Hirshfeld Surface Studies Research Articles

Supramolecular Co (II) Complex Fabricated From Adenine Derivative: Synthesis, Crystal Structure, Hirshfeld Surface, DFT Optimization, Anticancer, and Molecular Docking Studies

ABSTRACTThis article presents the synthesis of a novel mononuclear Co (II) complex [Co(9‐BuA)2Cl2] (1), its characterization, supramolecular packing pattern, theoretical calculations, anticancer properties, and molecular docking studies. Complex 1 was generated from 9‐butyl adenine (9‐BuA) building block and characterized by spectroscopic methods (FT‐IR, mass, elemental analysis) and single crystal X‐ray diffraction analysis. The cobalt (II) ion in complex 1 is distorted in its tetrahedral environment. The Co+2 is coordinated to the two rare N1 binding sites of the pyrimidinate moiety of two 9‐BuA ligands and two chlorine atoms occupying the axial positions. Both intramolecular and intermolecular hydrogen bonds support the formation of supramolecular assembly and stabilize the crystal structure. The nature of the intermolecular interactions in the supramolecular network was also decoded by Hirshfeld surface analysis and molecular surface contours (dnorm). The percentage contributions are represented by 2D fingerprint plots. The average energy between dimers was determined by the energy framework analysis, and the crystal packing's three‐dimensional topology was also investigated. Density functional theory (DFT) has been used to ascertain the geometry and interactions in the complex. The cytotoxic effects of Co (II) complex 1 and corresponding 9‐BuA ligand were investigated in Dalton's lymphoma (DL) malignant cancer cells and on normal peripheral blood mononuclear cells (PBMCs) to evaluate their anticancer activity. Finally, molecular docking analyses have been carried out to analyze the nature of molecular interactions between Co (II) complex 1 and the receptor.

Synthesis, characterization, biological activity, DFT and Hirshfeld surface studies of Pd(II) and Pt(II)-1-cyclohexyl-3-phenylthiourea and amine ligands

A series of mixed ligand complexes of Pd(II) and Pt(II) of 1-cyclohexyl-3-phenylthiourea and diamine ligands {2,2'-bipyridyl (Bipy) and 1,10-phenanthroline (Phen)} were prepared and characterized by FT-IR, NMR spectroscopy, molar conductivity. Density functional theory (DFT) calculations and biological activity were carried out on the prepared complexes. In vitro antimicrobial activity was investigated against three pathogenic bacteria (Staphylococcus aureus, Bacillus cereus and Escherichia coli). The most active compound 6 was found more active than free ligand and other complexes. The crystal structure of the free ligand was determined by X-ray diffraction (XRD) analysis. Hirshfeld surface analysis was executed for the free ligand by finding and exploring the interatomic contacts that are important considering the supramolecular assembly of the crystal. The mechanical stability or response is prophesied by voids analysis. The supramolecular assembly is significantly uncovered by intermolecular interaction energies calculations performed at of the B3LYP/6-31G(d,p) electron density level. KEY WORDS: Thiourea, Diamine, Crystal structure, DFT, Hirshfeld surface Bull. Chem. Soc. Ethiop. 2025, 39(1), 15-27. DOI: https://dx.doi.org/10.4314/bcse.v39i1.2

Experimental and theoretical studies of alkyl 2-(2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1]nonan-9-ylidene)hydrazine carboxylates: Synthesis, spectroscopic, crystal structure, Hirshfeld surface, and antimicrobial studies

The nine alkyl 2-(2,4,6,8-Tetraaryl-3,7-diazabicyclo[3.3.1]nonan-9-ylidene)hydrazine carboxylates having bicyclic bispidine core were synthesized and characterized using FT-IR, NMR, and mass spectra. Further confirmation of the structure and positioning of the groups was obtained using single crystal XRD investigation. The analysis revealed that one piperidine ring adopts a chair and another a boat form. The aryl groups in the chair conformation are positioned equatorially, whereas those in the boat conformation are orientated axially. The carbazate group (C=N-NH-COOR) aligned the center of the two piperidine rings, with a small deviation towards the boat conformation piperidine ring. The dihedral angle between the chair and boat conformations of the piperidine ring (2f) is 48.51 Å and 45.12 Å, respectively. Hirshfeld and 2D fingerprint analysis show considerable H···H bonding interactions in the crystal. The intermolecular interaction and mechanical stability of crystals were investigated using interaction energy and crystal void analysis. Reduced density gradient and localized orbital locator analyses were used to investigate intramolecular interactions and electron delocalization. The molecule's higher and lower electron densities were investigated utilizing frontier molecular orbital analysis and Molecular Electrostatic Potential. The antimicrobial activity of the compounds was investigated using four bacterial and two fungus strains.

