Synthesis, crystal structure, and a molecular modeling approach to identify effective antiviral hydrazide derivative against the main protease of SARS-CoV-2.

In the fall of 2019, a new type of coronavirus took place in Wuhan city, China, and rapidly spread across the world and urges the scientific community to develop antiviral therapeutic agents. In our effort we have synthesized a new hydrazide derivative, (E)-N'-(1-(4-bromophenyl)ethylidene)-2-(6-methoxynaphthalen-2-yl)propanehydrazide for this purpose because of its potential inhibitory proprieties. The asymmetric unit of the title molecule consists of two independent molecules differing noticeably in conformation. In the crystal, the independent molecules are linked by N-H···O and C-H···O hydrogen bonds and C-H···π(ring) interactions into helical chains extending along the b-axis direction. The chains are further joined by additional C-H···π(ring) interactions into the full 3-D structure. To obtain a structure-activity relationship, the DFT-NBO analysis is performed to study the intrinsic electronic properties of the title compound. Molecular modeling studies were also conducted to examine the binding affinity of the compound for the SARS-CoV-2 main protease enzyme and to determine intermolecular binding interactions. The compound revealed a stable binding mode at the enzyme active pocket with a binding energy value of -8.1 kcal/mol. Further, stable dynamics were revealed for the enzyme-compound complex and reported highly favorable binding energies. The net MMGBSA binding energy of the complex is -37.41 kcal/mol while the net MMPBSA binding energy is -40.5 kcal/mol. Overall, the compound disclosed the strongest bond of ing the main protease enzyme and might be a good lead for further structural optimization.

Synthesis and antimicrobial activity of new heterocyclic compounds containing thieno[3,2-c] coumarin and pyrazolo[4,3-c] coumarin frameworks.

Reaction of 4-chlorocoumarin-3-carbonitrile with ethyl thioglycolate and ethyl glycinate hydrochloride leads to a series of title products. Hydrazinolysis of amino thienocoumarin carboxylate afforded the hydrazine derivative which underwent various reactions to build new heterocyclic rings containing thienocoumarin moiety. Chloro acetylation of aminoester compound afforded the chloro acetyl amino which underwent nucleophilic substitution reactions various amines. The following treatment with formaldehyde under Mannich conditions afforded the corresponding imidazo derivatives. Reaction of Ghloroacetylamino with potassium thiocyanate yielded ethylpyrimidothieno coumarin sulfanylacetate which was used as a versatile precursor for synthesis of other heterocycles. On the other hand, reaction of chloro coumarin carbo nitrile with hydrazine gave the aminopyrazolocoumaine which reacted with bifunctionally compounds to give the substituted pyrimido derivatives. Diazotization and coupling of aminopyrazole with ethylcyanoacetate yielded ethylaminotriazinopyrazolocoumarine carboxylate. Several of the compounds obtained demonstrated considerable antifungal and antibacterial activity in the in vitro test systems.

Solid-State Luminescent Materials Containing Both Indole and Pyrimidine Moieties: Design, Synthesis, and Density Functional Theory Calculations.

Heterocyclic compounds with effective solid-state luminescence offer a wide range of uses. It has been observed that combining pyrimidine and indole moieties in a single molecule can enhance material behavior dramatically. Here, different heterocyclic compounds with indole and pyrimidine moieties have been synthesized effectively, and their structures have been validated using NMR, IR, and mass spectroscopy. The photoluminescence behavior of two substances was investigated in powder form and solutions of varying concentrations. After aggregation, one molecule displayed a redshifted luminescence spectrum, whereas another homolog showed a blueshift. Thus, density functional theory calculations were carried out to establish that introducing a terminal group allows modifying of the luminescence behavior by altering the molecular packing. Because of the non-planarity, intermolecular interactions, and tiny intermolecular distances within the dimers, the materials demonstrated a good emission quantum yield (Φem) in the solid state (ex. 25.6%). At high temperatures, the compounds also demonstrated a stable emission characteristic.

Combined experimental and TD-DFT/DMOl3 investigations, optical properties, and photoluminescence behavior of a thiazolopyrimidine derivative.

We present here the FT-IR, DFT computation, XRD, optical, and photophysical characterization of a heterocyclic compound with thienopyrimidine and pyran moieties. TD-DFT/DMOl3 and TD-DFT/CASTEP computations were used to study the geometry of isolated and dimer molecules and their optical behavior. The indirect (3.93 eV) and direct (3.29 eV) optical energy bandgaps, HOMO-LUMO energy gap (3.02 eV), and wavelength of maximum absorption (353 nm) were determined in the gas phase with M062X/6-31+G (d, p). A thin film of the studied molecule was studied using XRD, FT-IR, and UV-Vis spectroscopy. The average crystallite size was found as 74.95 nm. Also, the photoluminescence spectroscopy revealed that the compound exhibited different emission bands at the visible range with different intensities depending on the degree of molecular aggregation. For instance, solutions with different concentrations emitted blue, cyan, and green light. On the other hand, the solid-state material produced a dual emission with comparable intensities at λmax = 455, 505, and 621 nm to cover the entire visible range and produce white emission from a single material with CIE coordinates of (0.34, 0.32) that are very similar to the ideal pure white light. Consequently, these findings could lead to the development of more attractive new luminous materials.

