Schiff bases exhibit a broad range of applications, including their use as catalysts, stabilizers, dyes, and intermediates in organic synthesis; and biological activities, such as antifungal properties. In this work, we synthesized and characterized three new pyridine Schiff bases L3 ((E)-2-{[(3-aminopyridin-4-yl)imino]-methyl}-4,6-di-chloro-phenol), L4 ((E)-2-{[(3-aminopyridin-4-yl)imino]-methyl}-6-chloro-phenol), and L5 ((E)-2-{[(3-aminopyridin-4-yl)imino]-methyl}-4-methyl-phenol) to explore their structure–bioactivity relationship as antifungal agents. We also synthesized and characterized a diamine-derived Schiff base (L6) that is similar to (E)-2-{[(3-aminopyridin-4-yl)imino]-methyl}-4,6-di-tert-butyl-phenol (L2, which previously demonstrated antifungal activity), but lacks the pyridine ring, to assess the impact of this structural modification on the biological properties. All the Schiff bases were characterized by FTIR, ¹H and ¹³C NMR, DEPT, HHCOSY, TOCSY, UV-vis, MS, cyclic voltammetry, DFT calculations, and NBO to assess the stability of the intramolecular hydrogen bond (IHB). In addition, we determined the antimicrobial properties by obtaining the minimal inhibitory concentration (MIC) for Cryptococcus spp. (yeast) and Salmonella enterica (bacteria), and growth inhibition of Botrytis cinerea (mold). We found that the antifungal activity of these Schiff bases relied on the nitrogen atom in the pyridine ring, and the antifungal activity can be modulated by different substituents in the phenolic ring. In this work we provide data supporting a correlation between the structure and bioactivity in this kind of Schiff base. The understanding of the structural prerequisites for antimicrobial activity could contribute to designing new drugs.

Biofilms correspond to complex communities of microorganisms embedded in an extracellular polymeric matrix. Biofilm lifestyle predominates in Pseudomonas aeruginosa, an opportunistic Gram negative pathogen responsible for a wide spectrum of infections in humans, plants and animals. In this context, anti-biofilm can be considered a key strategy to control P. aeruginosa infections, thereby more research in the field is required. On the other hand, Lactobacillus species have been described as beneficial due to their anti-biofilm properties and their consequent effect against a wide spectrum of pathogens. In fact, biofilm-forming Lactobacilli seem to be more efficient than their planktonic counterpart to antagonise pathogenic bacteria. In this work, we demonstrated that Lactobacillus kunkeei, a novel Lactobacillus species isolated from honeybee guts, can form biofilms in vitro. In addition, the L. kunkeei biofilm can, in turn, inhibit the formation of P. aeruginosa biofilms. Finally, we found that L. kunkeei strains attenuate infection of P. aeruginosa in the Galleria mellonella model, presumably by affecting P. aeruginosa biofilm formation and/or their stability. Since L. kunkeei presents characteristics of a probiotic, this work provides evidence arguing that the use of this Lactobacillus species in both animals (including insects) and humans could contribute to impair P. aeruginosa biofilm formation.

It has been reported that the structure of the Schiff bases is fundamental for their function in biomedical applications. Pyridine Schiff bases are characterized by the presence of a pyridine and a phenolic ring, connected by an azomethine group. In this case, the nitrogen present in the pyridine is responsible for antifungal effects, where the phenolic ring may be also participating in this bioactivity. In this study, we synthesized two new pyridine Schiff Bases: (E)-2-[(3-Amino-pyridin-4-ylimino)-methyl]-4,6-difluoro-phenol (F1) and (E)- 2-[(3-Amino-pyridin-4-ylimino)-methyl]-6-fluoro-phenol (F2), which only differ in the fluorine substitutions in the phenolic ring. We fully characterized both F1 and F2 by FTIR, UV-vis, ¹H; ¹³C; ¹⁹F-NMR, DEPT, HHCOSY, TOCSY, and cyclic voltammetry, as well as by computational studies (DFT), and NBO analysis. In addition, we assessed the antifungal activity of both F1 (two fluorine substitution at positions 4 and 6 in the phenolic ring) and F2 (one fluorine substitution at position 6 in the phenolic ring) against yeasts. We found that only F1 exerted a clear antifungal activity, showing that, for these kind of Schiff bases, the phenolic ring substitutions can modulate biological properties. In addition, we included F1 and F2 into in epichlorohydrin-β-cyclodextrin polymer (βCD), where the Schiff bases remained inside the βCD as determined by the k_i, TGA, DSC, and S_BET. We found that the inclusion in βCD improved the solubility in aqueous media and the antifungal activity of both F1 and F2, revealing antimicrobial effects normally hidden by the presence of common solvents (e.g., DMSO) with some cellular inhibitory activity. The study of structural prerequisites for antimicrobial activity, and the inclusion in polymers to improve solubility, is important for the design of new drugs.

