Hirshfeld Surface Research Articles

Exploring 2-(benzylthio)-5-(4-nitrophenyl)-1,3,4-oxadiazole as antiproliferative agent: Synthesis, single crystal XRD, DFT, Hirshfeld surface analysis, in vitro antiproliferative activity and molecular docking analysis

In this investigation, an oxadiazole derivative namely 2-(benzylthio)-5-(4-nitrophenyl)-1,3,4-oxadiazole (2-Btno) was synthesized. The study delves into the exploration of its anticancer efficacy against Dalton's lymphoma (DL) tumor cells, obtained from murine T-cell lymphoma. The compound 2-Btno has been characterized by elemental analysis, IR, UV–Vis., NMR, and single-crystal X-ray diffraction data. The compound 2-Btno crystallizes in a monoclinic system with space group P 21/n. The crystal structure is stabilized by weak CH···O and NH···N hydrogen bonding weak interactions, which are quantitively examined through Hirshfeld surface analysis. The DFT calculations are also performed to verify physiochemical properties of 2-Btno and the results obtained are in good agreement with the experimental results. The HOMO and LUMO energy gap of 3.402 eV for 2-Btno indicates good NLO properties. The cytotoxic activity of 2-Btno against Dalton's lymphoma cells was assessed through the MTT assay. The results indicated notable anticancer efficacy, with an IC50 value of 80 μg/mL. The mode of action of compound 2-Btno was examined through various assays, and the findings indicate that compound 2-Btno functions by downregulating mitochondrial membrane potential and upregulating the reactive oxygen species (ROS) production. Molecular docking study was conducted to establish the correlation between the cytotoxicity of the compound and its binding affinity within the active sites of crucial anti-cancer and anti-apoptotic target proteins MDM2 (PDB: 3JZK), Bcl-XL (PDB: 4QVX) and Bcl-2 (PDB: 6O0K).

Synthesis, structural characterization, and quantum chemical study of the 7-acetyl-5-nitrobenzofurans as anticancer agents with antioxidant properties

Synthesis of 7-acetyl-2-aryl-5-nitrobenzofurans 2a–j involved sequential Sonogashira cross-coupling of 2-hydroxy-3-iodo-5-nitroacetophenone with terminal acetylenes and in situ Cacchi-type cycloisomerization of 5-alkynylated intermediates. Hirshfeld's fingerprint diagrams and surface analysis showed varied intermolecular interactions. Additionally, intramolecular interactions were examined using DFT and QTAIM calculations. Benzofuran derivatives were tested for antiproliferative efficacy in vitro against MDA-MB-231 and Caski cell lines. The 1-(5-nitro-2-(p-tolyl)benzofuran-7-yl)ethan-1-one 2h showed promising antiproliferative activity against Caski and MDA-MB-231 cell lines, with IC50 values of 26.96 ± 4.97 µM and 5.13 ± 0.86 µM, respectively, compared to Camptothecin (IC50 = 8.96 ± 0.23 and 24.69 ± 0.26 µM). Derivatives with 2-(4-fluorophenyl)-2c, 2-(4-methoxyphenyl)- 2g, and 2-(3,5-bis(trifluoromethyl)phenyl)-2j groups showed significant antioxidant activity, with Fe-reducing power values of 520.14 ± 1.34 µM, 433.50 ± 1.30 µM, and 466.08 ± 1.91 µM, respectively, compared to ascorbic acid (IC50 = 538.05 µM). The most active molecules that docked with protease (2c, 2g, and 2j) and FKBP12-mTOR (2d, 2h and 2j) active site residues showed significant interactions which were confirmed by Molecular dynamic simulation. ADME investigation indicated drug-like characteristics, safe in silico toxicity, and no carcinogenic or mutagenicity.

