The origin of long-range 5J coupling in aromatic aldehydes remains an important question in the interpretation of NMR spectra, particularly in systems where closely related structures exhibit different spectroscopic behavior. Herein, a series of brominated benzaldehydes was investigated using a combined approach based on ¹H NMR spectroscopy, single-crystal X-ray diffraction, and density functional theory (DFT) calculations to examine the structural and conformational factors associated with the experimental observation of this weak interaction. Observable long-range 5J couplings (0.6–0.8 Hz) were detected only for selected derivatives, whereas structurally related compounds displayed no measurable interaction or only borderline coupling values. Crystallographic analysis revealed similar geometric characteristics of the coupling pathway across the series, whereas NMR spectroscopy revealed marked differences in the experimental manifestation of the interaction. DFT calculations demonstrated that both the magnitude and experimental observability of long-range 5J coupling are governed by conformational preferences and rotational barriers about the aryl–carbonyl bond. Compounds exhibiting well-resolved couplings combine favorable populations of transoid conformations with sufficient conformational restriction to limit dynamic averaging on the NMR timescale. In contrast, lower rotational barriers promote conformational averaging and attenuate the observed interaction. Overall, the crystallographic, spectroscopic, and computational results demonstrate that the experimental observation of long-range 5J coupling is governed by the interplay between molecular geometry, conformational populations, and conformational dynamics. More broadly, this study highlights the value of integrating complementary experimental and computational approaches to understand structure–dynamics relationships in aromatic aldehydes.

Two chiral copper(II) Schiff base complexes (L1Cu and L2Cu) derived from the amino acid alanine and two salicylaldehydes (one of them chlorine substituted) were synthesized and characterized by SCXRD, spectroscopic techniques (FTIR, UV-Vis, EPR), and thermal analysis. SCXRD revealed distorted square-pyramidal geometries, with axial elongation and strong equatorial Cu–N/O bonds indicative of Jahn-Teller distortion. Spectroscopic data confirmed covalent metal-ligand interactions and a dx2−ᵧ2 ground state, consistent with their catalytic activity. In styrene cyclopropanation, both complexes achieved 99.9% yield, but L1Cu exhibited superior stereocontrol (100:0 trans:cis, 66:34 RR:SS) compared to L2Cu (98:2, 60:40), highlighting the electronic influence of the Cl substituent. For C–S coupling, L1Cu outperformed L2Cu (93% vs. 87% yield), with both generating minimal disulfide byproduct (~6.4%). These results demonstrate how subtle ligand modifications tune reactivity and selectivity in distinct transformations, offering insights for designing versatile Cu(II) catalysts.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) targeting human immunodeficiency virus (HIV) frequently exhibit suboptimal pharmacological properties and are often compromised by drug-resistant mutations. This underscores the ongoing need for the development of developing novel reverse transcriptase (RT) inhibitors. In this study, we report the synthesis of 20 novel amine-type cyclopentanepyridinone derivatives as NNRTIs. The chlorinated C-4 core was functionalized with various amines of differing chain lengths, yielding final products in 43-88% yields. Derivatives bearing alkyl and alkenyl chains at the C-4 position demonstrated anti-HIV activity at nanomolar to micromolar concentrations. Among them, compound 9 exhibited the most potent inhibitory activity against HIV and wild-type (WT) HIV-1 RT, with an EC50 of 540 nM and an IC50 of 33.89 μM, respectively, while maintaining low cytotoxicity (CC50 > 100 μM). Molecular docking analysis revealed interactions with key residues in the NNRTI binding pocket (NNIBP), including Lys101, Tyr181, Tyr188, and the conserved residues Phe227, Trp229, and Leu234, both in WT HIV-1 RT and Tyr188Leu HIV-1 RT. Moreover, molecular dynamics (MD) simulations with WT HIV-1 RT showed that compounds 6, 9, and 10 formed up to two hydrogen bonds with RT, supporting their ability to bind effectively within the NNIBP.

