Hirshfeld Surface Research Articles

Solvent free Potassium 3,5-dinitro-6-oxo-1,6-dihydropyrazin-2-olate 3D EMOF as thermally stable energetic material.

Heat-resistant explosives play a vital role in indispensable applications. For this, we have synthesized a novel, three-dimensional, solvent-free energetic metal-organic framework (EMOF) potassium 3,5-dinitro-6-oxo-1,6-dihydropyrazin-2-olate (KDNODP) straightforwardly. The synthesized EMOF was characterized through IR, NMR spectroscopy, elemental analysis, and differential scanning calorimetry studies. Furthermore, single-crystal X-ray diffraction provided a complete description of KDNODP. It exhibits a three-dimensional EMOF structure with remarkably balanced properties such as high density (2.11 g cm-3), excellent thermal stability (291 ℃), good detonation performance (8127 m s-1 and 26.94 GPa) and low mechanical sensitivity (IS = 35 J; FS = 360 N) than the commonly used heat-resistant explosives HNS (density = 1.74 g cm-3; VOD = 7164 m s-1, DP = 21.65 GPa, IS = 5 J) as well as the similar reported energetic potassium MOFs. To gain insights into the packing and intermolecular interactions, the Hirshfeld surface and a 2D fingerprint analysis were examined. Additionally, scanning electron microscopy was used to investigate the particle size and morphological characteristics of KDNODP. These outcomes highlight a successful method for creating 3D EMOF based on a six-membered heterocycle as a potential heat-resistant energetic material.

Stabilizing Bifurcated Hydrogen Bond in 8-Aminoquinoline Appended Peptides.

The hydrogen bonding interaction between an amide N-H and the amide N of the preceding residue is prevalent in proline-containing proteins and peptides. However, the N-H···N hydrogen bonding interaction is rare in non-prolyl natural peptides due to restricted dihedral angles. Herein, we stabilize this type of interaction in 8-aminoquinoline appended non-prolyl peptides through bifurcated N···H···N hydrogen bond. The 8-aminoquinoline-incorporated model peptides 2a-i were designed, synthesized, and the crystal structures of 2a-c and 2i were solved. Analysis of crystal data reveals that the amide N-H of aminoquinoline is involved in bifurcated hydrogen bonding interaction with the nitrogen of the preceding amino acid residue and the nitrogen in quinoline. Analysis of crystal packing, Hirshfeld surface and fingerprint plots confirms that the intermolecular O···H contacts significantly contribute to stabilizing bifurcated N···H···N hydrogen bonding interaction. Furthermore, NMR experiments and CD spectroscopy were conducted to examine the preferred conformation in solution, and the data corroborate with the crystal structure conformation.

Crystal Structure, Hirshfeld Surface, Vibrational Study, Optical Properties and Biological Activities of a Novel Hybrid Material 2-Methylpiperazine-1,4-Dium Tetrachlorocobaltate(II) based on DFT Calculation

Crystal Structure, Hirshfeld Surface, Vibrational Study, Optical Properties and Biological Activities of a Novel Hybrid Material 2-Methylpiperazine-1,4-Dium Tetrachlorocobaltate(II) based on DFT Calculation

Crystal structure characterization, Hirshfeld surface analysis, and DFT calculation studies of 1-(6-amino-5-nitronaphthalen-2-yl)ethanone

The title compound, C12H10N2O3, was obtained by the deacetylation reaction of 1-(6-amino-5-nitronaphthalen-2-yl)ethanone in a concentrated sulfuric acid methanol solution. The molecule comprises a naphthalene ring system bearing an acetyl group (C-3), an amino group (C-7), and a nitro group (C-8). In the crystal, the molecules are assembled into a two-dimensional network by N...H/H...N and O...H/H...O hydrogen-bonding interactions. n–π and π–π stacking interactions are the dominant interactions in the three-dimensional crystal packing. Hirshfeld surface analysis indicates that the most important contributions are from O...H/H...O (34.9%), H...H (33.7%), and C...H/H...C (11.0%) contacts. The energies of the frontier molecular orbitals were computed using density functional theory (DFT) calculations at the B3LYP-D3BJ/def2-TZVP level of theory and the LUMO–HOMO energy gap of the molecule is 3.765 eV.

