RESUMEN
A microwave-assisted synthesis of 7-amino-1,2,4-triazolo[1,5-a][1,3,5]triazine-2-propanamides was developed using a three-component, catalyst-free reaction of cyanamide and trimethyl orthoformate with 3-(5-amino-1H-1,2,4-triazol-3-yl)propanamides (3). The reaction tolerated structurally diverse substrates and proceeded chemo- and regio-selectively, affording the target compounds in high purity in 5-10â minutes. The convenient chromatography-free isolation and purification of the products add practicality to this method. The structural features of the prepared compounds were investigated using dynamic NMR spectroscopy, X-ray crystallography and computational chemistry calculations. X-ray crystallography performed on a representative compound, 3-(7-amino-1,2,4-triazolo[1,5-a][1,3,5]triazin-2-yl)-N-(4-benzyl)propanamide (4 l), showed the overall molecular conformation to adopt the shape of the letter C. Notable localisation of π-electron density is found within the 1,2,4-triazolo[1,5-a][1,3,5]triazine system; a relatively short C-NH2 bond is consistent with restricted rotation about this bond. This study also presents a detailed analysis of the molecular interactions in 4 l using DFT and QTAIM methods with a focus on the hydrogen-bonding and π-stacking interactions that influence the molecular packing of 4 l. The findings reveal the significant roles of N-Hâ O, N-Hâ N and C-Hâ N interactions, along with electrostatically enhanced πâ π contacts. A broad screening for insecticidal, fungicidal and herbicidal properties identified several compounds with potent herbicidal activity against Matricaria inodora.
RESUMEN
A new series of indolenines decorated with pyrazolo[3,4-b]pyridines were designed and synthesized in up to 96% yield from the acid-catalyzed cyclocondensation of 1,3-dialdehydes with 3-aminopyrazoles. X-ray crystallography on a representative derivative, 5n, revealed two close to planar conformations whereby the N-atom of the pyridyl residue was syn or anti to the pyrrole-N atom in the two independent molecules of the asymmetric unit. The computational and DNA binding data suggest that 5n is a strong DNA intercalator with the results in agreement with its potent cytotoxicity against two colorectal cancer cell lines (HCT 116 and HT-29). In contrast to doxorubicin, compounds 5k-o have higher druggability (compliance to more criteria stated in Lipinski's rule of five and Veber's rule), higher bioavailability, and better medicinal chemistry properties, indicative of their potential application as chemotherapeutical agents.
Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Neoplasias Colorrectales/tratamiento farmacológico , ADN , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Piridinas/farmacología , Piridinas/química , Relación Estructura-Actividad , Pirazoles/química , Pirazoles/farmacología , Indoles/química , Indoles/farmacologíaRESUMEN
Despite significant progress in immunotherapy and chimeric antigen receptor T cell therapy of leukemia, chemotherapy is the major treatment option for the disease. Therefore, the development of potent and safe drugs for standard and targeted chemotherapy of leukemia remains an important task for medicinal chemists. A library of 94 diverse 6-aryl-4-cycloamino-1,3,5-triazine-2-amines was prepared using a one-pot microwave-assisted protocol, which involves a three-component reaction of cyanoguanidine, aromatic aldehydes and cyclic amines, and subsequent dehydrogenative aromatization of the dihydrotriazine intermediates in the presence of alkali. The cytotoxic properties of prepared compounds were evaluated against the leukemic Jurkat T cell line and the selectivity of the 24 most active compounds was also assessed using a normal fibroblast MRC-5 cell line, indicating selective antiproliferative activity against leukemic cells. The structure-activity relationship was analysed, and the prepared 3D-QSAR model was found to predict the antileukemic activity of the compounds with reasonable accuracy. In the cell morphology study, both apoptosis and necrosis features were observed in Jurkat T cells after treatment with the most active compound.
