Polymorphism of methyl 4-amino-3-phenylisothiazole-5-carboxylate: an experimental and theoretical study

Being a close analogue of amflutizole, methyl 4-amino-3-phenylisothiazole-5-carboxylate (C11H10N2O2S) was assumed to be capable of forming polymorphic structures. Noncentrosymmetric and centrosymmetric polymorphs have been obtained by crystallization from a series of more volatile solvents and from denser tetrachloromethane, respectively. Identical conformations of the molecule are found in both structures. The two polymorphs differ mainly in the intermolecular interactions formed by the amino group and in the type of stacking interactions between the π-systems. The most effective method for revealing packing motifs in structures with intermolecular interactions of different types (hydrogen bonding, stacking, dispersion, etc.) is to study the pairwise interaction energies using quantum chemical calculations. Molecules form a column as the primary basic structural motif due to stacking interactions in both polymorphic structures under study. The character of a column (straight or zigzag) is determined by the orientations of the stacked molecules (in a `head-to-head' or `head-to-tail' manner). Columns bound by intermolecular N—H...O and N—H...N hydrogen bonds form a double column as the main structural motif in the noncentrosymmetric structure. Double columns in the noncentrosymmetric structure and columns in the centrosymmetric structure interact strongly within the ab crystallographic plane, forming a layer as a secondary basic structural motif. The noncentrosymmetric structure has a lower density and a lower (by 0.59 kJ mol−1) lattice energy, calculated using periodic calculations, compared to the centrosymmetric structure.

Download Full-text

A theoretical study of weak interactions in phenylenediamine homodimer clusters

Physical Chemistry Chemical Physics ◽

10.1039/c6cp04922b ◽

2016 ◽

Vol 18 (42) ◽

pp. 29249-29257 ◽

Cited By ~ 16

Author(s):

Chengqian Yuan ◽

Haiming Wu ◽

Meiye Jia ◽

Peifeng Su ◽

Zhixun Luo ◽

...

Keyword(s):

Density Functional Theory ◽

Dft Calculations ◽

Intermolecular Interactions ◽

Density Functional ◽

Theoretical Study ◽

Natural Bond Orbital ◽

Weak Interactions ◽

Interaction Energies ◽

Functional Theory ◽

Weak Intermolecular Interactions

Utilizing dispersion-corrected density functional theory (DFT) calculations, we demonstrate the weak intermolecular interactions of phenylenediamine dimer (pdd) clusters, emphasizing the local lowest energy structures and decomposition of interaction energies by natural bond orbital (NBO) and atoms in molecule (AIM) analyses.

Download Full-text

Quantitative Crystal Structure Analysis of (E)-1-[(2-Chloro-1,3-thiazol-5-yl)methyl]-3-methyl-2-nitroguanidine

Journal of Crystallography ◽

10.1155/2014/585282 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Dhananjay Dey ◽

Chetan S. Shripanavar ◽

Kaushik Banerjee ◽

Deepak Chopra

Keyword(s):

Crystal Structure ◽

Intermolecular Interactions ◽

Molecular Conformation ◽

Crystal Packing ◽

Lattice Energy ◽

Crystal Structure Analysis ◽

Hirshfeld Surface ◽

Biologically Active ◽

Molecular Formula ◽

Periodic Calculations

The crystal structure of a biologically active (E)-1-[(2-chloro-1,3-thiazol-5-yl)methyl)]-3-methyl-2-nitroguanidine with molecular formula C6H8N5O2ClS has been investigated based on the molecular conformation and the supramolecular packing in terms of intermolecular interactions involving N–H⋯O, N–H⋯N, and C–H⋯O–N (nitro group), C–H⋯N (thiazol) hydrogen bonds, offset π–π stacking, C–H⋯π and N(–NO2)⋯C=N intermolecular interactions. Furthermore, a short C–Cl⋯O–N contact is also present which contributes towards the crystal packing. The lattice energy of the title compound has been calculated using the PIXEL approach (the Coulomb-London-Pauli (CLP) model) and compared with periodic calculations performed using CRYSTAL09. In addition, Hirshfeld surface analysis and fingerprint plots provide a platform for the evaluation of the contribution of different intermolecular interactions towards the packing behaviour.

