Manuel Gacitúa

Spectral, theoretical characterization and antifungal properties of two phenol derivative Schiff bases with an intramolecular hydrogen bond

Schiff bases show a wide variety of applications of great importance in medicinal research due to their range of biological activities. In this article we describe the electronic structure, optical, redox and wide antifungal properties of (E)-2-{[(2-aminopyridin-3-yl)imino]-methyl}-4,6-di-tert-butyl-phenol (L1) and (E)-2-{[(3-aminopyridin-4-yl)imino]-methyl}-4,6-di-tert-butyl-phenol (L2), two isomer phenol derivative Schiff bases exhibiting a strong intramolecular hydrogen bond (O–H⋯N). These compounds were characterized by their 1H, HHCOSY, 13C-NMR, FT-IR spectra, and by cyclic voltammetry. All the experimental results were complemented with theoretical calculations using density functional theory (DFT) and time-dependent DFT (TDDFT). The antimicrobial activity of the compounds described herein was assessed by determining the minimal inhibitory concentration (MIC) and by a modification of the Kirby–Bauer method. We tested Salmonella enterica serovar Typhi (S. Typhi, Gram-negative bacteria), Cryptococcus spp. (yeast), and Candida albicans (yeast). We found that neither L1 nor L2 showed antimicrobial activity against S. Typhi or Candida albicans. On the other hand, L2, in contrast to L1, exhibited antifungal activity against a clinical strain of Cryptococcus spp. (MIC: 4.468 μg ml−1) even better than ketoconazole antifungal medicaments. We mentioned above that L1 and L2 are isomer species, because the amino group is in the ortho-position in L1 and in the para-position in L2, however no significant differences were detectable by UV-vis, FT-IR, oxidation potentials and TDDFT calculations, but importantly, the antifungal activity was clearly discriminated between these two isomers.

Synthesis, characterization and computational studies of (E)-2-{[(2-aminopyridin-3-yl)imino]-methyl}-4,6-di-tert-butylphenol

(E)-2-{((2-Aminopyridin-3-yl)imino)-methyl}-4,6-di-tert-butyl-phenol (3), a ligand containing an intramolecular hydrogen bond, was prepared according to a previous literature report, with modifications, and was characterized by UV-vis, FTIR, 1H-NMR, 13C-NMR, HHCOSY, TOCSY and cyclic voltammetry. Computational analyses at the level of DFT and TD-DFT were performed to study its electronic and molecular structures. The results of these analyses elucidated the behaviors of the UV-vis and electrochemical data. Analysis of the transitions in the computed spectrum showed that the most important band is primarily composed of a HOMO→LUMO transition, designated as an intraligand (IL) charge transfer.

Experimental and theoretical studies of the ancillary ligand (E)-2-((3-amino-pyridin-4-ylimino)-methyl)-4,6-di-tert-butylphenol in the rhenium(I) core

The fac-[Re(CO)3(deeb)L]+ complex (C2) where L is the (E)-2-((3-amino-pyridin-4-ylimino)-methyl)-4,6-di-tert-butylphenol ancillary ligand, which presents an intramolecular hydrogen bond, has been synthesized and characterized using UV-vis, 1H-NMR, FT-IR, cyclic voltammetry and DFT calculations. The UV-vis absorption and emission properties have been studied at room temperature and the results were compared with TDDFT calculations including spin–orbit effects. We report an alternative synthesis route for the fac-Re(CO)3(deeb)Br (C1) complex where deeb = (4,4′-diethanoate)-2,2′-bpy. Besides, we have found that the C1 shows a red shift in the emission spectrum due to the nature of the ancillary electron donating ligand, while the C2 complex shows a blue shift in the emission spectrum suggesting that the ancillary ligand L has electron withdrawing ability and the importance of the intramolecular hydrogen bond. The calculations suggest that an experimental mixed absorption band at 361 nm could be assigned to MLCT and LLCT transitions. The electron withdrawing nature of the ancillary ligand in C2 explains the electrochemical behavior, which shows the oxidation of ReI at 1.83 V and the reduction of deeb at −0.77 V.