Chitosan/La catalyzed synthesis of novel ferrocenated spiropyrrolizidines: Green synthesis, crystallographic, DFT and Hirshfeld surface studies

A novel polymeric catalytic system, utilizing chitosan-bounded lanthanum (chitosan/La), facilitated the formation of spiropyrrolizidine hybrids in higher yield. These hybrids were synthesized via one-pot three component 1,3-dipolar cycloaddition reaction involving ferrocenated chalcones, and azomethine ylides. The chemical structures were elucidated using various spectroscopic techniques and further confirmed via X-ray crystallography of a compound 3. Density functional theory (DFT) calculations executed followed by Gaussian 09 and GaussView 5.0 software provided insights into the optimal structure of molecular compounds. The computational analysis employed the 6–311G++ (d,p) higher-order basis set and the B3LYP method. Additionally, Hirshfeld surface analysis was utilized to predict crystallographic shapes, revealing van der Waals interaction contributing to crystal stabilization.

Acetylcholine and butyrylcholine esterase inhibitory potential of newly synthesized halogenated compounds: In vitro, in silico and MD simulation

Schiff bases have numerous applications especially in the medicinal chemistry. Keeping in view their importance, two new compounds; (E)-2-(((4‑bromo-2-(trifluoromethyl) phenyl)imino)methyl)-4-nitrophenol (1) and (E)-3-((4‑bromo-2-(trifluoromethyl)phenylimino) methyl)pyridin-2-amine (2) have been synthesized. These Schiff bases were characterized with modern spectral tools while precise structures were confirmed through XRD which revealed that compound 1 was monoclinic and compound 2 was orthorhombic. The synthesized compounds were further evaluated theoretically by applying density functional theory approach. Regression coefficient (R2) was utilized to compare the different parameters between DFT and XRD data. Hirshfeld surface study was used to find out the different interactions between the atoms presented in the crystalline molecules. Online free tool was used against AChE and BChE for accomplishment of the molecular modeling study. The molecular dynamics simulation study was also conducted to check the binding mechanism of the most active compound on AChE. On the basis of the docking score and MD simulation, compound 1 depicted more inhibition potential. The in-vitro studies further confirmed that synthesized Schiff bases have potential to cure the Alzheimer disease by inhibiting enzymes related to this disease.

Crystal structure and Hirshfeld surface analysis of 1-[6-bromo-2-(3-bromo-phen-yl)-1,2,3,4-tetra-hydro-quinolin-4-yl]pyrrolidin-2-one.

This study presents the synthesis, characterization and Hirshfeld surface analysis of 1-[6-bromo-2-(3-bromo-phen-yl)-1,2,3,4-tetra-hydro-quinolin-4-yl]pyrrolidin-2-one, C19H18Br2N2O. In the title compound, the pyrrolidine ring adopts a distorted envelope configuration. In the crystal, mol-ecules are linked by inter-molecular N-H⋯O, C-H⋯O and C-H⋯Br hydrogen bonds, forming a three-dimensional network. In addition, pairs of mol-ecules along the c axis are connected by C-H⋯π inter-actions. According to a Hirshfeld surface study, H⋯H (36.9%), Br⋯H/H⋯Br (28.2%) and C⋯H/H⋯C (24.3%) inter-actions are the most significant contributors to the crystal packing.

Synthesis, crystal structure, Hirshfeld surface, computational and biological studies of spiro-oxindole derivatives as MDM2-p53 inhibitors.

