Ethyl 5-cyano-1,6-dihydro-2-methyl-4-styryl-6-thioxonicotinate, its piperidinium pyridine-6-thiolate and 3-
acetyl-5-cyano-1,6-dihydro-2-methyl-4-styryl-6-thioxopyridine were used as starting materials for synthesizing
novel series of S-substituted methylthiopyridine-5-carbonitriles and thieno[2,3-b]pyridines with expected
biological activity. Also, some novel thieno[2,3-c][2,7]naphthyridinones were synthesized. Moreover, 1,7-
diamino-8,9-dihydro-5-methyl-8-phenyl-3H-pyrazolo[3,4-c][2,7]naphthyridine-6(7H)-one was synthesized by
heating ethyl 5-cyano-1,6-dihydro-2-methyl-4-styryl-6-thioxonicotinate with hydrazine hydrate 99% under
neat conditions. The obtained promising aminopyrazolo[3,4-c][2,7]naphthyridine-6(7H)-one was used as a
precursor to get other novel derivatives with expected biological and medicinal importance. Structures of all
new compounds were elucidated by elemental and spectral analysis.

Biopolymers are organic substances extracted from natural renewable sources, including plants, animals, and microorganisms. Chitin, the parent source of chitosan (CS), is the second most abundant natural biopolymer available in seafood-processing wastes and fungal cell walls. Pure and conjugated CS nanocomposites are extensively explored in environmental remediation, agriculture, food packaging, and biomedicine due to their affordability, superior heavy metals and dye chelation, biodegradability, flocculating, and film-forming and antimicrobial properties. CS reactive hydroxyl and amino groups enable surface functionalization for enhanced solubility over a wider range of pH, thermal stability, and mechanical strength. This chapter gives an overview on sources, extraction techniques, modifications, properties, and applications of CS.

In this study, two new thieno[2,3-b]pyridine derivatives (2 and 3) have been synthesized and characterized by single X-ray diffraction. While compound 2 crystallizes in monoclinic space group P2₁/c, compound 3 crystallizes in triclinic space group P. These compounds were further subjected to molecular docking simulation with p38 alpha MAP kinase to understand the binding interaction mechanism, in addition to that ADMET analysis was also performed to explore the title compounds to characterize the future drug candidate. To rationalize their structure-activity relationship, a DFT study based on the B3LYP/6-311++G** theoretical level was also done in this study.

5-Acetyl-4-(4-methoxyphenyl)-6-methyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile has been successfully prepared by the condensation between the acetylacetone and 2-cyano-3-(4'-methoxyphenyl)thio acrylamide and used to search for a potential drug that could be used to treat COVID-19. The structure was characterized and confirmed by X-ray diffraction analysis, and the crystal packing stability was also performed by the Hirshfeld surface analysis. The chemical reactivity and other properties of the title compound were determined using the density functional theory (DFT) computation and the NBO analysis. Also, the molecular electrostatic potential (MEP) surface was investigated. The CN group was the most nucleophilic site in the entire molecule based on the results. The title compound’s in-silico molecular docking revealed a strong binding potential. Eventually, molecular dynamic (MD) simulation studies are conducted to examine the stability of the molecule inside the receptor cavity. The findings of the in-silico analysis manifested affirmative evidence for the title molecule with good binding, as a potent inhibitor for the main protease of SARS-Cov-2. Hence, it holds the striking potential to serve as a prospective lead compound for designing efficacious drugs against COVID-19.

Ethyl-5,8-dimethyl-6-phenyl-(1H-pyrrol-1-yl)-6,7-dihydrothieno[2,3-c]isoquinoline-2-carboxylate has been synthesized and single-crystal X-ray diffraction at 170 K and DFT calculations were performed to characterize the reactivity and its electronic structure. The asymmetric unit of the title molecule, C₂₆H₂₄N₂O₂S, contains two independent molecules differing primarily in the rotational orientations of the pyrrolyl substituent. The two independent molecules are connected by a C—H···O hydrogen bond and in the crystal, two asymmetric units are linked by inversion-related C—H···N hydrogen bonds. The Hirshfeld surface (HS) analysis reveals intermolecular interactions and surface reactivity in a single crystal. The highest fraction of intermolecular contact of 64% can be seen for H⋅⋅⋅H while the lowest contribution of 3.9% was observed for O⋅⋅⋅H contact in crystal packing. The interaction energies between chemical pairs in the crystal structure are investigated by energy framework analysis which indicates repulsion outweighs the coulomb energy and dispersion energy. The performed density functional theory (DFT) investigation has provided us an electronic picture the of structure and fabulous reactivity. The frontier molecular orbital (FMO) analysis reveals a narrow HOMO-LUMO gap (3.81 eV) and global reactivity descriptors also agree with molecular reactivity and remarkable electronic properties. The density of state (DOS) study shows a pictorial representation the of density of states while MESP shows reactive sites (electron-rich) of the compound for electrophilic attack.

The present study elaborates on the synthesis, crystal structure, and computational studies of two new ionic liquids. In the crystal structure, [C₅H₁₂N][C₂₁H₁₄ClN₂O₂S] (4a), the anions form chains along the a-axis direction through C—H···π(ring) interactions. These are connected into layers that run approximately parallel to the ac plane by a variety of hydrogen bonds. In the compound structure, [C₅H₁₂N][C₁₈H₁₅N₂O₂S] (4b), the two ions are primarily associated by an N—H···N hydrogen bond. In the crystal structure, layers parallel to the bc plane are formed by pairs of C—H···O and N—H···S hydrogen bonds and by C—H···π(ring) interactions. A theoretical study reveals that 4a has lower energy than 4b and is more stable. The NBO and DOS studies further confine the liquids’ structural reactivity and electronic properties. The quantum theory of atoms in a molecule (QTAIM) analysis reveals the important non-covalent interactions among the fragments and charge transfer. The global reactivity descriptors indicate their molecular reactivity relationship with the presence of functional groups. The remarkable polarizability (α_o) and hyperpolarizability (β_o) values indicate their optical and nonlinear optical (NLO) properties. Furthermore, the analysis performed by CrystalExplorer shows the intermolecular interactions and reactive sites between cations and anions in ionic liquids. The 2D fingerprint plots and Hirshfeld surfaces indicate the major interactions of crystals with neighboring elements in crystal packing. For both compounds, the H···H interactions are significantly higher than the other element interactions.