Bifonazole caffeate: The first molecular salt of bifonazole with enhanced biopharmaceutical property based on experiments and quantum chemistry research

In order to make novel breakthroughs in molecular salt studies of BCS class-IV antifungal medication bifonazole (BIF), a salification-driven strategy towards ameliorating attributes and aiding augment efficiency is raised. This strategy fully harnesses structural characters together attributes and benefits of caffeic acid (CAF) to concurrently enhance dissolvability and permeability of BIF by introducing the two ingredients into the identical molecular salt lattice through the salification reaction, which, coupled with the aroused potential activity of CAF significantly amplifies the antifungal efficacy of BIF. Guided by this route, the first BIF-organic molecular salt, BIF-CAF, is directionally designed and synthesized with satisfactorily structural characterizations and integrated theoretical and experimental explorations on the pharmaceutical properties. Single-crystal X-ray diffraction resolving confirms that there is a lipid-water amphiphilic sandwich structure constructed by robust charge-assistant hydrogen bonds in the salt crystal, endowing the molecular salt with the potential to enhance both dissolvability and permeability relative to the parent drug, which is validated by experimental evaluations. Remarkably, the comprehensive DFT-based theoretical investigations covering frontier molecular orbital, molecular electrostatic potential, Hirshfeld surface analysis, reduced density gradient, topology, sphericity and planarity analysis strongly support these observations, thereby allowing some positive relationships between macroscopic properties and microstructures of the molecular salt can be made. Intriguingly, the optimal properties, together with the stimulated activity of CAF markedly augment in vitro antifungal ability of the molecular salt, with magnifying inhibition zones and reducing minimum inhibitory concentrations. These findings fill in the gaps on researches of BIF-organic molecular salt, and adequately exemplify the feasibility and validity by integrating theoretical and experimental approaches to resolve BIF’s problems via the salification-driven tactic.

Insights on molecular modeling and supramolecular arrangement of bilastine polymorphs.

The advancement in the development of second-generation drugs in the field of antihistamines represents a significant milestone in the management of allergic diseases, targeting the effects of histamine. The efficacy of bilastine in treating allergic disorders has sparked interest in investigating its polymorphism, a crucial property that impacts quality, safety, and effectiveness as per regulatory guidelines. This study examines the polymorphism of bilastine, focusing on two crystalline forms labeled as Form I and Form II. Utilizing advanced analytical techniques, the research explores the structural characteristics and molecular interactions within these forms. Geometric parameters, such as bond lengths, bond angles, and torsion angles, are examined to comprehend molecular conformations and crystal packing arrangements. Hydrogen bonding, covalent bonds, and van der Waals forces contribute to the unique supramolecular arrangements in these forms.This study provides a significant contribution to understanding bilastine's polymorphism, offering critical insights to researchers and regulatory bodies to ensure the quality, efficacy, and safety of antihistamine products. The molecular conformation of two bilastine forms was obtained through DFT with the exchange-correlation functional M06-2X and the 6-311 +  + G(d,p) basis set, and the results were compared with the experimental X-ray. The atomic coordinates were obtained directly from the crystalline structures, and charge transfer was also investigated using frontier molecular orbitals (HOMO and LUMO), and MEP map in order to evaluate the energies associated with charge transfers and regions of high electron affinity. The geometric and topological parameters and intermolecular interactions in the crystals were analyzed using Hirshfeld Surface.

