Hirshfeld Surface Analysis Research Articles

Thermal Behavior of the “α‐Diimine‐NiII‐Catecholate” Chromophores

AbstractStudy of the thermal behavior were performed for the first time for a series of ligand‐to‐ligand charge transfer complexes of “α‐diimine‐NiII‐catecholate” type: NiII(3,6‐Cat)(bipy) (1), NiII(3,6‐Cat)(bipytBu) (2) and NiII(3,6‐Cat)(DADdipp) (3), where 3,6‐Cat is 3,6‐di‐tert‐butyl‐catecholate, bipy and bipytBu are 2,2′‐bipyridine and its 4,4′‐di‐tert‐butyl‐substituted analog, DADdipp is 1,4‐bis(2,6‐di‐iso‐propylphenyl)‐1,4‐diaza‐1,3‐butadiene. The phase transition behavior, vapor phase composition, volatility, and thermodynamics of the sublimation process (enthalpy and entropy calculations) of chromophores 1–3 were examined using DSC, TGA, EI‐MS, and the Knudsen effusion method with weight registration of the sublimated substance. The Hirshfeld surface analysis was implemented to establish a relationship between the characteristics of the crystal packing, and the thermal properties. The compounds 1–3 are distinguished by the high thermal stability and good volatility, as well as the completeness of the transition to the gas phase under low pressure conditions. An increase in ligand's bulkiness leads to a “rarefaction” of the crystal packing of the chromophore, and a corresponding rise of volatility in the order 1≤2<3.

Three 3D Supramolecular Organic Salts Assembled from Melamine and Aliphatic Carboxylic Acids: Preparation, Crystallographic Characterization, and Hirshfeld Surface Analysis

Three 3D Supramolecular Organic Salts Assembled from Melamine and Aliphatic Carboxylic Acids: Preparation, Crystallographic Characterization, and Hirshfeld Surface Analysis

Improving the Dissolution Rate and Bioavailability of Curcumin via Co-Crystallization

Curcumin (CUR) is a natural polyphenolic compound with various pharmacological activities. Low water solubility and bioavailability limit its clinical application. In this work, to improve the bioavailability of CUR, we prepared a new co-crystal of curcumin and L-carnitine (CUR-L-CN) via liquid-assisted grinding. Both CUR and L-CN have high safe dosages and have a wide range of applications in liver protection and animal nutrition. The co-crystal was fully characterized and the crystal structure was disclosed. Dissolution experiments were conducted in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF). CUR-L-CN exhibited significantly faster dissolution rates than those of pure CUR. Hirshfeld surface analysis and wettability testing indicate that CUR-L-CN has a higher affinity for water and thus exhibits faster dissolution rates. Pharmacokinetic studies were performed in rats and the results showed that compared to pure CUR, CUR-L-CN exhibited 6.3-times-higher AUC0–t and 10.7-times-higher Cmax.

Crystal structure and Hirshfeld surface analysis of (1H-imidazole-κN 3)[4-methyl-2-({[2-oxido-5-(2-phenyldiazen-1-yl)phenyl]methylidene}amino)pentanoate-κ3 O,N,O′]copper(II)

The title copper(II) complex, [Cu(C18H19N3O3)(C3H4N2)], consists of a tridentate ligand synthesized from L-leucine and azobenzene-salicylaldehyde. One imidazole molecule is additionally coordinated to the copper(II) ion in the equatorial plane. The crystal structure features N—H...O hydrogen bonds. A Hirshfeld surface analysis indicates that the most important contributions to the packing are from H...H (52.0%) and C...H/H...C (17.9%) contacts.

Synthesis, crystal structure and Hirshfeld analysis of N-ethyl-2-{3-methyl-2-[(2Z)-pent-2-en-1-yl]cyclopent-2-en-1-ylidene}hydrazinecarbothioamide