Download Full-text

Concomitant polymorphic forms of 3-cyclopropyl-5-(2-hydrazinylpyridin-3-yl)-1,2,4-oxadiazole

Acta Crystallographica Section C Structural Chemistry ◽

10.1107/s2053229620010414 ◽

2020 ◽

Vol 76 (8) ◽

pp. 836-844 ◽

Cited By ~ 2

Author(s):

Svitlana V. Shishkina ◽

Irina S. Konovalova ◽

Veronika R. Karpina ◽

Svitlana S. Kovalenko ◽

Sergiy M. Kovalenko ◽

...

Keyword(s):

Hydrogen Bonds ◽

Lone Pair ◽

Lattice Energy ◽

Structural Motif ◽

Stacking Interactions ◽

Centrosymmetric Dimer ◽

Triclinic Structure ◽

Isopropanol Solution ◽

Polymorphic Forms ◽

Head Type

The dipharmacophore compound 3-cyclopropyl-5-(2-hydrazinylpyridin-3-yl)-1,2,4-oxadiazole, C10H11N5O, was studied on the assumption of its potential biological activity. Two concomitant polymorphs were obtained on crystallization from isopropanol solution and these were thoroughly studied. Identical conformations of the molecules are found in both structures despite the low difference in energy between the four possible conformers. The two polymorphs differ crucially with respect to their crystal structures. A centrosymmetric dimer formed due to both stacking interactions of the `head-to-tail' type and N—H...N(π) hydrogen bonds is the building unit in the triclinic structure. The dimeric building units form an isotropic packing. In the orthorhombic polymorphic structure, the molecules form stacking interactions of the `head-to-head' type, which results in their organization in a column as the primary basic structural motif. The formation of N—H...N(lone pair) hydrogen bonds between two neighbouring columns allows the formation of a double column as the main structural motif. The correct packing motifs in the two polymorphs could not be identified without calculations of the pairwise interaction energies. The triclinic structure has a higher density and a lower (by 0.60 kcal mol−1) lattice energy according to periodic calculations compared to the orthorhombic structure. This allows us to presume that the triclinic form of 3-cyclopropyl-5-(2-hydrazinylpyridin-3-yl)-1,2,4-oxadiazole is the more stable.

Download Full-text

Intermolecular interactions and unexpected isostructurality in the crystal structures of the dichlorobenzaldehyde isomers

Acta Crystallographica Section B Structural Science ◽

10.1107/s0108768111035786 ◽

2011 ◽

Vol 67 (5) ◽

pp. 437-445 ◽

Cited By ~ 10

Author(s):

Katarzyna A. Solanko ◽

Andrew D. Bond

Keyword(s):

Crystal Structures ◽

Intermolecular Interaction ◽

Intermolecular Interactions ◽

Crystallographic Axis ◽

Stacking Interactions ◽

Interaction Energies ◽

Asymmetric Unit ◽

Consistent Feature ◽

Whole Molecule Disorder

The crystal structures of the six dichlorobenzaldehyde isomers, four of them newly determined, are analyzed in terms of the geometry and energies of their intermolecular interactions, quantified using the semi-classical density sums (SCDS-PIXEL) method. A consistent feature in all six structures is molecular stacks propagating along a short crystallographic axis of ca 3.8 Å. The stacks have a closely comparable geometry in each isomer, but the interaction energies between stacked molecules are variable on account of the differing relative positions of the Cl substituents. In the majority of the isomers the stacking interactions are the most stabilizing in the structure. Exceptions are the 2,4- and 3,5-isomers, where more stabilizing interactions are made between stacks. In general, the most stabilizing non-stacking intermolecular interactions in the structures are those involving C—H...O contacts. Observed motifs based on Cl...Cl interactions appear to be largely imposed by the constraints of other more stabilizing intermolecular interactions. The isomeric series displays the following noteworthy features: (i) the 2,3- and 2,6-isomers are isostructural despite having different orientations of the Cl and aldehyde functionalities; (ii) the 2,5-isomer exhibits whole-molecule disorder; (iii) the 2,5- and 3,5-isomers have more than one molecule in the crystallographic asymmetric unit (Z′ > 1). These features in particular are considered on the basis of the intermolecular interaction energies.