Effect of hydroxy groups on structural, electronic, and biological properties of methyl carbazate containing hydroxy benzaldehyde-based imines. A combined experimental and theoretical investigation

Interactions present in differently substituted hydroxy based imine derivatives were characterised and identified by the utilisation of spectroscopic techniques in conjunction with X-ray crystallography and theoretical computations. All the target compounds ‘a-c’ crystallises in monoclinic crystal system with P21/c and C2/c space groups. CH…Pi and Pi…Pi interaction are the characteristic interactions present in the target compounds ‘a-c’ The most significant contributions to the crystal packing were found using Hirshfeld surface analysis, and potential contact points were identified. H…H, O…H and C…H contacts and π stacking interactions are the dominant contacts observed in all the crystals these results showed that hydrogen bonding and hydrophobic interactions were significantly present. Furthermore, investigations related to calculations of the molecular electrostatic potential and frontier molecular orbital (highest occupied–lowest unoccupied) were carried out for the optimised structure. The HOMO-LUMO energy gap made it possible to determine the molecule's chemical hardness, chemical inertness, electronegativity, and electrophilicity index, which showed its possible kinetic stability and reactivity. The target compounds' predicted activity spectra (PASS) showed that these compounds exhibit significant Testosterone 17beta-dehydrogenase (NADP+) inhibition activity, with Pa 7.18–7.95. Finally, Testosterone 17beta-dehydrogenase (NADP+) (PDB-ID 3KLP) was used to conduct molecular docking investigations of compounds ‘a-c’. Due to their tiny size and lack of rigidity, which enable them to bind well at any position, a and b exhibit higher binding free energies of -7.08 and -7.00 kcal/mol and inhibition constants of 0.1 and 1.2 µM than compound c.

A copper(II) aminopyrimidinone complex: X-ray crystallography, computational analysis, dielectric spectroscopy and molecular docking

A new copper(II) complex with 2-amino-6-methylpyrimidin-4-(1H)-one, [Cu(C5H7N3O)4](NO3)2·H2O (Cupyrim), has been synthesized and studied by X-ray diffraction, elemental analysis and FT-IR spectroscopy. The Cu(II) is four-coordinate in a square planar geometry by four nitrogen atoms of the four organic ligands. Hirshfeld Surface Analysis was conducted to understand crystalline packing. Overall, the structure is maintained by metal coordination as well as strong and weak (C,N)–H···O hydrogen bonds and C–H…π interactions. The IR spectrum primary peaks have been assigned to the vibration modes of the ligand functional groups. An investigation of the inhibitory properties of Cupyrim toward “Cyclin-dependent Kinase 2” (CdK2) and “inducible nitric oxide synthase” (iNOS) proteins was aided by molecular docking research. According to molecular docking, Cupyrim exhibits promising inhibitory efficacy against Parkinson’s, schizophrenia, and Alzheimer’s disorders. The temperature dependence of the real and imaginary part of the dielectric permittivity was analyzed with the Cole-Cole formalism as well as DSC diagrams from 45-147 °C.

Supramolecular architecture of Mn(II) complex with 5,5´-dimethyl-2,2´-bipyridine and 4-hydroxybenzoic acid: Synthesis, crystal structure, Hirshfeld surface analyses, catalytic and antimicrobial activities

A novel complex [Mn(5,5´-dmbipy)2Cl2](4-hba)2 (1) (5,5´-dmbipy=5,5´-dimethyl-2,2´-bipyridine and 4-hba=4-hydroxybenzoic acid) was successfully synthesized using methanol by steam reflux. The complex is characterized using SC-XRD, IR, UV and thermogravimetric analysis. Single crystal X-ray analysis of 1 indicates a distorted octahedral coordinated Mn2+ centre with two molecules of 5,5´-dmbipy and two chlorine ions and the presence of two uncoordinated 4-hba in the complex. The two chlorine atoms (Cl1 and Cl2) form intermolecular H-bonding with 4-hba. The complex crystallizes in monoclinic space group P21/c forming a helical like 1D polymeric supramolecular architech through H- bonding. Presence of halogen-hydrogen bond C(sp2)-OH—Cl-M between uncoordinated -OH and Cl ion in 1 significantly provides a path of extending supramolecular network forming a unique architect of the complex. Interestingly, presence of pyridine-benzene system forming π-π stacking is confirmed from SC-XRD. Hirshfeld surface analysis is carried out to explore the noncovalent interactions in the crystal. Mn3O4 nanoparticles synthesized from complex 1 are characterized using PXRD and HRTEM, and successfully employed as catalyst for the degradation of dyes. Both complex 1 and Mn3O4 nanoparticles show appreciable biological activities.