RESUMEN
Three triorganotin(IV) compounds, R3Sn(L), with R = CH3 (1), n-C4H9 (2) and C6H5 (3), and LH = 4-[(2-chloro-4-methylphenyl)carbamoyl]butanoic acid, were prepared and confirmed by various techniques. A five-coordinate, distorted trigonal-bipyramidal geometry was elucidated for tin(IV) centres both in solution and solid states. An intercalation mode was confirmed for the compound SS-DNA interaction by UV-visible, viscometric techniques and molecular docking. MD simulation revealed stable binding of LH with SS-DNA. Anti-bacterial investigation revealed 2 to be generally the most potent, especially against Sa and Ab, i.e. having the lowest MIC values (≤0.25 µg/mL) compared to the standard anti-biotics vancomycin-HCl (MIC = 1 µg/mL) and colistin-sulphate (MIC = 0.25 µg/mL). Similarly, the anti-fungal profile shows 2 exhibits 100% inhibition against Ca and Cn fungal strains and has MIC values (≤0.25 µg/mL) comparatively lower than standard drug fluconazole (0.125 and 8 µg/mL for Ca and Cn, respectively). Compound 2 has the greatest activity with CC50 ≤ 25 µg/mL and HC50 > 32 µg/mL performed against HEC239 and RBC cell lines. The anti-cancer potential was assessed against the MG-U87 cell line, using cisplatin as the standard (133 µM), indicates 2 displays the greatest activity (IC50: 5.521 µM) at a 5 µM dose. The greatest anti-leishmanial potential was observed for 2 (87.75 at 1000 µg/mL) in comparison to amphotericin B (90.67). The biological assay correlates with the observed maximum of 89% scavenging activity exhibited by 2. The Swiss-ADME data publicised the screened compounds generally follow the rule of 5 of drug-likeness and have good bioavailability potential.
Asunto(s)
ADN , Simulación del Acoplamiento Molecular , Ácido Butírico , Línea Celular , ADN/química , Simulación por Computador , Pruebas de Sensibilidad MicrobianaRESUMEN
Staphylococcus aureus is a highly adaptable opportunistic pathogen that can form biofilms and generate persister cells, leading to life-threatening infections that are difficult to treat with antibiotics alone. Therefore, there is a need for an effective S. aureus biofilm inhibitor to combat this public health threat. In this study, a small library of indolenine-substituted pyrazoles and pyrimido[1,2-b]indazole derivatives were synthesised, of which the hit compound exhibited promising antibiofilm activities against methicillin-susceptible S. aureus (MSSA ATCC 29213) and methicillin-resistant S. aureus (MRSA ATCC 33591) at concentrations significantly lower than the planktonic growth inhibition. The hit compound could prevent biofilm formation and eradicate mature biofilms of MSSA and MRSA, with a minimum biofilm inhibitory concentration (MBIC50) value as low as 1.56 µg/mL and a minimum biofilm eradication concentration (MBEC50) value as low as 6.25 µg/mL. The minimum inhibitory concentration (MIC) values of the hit compound against MSSA and MRSA were 50 µg/mL and 25 µg/mL, respectively, while the minimum bactericidal concentration (MBC) values against MSSA and MRSA were > 100 µg/mL. Preliminary structure-activity relationship analysis reveals that the fused benzene ring and COOH group of the hit compound are crucial for the antibiofilm activity. Additionally, the compound was not cytotoxic to human alveolar A549 cells, thus highlighting its potential as a suitable candidate for further development as a S. aureus biofilm inhibitor.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Staphylococcus aureus , Indazoles/farmacología , Antibacterianos/farmacología , Biopelículas , Pirazoles/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
Five new compounds of benz[e]indole pyrazolyl-substituted amides (2a-e) were synthesised in low to good yields via the direct amide-coupling reaction between a pyrazolyl derivative containing a carboxylic acid and several amine substrates. The molecular structures were determined by various spectroscopic methods, such as NMR (1H, 13C and 19F), FT-IR and high-resolution mass spectrometry (HRMS). X-ray crystallographic analysis on the 4-fluorobenzyl derivative (2d) reveals the amide-O atom to reside to the opposite side of the molecule to the pyrazolyl-N and pyrrolyl-N atoms; in the molecular packing, helical chains feature amide-NâHâ¯N(pyrrolyl) hydrogen bonds. Density-functional theory (DFT) at the geometry-optimisation B3LYP/6-31G(d) level on the full series shows general agreement with the experimental structures. While the LUMO in each case is spread over the benz[e]indole pyrazolyl moiety, the HOMO spreads over the halogenated benzo-substituted amide moieties or is localised near the benz[e]indole pyrazolyl moieties. The MTT assay showed that 2e, exhibited the highest toxicity against a human colorectal carcinoma (HCT 116 cell line) without appreciable toxicity towards the normal human colon fibroblast (CCD-18Co cell line). Based on molecular docking calculations, the probable cytotoxic mechanism of 2e is through the DNA minor groove binding.