Re(I) complexes have exposed highly suitable properties for cellular imaging (especially for fluorescent microscopy) such as low cytotoxicity, good cellular uptake, and differential staining. These features can be modulated or tuned by modifying the ligands surrounding the metal core. However, most of Re(I)-based complexes have been tested for non-walled cells, such as epithelial cells. In this context, it has been proposed that Re(I) complexes are inefficient to stain walled cells (i.e., cells protected by a rigid cell wall, such as bacteria and fungi), presumably due to this physical barrier hampering cellular uptake. More recently, a series of studies have been published showing that a suitable combination of ligands is useful for obtaining Re(I)-based complexes able to stain walled cells. This review summarizes the main characteristics of different fluorophores used in bioimage, remarking the advantages of d⁶-based complexes, and focusing on Re(I) complexes. In addition, we explored different structural features of these complexes that allow for obtaining fluorophores especially designed for walled cells (bacteria and fungi), with especial emphasis on the ligand choice. Since many pathogens correspond to bacteria and fungi (yeasts and molds), and considering that these organisms have been increasingly used in several biotechnological applications, development of new tools for their study, such as the design of new fluorophores, is fundamental and attractive.

Searching for adequate and effective compounds displaying antimicrobial activities, especially against Gram-positive bacteria, is an important research area due to the high hospitalization and mortality rates of these bacterial infections in both the human and veterinary fields. In this work, we explored (E)-4-amino-3-((3,5-di-tert-butyl-2-hydroxybenzylidene)amino) benzoic acid (SB-1, harboring an intramolecular hydrogen bond) and (E)-2-((4-nitrobenzilidene)amino)aniline (SB-2), two Schiff bases derivatives. Results demonstrated that SB-1 showed an antibacterial activity determined by the minimal inhibitory concentration (MIC) against Staphylococcus aureus, Enterococcus faecalis, and Bacillus cereus (Gram-positive bacteria involved in human and animal diseases such as skin infections, pneumonia, diarrheal syndrome, and urinary tract infections, among others), which was similar to that shown by the classical antibiotic chloramphenicol. By contrast, this compound showed no effect against Gram-negative bacteria (Klebsiella pneumoniae, Escherichia coli, and Salmonella enterica). Furthermore, we provide a comprehensive physicochemical and theoretical characterization of SB-1 (as well as several analyses for SB-2), including elemental analysis, ESMS, ¹H and ¹³C NMR (assigned by 1D and 2D techniques), DEPT, UV-Vis, FTIR, and cyclic voltammetry. We also performed a computational study through the DFT theory level, including geometry optimization, TD-DFT, NBO, and global and local reactivity analyses.

Rhenium(I) tricarbonyl complexes with heteroaromatic ligands have been intensely investigated with respect to their properties as imaging probes, although they have only recently been tested in vivo. In this context, fac-Re(CO)₃(N,N)L complexes (N,N: substituted bidentate ligand; L: ancillary ligand) are the most studied complexes due to their photophysical properties. However, the role of the N,N bidentate ligand in classical fac-Re(CO)₃(N,N)L complexes (i.e. where L is a halogen such as Br) has not been explored regarding cytotoxicity and staining capabilities in walled cells (i.e. yeasts and bacteria). In the present study, we tested different rhenium(I) tricarbonyl complexes of type fac-Re(CO)₃(N,N)Br [where N,N are 1,10-phenanthroline (phen) (C1); 5,6-dione-1,10-phenanthroline (dione) (C2); 2,2′-bpy (bpy) (C3); 4,4′-dimethyl-2,2′-bpy (dmb) (C4); and 4,4′-diethanoate-2,2′-bpy (deeb) (C5)] in order to characterize the properties of the N,N bidentate ligand in cellular biomarkers. We also compared these classical rhenium(I) tricarbonyl complexes (C1 to C5) with a fac-Re(CO)₃(deeb)L⁺ complex, where L is the Schiff base (E)-2-((3-amino-pyridin-4-ylimino)-methyl)-4,6-di-tert-butylphenol, with respect to its potential for cell labelling. In our study, we found that both the N,N substituted bidentate ligand and the ancillary ligand L contributed to modulating the suitability in cell bioimaging, showing that it is possible to perform molecular engineering design to obtain improved biomarkers for walled cells, and eventually for other cell types.