Copper and Zinc Metal-Organic Frameworks with Bipyrazole Linkers Display Strong Antibacterial Activity against Both Gram+ and Gram- Bacterial Strains.

Here, we report a new synthetic protocol based on microwave-assisted synthesis (MAS) for the preparation of higher yields of zinc and copper in MOFs based on different bis(pyrazolyl)-tagged ligands ([M(BPZ)]n where M = Zn(II), Cu(II), H2BPZ = 4,4'-bipyrazole, [M(BPZ-NH2)]n where M = Zn(II), Cu(II); H2BPZ-NH2 = 3-amino-4,4'-bipyrazole, and [Mx(Me4BPZPh)] where M = Zn(II), x = 1; Cu(II), x = 2; H2Me4BPZPh = bis-4'-(3',5'-dimethyl)-pyrazolylbenzene) and, for the first time, a detailed study of their antibacterial activity, tested against Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria, as representative agents of infections. The results show that all MOFs exert a broad-spectrum activity and strong efficiency in bacterial growth inhibition, with a mechanism of action based on the surface contact of MOF particles with bacterial cells through the so-called "chelation effect" and reactive oxygen species (ROS) generation, without a significant release of Zn(II) and Cu(II) ions. In addition, morphological changes were elucidated by using a scanning electron microscope (SEM) and bacterial cell damage was further confirmed by a confocal laser scanning microscopy (CLSM) test.

Bioactive Ag(I) coordination complexes as dopants for castor oil plasticized ethylcellulose films.

The effects exerted by new bioactive acylpyrazolonate Ag(I) derivatives of the general formula [Ag(QPy,CF3)(R-Im)] containing different substituents on the imidazole (R-Im) ancillary ligands and the natural plasticizer castor oil when both are added to the ethylcellulose (EC) biopolymer in the preparation of thin films as potential active food packaging materials are presented. The Ag(I) complexes [Ag(QPy,CF3)(Bn-Im)] and [Ag(QPy,CF3)(Bu-Im)], having benzyl and butyl substituents, whose single crystal molecular structures are reported, have proved to be highly compatible for efficient incorporation between the EC polymer and the hydrophobic plasticizer chains, giving rise, even at low concentrations, to homogeneous, robust and elastic films. The concomitant presence of these Ag(I) complexes and castor oil in the polymer EC matrix gives rise to thin films with improved antibacterial activity against Escherichia coli (E. coli) as a model of Gram-negative bacterial strains when compared to the non-plasticized ones, with very low Ag(I) migration in the three food simulants used (distilled water, ethanol 10% v/v and acetic acid 3% v/v) under two assay conditions (70 °C for 2 h and 40 °C for 10 days).

Pyrazolone-Based Zn(II) Complexes Display Antitumor Effects in Mutant p53-Carrying Cancer Cells.

The synthesis and characterization of nine Schiff bases of pyrazolone ligands HLn (n = 1-9) and the corresponding zinc(II) complexes 1-9 of composition [Zn(Ln)2] (n = 1-9) are reported. The molecular structures of complexes 2, 3, 4, 8, and 9 were determined by single-crystal X-ray diffraction analysis, highlighting in all cases a distorted tetrahedral geometry around the Zn(II) ion. Density functional theory studies are performed on both the HLn ligands and the derived complexes. A mechanism of dissociation and hydrolyzation of the coordinated Schiff base ligands is suggested, confirmed experimentally by powder X-ray diffraction study and photophysical studies. Complexes 1-9 were investigated in vitro as anticancer agents, along with mutant p53 (mutp53) protein levels in human cancer cell lines carrying R175H and R273H mutp53 proteins. Only those complexes with the highest Zn(II) ion release via dissociation have shown a significant cytotoxic activity with reduction of mutp53 protein levels.

Metformin and Covid-19: a systematic review of systematic reviews with meta-analysis.