Synthesis, X-ray, Spectroscopic characterizations, DFT calculations, Hirschfeld surface analyses, Molecular docking, and molecular dynamic simulations of some 1,4-benzothiazine-1,1-dioxide derivatives as human kinase CK2 inhibitors

Several derivatives (4a-d - 5a-d) based on 1,4-benzothiazine-1,1-dioxide were synthesized in this study. The process began by preparing 1,4-benzothiazin-3-one 2 from 2-aminothiophenol 1 and 2-chloroacetic acid under alkaline conditions in water. Compound 2 was then oxidized using potassium permanganate to yield 1,4-benzothiazin-3-one-1,1-dioxide 3, which was used to undergo Knoevenagel condensation with various aromatic aldehydes in dimethylformamide with sodium methoxide under different conditions. Bis 3-oxo-1,4-benzothiazine-1,1-dioxide derivatives 4a-d were obtained at room temperature while heating the reaction mixture produced 2-benzyl-1,4-benzothiazine dioxide compounds 5a-d. The structural characterization was performed using spectroscopic techniques, and 4c and 5a-5d were further confirmed by single-crystal X-ray diffraction (XRD) analysis. Moreover, theoretical calculations using the DFT method and Hirshfeld surface analysis showed good agreement with experimental data. Lastly, molecular docking studies revealed that 4c, 5a-5d have a binding affinity with Human Kinase CK2, with 4c exhibiting the highest binding affinity. Molecular dynamics simulation of the CK2-4c complex indicated stable interaction, suggesting potential therapeutic use against various diseases.

Synthesis, Crystal Structure, Hirshfeld Surface, Energy Frame Work and DFT Analysis of Ethyl-4-aminobenzoate Oxalate Monohydrate Salt

Using the single crystal X-ray diffraction method, the title molecule ethyl-4-aminobenzoate oxalate monohydrate has been synthesized, crystallized and characterized. The Hirshfeld surfaces computational approach was used to analyze the intermolecular interactions in the crystal structure. The aforementioned compound crystallizes in a monoclinic crystal system of space group P21/c with the following cell parameters: a = 15.475(3), b = 5.7117(9), c = 14.029(3), = 101.764(6)º, V = 1214.0(4) 3 and Z = 4. The molecules in the crystal structure are connected by the N1-H1C···O7, O5-H2···O3, O7-H1···O4 and C8-H8A···Cg type intermolecular interaction, where Cg is the centroid of the ring. For the title molecule, the inter contact O···H (48.4%) contributes more to the Hirshfeld surfaces. The proton transfer from oxalic acid’s phenolic group to ethyl-4-aminobenzoate’s amine group, which results in the creation of salt, is revealed by the crystal structure. The ground state of ethyl-4-aminobenzoate oxalate monohydrate was also studied theoretically using the density functional method (DFT/B3LYP) with a basis set of 6–311++G(d,p). Charge transfer happens within the molecule, as shown by the computed HOMO and LUMO energies, DOS and MESP, as well as by the optimized molecular structure, electronic structural analysis and UV spectrum analysis.

Synthesis, structure characterization, Hirshfeld surface analysis, and computational studies of 3-nitro-1,2,4-triazol-5-one (NTO):acridine

Synthesis, structure characterization, Hirshfeld surface analysis, and computational studies of 3-nitro-1,2,4-triazol-5-one (NTO):acridine

Synthesis and π-Hole vs. π Effects of Pt(II) Complexes with Pentafluorophenyl and Phenyl-Substituted Bipyridines

Four types of perfluoroarene-substituted and the corresponding non-fluorinated Pt(II) complexes, [PtCl2L] (L = 1 and 2), were prepared with 4,4′-bis(pentafluorophenyl)-2,2′-bipyridine (1a), 4,4′-diphenyl-2,2′-bipyridine (1b), 4,4′-bis(2-pentafluorophenylethynyl)-2,2′-bipyridine (2a), and 4,4′-bis(2-phenylethynyl)-2,2′-bipyridine (2b), respectively, to understand the role of perfluoroaromatic substitution and acetylene linkers on molecular structures and their induced supramolecular associations. The pentafluorophenyl groups lead to significant changes in electron distribution within the Pt(II) complexes, notably causing absorption bands to red-shift due to a metal-to-ligand charge transfer from nucleophilic platinum ions and demonstrating stabilization effects on the bands by fluorination in experimental and theoretical studies. The results of altering electron density and reducing the metal’s nucleophilic tendencies through fluorination and the use of an acetylene linker are discussed, accompanied by crystal structures, the corresponding Hirshfeld surface analysis, and DFT calculations.

Exploring nonlinear optical properties in a hybrid dihydrogen phosphate system: an experimental and theoretical approach.