RESUMEN
A convenient method for the synthesis of N3,N4-disubstituted 3,4-diaminopyrazolo[3,4-d]pyrimidines was developed using a three-component reaction of 3,5-diaminopyrazole-4-carbonitriles with primary amines and orthoesters. The preparation of 116 examples demonstrated the good scope of the reaction, which tolerated variations in the substrate structure and was particularly efficient under microwave irradiation. The short reaction time and chromatography-free product isolation add practicality to this method. The anti-leukemic activity was assessed in vitro using K562 and Jurkat T cells, and the selectivity of the most active compounds was evaluated using non-cancerous MRC5 cells. The most promising compound inhibited Jurkat T cells with a GI50 value of 0.5 µM and a selectivity index of 65.
Asunto(s)
Microondas , Pirimidinas , Pirimidinas/químicaRESUMEN
Dibenzo[1,5]diazocine scaffolds are present in a wide range of organic building blocks, for example in pharmaceuticals, materials and structural chemistry. However, the development of these structural frameworks has not received significant attention owing to limited synthetic protocols and strategies. Herein, a summary of the attractive synthetic approaches for the construction of dibenzo[1,5]diazocines, epiminodibenzo[1,5]diazocines and epoxydibenzo[1,5]diazocines developed over the past two decades is presented. The spectroscopic, synthetic mechanisms for the formation of the heterocyclic rings and remarkable structural features, including in the solid-state, are discussed.
RESUMEN
The isomeric ligand LC, a saturated analogue of 2,9-C-meso-Me8[14]diene, on reflux with excess acrylonitrile afforded 1,8-N-pendant cyanoethyl derivative LCX. Interaction of LCX with cadmium(II) perchlorate, nitrate, acetate, and chloride salts produced six coordinated octahedral compounds, [Cd(LCX) (ClO4)2]â2H2O, [Cd(LCX) (NO3)2], [Cd(LCX) (CH3COO)2], and [Cd(LCX)Cl2], respectively. Further, axial substitution reactions between [Cd(LCX) (ClO4)2]â2H2O and KI, KBr, KCl, KSCN, and NaNO2 in a 1:2 ratio yielded six coordinated octahedral compounds, [Cd(LCX)I2]âH2O, [Cd(LCX)Br2]â2H2O, [Cd(LCX)Cl(ClO4)]â2H2O, [Cd(LCX) (NCS)2]âH2O, and [Cd(LCX) (NO2) (ClO4)]â2H2O, respectively. All of the newly prepared compounds have been characterized by analytical, spectroscopic, molar conductivity, and magnetochemical data. The crystal structure of the ligand LCX was determined by x-ray crystallography which showed the 14-membered ring to adopt an extended chair conformation. Antibacterial activities of the newly formed cadmium(II) complexes against selected bacteria showed these to exhibit moderate and selective activity with 1-4 and 8 exhibiting greatest potency against the gram negative bacterium Salmonella typhi, and 5, 6, and 7 against the gram positive bacterium Bacillus wiedmannii.
RESUMEN
A practical three-component method for the synthesis of pyrazolo[3,4-d]pyrimidin-4-ones was developed. The reaction was performed in a one-pot manner under controlled microwave irradiation using easily accessible methyl 5-aminopyrazole-4-carboxylates, trimethyl orthoformate, and primary amines. Under the optimized conditions, challenging substrates, such as N-1 unsubstituted 5-aminopyrazole-4-carboxylates with another substituted amino group in position 3, reacted selectively affording 5-substituted 3-arylamino-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones. The reaction tolerated a range of primary amines, including anilines. The advantages of the developed protocol include short reaction time, pot- and step-economy, and convenient chromatography-free product isolation. The structural features of representative products were explored by X-ray crystallography.
