities, micromolar was found for Cu(II), and less than nanomolar is proposed for Cu(I). Considering that CrdA is a periplasmic protein involved in chaperoning copper export and delivery in the H. pylori cell and that the affinity of the interaction corresponds to a middle or strong metal–protein interaction depending on the copper oxidation state, we conclude that the interaction also occurs in vivo and is physiologically relevant for H. pylori.     

Lanthanide Identity Governs Guest-Induced Dimerization in LnIII[15-MC N(L-pheHA)-5])3+ Metallacrowns

Series of lanthanide-containing metallic coordination complexes are frequently presented as structurally analogous, due to the similar chemical and coordinative properties of the lanthanides. In the case of chiral (Ln^III[15-MC _N(L-pheHA)-5])³⁺ metallacrowns (MCs), which are well established supramolecular hosts, the formation of dimers templated by a dicarboxylate guest (muconate) in solution of neutral pH is herein shown to have a unique dependence on the identity of the MC's central lanthanide. Calorimetric data and nuclear magnetic resonance diffusion studies demonstrate that MCs containing larger or smaller lanthanides as the central metal only form monomeric host-guest complexes whereas analogues with intermediate lanthanides (for example, Eu, Gd, Dy) participate in formation of dimeric host-guest-host compartments. The driving force for the dimerization event across the series is thought to be a competition between formation of highly stable MCs (larger lanthanides) and optimally linked bridging guests (smaller lanthanides).     

Colourings of cubic graphs inducing isomorphic monochromatic subgraphs

A -bisection of a bridgeless cubic graph is a -colouring of its vertex set such that the colour classes have the same cardinality and all connected components in the two subgraphs induced by the colour classes ( monochromatic components in what follows) have order at most . Ban and Linial Conjectured that every bridgeless cubic graph admits a -bisection except for the Petersen graph. A similar problem for the edge set of cubic graphs has been studied: Wormald conjectured that every cubic graph with has a -edge colouring such that the two monochromatic subgraphs are isomorphic linear forests (ie, a forest whose components are paths). Finally, Ando conjectured that every cubic graph admits a bisection such that the two induced monochromatic subgraphs are isomorphic. In this paper, we provide evidence of a strong relation of the conjectures of Ban-Linial and Wormald with Ando's Conjecture. Furthermore, we also give computational and theoretical evidence in their support. As a result, we pose some open problems stronger than the above-mentioned conjectures. Moreover, we prove Ban-Linial's Conjecture for cubic-cycle permutation graphs. As a by-product of studying -edge colourings of cubic graphs having linear forests as monochromatic components, we also give a negative answer to a problem posed by Jackson and Wormald about certain decompositions of cubic graphs into linear forests.     

CONFORMATIONAL PREFERENCES ABOUT Cpy-S BONDS IN DI-2-PYRIDYL DISULFIDE

Abstract

The total energy, dipole moment and electron densities for each possible rotational conformation about the C_py-S bonds of di-2-pyridyl disulfide were evaluated by using the semi-quantitative CNDO/2 method. The conformations in which the pyridine rings are coplanar with the valency plane of the bonded sulfur atom (cis-cis, cis-trans and trans-trans) were predicted to be the most favored ones.

Results of the theoretical study, when compared to some experimental determinations such as dipole moment and variable temperature pmr spectra, provided evidence that easy interconversion between these conformations can occur.     

THE STAUDINGER REACTION BETWEEN 2-H-1,2,3-DIAZAPHOSPHOLENES AND AROMATIC AZIDES

Abstract

The title reaction between substituted phenyl azides 2 and diastereomeric diazaphospholenes 1 gives the corresponding cyclic phosphazenes 3 with different stereochemical results. Hydrolysis of some phosphazenes 3 yield the corresponding ring-opened compounds Z-4I together with small amounts of diazaphospholene-oxide 5 and anilines 6. The configuration of the compounds obtained are established by ¹H n.m.r. spectroscopy. The results are explained invoking the formation of pentacoordinate phosphorus intermediates.     

SYNTHESIS AND THERMAL REARRANGEMENT OF 2-ALKOXYCARBONYL-3-ALKYL-4H-BENZO[b][1,4]THIAZINES

Abstract

The title compounds (4b-d) together with the benzothiazolines (5b-d) have been obtained by a reaction between 2,2′-dithiodianiline (1) and β-keto esters (2b-d). The reaction between 1 and the β-keto ester 2a gives 1,4-benzothiazine 3a in addition to the benzothiazoline 5a.

It has been established that the 1,4-benzothaizines 4b-d undergo an acid-catalysed thermal rearrangement involving a [1,3] shift of the sulfur atom, giving rise to the isomeric 1,4-benzothiazines 3b-d.