The reaction of ethyl 5-cyano-2-methyl-4-(thiophen-2-yl)-6-thioxo-1,6-dihydropyridine-3-carboxylate (1) with 2-chloroacetamide or its N-aryl derivatives gave ethyl 6-((2-amino-2-oxoethyl)thio)-5-cyano-2-methyl-4-(thiophen-2-yl) nicotinate (2a) or its N-aryl derivatives 2b–f, respectively. Cyclization of 2a–f into their isomers 3a–f was carried out by heating in absolute ethanol in the presence of a catalytic amount of sodium ethoxide. The o-aminoamide 3a was reacted with some aryl aldehydes in refluxing ethanol containing a few drops of conc. HCl to afford the corresponding tetrahydropyrimidinones 4a–d. The cyclocondensation reaction of 3a with some cycloalkanones such as cyclopentanone and cyclohexanone gave the corresponding spiro compounds 5a,b. The crystal structures of compounds 2a and 2d were determined by single-crystal X–ray diffraction techniques. All new compounds were evaluated for their insecticidal activity toward nymphs and adults of Aphis gossypi.

Isoquinoline and its derivatives, which constitute an important category of heterocyclic compounds and are found in a variety of naturally occurring alkaloids, serve a variety of biological purposes such as a potent agonist for human melatonin receptors 1. This research was conducted in an attempt to develop new dihydroisoquinoline molecules (III and IV). Single-crystal X-ray crystallography study validated their structures. The Hirshfeld surface analysis identifies intermolecular interactions by using a 2-D fingerprint map to recognize each type's relative contribution H⋅⋅⋅H connections are discovered to be dominating. The interaction energies between chemical pairs in crystal structures were found using an energy framework analysis. The DFT investigation demonstrates the electronic stability and reactivity of the compounds using the HOMO-LUMO and global reactivity descriptors, indicating that IV has higher chemical reactivity than III. The derived polarizability (αo) and hyperpolarizability (βo) values were used to calculate the optical and nonlinear optical characteristics of III and IV. The IV's significant βo value (488.94 au) indicates that it has good optical and NLO qualities. Molecular docking simulation using human melatonin receptors 1 was used to better understand the binding interaction mechanism of the title compounds. In addition, ADMET evaluations were performed to establish the therapeutic potential of III and IV.

In the present work, we describe the synthesis of new tetrahydroisoquinoline derivatives and the crystal structures of two of them. Density functional theory (DFT) investigations at the B3LYP/6-31+G(d,p) level provided their structural reactivity and nonlinear optical properties. The low HOMO-LUMO gaps (E_H-L) suggest a soft nature and higher reactivity, while calculated global reactivity descriptors provide assessments of their reactivity and electronic stability. The calculated natural bonding molecular orbital (NBO) charges show excellent charge separation (charge transfer) and identify the donor and acceptor parts of the molecules. Density of states (DOS) analyses show the newly generated energy states and reduced band gaps, which impart higher conductive properties. For surface reactivity, 3D MESP surfaces are plotted and show electron-rich sites near the nitrogen atoms of the tetrahydroisoquinoline rings. Nonlinear optical (NLO) properties of the crystals are predicted from calculated polarizability (α_o) and hyperpolarizability (β_o) values. For IVb, the α_o and β_o values are 415.53 and 1003.44 au. The remarkable value (1003.44 au) of the hyperpolarizability (β_o) shows IVb has excellent NLO properties. Structural activity relationship analysis suggests that nitric oxide synthases are better targets for both compounds, and they were further subjected to molecular docking simulations to understand the binding efficiency. In addition, ADMET analyses were carried out to understand the potential activity of the molecules as drug candidates.

In the era of modern synthetic methodology and advanced bio-evaluation techniques and considering the notorious history of hepatocellular carcinoma (HCC), hopeful expectations regarding novel bioactive chemotypes have grown dramatically. Among the widely versatile motifs in drug discovery studies are isoquinoline and thieno[2,3-b]pyridine. Herein, the molecular merging of both motifs evoked thieno[2,3-c]isoquinoline as a novel antiproliferative chemotype being hardly studied against HCC. Accordingly, compound series 4, 5, 7 and 8 were synthesized and bioevaluated against the HepG2 cell line. The role of C7-Ac/C8-OH substituents, C8-C9 unsaturation, 1H-pyrrol-1-yl ring closure at C1-NH₂ and C6-Ph p-halo-substitution were biologically studied and successfully furnished the lead 5b while showing safe profile against Vero cells. Further, flow cytometric and Annexin V-FITC/PI apoptotic bio-investigations of 5b unveiled remarkable cell cycle arrest at the G2/M phase besides a 60-fold increase in apoptosis. The use of a DFT conformational study followed by Molecular docking and molecular mechanics/generalized born surface area scoring evoked potential tubulin-targeting activity of 5b at colchicine-binding site, which was confirmed by experimental evidence (Tub Inhib IC₅₀ = 71 µM vs. 14 µM for colchicine). Accordingly, preserving C7-acetyl and optimizing halogen position while preserving [6S,7R]-stereochemistry is crucial for optimum binding to colchicine binding site of tubulin.