ALBERT

Description: Intermolecular and intramolecular non-bonding interactions play a crucial role in determining physical and biological properties of relevant amines, and we have recently reported that they are also responsible for changing mechanisms in aromatic nucleophilic substitution (ANS) involving amine nucleophiles, when they are carried out in solvents of low permittivity. The present work describes ANS in toluene with a series of biological amines that can set specific hydrogen bonding (H bonding) interactions due to their special molecular structures. Kinetic studies of ANS with 2-amino-5-guanidinopentanoic acid (arginine), (4-aminobutyl)guanidine (agmatine), 2,6-diaminohexanoic acid (lysine) and 3,4-dihydroxyphenethylamine (dopamine) towards 1-chloro-2,4-dinitrobenzene in toluene are reported. The kinetic results are compared with those obtained with 2-guanidinobenzimidazole and 2-(1H-imidazole-4-yl)ethanamine (histamine); both amines form intramolecular H bonds. The special types of H bonding were also investigated by ab initio density functional theory calculations, at the B3LYP/6-31++G(d,p) level, including counterpoise corrections to account for basis set superposition errors and solvent effects at the polarized continuum model level. Copyright © 2015 John Wiley & Sons, Ltd. Kinetic studies on aromatic nucleophilic substitution where the nucleophiles are amines that can set specific hydrogen bonding in toluene due to their special molecular structures are reported. An additional strong support to the dimer nucleophile mechanism is provided by the quantum chemical calculations on monomers and dimers that show that the calculated order in dimer stability is nicely correlated with kinetic results and strongly indicates that these studies are useful to enlighten the type of mechanism occurring in aprotic solvents.

Description: Three novel diarylethenes derived from benzothiophene were synthesized and their photochemical optical properties studied in four solvents ( n -hexane, toluene, acetonitrile and methanol). It was determined that these compounds dramatically increase the light absorption in the visible region upon exposure to UV light, showing two absorption maxima at 420 nm and 520 nm, respectively. The observed change is completely reverted upon exposure to visible light. The three compounds demonstrate negligible fatigue, excellent stability in the four solvents, and absence of photodegradation and thermal back reactions. This paper also describes a complete study of solvent effects on the kinetics of the ring opening and cycloreversion. While, the UV spectra are little sensitive both to the substitution pattern and to the solvent influence, the kinetics of ring opening/cycloreversion reactions exhibit a more interesting behavior that differs from other diarylethenes reported in the literature. The cyclization kinetics shows a complex order, well fitted by an exponential equation, while the cycloreversion presents first-order kinetics. The whole complex reaction scheme can be explained by the unusual presence of two conformers of the open form, a parallel and an antiparallel conformation. Though other alternative mechanism could explain the kinetics, additional evidence is consistent with the conformational equilibrium proposed: i.e. the solvent influence on the kinetics of the nitro-substituted substrate, and the double signals for the methyl protons and for the methoxy protons (when present) observed in the nuclear magnetic resonance spectra. These observations are relevant in relation to the application of these novel diarylethenes as potential optical materials. Copyright © 2012 John Wiley & Sons, Ltd. Three novel diarylethenes were synthesised and their photochemical properties examined in four different solvents. While the UV spectra are almost insensitive to the substitution pattern and to the solvent effects, the kinetics of ring opening/cycloreversion reactions exhibit a more complex behavior. The whole reaction scheme can be explained by the presence of two conformers of the open form, a parallel and an antiparallel conformation.

Description: Inter- and intramolecular hydrogen bonding play an important role in determining the arrangement, physical properties, and reactivity of a great diversity of structures in chemical and biological systems. Several aromatic nucleophilic substitutions (ANS) in nonpolar aprotic, (non-HBD), solvents recently studied in our laboratory have demonstrated the importance of self-association of amines by hydrogen-bond interactions. In this paper, we describe 1 H-NMR studies carried out at room temperature on bi- and polyfunctionalized amines, namely: N -(3-amino-1-propyl)morpholine (3-APMo), histamine, 2-guanidinobenzimidazole (2-GB), 1,2-diaminoethane (EDA), 3-dimethylamino-l-propylamine (DMPA), and 1-(2-aminoethyl)piperidine (2-AEPip). By 1 H-NMR measurements of amine solutions at variable concentrations we have shown that 3-APMo, histamine and 2-GB are able to form a six-membered ring by intramolecular hydrogen bonding, while EDA, DMPA, and 2-AEPip form dimers by intermolecular hydrogen bonds. Likewise, variable concentration 1 H-NMR studies allowed estimation of the corresponding equilibrium constants for the dimerization. These results are correlated with experimental kinetic results of ANS, confirming hereto the relevance of the “dimer mechanism” in reactions involving these amines. Copyright © 2011 John Wiley & Sons, Ltd. 1 H-NMR studies on polyamine solutions of variable concentrations in nonpolar aprotic solvents allowed differentiation between inter- and intramolecular hydrogen bond formation and estimation of the corresponding dimerization equilibrium constants. These results are correlated with experimental kinetic results of ANS, and afford additional evidence on the “dimer nucleophile” mechanism observed in ANS reactions with amines in nonpolar aprotic solvents.