The spiro-oxindole derivatives were synthesized via a 1,3-dipolar cycloaddition approach and characterized by FT-IR, 1H, 13C NMR and mass spectral techniques. The single crystal XRD of 6d further validates the formation of compounds. DFT calculations indicated the reactive nature of compound 6d. Docking studies with 5LAW disclosed the minimum binding energy of - 10.83kcal/mol for 6d. Furthermore, safe oral bioavailability was ensured by the physicochemical, pharmacokinetic, and toxicity predictions. The anticancer analysis of synthesized compounds showed substantial activity against A549 cells, notably with an IC50 value of 8.13 ± 0.66µM for 6d compared to standard doxorubicin. 6d was also evaluated for cytotoxicity against L929 healthy cells and A549, showing selectivity towards A549 than healthy cells. AO/EB staining method showed early apoptotic cellular death in the A549 cell line in a dose-dependent manner.

Novel base‐catalyzed acylation of benzenediols with vinyl acetate: a Hirshfeld surface study

AbstractBACKGROUNDThe present work describes the facile, fast and economic base‐catalyzed acylation of benzenediols with vinyl acetate. The Hirshfeld surface analysis of benzene‐1,4‐diol O,O′‐diacetate is also described. NaOH, KOH and K2CO3 were the bases used for the catalysis of the acylation of benzene‐1,x‐diols (x = 2, 3, 4) with vinyl acetate to obtain the corresponding O,O′‐diacetyl derivatives.RESULTSThe yields were quite good, up to 99% under solvent‐free conditions. This method represents an alternative ‘green’ process for the preparation of O‐acetyl derivatives of hydroxyaryls. The benzene‐1,4‐diol O,O′‐diacetate crystal structure was obtained and described using Hirshfeld surface analysis. A noticeable contribution of the C⋯H contacts is shown (16.7%), despite the insignificant area of the Hirshfeld surface occupied by the carbon atoms (9.4%). By using two‐dimensional fingerprint plots, it was proved that C⋯H contacts were due to the presence of π‐stacking. The O⋯H contacts (41.4%) were the most numerous ones, relating mainly to typical hydrogen bonds (de + di ≈ 2.6 Å). The high saturation of the C⋯H and O⋯H contacts (enrichment ratios (E) = 1.30 and 1.36, respectively), despite their smaller contribution to the overall surface as compared to the H⋯H contacts (E = 0.84), is shown.CONCLUSIONThe novelty of this work is the development of a method based on an inexpensive, safe and easy‐to‐use catalyst (K2CO3). This method is fast with high yields. Besides, it may be used for acylation at an industrial scale. © 2024 Society of Chemical Industry (SCI).

Unveiling the molecular insights of 2-(carboxymethyl) benzoic acid: A density functional theory approach towards structural and biological attributes

Nowadays density functional theory (DFT) is one of the best methods to explore the vibrational modes and structure of the biological system. Quantum mechanical calculations are performed using gas phase and different solvents (DMSO, methanol and water). The derived global reactive parameters, structural and topological study provides the clear insight of the 2-(Carboxymethyl) benzoic acid. Depth studies of DFT proves the existence of hydrogen bonds between donor and acceptor in the compound, which is supportive for the biological applications. In this paper, different experimental and computational simulated FT-IR, FT-Raman, UV–Vis spectral studies are used to explicate vibration assignments of the 2-(Carboxymethyl) benzoic acid. Experimentally observed vibrational frequency is compared with theoretically simulated spectrum. B3LYP method with 6–311++G (d, p) basis set is used in DFT to optimize the 2-(Carboxymethyl)benzoic acid structure. The most stable lower energy conformer is identified using potential energy surface (PES) analysis using Gaussian 16 W software. ESP, HOMO-LUMO, NBO, and QTAIM calculations have evinced an adequate electronic characterization of 2-(Carboxymethyl) benzoic acid. Further, van der Waals and steric interactions among 2-(Carboxymethyl) benzoic acid have been discussed with the help of RDG study. Hirshfeld surface studies establish the existing various interaction among molecules and total packing arrangement of the crystal structure. Due to the high biological activity score, 2-(Carboxymethyl) benzoic acid is a good therapeutic candidate. Lipophilicity analysis of 2-(Carboxymethyl)benzoic acid clearly explicates the bioactivity properties and its effective drug applications. Further, molecular docking investigates that the compound can be used as anticancer medication. The detailed DFT study of the 2-(Carboxymethyl) benzoic acid justified its biological applications of the present communication. The calculated NLO parameters of 2-(Carboxymethyl)benzoic acid evidenced for good efficacy in diverse filed application has been discussed.