INTRODUCTION: the COVID-19 infection, caused by severe Coronavirus 2 syndrome (Sars-Cov-2), immediately appeared to be the most tragic global pandemic event of the twentieth century. Right from the start of the pandemic, diabetic patients treated with metformin experienced a reduction in mortality and complications from COVID-19 compared to those with different treatments or no treatment. Objective The main objective of the study was to observe the effects of metformin in hospitalized subjects infected with COVID-19. Specifically, the outcomes of hospitalization in Intensive Care Units or death were examined. Materials and Methods A specific research PICOS was developed and the Pubmed, Embase and Scopus databases were consulted down to April 30, 2022. To estimate the extent of the metformin effect and risk of severity in SARS-CoV-2 infection, the Odd Ratio (OR) with 95% Confidence Interval (CI) published by the authors of the selected systematic reviews was used. Results from five systematic reviews 36 studies were selected. The final meta-analysis showed that thanks to treatment with metformin, DM2 patients affected by COVID-19 had protection against risk of disease severity, complications (ES 0.80; 95% CI) and mortality (ES 0.69; 95% CI). Conclusions More in-depth studies on the use of metformin, compared to other molecules, may be required to understand the real protective potential of the drug against negative outcomes caused by COVID-19 infection in DM2 patients.

Role of hydrazone substituents in determining the nuclearity and antibacterial activity of Zn(II) complexes with pyrazolone-based hydrazones.

Hydrazones and their metal derivatives are very important compounds in medicinal chemistry due to their reported variety of biological activities, such as antibacterial, antifungal and anticancer action. Five hydrazone-pyrazolone ligands H2Ln (n = 1-5) were prepared and fully characterized and their tautomerism was investigated in the solid state and solution. Five zinc(II) complexes 1-5 of composition [Zn(HLn)2] (n = 1 and 2), [Zn(HLn)2(H2O)2] (n = 3 and 5) and [Zn(HL4)2]n were synthesized and characterized by elemental analysis, IR, 1H, 19F, 13C, and 15N NMR spectroscopy, and ESI mass spectrometry. In addition, the structures of two ligands and three complexes were determined by single-crystal X-ray diffraction. The ligands H2L2 and H2L4 exist both in the NH,NH tautomeric form. Complexes 1 and 2 are mononuclear compounds, while complex 4 is a one-dimensional coordination compound. Density functional theory (DFT) calculations were carried out on proligands, their anions and all zinc complexes, confirming the experimental results, supporting IR and NMR assignments and giving proofs of the mononuclear diaqua structure of complexes 3 and 5. The antibacterial activity of the free ligands and the Zn(II) complexes was established against Escherichia coli and Staphylococcus aureus, and a strong efficiency has been found for Zn(II) complexes, particularly for the polynuclear 4 and the mononuclear diaqua complex 5, the latter containing a ligand with aliphatic and fluorinated substituents able to compromise the permeability of and disrupt the bacterial cell membrane.

New Zinc-Based Active Chitosan Films: Physicochemical Characterization, Antioxidant, and Antimicrobial Properties.

The improvement of the antioxidant and antimicrobial activities of chitosan (CS) films can be realized by incorporating transition metal complexes as active components. In this context, bioactive films were prepared by embedding a newly synthesized acylpyrazolonate Zn(II) complex, [Zn(QPhtBu)2(MeOH)2], into the eco-friendly biopolymer CS matrix. Homogeneous, amorphous, flexible, and transparent CS@Znn films were obtained through the solvent casting method in dilute acidic solution, using different weight ratios of the Zn(II) complex to CS and characterized by powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR), Raman, and scanning electron microscopy (SEM) techniques. The X-ray single-crystal analysis of [Zn(QPhtBu)2(MeOH)2] and the evaluation of its intermolecular interactions with a protonated glucosamine fragment through hydrogen bond propensity (HBP) calculations are reported. The effects of the different contents of the [Zn(QPhtBu)2(MeOH)2] complex on the CS biological proprieties have been evaluated, proving that the new CS@Znn films show an improved antioxidant activity, tested according to the DPPH method, with respect to pure CS, related to the concentration of the incorporated Zn(II) complex. Finally, the CS@Znn films were tried out as antimicrobial agents, showing an increase in antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus) with respect to pure CS, when detected by the agar disk-diffusion method.