Insight into the dissolution behavior of valsartan (form E) in twelve pure solvents: Solubility, modelling and molecular simulation

Valsartan is an angiotensin II receptor antagonist used to treat hypertension. Crystals of valsartan were prepared and the stability of the valsartan (form E) at different solvents and temperatures was investigated. The solid-liquid equilibrium solubility of valsartan (form E) in twelve pure solvents was determined by a dynamic method at the temperature from 278.15 K to 323.15 K. Among the solvents used in the experiment, the solubility of valsartan (form E) was found to be highest in methanol and lowest in acetonitrile. In straight-chain alcohols, the solubility decreases with the increase of carbon chain length. The modified Apelblat model, λh model and NRTL model were used to correlate the solubility data. The thermodynamic properties of the mixing process such as Gibbs free energy, enthalpy and entropy were estimated by applying the NRTL model. The KAT-LSER model was adopted to explore solvent effects. Hirshfeld surface analysis and molecular electrostatic potential (ESP) were employed to visualize close contacts and charge distribution of valsartan and solvents. In addition, molecular dynamics (MD) simulation was performed to calculate intermolecular interactions between solute and solvent. Radial distribution function (RDF) and the mean square displacement (MSD) analyses were also carried out to explore molecular association and molecular diffusion.

Crystal structure and Hirshfeld surface analysis of 2,4-di-amino-6-[(1Z,3E)-1-cyano-2,4-di-phenyl-penta-1,3-dien-1-yl]pyridine-3,5-dicarbo-nitrile monohydrate.

The asymmetric unit of the title compound, C25H18N6·H2O, comproses two mol-ecules (I and II), together with a water mol-ecule. The terminal phenyl groups attached to the methyl groups of the mol-ecules I and II do not overlap completely, but are approximately perpendicular. In the crystal, the mol-ecules are connected by N-H⋯N, C-H⋯N, O-H⋯N and N-H⋯O hydrogen bonds with each other directly and through water mol-ecules, forming layers parallel to the (001) plane. C-H⋯π inter-actions between these layers ensure the cohesion of the crystal structure. A Hirshfeld surface analysis indicates that H⋯H (39.1% for mol-ecule I; 40.0% for mol-ecule II), C⋯H/H⋯C (26.6% for mol-ecule I and 25.8% for mol-ecule II) and N⋯H/H⋯N (24.3% for mol-ecules I and II) inter-actions are the most important contributors to the crystal packing.

Crystal structure, optical properties, Hirshfeld surface analysis and antibacterial activity of a new organic-inorganic metal halide: 4-nitrobenzyl-4-methylpyridinium tetrachlorocobaltate(II)