Description: The intramolecular carbolithiation-cyclization-electrophilic substitution sequence proves to be a promising strategy for synthetic organic chemists. Our current research in this area focuses on the one-pot halogen/lithium exchange of 2-bromophenyl-3-phenylprop-2-enyl ether, followed by intramolecular carbolithiation, and trapping of the new lithiated cyclic intermediate by several electrophiles, affording 3-substituted 2,3-dihydrobenzofurans with some diastereoselectivity. Within this context, a study on the product distribution solvent dependence was carried out using different types of solvents, namely: polar coordinating, polar non-coordinating, and non-polar solvents. The results show that the coordinating features of the solvent affect specially the carbolithiation step, whereas the halogen/lithium exchange seems to be barely affected. Theoretical calculations were carried out to investigate the unexpected diastereoselectivity of the tandem reaction , where two stereocenters are generated. Insights gained from our mechanistic investigations enabled us to propose an inversion of configuration at the lithiated intermediate prior to the reaction, being the electrophile the likely cause for the observed distereoselectivity. Copyright © 2013 John Wiley & Sons, Ltd. A study of the intramolecular carbolithiation-cyclization-electrophilic substitution sequence of the of 2-bromophenyl-3-phenylprop-2-enyl ether was carried out. Focus on the product distribution solvent dependence different types of solvents, polar coordinating, polar non-coordinating, and non-polar solvents were tested. Theoretical calculations were carried out to investigate the unexpected diastereoselectivity of the tandem reaction, where two stereocenters were generated.

Description: The HDAC inhibitory activity of valproic acid (VPA) has led to on-going evaluation of it as an anticancer agent. The histone deacetylase (HDAC) inhibitor AN446, a prodrug of VPA, releases the acid upon metabolic degradation. AN446 is 〉60 fold more potent than VPA in killing cancer cells in vitro. Herein, we compare the activities of AN446, as an anticancer agent, to those of representative types from each of the four major classes of HDAC inhibitors (HDACIs): vorinostat, romidepsin, entinostat and VPA. AN446 exhibited the greatest selectivity and HDAC inhibitory activity against cancer cells. In glioblastoma cells only AN446, and in MDA-MB-231 cells only AN446 and VPA interacted in synergy with doxorubicin (Dox). AN446 was superior to the studied HDACIs in inducing DNA-damage in cancer cells, while in normal astrocytes and cardiomyoblasts AN446 was the least toxic. AN446 was the only HDACI tested that exhibited selective HDAC inhibitory activity that was high in cancer cells and low in noncancerous cells. This discriminating inhibition correlated with the toxicity of the HDACIs, suggesting that their effects could be attributed to HDAC inhibition. In cardiomyoblasts, the HDACIs tested, except for AN446, hampered DNA repair by reducing the level of Rad 51. VPA and AN446 were the most effective HDACIs in inhibiting in vitro migration and invasion. The advantages of AN446 shown here, position it as a potentially improved HDACI for treatment of glioblastoma and triple negative breast cancer. This article is protected by copyright. All rights reserved

Description: The degree of changes in complex mixtures from crude oil (CO) and from oil residues in soils was determined by using heteronuclear single quantum coherence–nuclear magnetic resonance (HSQC-NMR) spectroscopy. The HSQC-NMR spectra of crude oil samples and two oil residues with natural attenuation (E1 and E2), and two biopiles (B1 and B2) were recorded using a 500-MHz spectrometer. The spectra could be divided into major regions according to the different types of protons and carbons. Twenty-three regions (A1–A5, B1–B11, C1–C3, D1–D3, and E) were defined on the basis of signal assignments. A multivariate method, the principal component analysis (PCA), was used to search the change in the structural parameters during the environmental exposure time. The first two principal components (PCs) accounted for the 83.3% of the total variance (51.8% and 31.5% for PC1 and PC2, respectively). The euclidean distances (3D) between the samples are 2.80 (CO–E2), 2.37 (CO–E1), 1.62 (CO–BP1), and 1.72 (CO–BP2). This suggests that the environmental transformation during exposure time follows the order E2 〉 E1 〉 BP2 〉 BP1 〉 CO. The disappearance of the signals (−CH, −CH 2 , and −CH 3 ) in the HSCQ-NMR spectra compared with the crude oil spectrum was conveniently quantified by PCA, and it helps in the characterization of the fate of the oil spills. Copyright © 2013 John Wiley & Sons, Ltd. The degree of changes in complex mixtures from crude oil and from oil residues was determined by using heteronuclear single quantum coherence–nuclear magnetic resonance spectroscopy. A multivariate method (principal component analysis) was used to search the change in the structural parameters. The disappearance of the signals (−CH, −CH 2 , and −CH 3 ) spectra compared with the crude oil spectrum were conveniently quantified by principal component analysis, and it helps in the characterization of the fate of the oil spills.