Synthesis and spectroscopic properties of highly water-soluble perylene derivatives

Most known perylene diimides are lipophilic, with few exceptions of hydrophilic derivatives. Even in the latter case, the compounds have limited water solubility and show a strong tendency to self-aggregation. In this paper we present the synthesis of four new perylene derivatives with three and four basic side chains, obtained by functionalizing the bay-area of perylene. These molecules show great solubility in aqueous media as hydrochlorides and their tendency to self-aggregate is remarkably reduced with respect to the previously synthesized two-chained perylene diimides. Their different spectroscopic properties in various solvents and conditions are reported and discussed.     

Polyketide double bond biosynthesis. Mechanistic analysis of the dehydratase-containing module 2 of the picromycin/methymycin polyketide synthase

Picromycin/methymycin synthase (PICS) is a modular polyketide synthase (PKS) that is responsible for the biosynthesis of both 10-deoxymethynolide (1) and narbonolide (2), the parent 12- and 14-membered aglycone precursors of the macrolide antibiotics methymycin and picromycin, respectively. PICS module 2 is a dehydratase (DH)-containing module that catalyzes the formation of the unsaturated triketide intermediate using malonyl-CoA as the chain extension substrate. Recombinant PICS module 2+TE, with the PICS thioesterase domain appended to the C-terminus to allow release of polyketide products, was expressed in Escherichia coli. Purified PICS module 2+TE converted malonyl-CoA and 4, the N-acetylcysteamine thioester of (2S,3R)-2-methyl-3-hydroxypentanoic acid, to a 1:2 mixture of the triketide acid (4S,5R)-4-methyl-5-hydroxy-2-heptenoic acid (5) and (3S,4S,5R)-3,5-dihydroxy-4-methyl-n-heptanoic acid-delta-lactone (10) with a combined kcat of 0.6 min(-1). The triketide lactone 10 is formed by thioesterase-catalyzed cyclization of the corresponding d-3-hydroxyacyl-SACP intermediate, a reaction which competes with dehydration catalyzed by the dehydratase domain. PICS module 2+TE showed a strong preference for the syn-diketide-SNAC 4, with a 20-fold greater kcat/K(m) than the anti-(2S,3S)-diketide-SNAC 14, and a 40-fold advantage over the syn-(2R,3S)-diketide-SNAC 13. PICS module 2(DH(0))+TE, with an inactivated DH domain, produced exclusively 10, while three PICS module 2(KR(0))+TE mutants, with inactivated KR domains, produced exclusively or predominantly the unreduced triketide ketolactone, (4S,5R)-3-oxo-4-methyl-5-hydroxy-n-heptanoic acid-delta-lactone (7). These studies establish for the first time the structure and stereochemistry of the intermediates of a polyketide chain elongation cycle catalyzed by a DH-containing module, while confirming the importance of key active site residues in both KR and DH domains.     

Excitation Dynamics in Hetero‐bichromophoric Calixarene Systems

In this work, the dynamics of electronic energy transfer (EET) in bichromophoric donor–acceptor systems, obtained by functionalizing a calix[4]arene scaffold with two dyes, was experimentally and theoretically characterized. The investigated compounds are highly versatile, due to the possibility of linking the dye molecules to the cone or partial cone structure of the calix[4]arene, which directs the two active units to the same or opposite side of the scaffold, respectively. The dynamics and efficiency of the EET process between the donor and acceptor units was investigated and discussed through a combined experimental and theoretical approach, involving ultrafast pump–probe spectroscopy and density functional theory based characterization of the energetic and spectroscopic properties of the system. Our results suggest that the external medium strongly determines the particular conformation adopted by the bichromophores, with a direct effect on the extent of excitonic coupling between the dyes and hence on the dynamics of the EET process itself.     

Diffusion-controlled solid-state reactions of spherical particles, a general model for multiphase binary systems

The formal treatment of the diffusion-controlled growth of n binary compounds with narrow homogeneity range during the reaction of a sphere of reactant A immersed in reactant B is presented and discussed. Both constituents are assumed to be mobile. The reaction products are assumed to grow simultaneously as uniform and compact concentric layers with ideal contact at the interfaces as well as at the external surface of the sphere. The kinetic equations follow from the coupling between chemical reactions and partitioning of the diffusion flux at phase boundaries. The results for the formation of two and three compounds are presented. The influence of the initial radius of the sphere, of the relative magnitude of the kinetic constants, and of the volume variation is discussed in detail.     

3-methylthiophene self-assembled monolayers on planar and nanoparticle Au surfaces

In this article the adsorption of 3-methylthiophene on planar and nanoparticle Au surfaces is investigated. The resulting systems are compared with a benchmark system based on 1-decanethiol. The characterization data collected evidence the formation of a packed 3-methylthiophene SAM on the planar surface. In particular, spectroscopic investigations suggest that 3-methylthiophene aromatic system is not adsorbed on the surface through the pi-electron system but rather through the S atom alone. On the other hand, the behavior of 3-methylthiophene on nanoparticle surfaces is notably different from that of the alkanethiol. Only a limited fraction of the surface of Au nanoparticles results to be actually coated after purification; this notwithstanding, the nanoparticle growth seems to be strongly influenced by the presence of such a labile encapsulating agent.     