Download Full-text

Intrinsic Stacking Interactions of Natural and Artificial Nucleobases

10.26434/chemrxiv.11400405 ◽

2019 ◽

Author(s):

Drew P. Harding ◽

Laura J. Kingsley ◽

Glen Spraggon ◽

Steven Wheeler

Keyword(s):

Gas Phase ◽

Electrostatic Interactions ◽

Density Functional ◽

Molecular Descriptors ◽

Stacking Interactions ◽

Interaction Energies ◽

Functional Theory ◽

Binding Partner ◽

Heavy Atoms ◽

Wide Range

The intrinsic (gas-phase) stacking energies of natural and artificial nucleobases were explored using density functional theory (DFT) and correlated ab initio methods. Ranking the stacking strength of natural nucleobase dimers revealed a preference in binding partner similar to that seen from experiments, namely G > C > A > T > U. Decomposition of these interaction energies using symmetry-adapted perturbation theory (SAPT) showed that these dispersion dominated interactions are modulated by electrostatics. Artificial nucleobases showed a similar stacking preference for natural nucleobases and were also modulated by electrostatic interactions. A robust predictive multivariate model was developed that quantitively predicts the maximum stacking interaction between natural and a wide range of artificial nucleobases using molecular descriptors based on computed electrostatic potentials (ESPs) and the number of heavy atoms. This model should find utility in designing artificial nucleobase analogs that exhibit stacking interactions comparable to those of natural nucleobases. Further analysis of the descriptors in this model unveil the origin of superior stacking abilities of certain nucleobases, including cytosine and guanine.

Download Full-text

A Chemical Perspective to the Anti-Amyloid Action of Compounds and a Nanoparticle Based Assay for Screening Amyloid Inhibitors

10.26434/chemrxiv.7819661 ◽

2020 ◽

Author(s):

Nidhi Gour ◽

Bharti Koshti

Keyword(s):

Memory Loss ◽

Cost Effective ◽

Structural Motif ◽

Rapid Screening ◽

Stacking Interactions ◽

Aromatic Rings ◽

Amyloid Fibers ◽

Aromatic Stacking ◽

Cost Effective Technique ◽

The Brain

Aggregation of amyloid beeta 1-42 (Aβ42) peptide causes the formation of clustered deposits knows as amyloid plaques in the brain which leads to neuronal dysfunction and memory loss and associated with many neurological disorders including Alzheimer’s and Parkinson’s. Aβ42 has core structural motif with phenylalanine at the 19 and 20 positions. The diphenylalanine (FF) residue plays a crucial role in the formation of amyloid fibers and serves as model peptide for studying Aβ42 aggregation. FF self-assembles to well-ordered tubular morphology via aromatic pi-pi stackings. Our studies, suggest that the aromatic rings present in the anti-amyloidogenic compounds may interact with the pi-pi stacking interactions present in the FF. Even the compounds which do not have aromatic rings, like cyclodextrin and cucurbituril show anti-amyloid property due to the binding of aromatic ring inside the guest cavity. Hence, our studies also suggest that compounds which may have a functional moiety capable of interacting with the aromatic stacking interactions might be tested for their anti-amyloidogenic properties. Further, in this manuscript, we have proposed two novel nanoparticle based assays for the rapid screening of amyloid inhibitors. In the first assay, interaction between biotin-tagged FF peptide and the streptavidin labelled gold nanoparticles (s-AuNPs) were used. In another assay, thiol-Au interactions were used to develop an assay for detection of amyloid inhibitors. It is envisaged that the proposed analytical method will provide a simple, facile and cost effective technique for the screening of amyloid inhibitors and may be of immense practical implications to find the therapeutic remedies for the diseases associated with the protein aggregation.

Download Full-text

Crystal structures of (2E)-1-(3-bromothiophen-2-yl)-3-(2-methoxyphenyl)prop-2-en-1-one and (2E)-1-(3-bromothiophen-2-yl)-3-(3,4-dimethoxyphenyl)prop-2-en-1-one

Acta Crystallographica Section E Crystallographic Communications ◽

10.1107/s2056989015013420 ◽

2015 ◽

Vol 71 (8) ◽

pp. 965-971 ◽

Cited By ~ 4

Author(s):

Vasant S. Naik ◽

Venkataraya Shettigar ◽

Tyler S. Berglin ◽

Jillian S. Coburn ◽

Jerry P. Jasinski ◽

...