This paper presented the synthesis, composition analysis, and structural characterization of a new organo-inorganic metal halide, 4-nitrobenzyl-4-methylpyridinium tetrachlorocobaltate(II) [4NO2Bz-4-MePy]2[CoCl4](1). The single-crystal X-ray diffraction analysis displayed that the compound crystallized in the monoclinic space group P21/c, consisting of two [4NO2Bz-4-MePy]+ cations and a [CoCl4]2− anion. The energy gap between the HOMO and LUMO orbitals, the polarizability, and the first hyperpolarizability were carried out based on the DFT calculation. The HOMO-LUMO energy gap and UV-visible diffuse reflectance spectrum illustrated the charge transfer interactions between the [CoCl4]2− anions and the [4NO2Bz-4-MePy]+ cations. In addition, the low band gap values (1.64 eV for the Tauc formula, 1.62 eV for the truncated line method, and 2.73 eV for the calculated value) indicated that the crystal was appropriate for optical applications. The first hyperpolarizability (βtot) was 342 times higher than that of standard KDP crystal (βKDP = 6.85 × 10−31 esu), suggesting that crystal 1 was a premium material for NLO applications. The scanning electron microscopy and energy dispersive spectrometer determined the morphology and elemental distribution of the crystal. Hirshfeld surface analysis was performed to quantify the contributions of the different intermolecular interactions. The result of antimicrobial experiments displayed that the compound had excellent antimicrobial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli).

Synthesis, crystal structure and Hirshfeld surface analysis of 4-{(1E)-1-[(car-bamo-thioyl-amino)-imino]-eth-yl}phenyl propano-ate.

The title compound, C12H15N3O2S, adopts an E configuration with respect to the C=N bond. The propionate group adopts an anti-periplanar (ap) conformation. There are short intra-molecular N-H⋯N and C-H⋯O contacts, forming S(5) and S(6) ring motifs, respectively. In the crystal, mol-ecules are connected into ribbons extending parallel to [010] by pairs of N-H⋯S inter-actions, forming rings with R 2 2(8) graph-set motifs, and by pairs of C-H⋯S inter-actions, where rings with the graph-set motif R 2 1(7) are observed. The O atom of the carbonyl group is disordered over two positions, with a refined occupancy ratio of 0.27 (2):0.73 (2). The studied crystal consisted of two domains.

Exploring the formation and diversity of secnidazole cocrystals

This study investigates the cocrystallization of secnidazole (SNZ), a potent antimicrobial drug, with several coformers, overcoming the inherent stability challenges posed by its hemihydrate form to produce novel solid states. We successfully synthesized and characterized three novel cocrystals with carvacrol (CAR), fumaric acid (FMA), and 3,5-dinitrobenzoic acid (DNZ), employing synchrotron single crystal analysis to elucidate their structures. The application of Hirshfeld surface and 2D fingerprint plots further enriched our understanding of the unique packing arrangements within these cocrystals. Moreover, preliminary powder X-ray diffraction (PXRD) patterns hinted at the emergence of additional novel solid forms with salicylic acid (SLC), oxalic acid (OXA), succinic acid (SUC), citric acid (CTR), and thymol (THY). Supported by literature and a thorough analysis of molecular interactions, we propose the existence of pharmaceutical cocrystals among these newly identified solid forms. Our findings not only augment the repertoire of SNZ based pharmaceuticals but also accentuates the strategic utilization of supramolecular synthons, offering significant advancements in the understanding of novel solid form formation, and the critical role of hydrogen bonding in these processes.

Synthesis, crystallographic structure, Hirshfeld surface analysis and DFT calculations of Schiff base (Z)-4-methyl-2-(((3-nitrophenyl)imino)methyl)phenol

The (Z)-4-methyl-2-(((3-nitrophenyl)imino)methyl)phenol (C15H14N2O3) (MNIMP) was prepared by condensation of 2-hydroxy-5-methyl-benzaldehyde and 2-methyl-4-nitro-phenylamine in ethanol and characterized by NMR (1H and 13C), IR and UV–Visible spectroscopy. The molecular crystal packing has been quantitatively explored via Hirshfeld surface analysis, where the intramolecular C−H⋯O bonding represents the principle contribution that stabilizes the crystal packing, with an overall 27.5 % for O⋯H interactions. The outcomes of a theoretical investigation conducted at the B3LYP/6–311++G(d,p) level using the DFT approach are in strong agreement with the results of the experiment. The experimental outcome is compatible with the optimized structure. Z)-4-methyl-2-(((3-nitrophenyl)imino)methyl)phenol vibrational spectrum is calculated at the same theoretical level (DFT/ B3LYP/6–311++G(d,p)), and it is discovered that the theoretically estimated vibrational frequencies and assignments accord well with experimental FT-IR values.

