Unexpected discovery: "A new 3,3'-bipyrazolo[3,4-b]pyridine scaffold and its comprehensive analysis".

In this study, a novel 3,3'-bipyrazolo [3,4-b]pyridine-type structure was synthesized from 5-acetylamino-3-methyl-1-phenylpyrazole using the Vilsmeier-Haack reaction as a key step. The spectroscopic properties and structural elucidation of the compound were determined with the use of FT-IR, HRMS, 1H NMR, and 13C NMR. Likewise, the theoretical analysis of the IR and NMR spectra allowed peaks to be assigned and a solid correlation was demonstrated between the experimental and theoretical results. Finally, ab initio calculations based on the density functional theory method at the B3LYP/6-311G (d,p) level of theory were used to determine the conformational energy barrier, facilitating the identification of the most probable conformers of the synthesized compound. Overall, our findings contribute to the understanding of bipyrazolo [3,4-b]pyridine derivatives.

Role of Triplet States in the Photolysis of Proteogenic Amino Acids.

This investigation delves into the UV photodissociation of pivotal amino acids (Alanine, Glycine, Leucine, Proline, and Serine) at 213 nm, providing insights into triplet-state deactivation pathways. Utilizing a comprehensive approach involving time-dependent density functional calculations (TD-DFT), multi-configurational methods, and ab-initio molecular dynamics (AIMD) simulations, we scrutinize the excited electronic states (T1 , T2 , and S1 ) subsequent to 213 nm excitation. Our findings demonstrate that α-carbonyl C-C bond-breaking in triplet states exhibits markedly lower barriers than in singlet states (below 5.0 kcal mol-1 ). AIMD simulations corroborate the potential involvement of triplet states in amino acid fragmentation, underscoring the significance of accounting for these states in photochemistry. Chemical bonding analyses unveil distinctive patterns for S1 and T1 states, with the asymmetric redistribution of electron density characterizing the C-C breaking in triplet states, in contrast to the symmetric breaking observed in singlet states. This research complements recent experimental discoveries, enhancing our comprehension of amino acid reactions in the interstellar medium.

Elucidating the N-N and C-N Bond-breaking Mechanism in the Photoinduced Formation of Nitrile Imine.

In this study, we revealed the significance of chemical bonding for the photochemically induced mechanism of 2-phenyl tetrazole derivatives generating nitrile imines. The correlated electron localization function shows that the formation of imine nitrile involves two key bond events: (i) the heterolytic C-N breakage taking place in the T1 state and (ii) the homolytic N-N rupture occurring in the T2 excited state. In particular, a cation-radical specie results from the C-N cleavage, whereas the N-N rupture creates a biradical resonant form of imine nitrile. Additionally, we noticed that the substantial pair delocalization of the C-C-N bonded structure could play a significant role in the conversion of the biradical imine nitrile into both the propargylic and allenic forms via the T1 →S0 deactivation.

Phenolic Profile and Cholinesterase Inhibitory Properties of Three Chilean Altiplano Plants: Clinopodium gilliesii (Benth.) Kuntze [Lamiaceae], Mutisia acuminata Ruiz & Pav. var. hirsuta (Meyen) Cabrera, and Tagetes multiflora (Kunth) [Asteraceae].

This research aimed to identify the phenolic profile and composition of the aerial parts of three native species used in traditional medicine in the Andean Altiplano of northern Chile: Clinopodium gilliesii (Benth.) Kuntze [Lamiaceae] (commonly known as Muña-Muña), Mutisia acuminata Ruiz & Pav. var. hirsuta (Meyen) Cabrera [Asteraceae] (commonly known as Chinchircoma), and Tagetes multiflora (Kunth), [Asteraceae] (commonly known as Gracilis), as well as to evaluate their potential inhibitory effects against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Polyphenolic enriched-extracts (PEEs) of the species were prepared and analyzed and the main components were quantified using HPLC-DAD. In total, 30 phenolic compounds were identified and quantified in all species, including simple phenolics, hydroxycinnamic acids, flavan-3-ols (monomers and polymers), flavanones, and flavonols. In addition, other main phenolics from the extracts were tentatively identified by ESI-MS-MS high-resolution analysis. T. multiflora extract showed the greatest anti-AChE and BChE activity in comparison with C. gilliesii and M. acuminata extracts, being the anti-AChE and BChE activity weak in all extracts in comparison to galantamine control. To comprise to better understand the interactions between cholinesterase enzymes and the main phenolics identified in T. multiflora, molecular docking analysis was conducted.

Design, synthesis, theoretical study, antioxidant, and anticholinesterase activities of new pyrazolo-fused phenanthrolines.

Pyrazole-fused phenanthroline compounds were obtained through several synthetic routes. NMR, HRMS, and IR techniques were used to characterize and confirm the chemical structures. Crystal structures were obtained from compounds 3a, 5b, 5j, 5k, and 5n and analyzed using X-ray diffraction. Compounds were evaluated as acetyl (AChE) and butyrylcholinesterase (BChE) inhibitors, and the results showed a moderate activity. Compound 5c presented the best activity against AChE (IC50 = 53.29 µM) and compound 5l against BChE enzyme (IC50 = 119.3 µM). Furthermore, the ability of the synthetic compounds to scavenge cationic radicals DPPH and ABTS was evaluated. Compound 5e (EC50 = 26.71 µg mL-1) presented the best results in the DPPH assay, and compounds 5e, 5f and 5g (EC50 = 11.51, 3.10 and <3 µg mL-1, respectively) showed better ABTS cationic radical scavenging results. Finally, in silico analyses indicated that 71% of the compounds show good oral availability and are within the ranges established by the Lipinski criteria.