Keyword(s):

Hydrogen Bonds ◽

Crystal Structures ◽

Intermolecular Interactions ◽

Intramolecular Interaction ◽

Intramolecular Interactions ◽

Inversion Symmetry ◽

Stacking Interactions ◽

Asymmetric Unit ◽

Space Group ◽

Independent Molecules

In the molecules of the title compounds, (2E)-1-(3-bromo-thiophen-2-yl)-3-(2-methoxyphenyl)prop-2-en-1-one, C14H11BrO2S, (I), which crystallizes in the space groupP-1 with four independent molecules in the asymmetric unit (Z′ = 8), and (2E)-1-(3-bromothiophen-2-yl)-3-(3,4-dimethoxyphenyl)prop-2-en-1-one, C15H13BrO3S, (II), which crystallizes withZ′ = 8 in the space groupI2/a, the non-H atoms are nearly coplanar. The molecules of (I) pack with inversion symmetry stacked diagonally along thea-axis direction. Weak C—H...Br intramolecular interactions in each of the four molecules in the asymmetric unit are observed. In (II), weak C—H...O, bifurcated three-center intermolecular interactions forming dimers along with weak C—H...π and π–π stacking interactions are observed, linking the molecules into sheets along [001]. A weak C—H...Br intramolecular interaction is also present. There are no classical hydrogen bonds present in either structure.

Download Full-text

O lúdico como contribuição para a aprendizagem

Revista Brasileira de Educação e Saúde ◽

10.18378/rebes.v6i1.4123 ◽

2016 ◽

Vol 6 (1) ◽

pp. 42

Author(s):

Givoneide Barbosa de Sousa ◽

José Ozildo dos Santos

Keyword(s):

Teacher Education ◽

Learning Process ◽

Theoretical Study ◽

Educational Environment ◽

Different Types ◽

The Subject

Este artigo aborda como o lúdico, por meio da formação do educador, interfere no processo de aprendizagem. Trata-se de um estudo teórico a respeito das estratégias voltadas para o conceito histórico de criança, concepção sobre o cuidar, fundamentos sobre as instituições escolares. Nele também aborda-se as atividades, nas quais são observados conteúdos que envolvessem as brincadeiras lúdicas e que possibilitam as crianças aprendem com mais facilidade brincando. Demonstrou-se que a ludicidade ajuda no aprimoramento da educação, pode ser crítica e criativa. De acordo com a demanda e realidade da sala de aula, cabe ao educador desenvolve possibilidades que permitam aos educandos possam experimentar situações que interfiram de forma positiva no ensino, tornando-o produtivo. A utilização de jogos e brincadeiras no meio educacional propicia as crianças o aprimoramento de diversos conhecimentos de forma lúdica. Aos educadores, estes além de estarem motivados também com o lúdico, é preciso um conhecimento mais elaborado acerca do tema, para poder intervir nas brincadeiras das crianças. Contudo, faz-se necessário auxiliar a criança, de maneira sutil, para que brinque com diversos tipos de brinquedos.The playful as a contribution to learningAbstract: This article discusses how the playful, through teacher education, interferes with the learning process. This is a theoretical study on the strategies for the historical concept of child conception of care, fundamentals of the schools. It also covers up the activities in which contents are observed involving the playful banter and enable children learn more easily playing. It was demonstrated that playfulness helps in the improvement of education, can be critical and creative. According to the demand and reality of the classroom, it is the educator develops possibilities that allow students to experience situations that interfere positively in the school, making it productive. The use of games and activities in the educational environment providing children the improvement of diverse knowledge in a playful manner. Educators, these besides being also motivated by the playful, we need a more elaborate knowledge on the subject, to be able to intervene in the games of children. However, it is necessary to help the child, subtly, to play with different types of toys.