Synthesis, structure analysis, Hirshfeld surface studies, molecular docking studies against cyclin-dependent kinases (CDKs) of sulfonamide decorated N6-benzyl aminopurines for cancer treatment

Cyclin-dependent kinases (CDKs) are recognized as the primary regulators of the cell cycle. CDKs are over-expressed in various types of cancer. Inhibiting CDKs with small molecules can reduce tumor growth and benefit cancer patients. In the current study, sulfonamide-decorated N6-benzyl aminopurines such as ligand 1: (α- alpha (Purin-6-ylamino)-p-toluenesulfonamide) and ligand 2: (α-(2-Amino purin-6-ylamino)-p-toluenesulfonamide)) purine were synthesized and explored for their anticancer efficacy. Crystallographic analysis revealed that ligand 1 crystallizes in P-1 of the triclinic and ligand 2 molecule in C2/c or P21/c of the monoclinic systems. Hirshfeld surface and X-ray crystallographic studies discovered that ligand 2 possesses stronger noncovalent interaction ability than roscovitine. In silico analysis showed that ligand 2 had a higher binding affinity for ATP binding sites of CDK1, CDK2, and CDK4 receptors than roscovitine (a known CDK inhibitor). The enhanced binding affinity of ligand 2 with CDKs was found to be associated with strong noncovalent interactions between ligand 2 and specific amino acids in CDKs. Cytotoxicity studies were conducted on the glioblastoma cell line (U251) by incubating cells with ligands 0, 1, and 2, roscovitine, and the established anticancer drug Temozolomide (TMZ). Ligand 2 (66.12 ± 1.09 µM) demonstrated better cytotoxicity compared to ligand 1 (81.22 ± 0.30 µM), roscovitine (127.10 ± 0.47 µM), and TMZ (165.11 ± 1 µM). It was well known that CDK inhibition can lead to cell cycle arrest. Intriguingly, ligand 2 induced G2/M phase cell cycle arrest by increasing the percentage of the G2/M phase cell population from 21.08 % to 47.79 % in U251 cells. Based on these results, ligand 2 showed anticancer properties by binding to the ATP binding site of CDKs. Hence, ligand 2 can serve as a potential lead molecule in the development of effective anticancer agents.

Supramolecular assemblies of Zn(II) complex based on dithiolate-amine binary ligands: Synthesis, crystal structure, Hirshfeld surface, DFT, molecular docking, and anticancer studies

In this article, synthesis of the novel zinc(II) complex [Zn(tren)(i-mnt)] from diethylenetriamine (tren) and 1,1-dicyano-2,2-ethylenedithiolate di-potassium salt (K2i-mnt) has been presented and characterized by spectroscopic methods. The trigonal bipyramidal geometry of [Zn(tren)(i-mnt)] in solid state has been confirmed by X-ray diffraction analysis where stacked assembly of parallel chains interlinked by N–H⋯S, N–H⋯N, and C–H⋯N type hydrogen bonds observed in 3D supramolecular packing. Hirshfeld Surface (HS) optimizations show prominent N⋯H/H⋯N (32%), S⋯H/H⋯S (21%), and C⋯H/H⋯C (18.5%) interactions that well corroborate with X-ray data. Moreover, Density Functional Theory (DFT) at B3LYP/6-31 g(d) and LMKLL/DZDP basis sets have been used to ascertain geometry and long-range interactions in the complex. In addition, DNA-binding analysis has been assessed by inspecting its binding capability to calf-thymus DNA (CT DNA) and cytotoxic effects of the complex, and K2i-mnt were investigated against Dalton’s Lymphoma (DL) malignant cancer cells to assess their anticancer activity. The molecular docking study shows that the complex has a better binding affinity for 3DK8 (Protein Data Bank ID), leading to a higher inhibition constant and interactions.

Crystal structure and Hirshfeld surface analysis of 6-imino-8-(4-methyl-phen-yl)-1,3,4,6-tetra-hydro-2H-pyrido[1,2-a]pyrimidine-7,9-dicarbo-nitrile.

