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Ammonia has recently gained attention as a potential alternative fuel for gas turbines due to its relatively high energy density and mainly its low environmental impact since there is no CO2 production during the combustion. In this study, we evaluate the integration of a Power to Ammonia to Power process(P2A2P) with a system for power generation and investigate the impact of the use of ammonia in gas turbines from technical, energetic, and environmental points of view. First, the P2A2P system layout is defined and then the scale-up of the process is evaluated to be integrated with a commercial medium-size Gas Turbine. The optimization of the size and Balance Of Plant (BOP) of the P2A2P process and the integration with the GT system are evaluated also considering the impact on the GT system. Moreover, a generic radial-tangential swirler representing a first design attempt to study the retrofittability of a natural gas-designed combustion chamber to operate with an NH3-H2 fuel blend is investigated. The results from dedicated experimental tests and the corresponding CFD simulations are discussed with a strong focus on the NOx pollutant emission representing one of the main limiting factors for ammonia as fuel.

Background: Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin which plays survival- and growth-promoting activity in neuronal cells and it is involved in cellular plasticity mechanisms as it controls activity dependent synaptic transmission. A functional polymorphism (Val66Met) in the pro-region of BDNF, which affects the intracellular trafficking of proBDNF has been associated with memory and cognitive deficits as well as to an increased susceptibility for several psychiatric disorders especially those with a neurodevelopmental origin. To date, no study has evaluated the influence of the Val66Met polymorphism on BDNF levels in a peripheral system that may reflect fetal neurodevelopment. Therefore we investigated in amniotic fluids (AF) obtained from 139 healthy women during 15-17 week of pregnancy, BDNF protein levels in correlation with the Val66Met polymorphism.Results: Interestingly we found a significant BDNF protein levels reduction in 55 Met carriers (Val/Met and Met/Met) (p = 0.002) as compared to 84 non carriers (Val/Val), and no effect of fetus gender, maternal age or gestation week on BDNF levels has been observed.Conclusion: These results, although explorative, indicate that during fetal life the Val66Met genotype might influences BDNF protein levels in AF supporting the involvement of this polymorphism in behavioral and functional brain individual differences in the adulthood. [ABSTRACT FROM AUTHOR]

A systematic study on the human antimicrobial peptide calcitermin (VAIALKAAHYHTHKE) and its carefully designed derivatives was undertaken to verify the impact of divalent copper and zinc ions on the stability, coordination and antimicrobial activity of the formed complexes. In this work we investigate the calcitermin mutants where the alanine in position 7 and 8 is substituted with an arginine residue, with the aim of enhancing the antibacterial activity. Additionally, the analogue where alanine in position 7 is replaced with a histidine is considered, to obtain a chelating sequence with four histidines in alternate position; the aim of this change was to increase the cationic properties of the peptide under acidic conditions and possibly enhance its binding ability towards the metal ions. Through a comprehensive analytical approach involving potentiometric titrations, mass spectrometry, UV-Vis spectrophotometry, NMR and circular dichroism, we delved into the formation equilibria and coordination chemistry of the formed copper(II) and zinc(II) complexes. Antimicrobial assays are also performed to assess the bioactivity of the compounds against a broad spectrum of microorganisms, revealing the pivotal role of positively charged residues in enhancing the antibacterial activity of calcitermin. The obtained results serve as an important stepping stone towards the development of novel metal-based antimicrobial agents., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The design of novel chelators for therapeutic applications has been the subject of extensive research to address various diseases. Many chelators can manipulate the levels of metal ions within cells and effectively modulate the metal excess. In some cases, chelators show significant toxicity to cells. We investigated polyimidazole ligands by potentiometry and UV-Vis spectroscopy for their ability to form copper(II) complexes. We also compared the antiproliferative activity of the polyimidazole ligands and their copper(II) complexes with polypyridine ligands in CaCo-2 (colorectal adenocarcinoma), SH-SY5Y (neuroblastoma) and K562 (chronic myelogenous leukemia) cells and normal HaCaT (keratinocyte) cells. Polyimidazole ligands are less cytotoxic than their analogous polypyridine ligands. All polyimidazole ligands, except the tetraimidazole ligand for K562 cells, did not show any significant effect on the viability of cancer and normal cells. In contrast, the cytotoxic activity of polypiridine ligands was also observed in normal cells with IC 50 values similar to those of cancer cells. Tetraimidazole ligand, the only ligand active on the leukemic K562 cell line, induced caspase-dependent apoptosis and increased intracellular reactive oxygen species production with mitochondrial damage. The low cytotoxicity of the polyimidazole ligands, even if it limits their use as anticancer agents, could make them useful in other medical applications, such as in the treatment of metal overload, microbial infections, inflammation or neurodegenerative disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Graziella Vecchio reports financial support was provided by Italian Ministry of Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Antimicrobial peptides are promising alternatives to classical antibiotics. Their microbicidal activity can arise from different mechanisms, one of which is known as nutritional immunity and has metal micronutrients and metal-binding biomolecules as its main players. Calcitermin is an antimicrobial peptide and an effective metal chelator. Its properties as an antibacterial and anti- Candida agent have been recently studied both as a free peptide and in the presence of zinc and copper ions, with which it forms stable complexes. Calcitermin derivatives have also gained attention thanks to the possibility of improving their properties, like metal-binding affinity and/or stability in biological fluids, through ad hoc modifications of the native peptide sequence. In this work, the Ala-to-Ser substitutions close to the coordination site of calcitermin have been introduced to study the impact on the biological activity and metal-binding properties. Our results show that metal coordination has a clear impact on the bioactivity of the studied compounds, to the point that the truncated fragment of calcitermin, solely containing the main metal-binding residues, also shows antimicrobial activity.