Download Full-text

Structural characterization and theoretical calculations of the monohydrate of the 1:2 cocrystal salt formed from acriflavine and 3,5-dinitrobenzoic acid

Acta Crystallographica Section C Structural Chemistry ◽

10.1107/s2053229621000681 ◽

2021 ◽

Vol 77 (2) ◽

pp. 116-122

Author(s):

Maria Marczak ◽

Kinga Biereg ◽

Beata Zadykowicz ◽

Artur Sikorski

Keyword(s):

Hydrogen Bonds ◽

Water Molecule ◽

Intermolecular Interactions ◽

Structural Characterization ◽

Theoretical Calculations ◽

Lattice Energy ◽

Monoclinic Space Group ◽

X Ray Diffraction ◽

Porous Organic Framework ◽

Organic Framework

The synthesis and structural characterization of the monohydrated 1:2 cocrystal salt of acriflavine with 3,5-dinitrobenzoic acid [systematic name: 3,6-diamino-10-methylacridin-10-ium 3,5-dinitrobenzoate–3,5-dinitrobenzoic acid–water (1/1/1), C14H14N3 +·C7H3N2O6 −·C7H4N2O6·H2O] are reported. Single-crystal X-ray diffraction measurements show that the title solvated monohydrate salt crystalizes in the monoclinic space group P21 with one acriflavine cation, a 3,5-dinitrobenzoate anion, a 3,5-dinitrobenzoic acid molecule and a water molecule in the asymmetric unit. The neutral and anionic forms of 3,5-dinitrobenzoic acid are linked via O—H...O hydrogen bonds to form a monoanionic dimer. Neighbouring monoanionic dimers of 3,5-dinitrobenzoic acid are linked by nitro–nitro N—O...N and nitro–acid N—O...π intermolecular interactions to produce a porous organic framework. The acriflavine cations are linked with carboxylic acid molecules directly via amine–carboxy N—H...O, amine–nitro N—H...O and acriflavine–carboxy C—H...O hydrogen bonds, and carboxy–acriflavine C—O...π, nitro–acriflavine N—O...π and acriflavine–nitro π–π interactions, or through the water molecule by amino–water N—H...O and water–carboxy O—H...O hydrogen bonds, and are located in the voids of the porous organic framework. The intermolecular interactions were studied using the CrystalExplorer program to provide information about the interaction energies and the dispersion, electrostatic, polarization and repulsion contributions to the lattice energy.

Download Full-text

The lines-of-force landscape of interactions between molecules in crystals; cohesive versus tolerant and `collateral damage' contact

Acta Crystallographica Section B Structural Science ◽

10.1107/s0108768110008074 ◽

2010 ◽

Vol 66 (3) ◽

pp. 396-406 ◽

Cited By ~ 40

Author(s):

Angelo Gavezzotti

Keyword(s):

Crystal Structures ◽

Structure Prediction ◽

Crystal Packing ◽

Minimum Energy ◽

Lattice Energy ◽

Interaction Force ◽

Coordination Shell ◽

Geometrical Parameters ◽

Interaction Energies ◽

Organic Salts

A quantitative analysis of relative stabilities in organic crystal structures is possible by means of reliable calculations of interaction energies between pairs of molecules. Such calculations have been performed by the PIXEL method for 1108 non-ionic and 98 ionic organic crystals, yielding total energies and separate Coulombic polarization and dispersive contributions. A classification of molecule–molecule interactions emerges based on pair energy and its first derivative, the interaction force, which is estimated here explicitly along an approximate stretching path. When molecular separation is not at the minimum-energy value, as frequently happens, forces may be attractive or repulsive. This information provides a fine structural fingerprint and may be relevant to the mechanical properties of materials. The calculations show that the first coordination shell includes destabilizing contacts in ∼ 9% of crystal structures for compounds with highly polar chemical groups (e.g. CN, NO2, SO2). Calculations also show many pair contacts with weakly stabilizing (neutral) energies; such fine modulation is presumably what makes crystal structure prediction so difficult. Ionic organic salts or zwitterions, including small peptides, show a Madelung-mode pairing of opposite ions where the total lattice energy is stabilized from sums of strongly repulsive and strongly attractive interactions. No obvious relationships between atom–atom distances and interaction energies emerge, so analyses of crystal packing in terms of geometrical parameters alone should be conducted with due care.

Download Full-text