In the ten-membered 1,3,4,6-tetra-hydro-2H-pyrido[1,2-a]pyrimidine ring system of the title compound, C17H15N5, the 1,2-di-hydro-pyridine ring is essentially planar (r.m.s. deviation = 0.001 Å), while the 1,3-diazinane ring has a distorted twist-boat conformation. In the crystal, mol-ecules are linked by N-H⋯N and C-H⋯N hydrogen bonds, forming a three-dimensional network. In addition, C-H⋯π inter-actions form layers parallel to the (100) plane. Thus, crystal-structure cohesion is ensured. According to a Hirshfeld surface study, H⋯H (40.4%), N⋯H/H⋯N (28.6%) and C⋯H/H⋯C (24.1%) inter-actions are the most important contributors to the crystal packing.

Synthesis, crystal structure, DFT, vibrational properties, Hirshfeld surface and antitumor activity studies of a new compound 2-(2-chloro-6-(m-tolyl)imidazo[1,2-a]pyridin-3-yl)-N,N-diethylacetamide

Imidazo[1,2-a]pyridine derivatives are a kind of fused heterocyclic substances, which play an important role in the chemical field and have been proved to be the core fragments of various drug molecules. In this study, a new title compound was finally synthesized by cyclization, substitution, Suzuki coupling, hydrolysis and condensation. And the crystal of the title compound was obtained by single crystal culture. The structure of 2-(2-chloro-6-(m-tolyl)imidazo[1,2-a]pyridin-3-yl)-N,N-diethylacetamide was confirmed by 1H NMR, 13C NMR, FT-IR and single crystal X-ray diffraction. In addition, the title compound was theoretically calculated at the level of 6–311+G (2d, p) based on density functional method B3LYP, and the molecular structure optimized by DFT was consistent with the results obtained by X-ray diffraction. By calculating the Hirschfield surfaces and 2D fingerprints of molecules, the interactions between molecules can be visually revealed based on the size and color of the spots near the atoms. In addition, according to the characteristic vibration absorption band, the vibration of the title compound is reliably attributed. Furthermore, MEP, RDG, and ELF analyses were conducted to characterize the reaction sites susceptible to electrophilic and nucleophilic attacks. FMOs was used to evaluate the stability of the molecular structure. Finally, the results of the determination of biological activity showed that the compound exhibited significant inhibitory activity against HCT116 cancer cell.

Synthesis, molecular self-assembly and anti-carcinogenic study of 2-pyridone molecules

4H-pyrans obtained from the multicomponent reactions of aromatic aldehyde, malononitrile, and ethyl acetoacetate were used as a starting scaffold for synthesizing 2-pyridone derivatives (1–3). Two catalytic methods were reported for the conversion of 4H-pyrans to 3,4-dihydropyridones. The non-aromatic 3,4-dihydropyridones obtained were then oxidized to give the final desired 2-pyridone derivatives (1–3). Crystals of the synthesized compounds were prepared and subjected to single-crystal X-ray crystallography (SCXRD) to acquire their structural parameters. Non-covalent interactions in the supramolecular systems 1–3 were studied, and it found that NH∙∙∙O interactions between the lactam groups are the most dominant hydrogen bonds. It is also observed that the aromatic rings are involved in lone pair∙∙∙π, CH∙∙∙π, and weak π∙∙∙π interactions in assisting the supramolecular framework. Hirshfeld surface studies are also performed to validate the interactions within the supramolecular crystals. The 2-pyridone derivatives (1–3) were also analyzed by in vitro techniques to evaluate their cytotoxic activities using human lung adenocarcinoma (A549). It is also found that ethyl 5-cyano-2-methyl-4-(3-nitrophenyl)-6-oxo-1,6-dihydropyridine-3-carboxylate (1) has shown the highest cytotoxic potency amongst the synthesized compound.

Experimental and theoretical studies of methyl 1-(2-chloroacetyl)-4-hydroxy-2,6-diphenyl-1,2,5,6-tetrahydropyridine-3-carboxylate: Insights from synthesis, spectroscopic, crystal structure, Hirshfeld surface, DFT, ELF, RDG, IRI, ADMET and docking studies

