The different modes of chiral [1,2,3]triazolo[5,1-b][1,3,4]thiadiazines: crystal packing, conformation investigation and cellular activity

2020 ◽  
Vol 76 (8) ◽  
pp. 795-809
Author(s):  
Konstantin L'vovich Obydennov ◽  
Tatiana Andreevna Kalinina ◽  
Olga Alexandrovna Vysokova ◽  
Pavel Alexandrovich Slepukhin ◽  
Varvara Alexandrovna Pozdina ◽  
...  
Keyword(s):  
Hydrogen Bonds ◽  
Intermolecular Interactions ◽  
Cell Lines ◽  
Inhibitory Concentration ◽  
Crystal Packing ◽  
Noncovalent Interactions ◽  
Racemic Mixtures ◽  
Normal Human Cell ◽  
Normal Human ◽  
Method Show

The crystal structures of four new chiral [1,2,3]triazolo[5,1-b][1,3,4]thiadiazines are described, namely, ethyl 5′-benzoyl-5′H,7′H-spiro[cyclohexane-1,6′-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine]-3′-carboxylate, C19H22N4O3S, ethyl 5′-(4-methoxybenzoyl)-5′H,7′H-spiro[cyclohexane-1,6′-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine]-3′-carboxylate, C20H24N4O4S, ethyl 6,6-dimethyl-5-(4-methylbenzoyl)-6,7-dihydro-5H-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine-3-carboxylate, C17H20N4O3S, and ethyl 5-benzoyl-6-(4-methoxyphenyl)-6,7-dihydro-5H-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine-3-carboxylate, C21H20N4O4S. The crystallographic data and cell activities of these four compounds and of the structures of three previously reported similar compounds, namely, ethyl 5′-(4-methylbenzoyl)-5′H,7′H-spiro[cyclopentane-1,6′-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine]-3′-carboxylate, C19H22N4O3S, ethyl 5′-(4-methoxybenzoyl)-5′H,7′H-spiro[cyclopentane-1,6′-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine]-3′-carboxylate, C19H22N4O4S, and ethyl 6-methyl-5-(4-methylbenzoyl)-6-phenyl-6,7-dihydro-5H-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine-3-carboxylate, C22H22N4O3S, are contrasted and compared. For both crystallization and an MTT assay, racemic mixtures of the corresponding [1,2,3]triazolo[5,1-b][1,3,4]thiadiazines were used. The main manner of molecular packing in these compounds is the organization of either enantiomeric pairs or dimers. In both cases, the formation of two three-centre hydrogen bonds can be detected resulting from intramolecular N—H...O and intermolecular N—H...O or N—H...N interactions. Molecules of different enantiomeric forms can also form chains through N—H...O hydrogen bonds or form layers between which only weak hydrophobic contacts exist. Unlike other [1,2,3]triazolo[5,1-b][1,3,4]thiadiazines, ethyl 5′-benzoyl-5′H,7′H-spiro[cyclohexane-1,6′-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine]-3′-carboxylate contains molecules of only the (R)-enantiomer; moreover, the N—H group does not participate in any significant intermolecular interactions. Molecular mechanics methods (force field OPLS3e) and the DFT B3LYP/6-31G+(d,p) method show that the compound forming enantiomeric pairs via weak N—H...N hydrogen bonds is subject to greater distortion of the geometry under the influence of the intermolecular interactions in the crystal. For intramolecular N—H...O and S...O interactions, an analysis of the noncovalent interactions (NCIs) was carried out. The cellular activities of the compounds were tested by evaluating their antiproliferative effect against two normal human cell lines and two cancer cell lines in terms of half-maximum inhibitory concentration (IC50). Some derivatives have been found to be very effective in inhibiting the growth of Hela cells at nanomolar and submicromolar concentrations with minimal cytotoxicity in relation to normal cells.

scholarly journals 4-Acetylpiperazinium picrate

2014 ◽  
Vol 70 (6) ◽  
pp. o717-o718 ◽  
Author(s):  
Channappa N. Kavitha ◽  
Manpreet Kaur ◽  
Jerry P. Jasinski ◽  
Hemmige S. Yathirajan
Keyword(s):  
Hydrogen Bonds ◽  
Benzene Ring ◽  
Intermolecular Interactions ◽  
Crystal Packing ◽  
Chair Conformation ◽  
Centroid Distance ◽  
Sheet Structure ◽  
Benzene Rings ◽  
Π Stacking Interaction ◽  
The Mean