Catalytic and Multicomponent Reactions for Green Synthesis of Some Pyrazolone Compounds and Evaluation as Antimicrobial Agents.

A green synthetic approach and facile method was developed to produce pyrazole compounds (6a-d) by the reaction of ethyl acetoacetate (1), hydrazines (2a-d), and catalytic imidazole (3) in aqueous media. 4-Dicyanomethylene-2-pyrazoline-5-one derivatives (14a-d) were synthesized through the reaction of 2-pyrazoline-5-one derivatives (6a-d) with tetracyanoethylene (TCE) (7) by using catalytic imidazole (3) in an aqueous medium. Moreover, the 4-dicyanomethylene derivative (16) was obtained via treatment of 1-phenyl-3,5-pyrazolidinedione (15) with TCE (7). The spiropyrazoleoxirane derivatives (18 and 20) were prepared by treating the precursor 4-dicyanomethylene-2-pyrazoline-5-one derivative (14b) with hydrogen peroxide in various polar solvents under alkaline conditions. The spiropyrazole oxirane derivative (18) was used as a precursor for the design of functionalized pyrazolone derivatives (24 and 27a, b). The chemical structure of the novel designed derivatives was ascertained based on elemental analyses, mp, thin-layer chromatography, and spectral analyses. Furthermore, some of the synthesized derivatives were examined against different pathogenic bacterial and fungal strains. Their results demonstrated that some of them revealed notable antimicrobial activities.

Base-Free Synthesis and Photophysical Properties of New Schiff Bases Containing Indole Moiety.

Schiff bases represent an essential class in organic chemistry with antitumor, antiviral, antifungal, and antibacterial activities. The synthesis of Schiff bases requires the presence of an organic base as a catalyst such as piperidine. Base-free synthesis of organic compounds using a heterogeneous catalyst has recently attracted more interest due to the facile procedure, high yield, and reusability of the used catalyst. Herein, we present a comparative study to synthesize new Schiff bases containing indole moieties using piperidine as an organic base catalyst and Au@TiO2 as a heterogeneous catalyst. In both methods, the products were isolated in high yields and fully characterized using different spectral analysis techniques. The catalyst was reusable four times, and the activity was slightly decreased. The presence of Au increases the number of acidic sites of TiO2, resulting in C=O polarization. Yields of the prepared Schiff bases in the presence of Au@TiO2 and piperidine were comparable. However, Au@TiO2 is an easily separable and recyclable catalyst, which would facilitate the synthesis of organic compounds without applying any hazardous materials. Furthermore, the luminescence behavior of the synthesized Schiff bases exhibited spectral shape dependence on the substituent group. Interestingly, the compounds also displayed deep-blue fluorescence with Commission Internationale de l'Éclairage (CIE) coordinates of y < 0.1. Thus, these materials may contribute to decreasing the energy consumption of the emitting devices.

Synthesis of Novel Biocompatible Thienopyrimidine Chromophores with Aggregation-Induced Emission Sensitive to Molecular Aggregation.

Biocompatible luminogens with aggregation-induced emission (AIE) have several applications in the biology field, such as in detecting biomacromolecules bioprobes and in bio-imaging. Due to their bioactivities and light-emitting properties, many heterocyclic compounds are good candidates for such applications. However, heterocyclic π-conjugated systems with AIE behavior remain rare as strong intermolecular π-π interactions usually quench their emission. In this work, new thienopyrimidine heterocyclic compounds were synthesized and their structures were verified by elemental analysis and Fourier transform infrared (FT-IR), 1H nuclear magnetic resonance (NMR), and 13C NMR spectra. The photophysical properties of some compounds were investigated in the solution and solid states. Density functional theory calculations were also performed to confirm the observed photophysical properties of the compounds. The studied dyes displayed AIE properties with spectral shapes related to the aggregate structure and a quantum yield up to 10.8%. The emission efficiency of the powder is attributed to the incorporation of multiply rotatable and twisted aryl groups to the fused heterocyclic moieties. The dyes also showed high thermal stability and potent antimicrobial activities against numerous bacterial and fungal strains. Additionally, the cytotoxicity of the new compounds was evaluated against the Caco-2 cell line, and molecular docking was used to investigate the binding conformation of the most effective compound with the MNK2 enzyme. Therefore, the presented structures may potentially be used for bioapplications.