Methyl 1-(2-chloroacetyl)-4‑hydroxy-2,6-diphenyl-1,2,5,6-tetrahydropyridine-3-carboxylate (compound 2) was synthesized by the condensation of 3-carboxymethyl-2,6-diphenylpiperidine-4-one with chloroacetylchloride, and characterized by FT-IR spectroscopy. Further confirmation of the molecular structure was obtained by the single crystal X-ray diffraction (SC-XRD) technique. The study revealed that the piperidine ring adopts boat conformation with equatorial orientation of two phenyl rings at C-2 and C-6. Intermolecular contacts and hydrogen bonding interactions were explored by Hirshfeld surface and 2D fingerprint analyses, showing that the major contact were H∙∙∙H (57.7 %), C∙∙∙H/H∙∙∙C (14.2 %), O∙∙∙H/H∙∙∙O (15.3), Cl∙∙∙H/H∙∙∙Cl (7.1 %) and C∙∙∙Cl/Cl∙∙∙C (12.7 %). Intramolecular interaction was examined through the Radiant density gradient (RDG), Interaction region indicator (IRI), Electron localization function (ELF), and localized orbital locator (LOL) to understand hyperconjugration and π-electrons delocalization in the molecule. DFT studies such as structure optimization, HOMO-LUMO orbital analysis and molecular electrostatic potential were conducted for the title compound. The topology of the molecular arrangement and intermolecular interaction energies were determined through 3D energy framework analysis. Subsequently, the compound 2 was subjected to ADMET analysis to extend its scope of bioavailability. Molecular docking studies were then employed using the tyrosine kinase inhibitor, epidermal growth factor receptor (EGFR) enzymes (PDB ID: 4WKQ and 6JOL). The study revealed significant interactions between the title ligand structure and active sites of selected proteins complex.

Crystal structure and Hirshfeld surface analysis of (E)-2-[2-(2-amino-1-cyano-2-oxoethylidene)hydrazin-1-yl]benzoic acid N,N-dimethylformamide monosolvate

In the title compound, C10H8N4O3·C3H7NO, the asymmetric unit contains two crystallographically independent molecules A and B, each of which has one DMF solvate molecule. Molecules A and B both feature intramolecular N—H...O hydrogen bonds, forming S(6) ring motifs and consolidating the molecular configuration. In the crystal, N—H...O and O—H...O hydrogen bonds connect molecules A and B, forming R 2 2(8) ring motifs. Weak C—H...O interactions link the molecules, forming layers parallel to the (\overline{2}12) plane. The DMF solvent molecules are also connected to the main molecules (A and B) by N—H...O hydrogen bonds. π–π stacking interactions [centroid-to-centroid distance = 3.8702 (17) Å] between the layers also increase the stability of the molecular structure in the third dimension. According to the Hirshfeld surface study, O...H/H...O interactions are the most significant contributors to the crystal packing (27.5% for molecule A and 25.1% for molecule B).

Investigation of the Molecular Structure and DFT Insights into (4-(4-Nitrophenyl)-9-(phenylsulfonyl)-9H-carbazole-2,3-diyl)bis(p-tolylmethanone)

Carboxylate molecules have been distinguished as the potential compound in the largely emergent chemical world of heterocyclic compounds shows likely pharmacological characteristics. The knowledge of a mixture of synthetic pathways and the different physicochemical parameters of such compounds describe the especial interest of medicinal chemists to produce combinatorial collection and carry out in-depth efforts in the search of lead molecules. Among the various group of compounds studied, carboxylate moieties stand out to be unique in features due to their biological, pharmacological and medicinal properties. Synthesis, crystal structure, conformation and density functional theory of (4-(4-Nitrophenyl)-9-(phenylsulfonyl)-9H-carbazole-2,3-diyl)bis(p-tolylmethanone) derivative have been investigated in detail. Carboxylate moiety is in planar conformation, C-H…O type of hydrogen bonds and van der Waals forces. Density functional theory was utilised to investigate the carboxylate derivative. Similar to co-crystal ligands, carboxylate compounds exhibited potent interactions with the target protein. The supramolecular properties were measured and validated using Hirshfeld surface studies.

Crystal structure and Hirshfeld surface analysis of dieth-yl (3aS,3a1R,4S,5S,6R,6aS,7R,9aS)-3a1,5,6,6a-tetra-hydro-1H,3H,4H,7H-3a,6:7,9a-di-epoxy-benzo[de]isochromene-4,5-di-carboxyl-ate.

In the title compound, C18H22O7, two hexane rings and an oxane ring are fused together. The two hexane rings tend toward a distorted boat conformation, while the tetra-hydro-furan and di-hydro-furan rings adopt envelope conformations. The oxane ring is puckered. The crystal structure features C-H⋯O hydrogen bonds, which link the mol-ecules into a three-dimensional network. According to a Hirshfeld surface study, H⋯H (60.3%) and O⋯H/H⋯O (35.3%) inter-actions are the most significant contributors to the crystal packing.