In the title salt, C6H13N2O+·C6H2N3O7−(systematic name: 4-acetylpiperazin-1-ium 2,4,6-trinitrophenolate), the piperazin-1-ium ring has a slightly distorted chair conformation. In the picrate anion, the mean planes of the twoo-NO2andp-NO2groups are twisted with respect to the benzene ring by 15.0 (2), 68.9 (4) and 4.4 (3)°, respectively. In the crystal, N—H...O hydrogen bonds are observed, linking the ions into an infinite chain along [010]. In addition, weak cation–anion C—H...O intermolecular interactions and a weak π–π stacking interaction between the benzene rings of the anions, with an inter-centroid distance of 3.771 (8) Å, help to stabilize the crystal packing, giving an overall sheet structure lying parallel to (100). Disorder was modelled for one of the O atoms in one of theo-NO2groups over two sites with an occupancy ratio of 0.57 (6):0.43 (6).

Salt formation, hydrogen-bonding patterns and supramolecular architectures of acridine with salicylic and hippuric acid molecules

2021 ◽  
Vol 77 (12) ◽  
Author(s):  
Suresh Suganya ◽  
Kandasamy Saravanan ◽  
Ramakrishnan Jaganathan ◽  
Poomani Kumaradhas
Keyword(s):  
Hydrogen Bonding ◽  
Intermolecular Interactions ◽  
Hippuric Acid ◽  
Crystal Packing ◽  
Noncovalent Interactions ◽  
Salt Formation ◽  
Aminosalicylic Acid ◽  
Dispersion Interactions ◽  
Supramolecular Architectures ◽  
Quantitative Contributions

The intermolecular interactions and salt formation of acridine with 4-aminosalicylic acid, 5-chlorosalicylic acid and hippuric acid were investigated. The salts obtained were acridin-1-ium 4-aminosalicylate (4-amino-2-hydroxybenzoate), C13H10N+·C7H6NO3 − (I), acridin-1-ium 5-chlorosalicylate (5-chloro-2-hydroxybenzoate), C13H10N+·C7H4ClO3 − (II), and acridin-1-ium hippurate (2-benzamidoacetate) monohydrate, C13H10N+·C9H8NO3 −·H2O (III). Acridine is involved in strong intermolecular interactions with the hydroxy group of the three acids, enabling it to form supramolecular assemblies. Hirshfeld surfaces, fingerprint plots and enrichment ratios were generated and investigated, and the intermolecular interactions were analyzed, revealing their quantitative contributions in the crystal packing of salts I, II and III. A quantum theory of atoms in molecules (QTAIM) analysis shows the charge–density distribution of the intermolecular interactions. The isosurfaces of the noncovalent interactions were studied, which allows visualization of where the hydrogen-bonding and dispersion interactions contribute within the crystal.

Polymorphism in two biologically active dihydropyrimidinium hydrochloride derivatives: quantitative inputs towards the energetics associated with crystal packing

2014 ◽  
Vol 70 (4) ◽  
pp. 681-696 ◽  
Author(s):  
Piyush Panini ◽  
K. N. Venugopala ◽  
Bharti Odhav ◽  
Deepak Chopra
Keyword(s):  
Hydrogen Bonds ◽  
Intermolecular Interactions ◽  
Density Functional ◽  
Crystal Packing ◽  
Lattice Energy ◽  
Biologically Active ◽  
Two Dimensional ◽  
Energy Calculations ◽  
X Ray ◽  
Fingerprint Plots