Ruthenium complexes (RuCat) of triazenide ligands bearing different N-heterocyclic moieties catalyze the hydrogenation of a myriad of substituted nitroarenes under mild reaction conditions.

We report herein the synthesis and application of enantiopure C2 -symmetric primary amine-1,3-bis-thiourea organocatalysts in enantioselective conjugate 1,4-Michael addition of carbonyl containing nucleophiles, to nitroalkenes and N-phenylmaleimide, leading to final products in good enantioselectivities (up to 99%) and yields (up to 99%). We propose supramolecular noncovalent interactions within the organocatalyst's cleft between the substrate and the catalyst, via hydrogen bonding. Supramolecular interaction thus lowers the transition state energy mimicking an enzyme. Mechanism underlying our experimental results is supported by theorical calculations.

An (IrCp)-Cp-III* complex (2) bearing a triazenide ligand functionalized with pyrazole was synthesized and fully characterized by spectroscopic methods and the structure confirmed by X-ray diffraction studies. The catalytic activity of 2 and the control complex 3, which lacks of pyrazole in its structure, was evaluated in the reduction of aryl-ketones, alkyl-ketones, alpha,beta-unsaturated and gamma, delta-unsaturated ketones. The catalytic system, using either 2 or 3, exhibited good to excellent selectivity when tested with ketones and alkenones at 90 degrees C in 2-propanol as hydrogen source under base-free conditions. Reactivity of 2 in 2-propanol and NaH gave a neutral metal hydride (4) while in the absence of base gave two major cationic hydrides species (5 and 6).

β-Alanine and its derivatives are important starting materials for the preparation of peptides or compounds with biological activity. In this work, the authors are presenting a new approach for the synthesis of N-alkyl-β-amino acids and N-alkyl-β-amino esters using dendrimeric intermediates in a one-pot reaction, with friendly reaction conditions. Dendrimeric compounds, with a pentaerythritol core, were easy prepared and used to obtain the β-amino acid derivatives and β-amino esters with good yields. This paper presents the first reaction where dendrimers are used for synthesizing organic compounds. Spectroscopic characterization by 1H- and 13C-NMR of dendrimers and final products is also presented.

Natural and synthetic naphthoquinones have demonstrated numerous biological activities; therefore, they provide an interesting scaffold for medicinal chemists in the search for new drugs. A series of amino alcohol derivatives from 1,4-naphthoquinone with a free (2a–e) and acetylated (3a–d) hydroxyl group were synthesized, characterized, and evaluated as antioxidant agents employing 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS·+) assays, as acetylcholinesterase (AChE) inhibitors and antiproliferative compounds. In the DPPH assay, compound 3d showed the better result with 51.52% of antioxidant activity at 1 mg/mL, while in ABTS·+ was 2e (47.12%). The antiproliferative activity was evaluated against six different tumor cell lines, where the particular best results were for products 2a, 2c, and 2e against cervix line HeLa, with 50% growth inhibition (GI50) of 5.6, 15.0, and 17.0 μM, respectively. All synthesized compounds presented varying degrees of response, some of them with similar results compared with the positive control 5-fluorouracil. AChE inhibition of the products was not as strong as the positive control galantamine; the most potent compound was 2e with a 50% inhibitory concentration (IC50) of 0.0586 mM, followed by 2a (0.0902 mM). No inhibition in the evaluated concentrations was observed for products 2d and 3a-d. Docking of 2a and 2e was realized against AChE in order to gain insight into the interactions made between them and the enzyme residues in its catalytic gorge. In silico calculations for all synthesized products showed their drug-like properties. Alcohol derivatives, specially 2a and 2e, could be further derivatized in the search for new and improved drugs.

