Environmental accounting for the lagoon of Venice and the case of fishing

This paper presents the application of the eMergy evaluation, introduced by H.T. Odum as an efficient methodology of environmental accounting. The results of this analysis are a part of a wider sustainability assessment for the Province of Venice realized in 2003. Within a territorial sustainability analysis, it is necessary to implement an environmental accounting method, which is able: to precisely consider the boundaries of the investigated system (spatial scale); to arbitrarily separate the life of the investigated system into periods (temporal scale); to account for both economic and natural support to a given territorial system in order to implement a sustainable management of resources; to assess all the items supporting the system on the basis of a physical unit that is objective (while the traditional economic evaluation method is based on individual preferences, hence it is subjective). The Province of Venice is a very complex system due, on one hand, to the heavy and consolidated presence of industrial activity since the beginning of the 20th century and, on the other hand, to the principal natural ecosystem which characterizes it: the lagoon, the largest wetland in the Mediterranean Sea. The role of the lagoon, as a provider of resources and services is represented by the analysis of two aspects: the lagoon as an ecosystem on the basis of the evaluation of all flows that cyclically support its biotic activity and the lagoon as a productive system on the basis of the contribution of both natural and "economic" inputs that support human activity. In particular, the case of clam fishing will be presented to put on evidence the importance of natural inputs that are systematically neglected by the traditional accounting methodologies.     

Molecular mechanics (MM2) calculations and cone angles of phosphine ligands

Molecular mechanics (MM2) calculations were performed on 54 conformations of 18 phosphines (PH₃; PH_3−nR_n, where n = 1,…3, and R = Me and Et, n = 1 or 2 and R =ⁱPr, and n = 1 and R =^tBu, PMe₂Et, PMeEt₂, and PPhMe₂, and PPh₂R where R = Me, Et, ⁱPr, ^tBu and Ph). The results are compared to those previously obtained from MINDO/3 and MNDO calculations, and to experimental data. Single conformer cone angles and weighted average cone angles were calculated from MM2 optimized geometries employing Tolman's general definition, and they are compared to Tolman's values, MINDO/3 results, and T.L. Brown's E_R values. Of the cone angle definitions used, the weighted average values are suggested as the best single representation of phosphine ligand sizes. The steric parameters (cone angle and E_R values) alone, and in conjunction with electronic parameters, are correlated with experimental data.     

Reaction Mechanism of CO2 with Choline-Amino Acid Ionic Liquids: A Computational Study

Carbon capture and sequestration are the major applied techniques for mitigating CO2 emission. The marked affinity of carbon dioxide to react with amino groups is well known, and the amine scrubbing process is the most widespread technology. Among various compounds and solutions containing amine groups, in biodegradability and biocompatibility perspectives, amino acid ionic liquids (AAILs) are a very promising class of materials having good CO2 absorption capacity. The reaction of amines with CO2 follows a multi-step mechanism where the initial pathway is the formation of the C−N bond between the NH2 group and CO2. The added product has a zwitterionic character and can rearrange to give a carbamic derivative. These steps of the mechanism have been investigated in the present study by quantum mechanical methods by considering three ILs where amino acid anions are coupled with choline cations. Glycinate, L-phenylalanilate and L-prolinate anions have been compared with the aim of examining if different local structural properties of the amine group can affect some fundamental steps of the CO2 absorption mechanism. All reaction pathways have been studied by DFT methods considering, first, isolated anions in a vacuum as well as in a liquid continuum environment. Subsequently, the role of specific interactions of the anion with a choline cation has been investigated, analyzing the mechanism of the amine–CO2 reaction, including different coupling anion–cation structures. The overall reaction is exothermic for the three anions in all models adopted; however, the presence of the solvent, described by a continuum medium as well as by models, including specific cation- -anion interactions, modifies the values of the reaction energies of each step. In particular, both reaction steps, the addition of CO2 to form the zwitterionic complex and its subsequent rearrangement, are affected by the presence of the solvent. The reaction enthalpies for the three systems are indeed found comparable in the models, including solvent effects.     

Resveratrol Analogues as Dual Inhibitors of Monoamine Oxidase B and Carbonic Anhydrase VII: A New Multi-Target Combination for Neurodegenerative Diseases?