RESUMEN
The title CuII macrocyclic complex salt tetra-hydrate, [Cu(C22H46N6O2)](C2H3O2)2·4H2O, sees the metal atom located on a centre of inversion and coordinated within a 4 + 2 (N4O2) tetra-gonally distorted coordination geometry; the N atoms are derived from the macrocycle and the O atoms from weakly associated [3.2048â (15)â Å] acetate anions. Further stability to the three-ion aggregate is provided by intra-molecular amine-N-Hâ¯O(carboxyl-ate) hydrogen bonds. Hydrogen bonding is also prominent in the mol-ecular packing with amide-N-Hâ¯O(amide) inter-actions, leading to eight-membered {â¯HNCO}2 synthons, amide-N-Hâ¯O(water), water-O-Hâ¯O(carboxyl-ate) and water-O-Hâ¯O(water) hydrogen bonds featuring within the three-dimensional architecture. The calculated Hirshfeld surfaces for the individual components of the asymmetric unit differentiate the water mol-ecules owing to their distinctive supra-molecular association. For each of the anion and cation, Hâ¯H contacts predominate (50.7 and 65.2%, respectively) followed by Hâ¯O/Oâ¯H contacts (44.5 and 29.9%, respectively).
RESUMEN
Five new anionic aqueous dioxidovanadium(V) complexes, [{VO2L1,2}A(H2O)n]α (1-5), with the aroylhydrazone ligands pyridine-4-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)hydrazide (H2L1) and furan-2-carboxylic acid (3-ethoxy-2-hydroxybenzylidene)hydrazide (H2L2) incorporating different alkali metals (A = Na+, K+, Cs+) as countercation were synthesized and characterized by various physicochemical techniques. The solution-phase stabilities of 1-5 were determined by time-dependent NMR and UV-vis, and also the octanol/water partition coefficients were obtained by spectroscopic techniques. X-ray crystallography of 2-4 confirmed the presence of vanadium(V) centers coordinated by two cis-oxido-O atoms and the O, N, and O atoms of a dianionic tridentate ligand. To evaluate the biological behavior, all complexes were screened for their DNA/protein binding propensity through spectroscopic experiments. Finally, a cytotoxicity study of 1-5 was performed against colon (HT-29), breast (MCF-7), and cervical (HeLa) cancer cell lines and a noncancerous NIH-3T3 cell line. The cytotoxicity was cell-selective, being more active against HT-29 than against other cells. In addition, the role of hydrophobicity in the cytotoxicity was explained in that an optimal hydrophobicity is essential for high cytotoxicity. Moreover, the results of wound-healing assays indicated antimigration in case of HT-29 cells. Remarkably, 1 with an IC50 value of 5.42 ± 0.15 µM showed greater activity in comparison to cisplatin against the HT-29 cell line.
Asunto(s)
Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , ADN/química , Hidrazonas/farmacología , Albúmina Sérica Bovina/química , Compuestos de Vanadio/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Hidrazonas/química , Interacciones Hidrofóbicas e Hidrofílicas , Ratones , Modelos Moleculares , Estructura Molecular , Células 3T3 NIH , Solubilidad , Compuestos de Vanadio/química , Agua/químicaRESUMEN
The title thio-urea derivative, C17H19N3OS, adopts a U-shaped conformation with the dihedral angle between the terminal aromatic rings being 73.64â (5)°. The major twist in the mol-ecule occurs about the ethane bond with the Ci-Ce-Ce-Cb torsion angle being -78.12â (18)°; i = imine, e = ethane and b = benzene. The configuration about the imine bond is E, the N-bound H atoms lie on opposite sides of the mol-ecule and an intra-molecular amine-N-Hâ¯N(imine) hydrogen bond is evident. In the mol-ecular packing, hydroxyl-O-Hâ¯S(thione) and amine-N-Hâ¯O hydrogen bonding feature within a linear, supra-molecular chain. The chains are connected into a layer in the ab plane by a combination of methyl-ene-C-Hâ¯S(thione), methyl-ene-C-Hâ¯O(hydrox-yl), methyl-C-Hâ¯π(phen-yl) and phenyl-C-Hâ¯π(hy-droxy-benzene) inter-actions. The layers stack without directional inter-actions between them. The analysis of the calculated Hirshfeld surface highlights the presence of weak methyl-C-Hâ¯O(hydrox-yl) and Hâ¯H inter-actions in the inter-layer region. Computational chemistry indicates that dispersion energy is the major contributor to the overall stabilization of the mol-ecular packing.