Theoretical and experimental characterization of a novel pyridine benzimidazole: suitability for fluorescence staining in cells and antimicrobial properties

Benzimidazoles presenting intramolecular hydrogen bonding interactions have been normally used to better understand the role of H-bonding in biological processes. Here, we present an experimental and theoretical study of a new compound [2,4-di-tert-butyl-6-(3H-imidazo[4,5-c]pyridine-2-yl)phenol]; (B2), a benzimidazole derivate, exhibiting an intramolecular hydrogen bond. B2 was synthesized and characterized by its 1H, HHCOSY, FT-IR and mass spectra (EI-MS 323 M+). The electronic and optical properties of B2 were studied with theoretical calculations using density functional theory (DFT) and time-dependent DFT (TDDFT). B2 showed luminescent emission at room temperature in different solvents, with a large Stokes shift (e.g.; λex = 335 nm; λem = 510 nm in acetonitrile). Also, the quantum yield (φ = 0.21) and theoretical band emission are reported. We found that B2 exhibited a fluorescence emission at around 500 nm in ethanol and in acetonitrile that could be quenched by aqueous solutions of Hg(NO3)2 in the range of micro molar concentrations. Cyclic voltammetry in acetonitrile showed a strong anodic response due to a quasireversible process, with reduction and oxidation waves at −1.28 and −0.47 V vs. SCE. Regarding the biological properties, we assessed the antimicrobial activity of B2 in Salmonella enterica (bacteria), Cryptococcus spp. (yeast), Candida albicans (yeast), Candida tropicalis (yeast) and Botrytis cinerea (mold). To this end, we determined the minimal inhibitory concentration (MIC) (for bacteria and yeasts), the growth inhibition halos (for yeasts), and the inhibition of mycelial growth (for the mold). We observed that B2 exerted an antifungal effect against Cryptococcus spp. and Botrytis cinerea. In addition, due to its fluorescence properties, B2 has proven to be a suitable marker to observe bacteria (Salmonella enterica and an Escherichia coli derivative), yeasts (Candida albicans), and even human cells (SKOV-3 and HEK-293) by confocal microscopy.

OLIGOMER CHAIN LENGTH EFFECT ON THE NUCLEATION AND GROWTH MECHANISMS (NGM) OF POLYTHIOPHENE

In this research a comparative study of the starting unit chain length effect on the electropolymerization of thiophene or its oligomers was carried out considering mono (1Th), bi (2Th), ter (3Th), tetra (4Th) and sexi (6Th)-thiophene as starting units. The deconvolved transient allows stating that the growth of polythiophene (PTh) employing each of the starting units have the same predominant contribution to the nucleation and growth mechanism (NGM). The others contributions disappear as the length of the starting unit chain increase. The results were validated by scanning electron microscopy (SEM) of PTh deposits obtained onto SnO2 coated glass, following a potential pulse program. Besides of corroborating the electropolymerization model, this study suggested the possibility of designing and performing suitable experiments leading to the attainment of electro-deposited conductive polymers bearing a desired morphology, appropriated for prospective applications.

K–Ca–Mg binary cation exchange in saline soils from the north of Chile

The selectivities of the K–Ca and K–Mg cation exchange reactions were studied in batch experiments carried out with 7 Chilean saline sandy soils with low organic matter (OM) content, and rich in quartz and halite, by using the experimental Gaines and Thomas procedure and the semi-empirical Rothmund–Kornfeld approach. The soils present high reactivity to the exchange process in terms of CEC and a preference order from the surface for the cation of K > Ca > Mg. In addition, the existence of different types of exchange sites was determined; some were specific for determined cations and others presented free competition. The proposed exchange reaction for both equilibria was thermodynamically possible and the studied cations presented a decreasing mobility order K > Ca > Mg, which follows the increasing order of hydrated ionic radii. As for the Rothmund–Kornfeld semi-empirical approach, it can be employed on soils classified as Aridisol due to good fit with the experimental data. On the other hand, the Gaines and Thomas approach is only experimentally applicable since poses some restrictions concerning to salinity and carbonate contents in the studied soils.