The controlled slow evaporation process conducted at room temperature has produced a novel hybridmaterial denoted as (2-hydroxyethyl) trimethylammonium dihydrogen phosphate [2-HDETDHP](C5H14NO+, H2PO4-), synthesized through the solution growth method. X-ray crystallographyanalysis reveals a triclinic structure with a filling rate of P and a Z value of 2. This hybrid materialdisplays noteworthy absorption characteristics in the middle and far ultraviolet regions. UV-visiblespectroscopy further establishes its transparency in the visible and near-visible ultraviolet domains.FT-IR spectroscopy examines various vibration modes, elucidating their relationships with thefunctional groups within the structure. Two- and three-dimensional fingerprint maps, coupled withthree-dimensional crystal structures through Hirshfeld Surface Analysis, unveil the dominance of O•••Hand H•••H interactions in the structure, comprising 49.40% and 50.40%, respectively. Fingerprint plotsderived from the Hirshfeld surface assess the percentages of hydrogen bonding interactions, with80.6% attributed to a fragment patch. The experiment of antimicrobial efficacy of a synthesizedproduct, conducted in triplicate, demonstrated the synthesized product's potential antimicrobial activity. Hirshfeld surfaces are employed to investigate intermolecular hydrogen bonding, specifically withinsingle phosphate groups. The molecular structure of 2-HDETDHP was refined using single-crystal X-ray analysis, while itsoptical characteristics were examined through UV-visible spectroscopy. FT-IR spectroscopy isemployed for the assignment of molecular vibrations of functional groups in the affined structure. Quantum calculations were executed with the GAUSSIAN 09 software package at B3LYP/6-311Glevel of theory, to optimize the molecular geometries. The antimicrobial efficacy of a synthesized product was evaluated using the disc diffusion methodagainst antibiotic-resistant Candida albicans, Candida tropicalis, Aspergillus niger, Staphylococcusaureus, and Escherichia coli. Microorganisms were cultured on nutrient agar, and inhibition zoneswere measured after incubation, with streptomycin and amphotericin as positive controls.

Two metastable high hydrates of energetic material 3,3',5,5'-tetranitro-4,4'-bipyrazole.

Poly-stoichiometry of hydrated phases is relatively uncommon for organic materials and extended libraries of such species adopting different aqua-to-substrate ratios are still rare. The kinetically controlled higher hydrates could be particularly interesting for their structural relationships, which presumably may imprint some features of the substrate/substrate and aqua/substrate bonding in solutions, and provide insights into the nucleation stage. Two metastable high hydrates are prepared by crash crystallization. The crystal structures of 3,3',5,5'-tetranitro-4,4'-bipyrazole tetrahydrate, C6H2N8O8·4H2O, (1), and 3,3',5,5'-tetranitro-4,4'-bipyrazole pentahydrate, C6H2N8O8·5H2O, (2), are intrinsically related to the previously reported anhydrate and monohydrate, while displaying natural evolution of the patterns upon progressive watering. The accumulation of the water molecules causes their clustering, with the generation of one-dimensional tapes and two-dimensional layers in the genuine channel hydrates (1) and (2), respectively, versus the pocket hydrate structure of C6H2N8O8·H2O. The hydration primarily affects the pyrazole sites. It conditions the emergence of N-H...O and O-H...N hydrogen bonds, which is a destructive factor for pyrazole/pyrazole N-H...N hydrogen bonding. At the same time, extensive noncovalent interactions of the organic molecules, namely, lone pair-π-hole O...N interactions of the NO2/NO2 and NO2/pyrazole types, are more competitive to the hydrogen bonding and the motifs of mutual organic/organic stacks remain intact with the increase in hydration. These trends agree with the results of Hirshfeld surface analysis. The contributions of the contacts involving H atoms are increased in line with the growing number of water molecules, while the fraction of O...N/N...O (NO2) contacts is nearly invariant. One may postulate the significance of the lone pair-π-hole interactions to the aggregation of nitro species in solutions and their relevance for the sebsequent development of the solid-state patterns through nucleation.