The employment of privileged scaffolds in medicinal chemistry supplies scientists with a solid start in the search for new and improved therapeutic molecules. One of these scaffolds is the imidazole ring, from which several derivatives have shown a wide array of biological activities. A series of 2,4,5-triphenyl imidazole derivatives were synthesized, characterized, and evaluated in vitro as antioxidant molecules using 1,1-diphenyl-2-picrylhydrazyl (DPPH.) and 2-2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS.+) assays, acetylcholinesterase (AChE) and xanthine oxidase (XO) inhibitors as well as antiproliferative agents. Additional in silico studies such as docking and determination of their absorption, distribution, metabolism, and excretion (ADME) properties were calculated. Compounds 3 and 10 were the most active antioxidants in both the DPPH and ABTS assays (EC50 of 0.141 and 0.174 mg/mL, and 0.168 and 0.162 mg/mL, respectively). In the enzymatic inhibition, compound 1 showed the best activity, inhibiting 25.8% of AChE at a concentration of 150 μg/mL, and compound 3 was the most active XO inhibitor with an IC50 of 85.8 μg/mL. Overall, against the six different evaluated cancerous cell lines, molecules 2, 10, and 11 were the most antiproliferative compounds. In silico predictions through docking point out 11, and ADME analysis to 11 and 12, as good candidates for being lead compounds for further derivations.

The aim of this study was the characterization of fatty acids, antioxidant activity, some physical properties, nutrient content, sugars, and minerals in the pulp and seeds of the date cultivar ‘Medjool’ (Phoenix dactylifera L.) grown in Mexico. The samples were obtained at maturity (Tamar) in the 2017 harvest season in the valleys of San Luis Rio Colorado and Mexicali, Mexico. The following average values were obtained on a % dry weight basis for pulp and seeds, respectively: protein, 3.14% and 4.84%; lipids, 0.75% and 9.94%; fiber, 6.34% and 66.79%; total sugars, 75.32% and 5.88%; reducing sugars, 70.26% and 4.40%; and sucrose, 5.06% and 1.46%. Analysis of the minerals revealed that the most abundant elements for the pulp were: potassium, 851.98 mg/100 g; magnesium, 142.97 mg/100 g; and phosphorus, 139.40 mg/100 g, whereas for the seeds, they were potassium, 413.36 mg/100 g; sulfur, 151.36 mg/100 g; and phosphorus, 92.42 mg/100 g. Gas chromatography-mass spectrometry analysis revealed that the major unsaturated fatty acid was oleic acid, at 52.34% and 45.92%, respectively, for pulp and seeds. The main saturated fatty acids were palmitic acid (6.75%) and lauric acid (17.24%) in pulp and seeds, respectively. The total phenolic content was 1.16 and 13.73 mg GAE/100 g for pulp and seeds, respectively. Finally, the antioxidant activities were: b-carotene, 65.50% and 47.75%; DPPH, 0.079 IC50 g/L and 0.0046 IC50 g/L; and ABTS, 13.72 IC50 g/L and 0.238 IC50 g/L, respectively. The results obtained in this study confirm that the ‘Medjool’ cultivar grown in Mexico has the same quality of nutrients and antioxidants as those grown in the other main date-producing countries.

A series of iridium and rhodium complexes have been synthesized using as ligand a triazenide monofunctionalized with an imidazole substituent. Steric hindrance at the imidazole moiety induced differences in the coordination modes as well in the catalytic behavior of complexes 4–7. Complexes 4–7 were tested in the transfer hydrogenation of acetophenone and 5-alken-2-ones. The hydrogenation of either the double bond or the carbonyl group in 5-alken-2-ones, showed to be selective in the presence of 6, 7, and 10 and has a dependence on the presence or absence of base. Control experiments point out that the imidazole moiety in the structure of complexes 4–7 speeds-up the catalysis.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

In the title compound, C12H14ClNO3, the aliphatic ring of the hexahydroquinoline system adopts a half-chair conformation while the ethyl carboxylate substituent is inclined to the hexahydroquinoline ring system by 85.1 (2)°. In the crystal, a pair of N–H...O hydrogen bonds form an inversion dimer. The structure is further stabilized by C—H...O and C—H...Cl hydrogen bonds, forming a three-dimensional network.