A new polymorph belonging to the tetrahydropyrimidinium class of compounds, namely 6-(4-chlorophenyl)-5-(methoxycarbonyl)-4-methyl-2-(3-(trifluoromethylthio)phenylamino)-3,6-dihydropyrimidin-1-ium chloride, and a hydrate of 2-(3-bromophenylamino)-6-(4-chlorophenyl)-5-(methoxycarbonyl)-4-methyl-3,6-dihydropyrimidin-1-ium chloride, have been isolated and characterized using single-crystal X-ray diffraction (XRD). A detailed comprehensive analysis of the crystal packing in terms of the associated intermolecular interactions and a quantification of their interaction energies have been performed for both forms of the two different organic salts (AandB) using X-ray crystallography and computational methods such as density functional theory (DFT) quantum mechanical calculations, PIXEL lattice-energy calculations (with decomposition of total lattice energy into the Coulombic, polarization, dispersion and repulsion contribution), the calculation of the Madelung constant (the EUGEN method), Hirshfeld and two-dimensional fingerprint plots. The presence of ionic [N—H]+...Cl−and [C—H]+...Cl−hydrogen bonds mainly stabilizes the crystal packing in both formsAandB, while in the case ofB·H2O [N—H]+...Owaterand Owater—H...Cl−hydrogen bonds along with [N—H]+...Cl−and [C—H]+...Cl−provide stability to the crystal packing. The lattice-energy calculations from both PIXEL and EUGEN methods revealed that in the case ofA, form (I) (monoclinic) is more stable whereas forBit is the anhydrous form that is more stable. The analysis of the `Madelung mode' of crystal packing of two forms ofAandBand its hydrates suggest that differences exist in the position of the charged ions/atoms in the organic solid state. TheR/E(distance–energy) plots for all the crystal structures show that the molecular pairs in their crystal packing are connected with either highly stabilizing (due to the presence of organicR+and Cl−) or highly destabilizing Coulombic contacts. The difference in crystal packing and associated intermolecular interactions between polymorphs (in the case ofA) or the hydrates (in the case ofB) have been clearly elucidated by the analysis of Hirshfeld surfaces and two-dimensional fingerprint plots. The relative contributions of the various interactions to the Hirshfeld surface for the cationic (dihydropyrimidinium) part and anionic (chloride ion) part for the two forms ofAandBand its hydrate were observed to be different.

Analysis of the less common hydrogen bonds involving ester oxygen sp 3 atoms as acceptors in the crystal structures of small organic molecules

2004 ◽  
Vol 60 (4) ◽  
pp. 424-432 ◽  
Author(s):  
Krešimir Molčanov ◽  
Biserka Kojić-Prodić ◽  
Nenad Raos
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Crystal Packing ◽  
Noncovalent Interactions ◽  
Secondary Amines ◽  
Structural Function ◽  
Hydroxyl Groups ◽  
Donor Group ◽  
Acta Cryst ◽  
Bifurcated Hydrogen Bond

An analysis of hydrogen bonds involving ester Osp 3 atoms as acceptors has been performed based on the data extracted from the Cambridge Structural Database [Allen (2002). Acta Cryst. B58, 380–388; version 5.25, November 2003], using the ConQuest package to evaluate the stereochemical and electronic properties of the acceptors. Evidence for the existence of this particular type of hydrogen bond and its structural function in crystal packing is presented. Using a cut-off limit on residual indices of R < 0.05 (for the structures with hydrogen bonds involving an oxygen as part of the donor group) and R < 0.085 (for nitrogen as part of the donor group), 230 structures out of the total CSD entries of 298 100 were found to contain hydrogen bonds with the ester Osp 3 atoms as acceptors. The hydrogen-bond donors include water molecules, hydroxyl groups, primary and secondary amines and, in a few cases, imino groups. Four modes of the participation of the ester Osp 3 atoms in hydrogen bonding are detected: as a single acceptor, as a double acceptor, as a single acceptor of a H atom involved in an intermolecular bifurcated hydrogen bond, and as a shared acceptor function with the ester Osp 2 atom in a bifurcated hydrogen bond. The role of such directed noncovalent interactions in crystal packing is demonstrated by a small gallery of selected structures.