Redetermination of germacrone type II based on single-crystal X-ray data

The extraction and purification procedures, crystallization and crystal structure refinement (single-crystal X-ray data) of germacrone type II, C15H22O, are presented. The structural results are compared with a previous powder X-ray synchrotron study [Kaduk et al. (2022). Powder Diffr. 37, 98–104], revealing significant improvements in terms of accuracy and precision. Hirshfeld atom refinement (HAR), as well as Hirshfeld surface analysis, give insight into the intermolecular interactions of germacrone type II.

Synthesis, crystal structure and Hirshfeld surface analysis of 2-[(4-hydroxyphenyl)amino]-5,5-diphenyl-1H-imidazol-4(5H)-one

In the title molecule, C21H17N3O2, the five-membered ring is slightly ruffled and dihedral angles between the pendant six-membered rings and the central, five-membered ring vary between 50.78 (4) and 86.78 (10)°. The exocyclic nitrogen lone pair is involved in conjugated π bonding to the five-membered ring. In the crystal, a layered structure is generated by O—H...N and N—H...O hydrogen bonds plus C—H...π(ring) and weak π-stacking interactions.

Crystal structure and Hirshfeld surface analysis of (Z)-4-({[2-(benzo[b]thiophen-3-yl)cyclopent-1-en-1-yl]methyl}(phenyl)amino)-4-oxobut-2-enoic acid

In the title compound, C24H21NO3S, the cyclopentene ring adopts an envelope conformation. In the crystal, molecules are linked by C—H...π interactions, forming ribbons along the a axis. Intermolecular C—H...O hydrogen bonds connect these ribbons to each other, forming layers parallel to the (0\overline{1}1) plane. The molecular packing is strengthened by van der Waals interactions between the layers. The intermolecular contacts were quantified using Hirshfeld surface analysis and two-dimensional fingerprint plots, revealing the relative contributions of the contacts to the crystal packing to be H...H 46.0%, C...H/H...C 21.1%, O...H/H...O 20.6% and S...H/H...S 9.0%.

Synthesis and Study of Steering of Azido-tetrazole Behavior in Tetrazolo[1,5-c]pyrimidin-5-amine-Based Energetic Materials.

Tetrazoles and their derivatives are essential for compound synthesis due to their versatility, effectiveness, stability in air, and cost-efficiency. This has stimulated interest in developing techniques for their production. In this work, four compounds, tetrazolo[1,5-c]pyrimidin-5-amine (1), N-(4-azidopyrimidin-2-yl)nitramide (2), tetrazolo[1,5-c]pyrimidin-5(6H)-one (3), and tetrazolo[1,5-a]pyrimidin-5-amine (4), were obtained from commercially available reagents and straightforward synthetic methodologies. These new compounds were characterized by infrared (IR), 13C, and 1H NMR spectroscopy, differential scanning calorimetry (DSC), and single-crystal X-ray diffraction. The solvent, temperature, and electron-donating group (EDG) factors that were responsible for the steering of azido-tetrazole equilibrium in all compounds were also studied. In addition, the detonation performance of the target compounds was calculated by using heats of formation (HOFs) and crystal densities. Hirshfeld surface analysis was used to examine the intermolecular interactions of the four synthesized compounds. The results show that the excellent properties of 1-4 are triggered by ionic bonds, hydrogen bonds, and π-π stacking interactions, indicating that these compounds have the potential to be used in the development of high-performance energetic materials. Additionally, DFT analysis is in support of experimental results, which proved the effect of different factors that can influence the azido-tetrazole equilibrium in the synthesized pyrimidine derivatives in the solution.

