Physicochemical and Theoretical Characterization of a New Small Non-Metal Schiff Base with a Differential Antimicrobial Effect against Gram-Positive Bacteria.

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.

New Cationic fac-[Re(CO)3(deeb)B2]+ Complex, Where B2 Is a Benzimidazole Derivative, as a Potential New Luminescent Dye for Proteins Separated by SDS-PAGE.

Sodium-dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) can be used to separate proteins based mainly on their size such as in denaturing gels. Different staining methods have been reported to observe proteins in the gel matrix, where the most used dyes are generally anionic. Anionic dyes allow for interactions with protonated amino acids, retaining the dye in the proteins. Fluorescent staining is an alternative technique considered to be sensitive, safe, and versatile. Some anionic complexes based on d6 transition metals have been used for this purpose, where cationic dyes have been less explored in this context. In this work, we synthesized and characterized a new monocationic rhenium complex fac-[Re(CO)3(deeb)B2]+ (where deeb is 4,4'-bis(ethoxycarbonyl)-2,2'-bpy and B2 is 2,4-di-tert-butyl-6-(3H-imidazo[4,5-c]pyridine-2-yl)phenol). We carried out a structural characterization of this complex by MS+, FTIR, 1H NMR, D2O exchange, and HHCOSY. Moreover, we carried out UV-Vis, luminescence, and cyclic voltammetry experiments to understand the effect of ligands on the complex's electronic structure. We also performed relativistic theoretical calculations using the B3LYP/TZ2P level of theory and R-TDDFT within a dielectric continuum model (COSMO) to better understand electronic transitions and optical properties. We finally assessed the potential of fac-[Re(CO)3(deeb)B2]+ (as well as the precursor fac-Re(CO)3(deeb)Br and the free ligand B2) to stain proteins separated by SDS-PAGE. We found that only fac-[Re(CO)3(deeb)B2]+ proved viable to be directly used as a luminescent dye for proteins, presumably due to its interaction with negatively charged residues in proteins and by weak interactions provided by B2. In addition, fac-[Re(CO)3(deeb)B2]+ seems to interact preferentially with proteins and not with the gel matrix despite the presence of sodium dodecyl sulfate (SDS). In future applications, these alternative cationic complexes might be used alone or in combination with more traditional anionic compounds to generate counterion dye stains to improve the process.

New Properties of a Bioinspired Pyridine Benzimidazole Compound as a Novel Differential Staining Agent for Endoplasmic Reticulum and Golgi Apparatus in Fluorescence Live Cell Imaging.

In this study, we explored new properties of the bioinspired pyridine benzimidazole compound B2 (2,4-di-tert-butyl-6-(3H-imidazo[4,5-c]pyridine-2-yl)phenol) regarding its potential use as a differential biomarker. For that, we performed 1D 1HNMR (TOCSY), UV-Vis absorption spectra in different organic solvents, voltammetry profile (including a scan-rate study), and TD-DFT calculations that including NBO analyses, to provide valuable information about B2 structure and luminescence. In our study, we found that the B2 structure is highly stable, where the presence of an intramolecular hydrogen bond (IHB) seems to have a crucial role in the stability of luminescence, and its emission can be assigned as fluorescence. In fact, we found that the relatively large Stokes Shift observed for B2 (around 175 nm) may be attributed to the stability of the B2 geometry and the strength of its IHB. On the other hand, we determined that B2 is biocompatible by cytotoxicity experiments in HeLa cells, an epithelial cell line. Furthermore, in cellular assays we found that B2 could be internalized by passive diffusion in absence of artificial permeabilization at short incubation times (15 min to 30 min). Fluorescence microscopy studies confirmed that B2 accumulates in the endoplasmic reticulum (ER) and Golgi apparatus, two organelles involved in the secretory pathway. Finally, we determined that B2 exhibited no noticeable blinking or bleaching after 1 h of continuous exposure. Thus, B2 provides a biocompatible, rapid, simple, and efficient way to fluorescently label particular organelles, producing similar results to that obtained with other well-established but more complex methods.

Chronic Intermittent Hypoxia-Induced Vascular Dysfunction in Rats is Reverted by N-Acetylcysteine Supplementation and Arginase Inhibition.

