Marcelo Preite

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.

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.

Hetero-Diels–Alder reaction of halogenated quinones with a polygodial-derived azadiene

The reaction between polygodial dimethylhydrazone and haloquinones under an air atmosphere is described. The terpene moiety undergoes a degradative oxidation to an 11-norsequiterpene ketone containing a quinolinequinone skeleton.

Synthesis and Plant Growth-Activity of three New Brassinosteroids Analogues

Abstract The chemical synthesis, starting from deoxycholic acid methyl ester, of several brassinosteroids analogues with different oxygenated functions in ring C, is described. Three of them showed growth-promoting activity

CONVERSION OF (+)-CONFERTIFOLIN INTO 11,12-BISNORDRIMAN-9-ONE AND (+)-8αH,9αH-11,12-DIACETOXYDRIMANE*

A short synthesis of naphthalenone (−)-1 and natural drimanic diacetate ((+)-3), from confertifolin ((+)-4), is reported. The proposed absolute configuration of (+)-3 was confirmed. *Dedicated to Prof. E. A. Rúveda on the occasion of his retirement.

Regiospecific Michael reaction of (+)-euryfuran with activated 1,4-benzoquinones

Abstract (+)-Euryfuran cycloadds regiospecifically to activated monosubstituted 1,4-benzoquinones under mild conditions to give the corresponding Michael adducts which, depending on the quinone substituent, undergo in situ redox reactions to the respective euryfurylbenzoquinones. One of the reported Michael adducts undergoes a facile stereoselective cyclisation under oxidant conditions to afford a naphthofuro[4,3- c ]benzopyran derivative. The regiospecificity of the Michael and cyclisation reactions are discussed.

Phenyl 3,5-di-tert-butyl-2-hy-droxy-benzoate.

The title molecule, C21H26O3, has a six-membered planar carbon ring as the central core, substituted at position 1 with phenoxycarbonyl, at position 2 with hydroxy and at positions 3 and 5 with tert-butyl groups. The structure shows two independent but very similar molecules within the asymmetric unit. For both independent molecules, the ester carboxylate group is coplanar with the central core, as reflected by the small C—C—O—C torsion angles [179.95 (17) and 173.70 (17)°]. In contrast, the phenyl substituent is almost perpendicular to the carboxylate –CO2 fragment, as reflected by C—O—C—C torsion angles, ranging from 74 to 80°. The coplanarity between the central aromatic ring and the ester carboxylate –CO2– group allows the formation of an intramolecular hydrogen bond, with O⋯O distances of 2.563 (2) and 2.604 (2) Å.

The Michael-Aldol Condensation Approach to the Construction of Key Intermediates in the Synthesis of Nimbolide and Nagilactone A

Abstract A short route for the preparation of highly oxygenated trans-decalines, key intermediates for the synthesis of nimbolide (2a) and nagilactone A (13), by a sequence involving a Michael addition followed by an aldol condensation, is described.