Solvent effects on spectroscopic, electronic, and topological analyses, Hirshfeld surface, ADME, and molecular docking studies on antiviral pyridine carboxamide derivatives

A theoretical study of three pyridine carboxamide derivatives in conjunction with the Density Functional Theory (DFT) approach at the 6-311+G(d,p) basis set is presented along with X-ray results. The pyridine carboxamide derivatives were analyzed with the help of FT-IR, UV–Vis, 1H and 13C NMR investigation. The spectral characterizations were made by vibrational energy distribution analysis (VEDA4), which helps to assign vibrational frequencies to specific molecular vibrations. A comparative analysis of computed 1H and 13C NMR chemical shift values with experimental chemical shifts for the pyridine carboxamide compounds by applying the gauge-including atomic orbitals method in chloroform and acetone solvents was carried out. UV–Vis spectroscopy and electronic transitions were conducted on both chloroform and acetone solvents through the assistance of the TD-DFT methodology. Hirshfeld Surface analysis was employed to analyze the intermolecular hydrogen bonds of the type N-H⋯N to the crystal packing. The chemical properties of frontier molecular orbital and global reactivity descriptors were analyzed for the different solvents such as chloroform and acetone. The Fukui functions were used to identify reactive sites in a molecule, including those susceptible to nucleophilic and electrophilic outbreaks. The weak interactions were analyzed using reduced density gradient (RDG) analysis, a computational method used to study noncovalent interactions, including hydrogen bonding. The Absorption, Distribution, Metabolism, and Excretion (ADME) attributes of the studied compounds have been evaluated for drug discovery initiatives. Molecular docking studies with antiviral SARS-CoV-2 Mpro and Omicron variant containing the Q493R mutation proteins of three pyridine carboxamide derivatives (L3–L5) have been performed, and L5 has maximum binding energy values of −7.13 kcal/mol for 6LU7.

Crystal growth, morphological, mechanical, spectroscopic studies, optical properties, molecular docking, ADME/T, Hirshfeld surfaces analysis and theoretical calculations of hybrid organic-inorganic phosphate compound

Molecular organic–inorganic single crystals of 4-carboxyanilinium dihydrogenphosphate [4-CADP] have been grown by the slow evaporation technique. The crystal structure was re-investigated by single-crystal X ray diffraction (SCXRD) analysis without signifiant differences from the previous study. 3D Hirshfeld surface and 2D fingerprint plot studies were performed to understand the intermolecular interactions of the 4-CADP crystal in graphical representation. Functional groups identification was studied with FT–IR spectroscopy. High transparency and a wide band gap of 5.44 eV were observed with UV–Vis spectroscopy. Geometrical structure of the 4-CADP compound was performed using the Density Function Theory (DFT) method at the B3LYP/3-21G and PBEPBE/3-21G levels of theory, along with the HF/3-21G basis set. The equilibrium geometry, highest occupied molecular orbitals (HOMO), lowest unoccupied molecular orbitals (LUMO), and molecular electrostatic potential map (MEP) were also calculated and presented. MEP a visual representation of the chemically active sites and comparative reactivity of atoms. Results revealed OH⋯O and NH⋯O contacts have the largest impact the Hirshfeld surface. The mechanical properties of the 4-CADP crystal were studied experimentally Vicker’s microhardness technique, which revealed that the grown crystal belonged to the softer category. 4-CADP crystal void estimation reveals the mechanical strength and porosity of the material.Last, it was tried to compare the biological activities of the studied hybrid molecule against enzymes: the crystal structure of acetylcholinesterase (AChE) (PDB ID: 4M0E), the crystal structure of butyrylcholinesterase (BChE) (PDB ID: 5NN0), crystal structure of alpha-galactosidase (α-Gly) (PDB ID: 1T0O), crystal structure of human carbonic anhydrase I (hCA I) (PDB ID: 2CAB), and the crystal structure of human carbonic anhydrase II (hCA II) (PDB ID: 5AML). Afterwards, ADME/T analysis was performed to predict the effects of molecules on human metabolism.