Chronic intermittent hypoxia (CIH), the main attribute of obstructive sleep apnea (OSA), produces oxidative stress, endothelial dysfunction, and hypertension. Nitric oxide (NO) plays a critical role in controlling the vasomotor tone. The NO level depends on the L-arginine level, which can be reduced by arginase enzymatic activity, and its reaction with the superoxide radical to produce peroxynitrite. Accordingly, we hypothesized whether a combination of an arginase inhibitor and an antioxidant may restore the endothelial function and reduced arterial blood pressure (BP) in CIH-induced hypertensive rats. Male Sprague-Dawley rats 200 g were exposed either to CIH (5% O2, 12 times/h 8 h/day) or sham condition for 35 days. BP was continuously measured by radio-telemetry in conscious animals. After 14 days, rats were treated with 2(S)-amino-6-boronohexanoic acid (ABH 400 µg/kg day, osmotic pump), N-acetylcysteine (NAC 100 mg/kg day, drinking water), or the combination of both drugs until day 35. At the end of the experiments, external carotid and femoral arteries were isolated to determine vasoactive contractile responses induced by KCL and acetylcholine (ACh) with wire-myography. CIH-induced hypertension (~8 mmHg) was reverted by ABH, NAC, and ABH/NAC administration. Carotid arteries from CIH-treated rats showed higher contraction induced by KCl (3.4 ± 0.4 vs. 2.4 ± 0.2 N/m2) and diminished vasorelaxation elicits by ACh compared to sham rats (12.8 ± 1.5 vs. 30.5 ± 4.6%). ABH reverted the increased contraction (2.5 ± 0.2 N/m2) and the reduced vasorelaxation induced by ACh in carotid arteries from CIH-rats (38.1 ± 4.9%). However, NAC failed to revert the enhanced vasocontraction (3.9 ± 0.6 N/m2) induced by KCl and the diminished ACh-induced vasorelaxation in carotid arteries (10.7 ± 0.8%). Femoral arteries from CIH rats showed an increased contractile response, an effect partially reverted by ABH, but completely reverted by NAC and ABH/NAC. The impaired endothelial-dependent relaxation in femoral arteries from CIH rats was reverted by ABH and ABH/NAC. In addition, ABH/NAC at high doses had no effect on liver and kidney gross morphology and biochemical parameters. Thus, although ABH, and NAC alone and the combination of ABH/NAC were able to normalize the elevated BP, only the combined treatment of ABH/NAC normalized the vascular reactivity and the systemic oxidative stress in CIH-treated rats.

1,1':4',1''-Terphenyl-2',5'-dicarb-oxy-lic acid dimethyl sulfoxide-d(6) disolvate.

The asymmetric unit of the title solvate, C(20)H(14)O(4)·2C(2)D(6)OS, contains half of the substituted terephthalic acid mol-ecule and one solvent mol-ecule. The centroid of the central benzene ring in the acid mol-ecule is coincident with a crystallographic inversion center. Neither the carboxyl nor the phenyl substituents are coplanar with the central aromatic ring, showing dihedral angles of 53.18 (11) and 47.83 (11)°, respectively. The dimethyl sulfoxide solvent mol-ecules are hydrogen bonded to the carb-oxy-lic acid groups.

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

The title mol-ecule, C(21)H(26)O(3), has a six-membered planar carbon ring as the central core, substituted at position 1 with phen-oxy-carbonyl, at position 2 with hy-droxy and at positions 3 and 5 with tert-butyl groups. The structure shows two independent but very similar mol-ecules within the asymmetric unit. For both independent mol-ecules, the ester carboxyl-ate 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 carboxyl-ate -CO(2) 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 carboxyl-ate -CO(2)- group allows the formation of an intra-molecular hydrogen bond, with O⋯O distances of 2.563 (2) and 2.604 (2) Å.

LTA-mediated synthesis and complete assignment of (1)H and (13)C NMR data of two natural 11-nordrimanes: isonordrimenone and polygonone.

Two naturally occurring 11-nordrimanes were synthesized, and their (1)H and (13)C NMR spectra were unambiguously assigned in full for the first time.

A new reaction: lead(IV) acetate-mediated oxidative fragmentation of homoallylic alcohols.

Treatment of a homoallylic alcohol with lead(IV) acetate in refluxing benzene for 2 hours results in an oxidative cleavage to give a carbonyl compound and an allylic acetate with high yield.

Synthesis and in vitro trypanocide activity of several polycyclic drimane-quinone derivatives.

The Diels-Alder reaction between two polygodial-derived dienes and simple quinones to yield substituted naphtho- and anthraquinones, is described. The in vitro trypanocide activity for the series was determined. Two of the new compounds showed an activity ten and two times higher, respectively, than nifurtimox and benznidazole, the medicines of choice for the treatment of the acute Chagas' disease.