Neurodegenerative diseases (NDs) are described as multifactorial and progressive syndromes with compromised cognitive and behavioral functions. The multi-target-directed ligand (MTDL) strategy is a promising paradigm in drug discovery, potentially leading to new opportunities to manage such complex diseases. Here, we studied the dual ability of a set of resveratrol (RSV) analogs to inhibit two important targets involved in neurodegeneration. The stilbenols 1–9 were tested as inhibitors of the human monoamine oxidases (MAOs) and carbonic anhydrases (CAs). The studied compounds displayed moderate to excellent in vitro enzyme inhibitory activity against both enzymes at micromolar/nanomolar concentrations. Among them, the best compound 4 displayed potent and selective inhibition against the MAO-B isoform (IC₅₀ MAO-A 0.43 µM vs. IC₅₀ MAO-B 0.01 µM) with respect to the parent compound resveratrol (IC₅₀ MAO-A 13.5 µM vs. IC₅₀ MAO-B > 100 µM). It also demonstrated a selective inhibition activity against hCA VII (K_I 0.7 µM vs. K_I 4.3 µM for RSV). To evaluate the plausible binding mode of 1–9 within the two enzymes, molecular docking and dynamics studies were performed, revealing specific and significant interactions in the active sites of both targets. The new compounds are of pharmacological interest in view of their considerably reduced toxicity previously observed, their physicochemical and pharmacokinetic profiles, and their dual inhibitory ability. Compound 4 is noteworthy as a promising lead in the development of MAO and CA inhibitors with therapeutic potential in neuroprotection.     

Design,Synthesis and Biological Assessment of Rhodanine-Linked Benzenesulfonamide Derivatives as Selective and Potent Human Carbonic Anhydrase Inhibitors

A novel series of twenty-five rhodamine-linked benzenesulfonamide derivatives (7a–u and 9a–d) were synthesized and screened for their inhibitory action against four physiologically relevant human (h) carbonic anhydrase (CA) isoforms, namely hCA I, hCA II, hCA IX, and hCA XII. All the synthesized molecules showed good to excellent inhibition against all the tested isoforms in the nanomolar range due to the presence of the sulfonamide as a zinc binding group. The target compounds were developed from indol-3-ylchalcone-linked benzenesulfonamide where the indol-3-ylchalcone moiety was replaced with rhodanine-linked aldehydes or isatins to improve the inhibition. Interestingly, the molecules were slightly more selective towards hCA IX and XII compared to hCA I and II. The most potent and efficient ones against hCA I were 7h (K_I 22.4 nM) and 9d (K_I 35.8 nM) compared to the standard drug AAZ (K_I 250.0 nM), whereas in case of hCA II inhibition, the derivatives containing the isatin nucleus as a tail were preferred. Collectively, all compounds were endowed with better inhibition against hCA IX compared to AAZ (K_I 25.8 nM) as well as strong potency against hCA XII. Finally, these newly synthesized molecules could be taken as potential leads for the development of isoform selective hCA IX and XII inhibitors.     

Investigation into the Use of Encorafenib to Develop Potential PROTACs Directed against BRAFV600E Protein

BRAF is a serine/threonine kinase frequently mutated in human cancers. BRAF^V600E mutated protein is targeted through the use of kinase inhibitors which are approved for the treatment of melanoma; however, their long-term efficacy is hampered by resistance mechanisms. The PROTAC-induced degradation of BRAF^V600E has been proposed as an alternative strategy to avoid the onset of resistance. In this study, we designed a series of compounds where the BRAF kinase inhibitor encorafenib was conjugated to pomalidomide through different linkers. The synthesized compounds maintained their ability to inhibit the kinase activity of mutated BRAF with IC₅₀ values in the 40–88 nM range. Selected compounds inhibited BRAF^V600E signaling and cellular proliferation of A375 and Colo205 tumor cell lines. Compounds 10 and 11, the most active of the series, were not able to induce degradation of mutated BRAF. Docking and molecular dynamic studies, conducted in comparison with the efficient BRAF degrader P5B, suggest that a different orientation of the linker bearing the pomalidomide substructure, together with a decreased mobility of the solvent-exposed part of the conjugates, could explain this behavior.     

Chiral Lewis acid catalysis in a visible light-triggered cycloaddition/rearrangement cascade

Cascade (domino) reactions facilitate the formation of complex molecules from simple starting materials in a single operation. It was found that 1-naphthaldehyde derivatives can be converted to enantioenriched (82–96% ee) polycyclic benzoisochromenes via a cascade of ortho photocycloaddition and ensuing acid-catalysed rearrangement reactions. The cascade was initiated by irradiation with visible light (λ = 457 nm) and catalysed by a chiral AlBr₃-activated 1,3,2-oxazaborolidine (14 examples, 65–93% yield). The absolute configuration of the products was elucidated by single crystal X-ray crystallography. Mechanistic experiments suggest that the ortho photocycloaddition occurs on the triplet hypersurface and that the chiral catalyst induces in this step the observed enantioselectivity.

Chiral Lewis acid catalysis enables the formation of enantioenriched polycyclic benzoisochromenes 2 from simple 1-naphthaldehydes 1 in an efficient cascade process triggered by a visible light-initiated ortho photocycloaddition.     

Meeting Report: Ten Years of Atomic and Molecular Science at Elettra

On the 31^st of May and the 1^st of June, 2007, a workshop to celebrate 10 years of atomic and molecular science was held at Elettra. The occasion marked the 10^th anniversary since the first beamtime was officially allocated to a user at the Gas Phase beamline, namely George King of Manchester University. As a satisfied user, King was not only present, but had beamtime during the workshop.