The title compound (C14H23N3S, common name: cis-jasmone 4-ethylthiosemicarbazone) was synthesized by the equimolar reaction of cis-jasmone and 4-ethylthiosemicarbazide in ethanol facilitated by acid catalysis. There is one crystallographically independent molecule in the asymmetric unit, which shows disorder of the terminal ethyl group of the jasmone carbon chain [site-occupancy ratio = 0.911 (5):0.089 (5)]. The thiosemicarbazone entity [N—N—C(=S)—N] is approximately planar, with the maximum deviation of the mean plane through the N/N/C/S/N atoms being 0.0331 (8) Å, while the maximum deviation of the mean plane through the five-membered ring of the jasmone fragment amounts to −0.0337 (8) Å. The dihedral angle between the two planes is 4.98 (7)°. The molecule is not planar due to this structural feature and the sp 3-hybridized atoms of the jasmone carbon chain. Additionally, one H...N intramolecular interaction is observed, with graph-set motif S(5). In the crystal, the molecules are connected through pairs of H...S interactions with R 2 2(8) and R 2 1(7) graph-set motifs into centrosymmetric dimers. The dimers are further connected by H...N interactions with graph-set motif R 2 2(12), which are related by an inversion centre, forming a mono-periodic hydrogen-bonded ribbon parallel to the b-axis. The crystal structure and the supramolecular assembly of the title compound are compared with four known cis-jasmone thiosemicarbazone derivatives (two crystalline modifications of the non-substituted form, the 4-methyl and the 4-phenyl derivatives). A Hirshfeld surface analysis indicates that the major contributions for the crystal cohesion are from H...H (70.7%), H...S/S...H (13.5%), H...C/C...H (8.8%), and H...N/N...H (6.6%) interfaces (only the disordered atoms with the highest s.o.f. were considered for the evaluation).

Synthesis, structure, Hirshfeld surface analysis, and molecular docking studies of the Cu(II) complex with 3-nitro-4-aminobenzoic acid

Synthesis, structure, Hirshfeld surface analysis, and molecular docking studies of the Cu(II) complex with 3-nitro-4-aminobenzoic acid

Crystal structure and Hirshfeld surface analysis of 5-hydroxypentanehydrazide

Carboxyhydrazides are widely used in medicinal chemistry because of their medicinal properties and many drugs have been developed containing this functional group. A suitable intermediate to obtain potential hydrazide drug candidates is the title compound 5-hydroxypentanehydrazide, C5H12N2O2 (1). The aliphatic compound can react both via the hydroxyl and hydrazide moieties forming derivatives, which can inhibit Mycobacterium tuberculosis catalase-peroxidase (KatG) and consequently causes death of the pathogen. In this work, the hydrazide was obtained via a reaction of a lactone with hydrazine hydrate. The colourless prismatic single crystals belong to the orthorhombic space group Pca21. Regarding supramolecular interactions, the compound shows classic medium to strong intermolecular hydrogen bonds involving the hydroxyl and hydrazide groups. Besides, the three-dimensional packing also shows weak H...H and C...H contacts, as investigated by Hirshfeld surface analysis (HS) and fingerprint plots (FP).

Zn(II), Mn(III), and Co(III) complexes of Schiff base derived from 2‐hydroxy‐1‐naphthaldehyde: Synthesis, spectral surveys, single crystal structure studies, Hirshfeld surface analysis, density functional theory calculation, molecular electrostatic potential, and molecular docking evaluations

A new series of transition metal complexes of bidentate Schiff base compound derived from 2‐hydroxy‐1‐(2‐methoxyethylimino)‐naphthalene (HL) were synthesized and characterized using elemental analysis, Fourier transform infrared spectroscopy (FT‐IR), and UV–vis spectroscopies. X‐ray single crystal structures of Zn(II), Mn(III), and Co(III) complexes (1–4) have also been determined, and it was indicated that these Zn(II) and Co(III) complexes (1, 4) are in an octahedral geometry. Whereas, it was found that the Zn complex (2) is in quite a regular tetrahedral environment. Also, the Mn center in complex (3) is ligated by two azomethine nitrogen atoms, two ligand oxygen atoms, and one Cl atom of metal salt forming five coordinated tetragonal pyramid geometry around the Mn atoms. The cyclic voltammetry of the complexes specifies an irreversible redox behavior for all complexes (1–4). Next, DFT/B3LYP theoretical method was used to determine the optimal geometrical configurations and comparison between experimental and theoretical data, as well as for calculations of molecular electrostatic potential, highest‐occupied molecular orbital (HOMO)‐lowest‐unoccupied molecular orbital (LUMO) energy values of selected compounds. The study of non‐covalent interactions was done by Hirshfeld surface analysis using CrystalExplorer program. Furthermore, molecular docking inspection was carried out to study the binding affinity of the tested complexes towards protein B‐cell lymphorna (PDB ID: 4LXD). Using the results obtained from the molecular docking and the summarized interaction of the binding processes, these structures show the validity of effective inhibition against liver cancer.