Tetrahydroquinoline-Isoxazole/Isoxazoline Hybrid Compounds as Potential Cholinesterases Inhibitors: Synthesis, Enzyme Inhibition Assays, and Molecular Modeling Studies.

A series of 44 hybrid compounds that included in their structure tetrahydroquinoline (THQ) and isoxazole/isoxazoline moieties were synthesized through the 1,3-dipolar cycloaddition reaction (1,3-DC) from the corresponding N-allyl/propargyl THQs, previously obtained via cationic Povarov reaction. In vitro cholinergic enzymes inhibition potential of all compounds was tested. Enzyme inhibition assays showed that some hybrids exhibited significant potency to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Especially, the hybrid compound 5n presented the more effective inhibition against AChE (4.24 µM) with an acceptable selectivity index versus BChE (SI: 5.19), while compound 6aa exhibited the greatest inhibition activity on BChE (3.97 µM) and a significant selectivity index against AChE (SI: 0.04). Kinetic studies were carried out for compounds with greater inhibitory activity of cholinesterases. Structure-activity relationships of the molecular hybrids were analyzed, through computational models using a molecular cross-docking algorithm and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) binding free energy approach, which indicated a good correlation between the experimental inhibition values and the predicted free binding energy.

Efficient synthesis and antioxidant activity of novel N-propargyl tetrahydroquinoline derivatives through the cationic Povarov reaction.

New N-propargyl tetrahydroquinolines 6a-g have been synthesized efficiently through the cationic Povarov reaction (a domino Mannich/Friedel-Crafts reaction), catalyzed by Indium (III) chloride (InCl3), from the corresponding N-propargylanilines preformed, formaldehyde and N-vinylformamide, with good to moderate yields. All tetrahydroquinoline derivatives obtained were evaluated in vitro as free radical scavengers. Results showed that compound 6c presents a potent antioxidant effect compared with ascorbic acid, used as a reference compound. ADME predictions also revealed favorable pharmacokinetic parameters for the synthesized compounds, which warrant their suitability as potentials antioxidant. Additionally, a theoretical study using Molecular Quantum Similarity and reactivity indices were developed to discriminate different reactive sites in the new molecules in which the oxidative process occurs.

Preparation of Hydrogel/Silver Nanohybrids Mediated by Tunable-Size Silver Nanoparticles for Potential Antibacterial Applications.

In this study, a versatile synthesis of silver nanoparticles of well-defined size by using hydrogels as a template and stabilizer of nanoparticle size is reported. The prepared hydrogels are based on polyvinyl alcohol and maleic acid as crosslinker agents. Three hydrogels with the same nature were synthesized, however, the crosslinking degree was varied. The silver nanoparticles were synthesized into each prepared hydrogel matrix achieving three significant, different-sized nanoparticles that were spherical in shape with a narrow size distribution. It is likely that the polymer network stabilized the nanoparticles. It was determined that the hydrogel network structure can control the size and shape of the nanoparticles. The hydrogel/silver nanohybrids were characterized by swelling degree, Thermal Gravimetric Analysis (TGA), Fourier Transform Infrared (FT-IR), Scanning Electron Microscopy (SEM) and Transmission Electron Microscope (TEM). Antibacterial activity against Staphylococcus aureus was evaluated, confirming antimicrobial action of the encapsulated silver nanoparticles into the hydrogels.

Rational Development of a Novel Hydrogel as a pH-Sensitive Controlled Release System for Nifedipine.

This work depicts the rational development (in-silico design, synthesis, characterization and in-vitro evaluation) of polyvinyl alcohol hydrogels (PVAH) cross-linked with maleic acid (MA) and linked to γ-cyclodextrin molecules (γ-CDPVAHMA) as systems for the controlled and sustained release of nifedipine (NFD). Through computational studies, the structural blocks (PVA chain + dicarboxylic acid + γ-CD) of 20 different hydrogels were evaluated to test their interaction energies (ΔE) with NFD. According to the ΔE obtained, the hydrogel cross-linked with maleic acid was selected. To characterize the intermolecular interactions between NFD and γ-CDPVAHMA, molecular dynamics simulation studies were carried out. Experimentally, three hydrogel formulations with different proportions of γ-CD (2.43%, 3.61% and 4.76%) were synthesized and characterized. Both loading and release of NFD from the hydrogels were evaluated at acid and basic pH. The computational and experimental results show that γ-CDs linked to the hydrogels were able to form 1:1 inclusion complexes with NFD molecules. Finally, γ-CDPVAHMA-3 demonstrated to be the best pH-sensitive release platform for nifedipine. Its effectiveness could significantly reduce the adverse effects caused by the anticipated release of NFD in the stomach of patients.

Catalytic Divergent [3+3]- and [3+2]-Cycloaddition by Discrimination Between Diazo Compounds.

Highly selective divergent cycloaddition reactions of enoldiazo compounds and α-diazocarboximides catalyzed by copper(I) or dirhodium(II) have been developed. With tetrakis(acetonitrile)copper(I) tetrafluoroborate as the catalyst epoxypyrrolo[1,2-a]azepine derivatives were prepared in good yields and excellent diastereoselectivities through the first reported [3+3]-cycloaddition of a carbonyl ylide. Use of Rh2 (pfb)4 or Rh2 (esp)2 directs the reactants to regioselective [3+2]-cycloaddition generating cyclopenta[2,3]pyrrolo[2,1-b]oxazoles with good yields and excellent diastereoselectivities.