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.

Intermolecular Forces Regulating the Phase-Transition Temperatures in Organic-Inorganic Hybrid Materials.

Organic-inorganic hybrid phase-transition materials have attracted widespread attention in energy storage and sensor applications due to their structural adaptability and facile synthesis. However, increasing the phase-transition temperature (Tc) effectively remains a formidable challenge. In this study, we employed a strategy to regulate intermolecular interactions (different types of hydrogen bonds and other weak interactions), utilizing bismuth chloride as an inorganic framework and azetidine, 3,3-difluoro azetidine, and 3-carboxyl azetidine as organic components to synthesize three compounds with different Tc values: [C3H8N]2BiCl5 (1, 234 K), [C3H6NF2]3BiCl6 (2, 256 K), and [C4H8O2N]3BiCl6 (3, 350 K). 1 is a one-dimensional chain structure and 2 and 3 are zero-dimensional structures. Analysis of the crystal structure and the Hirshfeld surface and 2D fingerprints further suggests that the intermolecular forces are efficiently modulated. These findings emphasize the efficacy of our strategy in enhancing Tc and may facilitate further research in this area.

IIIA new ionic penta-nuclear Fe(III) cluster: Syntheses, structure, magnetic properties and Hirshfeld surface analysis

One new ionic penta-nuclear FeIII cluster, [HN(Et)3]·[Fe5(L3)4(ATZ)4(μ 3-O)2]·(H2O) (1), (H2L is 2-(((1H-tetrazol-5-yl)imino)methyl)-6-methoxyphenol; HATZ is 5-amino-1,2,3,4- tetrazole), was synthesized through a micro-vial reaction. Complex 1 was characterized by elemental analysis, FT-IR spectra, X-ray single crystal diffraction, thermogravimetric analysis. Complex 1 reveals high thermal stability, and displays intracluster antiferromagnetic coupling between the Fe(III) ions through μ 3-O bridges. In 1, HATZ was synthesized through in situ decomposition reaction of H2L. The Hirshfeld surface analysis results indicate that the N···H interaction is one of the most significant contacts for the complex.

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

Experimental and theoretical studies of trinuclear cadmium(II) complex containing pyridine ring: Synthesis, crystallographic, spectroscopic, TD/DFT calculations and Hirshfeld surface analysis

Two three-dimensional supramolecular structures of L and [Cd3L2(CH3OH)4Cl6] complex (L = 2-(6-bromopyridin-2-yl)-4-methyl-1,2-dihydroquinazoline-N3-oxide), were synthesized and characterized by X-ray crystallography and elemental analysis, as well as FT-IR, UV–Vis, and fluorescence spectroscopy. The photoluminescence behavior of the Cd(II) complex was also investigated in different solvents. X-ray diffraction analysis results revealed that the Cd(II) complex was a trinuclear hexa-coordinate structure and made up of two L, three Cd2+ metal central, four methanol and six chlorine ions. In the crystal structures, it was noteworthy that L formed an infinite 1-D chain-like, 2-D square structure, parallelogram 3-D supramolecular skeleton, whereas the Cd(II) complex formed an infinite 1-D chain-like, 2-D ladder-like configuration, and even expanding into 3-D grid-like supramolecular frameworks. Density functional theory (DFT) calculation was used to compute the optimization, molecular frontier orbital energies (HOMO and LUMO). Specifically, owing to the combination of metal orbitals and the ligand, the energy gap of the complex was less than L. Electrostatic potential (ESP) was used to analyze the reaction sites of two compounds. On the basis of optimized geometry, time-dependent DFT (TD-DFT) simulated the electronic transitions rationalized the UV–Vis spectra peaks of L and Cd(II) complex. In addition, some non-covalent interactions were quantified by Hirshfeld surface and analyzed by Interaction region indicator (IRI).