Crystallographic and theoretical analysis of a spirohydantoin derivative: 3-(4‑tert-butylbenzoyl)-1,3-diazaspiro[4.5]decane-2,4‑dione

Providing structural information on drug-like compounds is a significant step in efforts to develop innovative drugs with balanced solubility, cell permeability and target binding. In this paper, a new cyclohexane-5-spirohydantoin tethered with a 4‑tert-butylbenzoyl group was synthesized and its crystal structure was determined using the single crystal X-ray diffraction. The Hirshfeld surface analysis was used to gain a preliminary insight into the proportion and nature of the intermolecular interactions in the crystal structure, while their quantitative description is further presented in terms of a systematic analysis of dimeric motifs representing different recognition modes. A combination of N–H∙∙∙O and C(sp3)–H∙∙∙O hydrogen bonds, C(sp3)–H∙∙∙π, lone-pair∙∙∙π and π∙∙∙π stacking interactions links the molecules into a bilayer having two carbonyl O atoms exposed to the exterior. Further stacking of the bilayers occurs through C(sp3)–H∙∙∙O hydrogen bonds involving these O atoms as acceptors, C(sp3)–H∙∙∙π and π∙∙∙π stacking interactions between the phenyl groups. The molecular electrostatic potential surface map reveals that the carbonyl O atoms of the hydantoin ring and the phenyl ring are electrophilic centers, while the N1–H1 group is a nucleophilic center. The calculated HOMO and LUMO energies were used to semiquantitatively estimate the global reactivity descriptors suggesting the soft nature of the molecule.

Syntheses, Crystal Structure and Theoretical Properties of Schiff Bases Obtained from Isoniazid and Pyridine‐2‐, 3‐, 4‐Carboxaldehyde and Their Zinc(II) Complexes

AbstractThe series of Schiff base ligands, N’‐(pyridine‐2‐ylmethylene)isonicotinohydrazide (I), N’‐(pyridine‐3‐ylmethylene)isonicotinohydrazide (II) and N’‐(pyridine‐4‐ylmethylene)isonicotinohydrazide (III), and the Zn(II) complexes of the ligands (I and II), [N’‐(pyridine‐2‐ylmethylene)isonicotinohydrazide]‐trichlorozincoate (IV) and [N’‐(Pyridin‐3‐ylmethylene) isonicotinohydrazide] trichlorozincoate (V) have been newly synthesized and their structures have been characterized by 1H, 13C NMR and FT‐IR spectroscopies, elemental analysis and single crystal X‐ray diffraction technique. The Hirshfeld surface analyses have been confirmed the importance of H‐atom contacts in establishing the packings. The ground state equilibrium geometries of the synthesized compounds are optimized at DFT/B3LYP/6‐311++G (d, p) and HF/6‐311++G (d, p) levels of theory (for the ligands) and B3LYP/GENECP method is used as the mixed basis sets of LANL2DZ (for Zn) and 6–311G (for other atoms) in the gas‐phase. The structural parameters obtained from the theoretical studies of the compounds are compared with their experimental ones. Their linear and nonlinear optical (NLO) properties are also calculated by the same methods. In the ground state, the energy band gaps (Eg) of the Schiff bases (I, II and III) have been calculated as 4.38 eV, 4.36 eV and 4.46 eV (at B3LYP) and 9.94 eV, 9.81 eV and 10.20 eV (at HF), respectively.