Benzene-assisted atmospheric-pressure chemical ionization: a new liquid chromatography/mass spectrometry approach to the analysis of selected hydrophobic compounds

Charge-exchange reactions involving benzene have been successfully exploited to increase the sensitivity of atmospheric-pressure chemical ionization mass spectrometry (APCI-MS) towards hydrophobic compounds of significant environmental relevance which are not detectable with the ordinary APCI techniques. Among them, good sensitivity have been found for (a) highly chlorinated biphenyl derivatives such as dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethane (DDD) and dichlorodiphenyldichloroethene (DDE); (b) cyclopentadienes such as Aldrin and its epoxy derivatives Dieldrin and Endrin; and (c) dibenzofurans and dibenzo-para-dioxins such as 2,3,7,8-tetrachlorodibenzofuran (2,3,7,8-TCDF) and 2,3,7,8-tetrachloro-dibenzo-para-dioxin (2,3,7,8-TCDD). The reactant benzene molecules were introduced into the source either through the nebulizer gas or by direct post-column addition of neat liquid, whereas the targeted compounds were analyzed using a high-performance liquid chromatography (HPLC) RP-18 column using methanol/water solutions as mobile phase. By using benzene as post-column reagent, positive ion mode detection was proven to be significantly enhanced as compared with APCI measurements carried out without benzene assistance.     

Affinity Chromatography-Based Assays for the Screening of Potential Ligands Selective for G-Quadruplex Structures

DNA G-quadruplexes (G4s) are key structures for the development of targeted anticancer therapies. In this context, ligands selectively interacting with G4s can represent valuable anticancer drugs. Aiming at speeding up the identification of G4-targeting synthetic or natural compounds, we developed an affinity chromatography-based assay, named G-quadruplex on Oligo Affinity Support (G4-OAS), by synthesizing G4-forming sequences on commercially available polystyrene OAS. Then, due to unspecific binding of several hydrophobic ligands on nude OAS, we moved to Controlled Pore Glass (CPG). We thus conceived an ad hoc functionalized, universal support on which both the on-support elongation and deprotection of the G4-forming oligonucleotides can be performed, along with the successive affinity chromatography-based assay, renamed as G-quadruplex on Controlled Pore Glass (G4-CPG) assay. Here we describe these assays and their applications to the screening of several libraries of chemically different putative G4 ligands. Finally, ongoing studies and outlook of our G4-CPG assay are reported.     

New Promising Therapeutic Avenues of Curcumin in Brain Diseases

Curcumin, the dietary polyphenol isolated from Curcuma longa (turmeric), is commonly used as an herb and spice worldwide. Because of its bio-pharmacological effects curcumin is also called “spice of life”, in fact it is recognized that curcumin possesses important proprieties such as anti-oxidant, anti-inflammatory, anti-microbial, antiproliferative, anti-tumoral, and anti-aging. Neurodegenerative diseases such as Alzheimer’s Diseases, Parkinson’s Diseases, and Multiple Sclerosis are a group of diseases characterized by a progressive loss of brain structure and function due to neuronal death; at present there is no effective treatment to cure these diseases. The protective effect of curcumin against some neurodegenerative diseases has been proven by in vivo and in vitro studies. The current review highlights the latest findings on the neuroprotective effects of curcumin, its bioavailability, its mechanism of action and its possible application for the prevention or treatment of neurodegenerative disorders.     

Label-Free Quantitative Proteomics to Explore the Action Mechanism of the Pharmaceutical-Grade Triticum vulgare Extract in Speeding Up Keratinocyte Healing

Plant extracts have shown beneficial properties in terms of skin repair, promoting wound healing through a plethora of mechanisms. In particular, the poly-/oligosaccharidic aqueous extract of Triticum vulgare (TVE), as well as TVE-based products, shows interesting biological assets, hastening wound repair. Indeed, TVE acts in the treatment of tissue regeneration mainly on decubitus and venous leg ulcers. Moreover, on scratched monolayers, TVE prompts HaCat cell migration, correctly modulating the expression of metalloproteases toward a physiological matrix remodeling. Here, using the same HaCat-based in vitro scratch model, the TVE effect has been investigated thanks to an LFQ proteomic analysis of HaCat secretomes and immunoblotting. Indeed, the unbiased TVE effect on secreted proteins has not yet been fully understood, and it could be helpful to obtain a comprehensive picture of its bio-pharmacological profile. It has emerged that TVE treatment induces significant up-regulation of several proteins in the secretome (153 to be exact) whereas only a few were down-regulated (72 to be exact). Interestingly, many of the up-regulated proteins are implicated in promoting wound-healing-related processes, such as modulating cell–cell interaction and communication, cell proliferation and differentiation, and prompting cell adhesion and migration.