RESUMEN
The title zinc bis-(thio-semicarbazone) complex, [Zn(C22H17N4O2S)2], comprises two N,S-donor anions, leading to a distorted tetra-hedral N2S2 donor set. The resultant five-membered chelate rings are nearly planar and form a dihedral angle of 73.28â (3)°. The configurations about the endocyclic- and exocyclic-imine bonds are Z and E, respectively, and that about the ethyl-ene bond is E. The major differences in the conformations of the ligands are seen in the dihedral angles between the chelate ring and nitro-benzene rings [40.48â (6) cf. 13.18â (4)°] and the N-bound phenyl and nitro-benzene ring [43.23â (8) and 22.64â (4)°]. In the crystal, a linear supra-molecular chain along the b-axis direction features amine-N-Hâ¯O(nitro) hydrogen bonding. The chains assemble along the 21-screw axis through a combination of phenyl-C-Hâ¯O(nitro) and π(chelate ring)-π(phen-yl) contacts. The double chains are linked into a three-dimensional architecture through phenyl-C-Hâ¯O(nitro) and nitro-Oâ¯π(phen-yl) inter-actions.
RESUMEN
The title diorganotin Schiff base derivative, [Sn(C4H9)2(C15H13N3O2S)], features a penta-coordinated tin centre defined by the N,O,S-donor atoms of the di-anionic Schiff base ligand and two methyl-ene-C atoms of the n-butyl substituents. The resultant C2NOS donor set defines a geometry inter-mediate between trigonal-bipyramidal and square-pyramidal. In the crystal, amine-N-Hâ¯O(meth-oxy) hydrogen bonding is found in a helical, supra-molecular chain propagating along the b-axis direction. The chains are assembled into a layer parallel to (01) with methyl-ene-C-Hâ¯π(phen-yl) inter-actions prominent; layers stack without directional inter-actions between them. The analysis of the calculated Hirshfeld surface showed the presence of weak methyl-ene-C-Hâ¯π(phen-yl) inter-actions and short Hâ¯H contacts in the inter-layer region. Consistent with the nature of the identified contacts, the stabilization of the crystal is dominated by the dispersion energy term.
RESUMEN
A new series of pyrimido[1,2-b]indazoles bearing indolenine moieties was synthesized through a simple condensation reaction with up to 94% yield. The present method features the versatile formation of a pyrimidine ring with a broad range of substrates, great functional group compatibility and facile synthetic operation. The work offers opportunities in drug development as well as in materials science.
RESUMEN
The Cambridge Structural Database was evaluated for crystals containing Se O chalcogen bonding interactions. These secondary bonding interactions are found to operate independently of complementary intermolecular interactions in about 13% of the structures they can potentially form. This number rises significantly when more specific interactions are considered, e.g. Se O(carbonyl) interactions occur in 50% of cases where they can potentially form. In about 55% of cases, the supramolecular assemblies sustained by Se O(oxygen) interactions are one-dimensional architectures, with the next most prominent being zero-dimensional assemblies, at 30%.
RESUMEN
The complete mol-ecule of the title hydrazine carbodi-thio-ate derivative, C32H30N4O2S4, is generated by a crystallographic twofold axis that bis-ects the di-sulfide bond. The mol-ecule is twisted about this bond with the C-S-S-C torsion angle of 90.70â (8)° indicating an orthogonal relationship between the symmetry-related halves of the mol-ecule. The conformation about the imine bond [1.282â (2)â Å] is E and there is limited delocalization of π-electron density over the CN2C residue as there is a twist about the N-N bond [C-N-N-C torsion angle = -166.57â (15)°]. An intra-molecular hydroxyl-O-Hâ¯N(imine) hydrogen bond closes an S(6) loop. In the crystal, methyl-ene-C-Hâ¯π(tol-yl) contacts assemble mol-ecules into a supra-molecular layer propagating in the ab plane: the layers stack without directional inter-actions between them. The analysis of the calculated Hirshfeld surfaces confirm the importance of Hâ¯H contacts, which contribute 46.7% of all contacts followed by Hâ¯C/Câ¯H contacts [25.5%] reflecting, in part, the C-Hâ¯π(tol-yl) contacts. The calculation of the inter-action energies confirm the importance of the dispersion term and the influence of the stabilizing Hâ¯H contacts in the inter-layer region.