Comprehensive insights of a Salamo-like Oligo(N,O-donor) ligand and its self-assembled di-nuclear Mn(III) and tetra-nuclear Cd(II) complexes

The self-assembled di-nuclear Mn(III) & tetra-nuclear Cd(II) salamo-like oligo(N,O-donor) complexes, [Mn2(L)2(CH3OH)2]·4CH3OH (1) and [Cd4(L)2(η-OAc)2(CH3OH)2] (2) have been constructed successfully applying the measure of solvent evaporation and characterized structurally by X-ray diffraction analyses of single crystal, IR & UV visible analyses. The single crystals of the salamo-like oligo(N,O-donor) compound H3L have been obtained by wet-chemical technique, its established structure is H3L∙CH3OH. The structure of complex 1 is centrally symmetrical, and both Mn(III) atoms are hexa-coordination and have slightly distorted octahedral geometries. There are two sets of intermolecular H-bonding interactions which are connected with adjacent units of the Mn(III) complexes and form a two-dimensional network structure. For the complex 2, all of the Cd(II) atoms are also hexa-coordination and possess slightly twisted octahedral configurations. And five groups of intermolecular H-bonding interactions form a honeycomb shaped three-dimensional supramolecular structure. Additionally, the intermolecular interactions of H3L, complexes 1 and 2 have been quantified by Hirshfeld surface analysis for further study. Fluorescence emission spectra of H3L, complexes 1 and 2 were also investigated.

Eight anhydrous organic salt forms of 2-amino-4,6-dimethoxypyrimidine and organic acids: Preparation, structure, characterizations, synthons diversity, and hirshfeld surface analysis

The intricate part of the non-covalent associates in numerous realms covering from chemistry, biology, catalysis, material science, to medicinal chemistry inspires a continuous motivation towards the discovery of new synthons that stabilize the supramolecular systems. In this work the co-crystallization between 2-amino-4,6-dimethoxypyrimidine (admpym) and eight organic acids resulted in the manufacturing of eight new crystalline salts, which were further fully characterized via the single crystal X-ray diffraction (SCXRD), spectroscopic (FT-IR) and elemental analysis methods. Their melting points were also measured. All the fabricated salts exhibited the identical stoichiometry regarding the number of the acidic unit and the admpym, namely with the 1:1 ratio at the monacids and 2 : 1 ratio in the diacids.Among the eight crystals, the H-shift from the acid to pyrimidine ring N atom has occurred, yet the NH2 group was not protonated ever. In all the crystals, the respective molecular fragments are permanently tethered to each other via the energetic H-bonds as the Npyrimidinium-Ophenolate/carboxylate type. The various weaker intermolecular linkages, embodying CH···O/CH3···O, CH···CH, CH3···N, CH···Br, CH3···CH, CH3···Cl, Cl···O, CH···π/CH3···π, C···π, O···π and π···π also contributed to the stabilization of the crystal structures in the respective conglomerates. The percentage contribution of the significant non-covalent contacts were calculated via the Hirshfeld surface analysis. The R22(8) graph was enclosed in all the systems when an acid pairs with an admpym. The job ensures that there engender both principle contact modes between the admpym and the acids, which appear in the relative higher frequency, linear heterotetramer (LHT), and cyclic heterotetramer (CHT). LHT is dominant as it appears in 5 cases, CHT in 2 ones, with the rest one structure building a rare heterodimer. The heterotrimer (HT) was never occurred here.

Crystal structure and Hirshfeld surface analysis of dimethyl 4′-bromo-3-oxo-5-(thiophen-2-yl)-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2,4-dicarboxylate

In the title compound, C20H17BrO5S, molecules are connected by intermolecular C—H...S hydrogen bonds with R 2 2(10) ring motifs, forming ribbons along the b-axis direction. C—H...π interactions consolidate the ribbon structure while van der Waals forces between the ribbons ensure the cohesion of the crystal structure. According to a Hirshfeld surface analysis, H...H (40.5%), O...H/H...O (27.0%), C...H/H...C (13.9%) and Br...H/H...Br (11.7%) interactions are the most significant contributors to the crystal packing. The thiophene ring and its adjacent dicarboxylate group and the three adjacent carbon atoms of the central hexene ring to which they are attached were refined as disordered over two sets of sites having occupancies of 0.8378 (15) and 0.1622 (15). The thiophene group is disordered by a rotation of 180° around one bond.

Synthesis, crystal and structural studies of 5-alkynyl-1,2,3-triazoles

The structures of diverse 5-alkynyl-1,2,3-triazoles were analyzed by the conventional spectroscopic techniques and corroborated by X-ray diffraction analyses. In addition, Hirshfeld surface analysis was carried out on these compounds, highlighting the presence of π−π stacking interactions together with a C–H–N triazole-methylene interaction observed in compound 3 as the main intermolecular interactions which define the crystal packing and supramolecular network in these compounds. Further theoretical calculations of global descriptors and molecular electrostatic maps demonstrate a charge distribution connecting phenyl substituents, triazole ring and the triple bond which is related to π−π stacking interactions supporting experimental observations.

