SARS-CoV-2 and its variants, especially the Omicron variant, remain a great threat to human health. The need to discover potent compounds that may control the SARS-CoV-2 virus pandemic and the emerged mutants is rising. A set of 1,2,3-triazole and/or 1,2,4-triazole was synthesized either from benzimidazole or isatin precursors. Molecular docking studies and in vitro enzyme activity revealed that most of the investigated compounds demonstrated promising binding scores against the SARS-CoV-2 and Omicron spike proteins, in comparison to the reference drugs. In particular, compound 9 has the highest scoring affinity against the SARS-CoV-2 and Omicron spike proteins in vitro with its IC50 reaching 75.98 nM against the Omicron spike protein and 74.51 nM against the SARS-CoV-2 spike protein. The possible interaction between the synthesized triazoles and the viral spike proteins was by the prevention of the viral entry into the host cells, which led to a reduction in viral reproduction and infection. A cytopathic inhibition assay in the human airway epithelial cell line (Vero E6) infected with SARS-CoV-2 revealed the effectiveness and safety of the synthesized compound (compound 9) (EC50 and CC50 reached 80.4 and 1028.28 µg/mL, respectively, with a selectivity index of 12.78). Moreover, the antiinflammatory effect of the tested compound may pave the way to reduce the reported SARS-CoV-2-induced hyperinflammation.

Matrix metalloproteinases (MMPs) are key signaling modulators in the tumor microenvironment. Among MMPs, MMP-2 and MMP-9 are receiving renewed interest as validated druggable targets for halting different tumor progression events. Over the last decades, a diverse range of MMP-2/9 inhibitors has been identified starting from the early hydroxamic acid-based peptidomimetics to the next generation non-hydroxamates. Herein, focused 1,2,4-triazole-1,2,3-triazole molecular hybrids with varying lengths and decorations, mimicking the thematic features of non-hydroxamate inhibitors, were designed and synthesized using efficient protocols and were alkylated with pharmacophoric amines to develop new Mannich bases. After full spectroscopic characterization the newly synthesized triazoles tethering Mannich bases were subjected to safety assessment via MTT assay against normal human fibroblasts, then evaluated for their potential anticancer activities against colon (Caco-2) and breast (MDA-MB 231) cancers. The relatively lengthy bis-Mannich bases 15 and 16 were safer and more potent than 5-fluorouracil with sub-micromolar IC₅₀ and promising selectivity to the screened cancer cell lines rather than normal cells. Both compounds upregulated p53 (2–5.6-fold) and suppressed cyclin D expression (0.8–0.2-fold) in the studied cancers, and thus, induced apoptosis. 15 was superior to 16 in terms of cytotoxic activities, p53 induction, and cyclin D suppression. Mechanistically, both were efficient MMP-2/9 inhibitors with comparable potencies to the reference prototype hydroxamate-based MMP inhibitor NNGH at their anticancer IC₅₀ concentrations. 15 (IC₅₀ = 0.143 µM) was 4-fold more potent than NNGH against MMP-9 with promising selectivity (3.27-fold) over MMP-2, whereas 16 was comparable to NNGH. Concerning MMP-2, 16 (IC₅₀ = 0.376 µM) was 1.2-fold more active than 15. Docking simulations predicted their possible binding modes and highlighted the possible structural determinants of MMP-2/9 inhibitory activities. Computational prediction of their physicochemical properties, ADMET, and drug-likeness metrics revealed acceptable drug-like criteria.

Three rings 2-hydroxypyridine liquid crystalline compounds have been prepared and fully characterized. The mesomorphic behavior of the prepared compounds has been investigated in terms of differential scanning calorimetry (DSC) and polarized optical microscopy (POM). Moreover, a comparative study between the prepared compounds and previously reported analogs has been discussed in terms of the orientation and position of the mesogenic core, in addition to the direction of the terminal alkyl chains. Furthermore, a detailed computational approach has been studied to illustrate the effect of geometrical and dimensional parameters on the type of the enhanced texture and the mesomorphic range and stability. The results of the DFT study revealed that the orientation of the mesogen could affect the mesomorphic behavior and this has been attributed in terms of the degree of the polarizability of the linking groups. This result has been confirmed by calculation of the net dipole moment and the molecular electrostatic potential that show how the mesogen orientation and position could impact the molecular charge separation. Finally, the effect of the pyridyl group has been also investigated in terms of the calculated aromaticity index and the π-π stacking.