RESUMEN
The title phosphanegold(I) thiol-ate, C26H22AuFNOPS or [Au(C8H7FNOS)(C18H15P)], has the AuI centre coordinated by phosphane-P [2.2494â (8)â Å] and thiol-ate-S [2.3007â (8)â Å] atoms to define a close to linear geometry [P-Au-S = 176.10â (3)°]. The thiol-ate ligand is orientated so that the meth-oxy-O atom is directed towards the Au atom, forming an Auâ¯O close contact of 2.986â (2)â Å. In the crystal, a variety of inter-molecular contacts are discerned with fluoro-benzene-C-Hâ¯O(meth-oxy) and phenyl-C-Hâ¯F inter-actions leading to dimeric aggregates. These are assembled into a three-dimensional architecture by phenyl-C-Hâ¯S(thiol-ate) and phenyl-C-Hâ¯π(fluorobenzene, phen-yl) inter-actions. Accordingly, the analysis of the calculated Hirshfeld surface shows 30.8% of all contacts are of the type Câ¯H/Hâ¯C but this is less than the Hâ¯H contacts, at 44.9%. Other significant contributions to the surface come from Hâ¯F/Fâ¯H [8.1%], Hâ¯S/Sâ¯H [6.9%] and Hâ¯O/Oâ¯H [3.2%] contacts. Two major stabilization energies have contributions from the phenyl-C-Hâ¯π(fluoro-benzene) and fluoro-benzene-C-Hâ¯C(imine) inter-actions (-37.2 kcal mol-1), and from the fluoro-benzene-C-Hâ¯F and phenyl-C-Hâ¯O inter-actions (-34.9 kcal mol-1), the latter leading to the dimeric aggregate.
RESUMEN
The title hydrazine carbodi-thio-ate chloro-form hemisolvate, 2C15H14N2O2S2·CHCl3, comprises two independent hydrazine carbodi-thio-ate mol-ecules, A and B, and a chloro-form mol-ecule; the latter is statistically disordered about its mol-ecular threefold axis. The common features of the organic mol-ecules include an almost planar, central CN2S2 chromophore [r.m.s. deviation = 0.0203â Å (A) and 0.0080â Å (B)], an E configuration about the imine bond and an intra-molecular hydroxyl-O-Hâ¯N(imine) hydrogen bond. The major conformational difference between the mol-ecules is seen in the relative dispositions of the phenyl rings as indicated by the values of the dihedral angles between the central plane and phenyl ring of 71.21â (6)° (A) and 54.73â (7)° (B). Finally, a difference is seen in the disposition of the outer hydroxyl-H atoms, having opposite relative orientations. In the calculated gas-phase structure, the entire mol-ecule is planar with the exception of the perpendicular phenyl ring. In the mol-ecular packing, the A and B mol-ecules assemble into a two-mol-ecule aggregate via N-Hâ¯S hydrogen bonds and eight-membered {â¯HNCS}2 synthons. The dimeric assemblies are connected into supra-molecular chains via hydroxyl-O-Hâ¯O(hydrox-yl) hydrogen bonds and these are linked into a double-chain through hy-droxy-O-Hâ¯π(phen-yl) inter-actions. The double-chains are connected into a three-dimensional architecture through phenyl-C-Hâ¯O(hydrox-yl) and phenyl-C-Hâ¯π(phen-yl) inter-actions. The overall assembly defines columns along the a-axis direction in which reside the chloro-form mol-ecules, which are stabilized by chloro-form-methine-C-Hâ¯S(thione) and phenyl-C-Hâ¯Cl contacts. The analysis of the calculated Hirshfeld surfaces, non-covalent inter-action plots and inter-action energies confirm the importance of the above-mentioned inter-actions, but also of cooperative, non-standard inter-actions such as π(benzene)â¯π(hydrogen-bond-mediated-ring) contacts.