The synthesis and characterization of a series dipalladium(I) complexes of formulae [Pd{1-[2'-(methoxycarbonyl)phenyl]-3-[4'-X-phenyl]triazenide}](2) [X = F (4), Cl (5), Br (6)] are reported. The crystal structure of complex 4 was determined by X-ray diffraction studies. The previously reported dipalladium(I) 1-3 as well as the new complexes 4-6 were used as catalysts in the Heck and Suzuki couplings of different p-substituted bromobenzenes.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

With the goal of suggesting dual inhibitors of HIV reverse transcriptase (RT) and integrase (IN), herein we report the molecular docking of an initial set of 556 compounds related to the pyridinone class. Docking with multiple crystallographic structures of HIV-1 RT led to 160 potential binders of RT interacting with key amino acid residues at the enzyme’s allosteric site. Compounds selected from the docking with RT were further docked with a crystallographic structure of HIV-1 IN. A total of 31 structures had the potential to make contacts with Mg2+ ions located in a small space between DNA and IN. Interactions with Mg2+ ions are relevant because they participate in the stabilization of the IN-DNA complex. In conclusion, 31 compounds synthetically accessible are proposed as dual inhibitors of RT and IN. It is hypothesized that the suggested compounds will inhibit RT by occupying the allosteric site for NNRTIs and will inhibit the catalytic activity of IN by destabilizing the IN-DNA complex. The main perspective of this work is the synthesis and biological testing of the candidate molecules.

Herein, we report the synthesis of C2 -symmetric sulfonamides as homogeneous and heterogeneous organocatalysts and their application in the enantioselective conjugate 1,4-Michael addition of carbonylic nucleophiles to β-nitrostyrene. Organocatalysts hydrogen bond to β-nitrostyrene and enamine in the transition state, mimicking an enzyme leading to final products in high yields (up to 98%) and good enantioselectivities (up to 96%). In addition, these results were supported by density functional calculations.

To potentially identify proteins that interact (i.e. bind) and may contribute to mediate (-)-epicatechin (Epi) responses in endothelial cells we implemented the following strategy: 1) synthesis of novel Epi derivatives amenable to affinity column use, 2) in silico molecular docking studies of the novel derivatives on G protein-coupled estrogen receptor (GPER), 3) biological assessment of the derivatives on NO production, 4) implementation of an immobilized Epi derivative affinity column and, 5) affinity column based isolation of Epi interacting proteins from endothelial cell protein extracts. For these purposes, the Epi phenol and C3 hydroxyl groups were chemically modified with propargyl or mesyl groups. Docking studies of the novel Epi derivatives on GPER conformers at 14 ns and 70 ns demostrated favorable thermodynamic interactions reaching the binding site. Cultures of bovine coronary artery endothelial cells (BCAEC) treated with Epi derivatives stimulated NO production via Ser1179 phosphorylation of eNOS, effects that were attenuated by the use of the GPER blocker, G15. Epi derivative affinity columns yielded multiple proteins from BCAEC. Proteins were electrophoretically separated and inmmunoblotting analysis revealed GPER as an Epi derivative binding protein. Altogether, these results validate the proposed strategy to potentially isolate and identify novel Epi receptors that may account for its biological activity. (C) 2018 Elsevier Ltd. All rights reserved.

An improved and simpler method for the synthesis of benzodiazepin-2,5-diones and 7-iodobenzodiazepin-2,5-diones catalyzed by glacial acetic acid using isatoic anhydride and 6-iodoisatoic anhydride, respectively, as starting materials is reported. The target products were achieved in good yields (up to 71%) using microwave irradiation as the activating mode of reaction in the presence of acetic acid instead of the traditional polar aprotic solvents as dimethylformamide (DMF), dimethyl sulfoxide (DMSO) or dimethylacetamide (DMAC). Moreover, relatively simple purification workup is required. The optimal temperature to obtain the benzodiazepin-2,5-dione derivatives was 130 degrees C, while the best irradiation time was 3 min. In addition, the methodology for the selective preparation of 6-iodoisatoic anhydride with an overall yield of 62% is presented.