Background: Positron emission tomography (PET) is a highly sensitive method that provides fine resolution images, useful in the field of clinical diagnostics. In this context, Zirconium-89 ( 89 Zr)-based imaging agents have represented a great challenge in molecular imaging with immuno-PET, which employs antibodies (mAbs) as biological vectors. Indeed, immuno-PET requires radionuclides that can be attached to the mAb to provide stable in vivo conjugates, and for this purpose, the radioactive element should have a decay half-life compatible with the time needed for the biodistribution of the immunoglobulin. In this regard, 89 Zr is an ideal radioisotope for immuno-PET because its half-life perfectly matches the in vivo pharmacokinetics of mAbs., Results: The main objective of this work was the design and synthesis of a series of bifunctional octadentate pseudopeptides able to generate stable 89 Zr complexes. To achieve this, here we investigated hydroxamate, N-methylhydroxamate and catecholate chelating moieties in complexing radioactive zirconium. N-methylhydroxamate proved to be the most effective 89 Zr-chelating group. Furthermore, the increased flexibility and hydrophilicity obtained by using polyoxyethylene groups spacing the hydroxamate units led to chelators capable of rapidly forming (15 min) stable and water-soluble complexes with 89 Zr under mild reaction conditions (aqueous environment, room temperature, and physiological pH) that are mandatory for complexation reactions involving biomolecules. Additionally, we report challenge experiments with the competitor ligand EDTA and metal ions such as Fe 3+ , Zn 2+ and Cu 2+ . In all examined conditions, the chelators demonstrated stability against transmetallation. Finally, a maleimide moiety was introduced to apply one of the most promising ligands in bioconjugation reactions through Thiol-Michael chemistry., Conclusion: Combining solid phase and solution synthesis techniques, we identified novel 89 Zr-chelating molecules with a peptide scaffold. The adopted chemical design allowed modulation of molecular flexibility, hydrophilicity, as well as the decoration with different zirconium chelating groups. Best results in terms of 89 Zr-chelating properties were achieved with the N-methyl hydroxamate moiety. The Zirconium complexes obtained with the most effective compounds were water-soluble, stable to transmetallation, and resistant to peptidases for at least 6 days. Further studies are needed to assess the potential of this novel class of molecules as Zirconium-chelating agents for in vivo applications., (© 2024. The Author(s).)

Zn(II) is essential for bacterial survival and virulence. In host cells, its abundance is extremely limited, thus, bacteria have evolved transport mechanisms that enable them to take up this essential metal nutrient. Paracoccus denitrificans encodes two solute binding proteins (SBPs) - ZnuA and AztC, which are responsible for zinc acquisition from the host cells. We focus on understanding the interactions of Zn(II) and Ni(II) (zinc's potential competitor, which is a biologically relevant metal ion essential for various bacterial enzymes) with the extracellular ZnuA and AztC's loops from P. denitrificans that are expected to be possible Zn(II) binding sites. In the case of Zn(II) complexes with ZnuA outercellular loop regions, the numerous histidines act as anchoring donors, forming complexes with up to four coordinated His residues, while in the AztC region, three imidazole nitrogens and one water molecule are involved in Zn(II) binding. In Zn(II) complexes with ZnuA His-rich loop regions, so-called polymorphic binding sites are observed. The large number of available imidazoles and carboxylic side chains also strongly affects the structure of Ni(II) complexes; the more histidines in the studied peptide, the higher the affinity to bind Ni(II) and the higher the pH value at which amide nitrogens start to participate in Ni(II) binding. Additionally, for Ni(II)-ZnuA complexes, a more rare octahedral geometry is observed and such complexes are more stable than the corresponding Zn(II) ones, in contrast to what was observed in the AztC region, suggesting that the numerous histidyl and glutamic acid side chains are more tempting for Ni(II) than for Zn(II).The general strong affinity of Zn(II)-zincophore complexes is also discussed.

The use of model peptides that can simulate the behaviour of a protein domain is a very successful analytical method to study the metal coordination sites in biological systems. Here we study zinc and copper binding ability of the sequence HTHEHSHDHSHAH, which serves as model for the metal interactions with YrpE, a putative metal-binding protein of the ZinT family identified in Bacillus subtilis. Compared to other ZinT proteins secreted by Gram-negative bacteria, the metal-coordination properties of YrpE N-terminal histidine-rich domain have not been yet characterized. Different independent analytical methods, aimed at providing information on the stability and structure of the formed species, have been employed, including potentiometric titrations, electrospray ionization mass spectrometry, UV-Vis spectrophotometry, circular dichroism and electron paramagnetic resonance spectroscopy. The obtained speciation models and equilibrium constants allowed to compare the metal-binding ability of the investigated polyhistidine sequence with that of other well-known histidine-rich peptides. Our thermodynamic results revealed that the YrpE domain HTHEHSHDHSHAH forms more stable metal complexes than other His-rich domains of similar ZinT proteins. Moreover, the studied peptide, containing the alternated (-XH-) n motif, proved to be even more effective than the His6-tag (widely used in immobilized metal ion affinity chromatography) in binding zinc ions., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)