Fluorescence probes for prokaryotic and eukaryotic cells using Re(CO)3+ complexes with an electron withdrawing ancillary ligand

Research in fluorescence microscopy presents new challenges, especially with respect to the development of new metal-based fluorophores. In this work, new fac-[Re(CO)3(bpy)L]PF6 (C3) and fac-[Re(CO)3(dmb)L]PF6 (C4) complexes, where L is an ancillary ligand, E-2-((3-amino-pyridin-4-ylimino)-methyl)-4,6-di-tert-butylphenol, both exhibiting an intramolecular hydrogen bond, have been synthesized for use as preliminary probes for fluorescence microscopy. The complexes were characterized using chemical techniques such as UV-vis, 1H-NMR, TOCSY, FT-IR, cyclic voltammetry, mass spectrometry (EI-MS 752.22 M+ for C3 and 780.26 M+ for C4) and DFT calculations including spin–orbit effects. The electron withdrawing nature of the ancillary ligand L in C3 and C4 explains their electrochemical behavior, which shows the oxidation of ReI at 1.84 V for C3 and at 1.88 V for C4. The UV-vis absorption and emission properties have been studied at room temperature in acetonitrile solution. The complexes show luminescent emission with a large Stokes shift (λex = 366 nm, λem = 610 nm for C3 and λex = 361 nm, λem = 560 nm for C4). The TDDFT calculations suggest that an experimental mixed absorption band at 360 nm could be assigned to MLCT (d(Re) → π*(dmb)) and LLCT (π(L) → π*(dmb)) transitions. We have also assessed the cytotoxicity of C3 and C4 in an epithelial cell line (T84). We found that 12.5 μg ml−1 of C3 or C4 is the minimum concentration needed to kill 80% of the cell population, as determined by neutral red uptake. Finally, the potential of C3 and C4 as biological dyes for use in fluorescent microscopy was assessed in bacteria (Salmonella enterica) and yeasts (Candida albicans and Cryptococcus spp.), and in an ovarian cancer cell line (SKOV-3). We found that in all cases, both C3 and C4 are suitable compounds to be used as fluorescent dyes for biological purposes. In addition, we present evidence suggesting that these rhenium(I) tricarbonyl complexes may be also useful as differential fluorescent dyes in yeasts (Candida albicans and Cryptococcus spp.), without the need for antibodies.

Substituted bidentate and ancillary ligands modulate the bioimaging properties of the classical Re(I) tricarbonyl core with yeasts and bacteria

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.

Electrosynthesis and Characterisation of Polymer Nanowires from Thiophene and its Oligomers

Validating methodology formerly reported, polythiophene electrosynthesised as nanowires from the monomer and some of its oligomers is now described. The work is conducted on a platinum electrode previously modified with a template that tunes the polymer growth inside the confined space of the pores. In addition, it was confirmed that the use of larger chain-length oligomers as starting unit helps to obtain more homogeneous wires, although its adhesion to the supporting substrate works against. Characterisation allows to verify the morphology and to confirm higher levels of doping/undoping of the nanostructures as compared to the corresponding bulky deposits, which points to improved macroscopic properties. It is demonstrated that this strategy allows obtaining nanowires of very small diameter, ranging from 2.8 to 4.0 nm; thus demonstrating that the use of this approach enables the direct obtainment of nanowires upon the electrode surface, with the obvious advantage that this implies.

Two New Fluorinated Phenol Derivatives Pyridine Schiff Bases: Synthesis, Spectral, Theoretical Characterization, Inclusion in Epichlorohydrin-β-Cyclodextrin Polymer, and Antifungal Effect

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 ki , TGA, DSC, and SBET. 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.