Synthesis and growth of organic 2-ethylimidazolium hydrogen diglycolate single crystal for nonlinear optical applications

A single crystal of 2-Ethylimidazolium hydrogen diglycolate (DAEI) has been grown by slow evaporation solution (SEST) technique at 35 °C. The DAEI crystal belongs to a monoclinic crystal system with a P21/c space group. The Hirshfeld surface analysis determined the grown crystal has the highest intermolecular contribution for O..H interaction. The phase purity and various planes (hkl) of the DAEI crystal system were determined by powder X-ray diffraction analysis (PXRD). The functional groups and their different vibrations of DAEI crystal were identified by Fourier transform infrared analysis. The band gap energy value of the DAEI crystal is found to be 5.32 eV. Photoluminescence measurement reveals that the DAEI crystal has green emission. The material shows major weight losses of around 82.45 % in the temperature between 140 °C and 300 °C. The dielectric analyses were carried out for different frequencies (1Hz–1MHz) and different temperatures. The third-order nonlinear optical properties such as refractive index (n2), absorption coefficient (β) and susceptibility (χ(3)) were determined using the Z-scan technique using a He–Ne laser (λ = 632.8 nm).

Exploring S-benzyl carbodithioates as urease inhibitors: synthesis, single crystal XRD, Hirshfeld surface analysis, enzyme inhibition and molecular modeling

Two S-benzyl substituted carbodithioates –namely benzyl benzylmethylcarbamodithioate (1) and 4-(trifluoromethyl)benzyl azepane-1-carbodithioate (2)– were synthesized by a single pot three-component reaction. Structures 1 and 2 were elucidated by means of FTIR, 1H-NMR, 13C-NMR, and single-crystal XRD analyses. Single crystal X-ray studies combined with Hirshfeld surface analysis manifestations outlined the opulent contributions of the intramolecular C-H⋯S interaction in stabilizing the molecular configuration of both compounds. Both carbodithioates under study showed encouraging indications for inhibition efficiency toward urease enzyme, with 1 (IC50 = 0.75 ± 0.04 μM) being more efficient than 2 (IC50 = 1.22 ± 0.02 μM), respectively. Docking computations revealed the binding modes of 1 and 2 with the targeted enzymes. The presented work would serve as a cornerstone for future investigations into potential new inhibitors for pharmaceutical and biological applications.

Hydrogen bonds and elastic anisotropy of nitrile molecular crystals: an investigation from first-principles

ABSTRACT Atomistic calculations based on semi-classical dispersion-corrected density functional theory were performed to investigate bonding and elastic properties of low temperature polymorphs of three nitrile molecular crystals. For that purpose, the DFT-PBE-D3ijk method, which account for both pair and three-body interactions, was applied. The analysis of Hirshfeld surfaces demonstrated that the (C-N…H) hydrogen bonds are the strongest and the dominant ones in the three nitrile molecular crystals. The latter were found to share a common structural feature, consisting of an antiparallel orientation of the terminal nitrile groups at their constituent molecules. Our prediction of the elastic properties demonstrated that malonitrile has the highest Young modulus and succinonitrile has the lower one. The three nitrile crystals are expected to have similar resistance to volume variation while succinonitrle is predicted to exhibit the lowest resistance to shape change. Otherwise, succinonitrile was found to be ductile while malononitrile and acetonitrile were shown to be brittle. Elasticity anisotropy analysis demonstrated that the directions of maximum Young’s modulus are always nearly parallel to the direction of alignment of strong (C-H…N) hydrogen bonds in the three nitrile crystals. The present analyses are relevant for understanding the structure and the properties of more complex high temperature phases.

Insight into the solution thermodynamic properties of cimetidine form A and form B based on experiments and molecular simulations

Cimetidine (CIM) is an antagonist of the type II histamine receptors, and act as a significant agent in the treatment of stomach ulcers. In this work, the effect of polymorphism and solvent type on the thermodynamic properties of CIM was investigated based on experimental results and molecular simulations. The solubility data of two polymorphs for CIM (forms A and B) in organic solvents were measured and correlated with four thermodynamic models. It could be found that the solubility of CIM form A is higher compared to form B. In addition, molecular simulations were adopted to investigate the mechanism of the solubility and stability of the two forms. Hirshfeld surface analysis shows that strong H···N interaction contributes to better stability of form B. Meanwhile, molecular electrostatic potential surface and radial distribution function results indicate that the solubility behavior is significantly influenced by the intensity of the solute–solvent interactions. Finally, the dissolution thermodynamic properties, including the enthalpy change, the Gibbs energy change, and the entropy change, were calculated and the results show that the dissolution process of CIM is endothermic, entropy-driven and spontaneous.