2-Cyano-2-isonitrosoacetamide–3,4-dimethylpyrazole (1/1): a co-crystal of two molecules with agrochemical activities

In the structure of the title co-crystal, C3H3N3O2·C5H8N2, the components are linked by a set of directional O—H...N, N—H...O, N—H...N and C—H...O hydrogen bonds to yield a two-dimensional mono-periodic arrangement. The structure propagates in the third dimension by extensive π–π stacking interactions of nearly parallel molecules of the two components, following an alternating sequence. The primary structure-defining interaction is very strong oxime-OH donor to pyrazole-N acceptor hydrogen bond [O...N = 2.587 (2) Å], while the significance of weaker hydrogen bonds and π–π stacking interactions is comparable. The distinct structural roles of different kinds of interactions agree with the results of a Hirshfeld surface analysis and calculated interaction energies. The title compound provides insights into co-crystals of active agrochemical molecules and features the rational integration in one structure of a fungicide, C3H3N3O2, and a second active component, C5H8N2, known for alleviation the toxic effects of fungicides on plants. The material appears to be well suited for practical uses, being non-volatile, air-stable, water-soluble, but neither hygroscopic nor efflorescent.

Synthesis, Crystal Structure, and Analysis of Hirshfeld Surface of Hexa (4‐Aminopyridine) Triscopper(II) Carbonate Trihydrate

AbstractSynthesized crystal of Hexa (4‐aminopyridine) triscopper(II) carbonate trihydrate with the chemical formula C33 H42 Cu3 N12 O12. Molecular structure of synthesized compound determined by single crystal X‐ray diffraction (SCXRD) of Hexa (4‐aminopyridine) triscopper(II) carbonate trihydrate. The 4‐aminopyridine molecular is bonded with copper atoms via the aromatic ring's nitrogen atoms (Cu‐N). The analysis of the Hirshfeld surface is essential to the crystal packing process because of the intermolecular interactions. Intermolecular interactions of hydrogen bonds are revealed through Hirshfeld surface analysis viewed by 3D and 2D fingerprint plots. A novel organic‐inorganic hybrid crystal is Hexa (4‐aminopyridine) triscopper(II) carbonate trihydrate determined, and their study of this crystal reveals various intermolecular interactions responsible for crystal stability.

Intra- and intermolecular hydrogen bonding in N,N'-Carbonyl bis(carbamates), -(S-thiocarbamates) and N,N'-biscarbamoyl ureas

The three structural related compound classes of N,N’-biscarbamoyl ureas, N,N’-carbonyl bis(carbamates) and N,N’-carbonyl bis(S-thiocarbamates) have been intensively studied. 13C NMR spectroscopy shows a specific chemical shift for each compound class. In the solid state the molecules undergo intramolecular ring formation and additionally intermolecular dimer or strand building both via hydrogen bonds. The influence of the organic groups is showcased by Hirshfeld surface analysis and the study is rounded off by findings from IR spectroscopy.

Effects of chlorine and nitro groups on the crystal structure of novel 4-quinolinone derivatives from sulfonamide chalcone

This study explores the impact of introducing chlorine and nitro groups into two novel quinolone derivatives, (E)-3-(4-nitrobenzylidene)-2-(3-nitrophenyl)-2,3-dihydro-1-(phenylsulfonyl)-quinolin-4(1H)-one (NPQ) and (E)-3-(4-chlorobenzylidene)-2-(3-nitrophenyl)-2,3-dihydro-1-(phenylsulfonyl)-quinolin-4(1H)-one (CPQ), using experimental techniques and density functional theory (DFT). The research focuses on crystalline packing, conformational changes, and intermolecular interactions. The investigation reveals that weak non-classical hydrogen interactions, hydrophobic, and CH···π interactions, predominantly stabilize the crystal structures. These interactions, quantified through a Hirshfeld surface analysis. Additionally, the Fukui function analysis indicates antioxidant potential in the crystals. NPQ and CPQ exhibit a small energy gap, implying low kinetic stability, high reactivity, and reduced resistance to charge transfer when compared. These findings provide valuable insights into the structural and electronic properties of these quinolone derivatives, aiding the design of novel compounds with desired characteristics and applications. The DFT analysis utiliazsed the M062-X functional and the 6–311++G(d,p) basis set in the Gaussian 09 package, and the result was visualized using the GaussView software.