Role of halogen-involved intermolecular interactions and existence of isostructurality in the crystal packing of —CF3 and halogen (Cl or Br or I) substituted benzamides

2018 ◽  
Vol 74 (6) ◽  
pp. 574-591 ◽  
Author(s):  
Pradip Kumar Mondal ◽  
Rahul Shukla ◽  
Subha Biswas ◽  
Deepak Chopra
Keyword(s):  
Solid State ◽  
Intermolecular Interactions ◽  
Crystal Packing ◽  
Noncovalent Interactions ◽  
X Ray Diffraction ◽  
Substituted Benzamides ◽  
Size Type ◽  
Substituted Benzamide ◽  
Van Der Waals Radii

A total of 23 benzamides are obtained through a simple reaction between chloro-/bromo-/iodoaniline and trifluoromethylbenzoyl chloride and characterized using single-crystal X-ray diffraction. Crystal structures of three series of benzamides based on N-chlorophenyl–trifluoromethyl–benzamide (nine compounds), N-bromophenyl–trifluoromethyl–benzamide (six compounds), and N-iodophenyl–trifluoromethyl–benzamide (eight compounds) are prepared to analyse the halogen-mediated noncovalent interactions. The influences of Cl/Br/I and trifluoromethyl substituents on the respective interactions are examined in the presence of a strong N—H...O hydrogen bond. This exercise has resulted in the documentation of frequently occurring supramolecular synthons involving halogen atoms in the crystal packing of benzamide molecules in the solid state. In the present study, a detailed quantitative evaluation has been performed on the nature, energetics, electrostatic contributions, and topological properties of short and directional intermolecular interactions derived from the electron density on halogenated benzamides in the solid state. Besides these, the occurrence of three-, two- and one-dimensional isostructurality in halogen (Cl or Br or I) substituted benzamide analogues is also investigated. A `region of co-existence' involving halogen-based intermolecular interactions in the vicinity of the sum of the van der Waals radii has been identified. Thus, the nature of the halogen (effective size), type of interaction and the packing characteristics via presence of additional interactions establish the subtle, yet important, role of cooperativity in intermolecular interactions in crystal packing.

scholarly journals Crystal structure and Hirshfeld surface analysis of 1-[(benzyldimethylsilyl)methyl]-1-ethylpiperidin-1-ium ethanesulfonate

2022 ◽  
Vol 78 (2) ◽  
Author(s):  
Jan-Lukas Kirchhoff ◽  
Stephan G. Koller ◽  
Kathrin Louven ◽  
Carsten Strohmann
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonds ◽  
Quantum Chemical Calculations ◽  
Surface Analysis ◽  
Intermolecular Interactions ◽  
Quantum Chemical ◽  
Crystal Packing ◽  
Hirshfeld Surface ◽  
Hirshfeld Surface Analysis ◽  
Molecular Salt

The title molecular salt, C17H30NSi+·C2H5O4S−, belongs to the class of a-aminosilanes and was synthesized by the alkylation of 1-[(benzyldimethylsilyl)methyl]piperidine using diethyl sulfate. This achiral salt crystallizes in the chiral space group P21. One of the Si—C bonds in the cation is unusually long [1.9075 (12) Å], which correlates with the adjacent quaternary N+ atom and was verified by quantum chemical calculations. In the crystal, the components are linked by weak C—H...O hydrogen bonds: a Hirshfeld surface analysis was performed to further investigate these intermolecular interactions and their effects on the crystal packing.

scholarly journals CHEMICAL AND PHARMACOLOGICAL EVALUATION OF MANGLICOLOUS LICHEN GRAPHIS AJAREKARII PATW. & C. R. KULK.

2019 ◽  
Vol 57 (3) ◽  
pp. 300
Author(s):  
Polimati Haritha ◽  
Sunil Kumar Patnaik ◽  
Vinay Bharadwaj Tatipamula
Keyword(s):  
Free Radicals ◽  
Cell Line ◽  
Cell Lines ◽  
Human Cell ◽  
Ethanolic Extract ◽  
Human Cell Line ◽  
Chemical Examination ◽  
Cytotoxicity Studies ◽  
Normal Human Cell ◽  
Normal Human

The chemical examination of ethanolic extract of manglicolous lichen Graphis ajarekarii (Ga-Et) resulted in isolation of three known metabolites – chiodectonic acid (1), graphenone (2) and graphisquinone (3). All the isolates (1-3) and Ga-Et were screened against DPPH and superoxide free radicals, six different cancer cell lines and one normal human cell line (NHME). This work is the first report of antioxidant and cytotoxicity studies on the isolated metabolites (1-3).

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