Molecular cosensitization is favorable for manipulating solar radiation through the judicious choice of cosensitizers having complementary absorption spectra. For greenhouse-integrated dye-sensitized solar cells (DSCs), the manipulation of solar radiation is crucial in order to maximize the flow of photosynthetically active radiation (PAR) for the effectual photosynthetic activity of plants; meanwhile, non-PAR is utilized in agrivoltaics for generating electricity. In this study, we report the synthesis of novel four UV-selective absorbers, based on the diimide scaffold, functionalized with carboxylate and pyridyl anchoring groups, for adequate adsorption onto the TiO₂ electrode in DSC. The UV/Vis absorption spectra of the DMF solution-based free dyes were measured experimentally. Basic photophysical and energetics requirements for operating greenhouse-integrated DSCs were examined at the molecular level via (time-dependent) density functional theory-based calculations. The computational results revealed the outperformance of the biphenyldiimide-structured DI-CA1 dye, especially for maximum charge transferred to its anchor, lower thermodynamic barrier for dissociating the photogenerated exciton, largest Stokes' shift, strong electronic coupling with TiO₂ nanoparticles, and higher degree of charge separation at the DI-CA1/TiO₂ interface. PDOS showed deeper existence for the LUMO level in the CB of TiO₂, which expedites the electron injection process. The chemical and optical compatibility of DI-CA1 were then investigated as a potential cosensitizer of a reference BTD–DTP1, a green light-absorbing dye. Considerable overlap between the fluorescence spectrum of DI-CA1 and absorption spectrum of the reference BTD–DTP1 advocated the opportunity of excitation energy transfer via the radiative trivial reabsorption mechanism, which confirms the cosensitization functionality. Energy decomposition analysis and reduced density gradient maps estimated the chemical compatibility owing to weak dispersion interactions as the dominant stabilizing attractive force. This noncovalent functionalization retains the chemical compatibility without distorting the π–π conjugation and the associated physicochemical properties of the individual dye molecules. Along with the expanded consumption of non-photosynthetically active solar radiation, an improved power conversion efficiency of greenhouse-integrated DSC is accordingly expected.

A new series of Schiff base liquid crystal have been prepared and studied. Schiff bases of p-alkyl aniline derivatives and 4-phenyl pyridine-4′-carbaldehyde were prepared. The terminal alkyl groups substituting aniline are of varied chain length, namely C8, C12 and C14. The structures of the compounds were elucidated by 1H NMR and 13C NMR. The mesomorphic thermal and optical characteristics of the samples were determined via differential thermal analysis (DSC) and polarization optical microscopy (POM). All compounds exhibit enantiotropic dimorphic mesophase behaviour, referred to as smectic X1 (SmX1) and smectic X2 (Sm A). Experimental results obtained for the mesophases were correlated with density functional theory (DFT) theoretical calculations. The results of the new series are further compared to two series of compounds bearing pyridine (two ring Schiff bases) and biphenyl, respectively, in their mesogens. The series of compounds of one pyridine ring are generally not mesomorphic. The results indicate that the alkyl chain length has a strong impact on the mesomorphic characteristics and thermal stabilities of the different mesophases. As a trend, the temperature ranges of both of smectic mesophases of all compounds are higher in new compounds bearing the 4-phenyl pyridine moiety. In addition, the total mesophase range is generally higher in the new compounds when compared to their biphenyl analogues. Finally, theoretical DFT calculations were performed to illustrate the experimental finding of the mesomorphic behaviour in terms of the molecular geometry and aromaticity, π–π stacking and LOL-π.