Comparing of the crystal structures and spectroscopic properties of p-hydroxy styrylquinolinium dye with those of its p-dimethylamino analogue

Two previously synthesized styrylquinolinium dyes, namely (E)-1-butyl-4-(4-(dimethylamino)styryl)quinolinium iodide (D36) and (E)-1-butyl-4-(4-hydroxystyryl)quinolinium iodide (D34), were compared in terms of their properties by single crystal X-ray diffraction (XRD), Hirshfeld surface analysis, Fourier Transform Raman (FT-Raman), Fourier Transform Infrared (FT-IR), Fluorescence, and Ultraviolet–visible (UV–Vis) spectroscopy, and 1H- and 13C-NMR methods. Both dyes D36 and D34 crystallized in the triclinic and monoclinic systems in the centrosymmetric space groups P-1 and P21/n, respectively. The unit cell of D36 contains 2 molecules of the dye, participating in weak intermolecular interactions, while that of D34 contains four formula units. The phenolic hydroxyl group of D34 participates in the formation of a hydrogen bond with the iodide anion. The 4-styrylquinolinium moieties of the cationic dye molecules are nearly planar. The dihedral angle between the mean planes through the ten-membered quinolinium system and the benzene ring is 7.5° in D36 and 5.9(1)° in D34. The structural parameters planarity and bond length alternation (BLA) are discussed, which are important for the evaluation of the first hyperpolarizability β at the molecular level, even in a centrosymmetric crystal. The UV–visible spectra of the dyes in 14 solvents of different polarities were investigated. The reversible solvatochromic behavior of the dyes is demonstrated experimentally and compared with known “binuclear dyes” by evaluating the Rezende model. Dye D36 does not fluoresce, and D34 has a very low emission in the solvents tested.

New thiazole derivatives: Synthesis, X-ray crystal structure, Hirshfeld surface analysis, and biological evaluations as potential antimicrobial and antitumor agents

Thiazole ring has a wide range of biological activities which is proven by its presence in more than eighteen FDA-approved drugs in addition to several compounds that are currently under clinical investigation. Substitution of the thiazole ring at positions 2,4, and 5 led to new derivatives with potent biological activities. Interestingly, the bromination of ethyl 2-cyano-2-(4-methyl-3-phenylthiazol-2(3H)-ylidene)acetate (1) in acetic acid afforded (Z)-ethyl 2-(5-bromo-4-(bromomethyl)-3-phenylthiazol-2(3H)-ylidene)-2-cyanoacetate (2) instead of the expected bromomethyl derivative 3. The reaction of thiazole derivative 2 with p-anisidine or aniline produced the corresponding thiazole derivatives 5a,b. The synthesized compounds were characterized based on their spectral and elemental data. Moreover, the structure of compound 2 was determined through X-ray crystallography. The molecular structure of 2 was crystallized in the orthorhombic, Pna21, a = 15.8144 (6) Å, b = 9.0238 (4) Å, c = 11.3296 (4) Å, V = 1616.80 (11) Å3, Z = 4. Analysis of the dnorm map and fingerprint plot for all possible intermolecular interactions in the crystal structure of thiazole 2 indicated the importance of the Br…O, O…H, and Br…H interactions in the molecular packing. The O1…H14A (2.548 Å), Br1…O1 (3.211 Å) and Br2…H7B (2.931 Å) interactions are the most short contacts. In addition, the percentages of the Br…O, O…H, and Br…H contacts are 2.3, 10.3 and 22.1%, respectively. The antimicrobial activity of thiazole derivative 5a was tested, and the results revealed that it is equipotent to both Ampicillin against Staphylococcus aureus and to Gentamycin against Salmonella SP. In comparison to Doxorubicin, thiazole 5a showed less antitumor activity against the hepatocellular carcinoma (HepG-2) and colon carcinoma (HCT-116) cell lines.