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-κN3)[4-methyl-2-({[2-oxido-5-(2-phenyl-diazen-1-yl)phen-yl]methyl-idene}amino)penta-noate-κ3O,N,O']copper(II).

The title copper(II) complex, [Cu(C18H19N3O3)(C3H4N2)], consists of a tridentate ligand synthesized from l-leucine and azo-benzene-salicyl-aldehyde. One imidazole mol-ecule 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, DFT calculations, NBO, Fukui function, NCI-RDG, Hirshfeld surface analysis, NLO properties and molecular docking analysis on (E)-N'-(3-methoxybenzylidene)-2-(quinolin-8-yloxy) acetohydrazide

In this study, we present the synthesis and characterization of a novel organic compound, (E)-N'-(3-methoxybenzylidene)-2-(quinolin-8-yloxy) acetohydrazide. Our characterization includes single crystal X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and UV–visible spectroscopy. We also conducted Hirshfeld surface (HS) analysis to investigate intermolecular interactions. The compound crystallizes in the triclinic system with space group P−1. We employed density functional theory (DFT) with the B3LYP function and the 6–311 G (d, p) basis set to calculate its electronic properties. Additionally, we explored its nonlinear optical (NLO) behavior, determining the electric dipole moment (μ), polarizability (α), and hyperpolarizability (β), second-order hyperpolarizabilities (γ) using the same basis set. To evaluate the NLO properties of MBQA, we conducted frontier molecular orbitals (FMO) analysis, examined HOMO-LUMO energies, determined the energy band gap, studied the density of states (DOS), and assessed global chemical reactivity descriptors. We also performed a molecular electrostatic potential (MEP) simulation to identify optimal sites for both electrophilic and nucleophilic attacks. Our analysis further included a reduced density gradient (RDG) analysis to investigate various types of intermolecular interactions in MBQA, such as repulsive, attractive, and Van der Waals interactions while also distinguishing between strong and weak interactions. To understand the molecular stability and interactions, we conducted natural bond orbital (NBO) analysis, which provided insights into hyperconjugative interactions, charge delocalization and electron density ED among the molecular components. Finally, we assessed the biological activity of the MBQA molecule by predicting its potential pharmacological activities using the prediction of activity spectra for substances (PASS) and conducting molecular docking analyses. This comprehensive study provides valuable insights into the structural, electronic, and biological properties of (E)-N'-(3-methoxybenzylidene)-2-(quinolin-8-yloxy) acetohydrazide (MBQA).

Synthesis, crystal structure and Hirshfeld analysis of N-ethyl-2-{3-methyl-2-[(2Z)-pent-2-en-1-yl]cyclo-pent-2-en-1-yl-idene}hydrazinecarbo-thio-amide.

The title compound (C14H23N3S, common name: cis-jasmone 4-ethyl-thio-semicarbazone) was synthesized by the equimolar reaction of cis-jasmone and 4-ethyl-thio-semicarbazide in ethanol facilitated by acid catalysis. There is one crystallographically independent mol-ecule 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 thio-semicarbazone 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 mol-ecule is not planar due to this structural feature and the sp 3-hybridized atoms of the jasmone carbon chain. Additionally, one H⋯N intra-molecular inter-action is observed, with graph-set motif S(5). In the crystal, the mol-ecules are connected through pairs of H⋯S inter-actions with R 2 2(8) and R 2 1(7) graph-set motifs into centrosymmetric dimers. The dimers are further connected by H⋯N inter-actions 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 supra-molecular assembly of the title compound are compared with four known cis-jasmone thio-semicarbazone 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%) inter-faces (only the disordered atoms with the highest s.o.f. were considered for the evaluation).