RESUMEN

Crystal engineering of multi-component molecular crystals, cocrystals, is a subject of growing interest, thanks in part to the potential utility of pharmaceutical cocrystals as drug substances with improved properties. Whereas molecular cocrystals (MCCs) are quite well studied from a design perspective, ionic cocrystals (ICCs) remain relatively underexplored despite there being several recently FDA-approved drug products based upon ICCs. Successful cocrystal design strategies typically depend on strong and directional noncovalent interactions between coformers, as exemplified by hydrogen bonds. Understanding of the hierarchy of such interactions is key to successful outcomes in cocrystal design. We herein address the crystal engineering of ICCs comprising azole functional groups, particularly imidazoles and triazoles, which are commonly encountered in biologically active molecules. Specifically, azoles were studied for their propensity to serve as coformers with strong organic (trifluoroacetic acid and p-toluenesulfonic acid) and inorganic (hydrochloric acid, hydrobromic acid and nitric acid) acids to gain insight into the hierarchy of NH+···N (azolium-azole) supramolecular heterosynthons. Accordingly, we combined data mining of the Cambridge Structural Database (CSD) with the structural characterization of 16 new ICCs (11 imidazoles, 4 triazoles, one imidazole-triazole). Analysis of the new ICCs and 66 relevant hits archived in the CSD revealed that supramolecular synthons between identical azole rings (A+B-A) are much more commonly encountered, 71, than supramolecular synthons between different azole rings (A+B-C), 11. The average NH+···N distance found in the new ICCs reported herein is 2.697(3) Å and binding energy calculations suggested that hydrogen bond strengths range from 31-46 kJ mol-1. The azolium-triazole ICC (A+B-C) was obtained via mechanochemistry and differed from the other ICCs studied as there was no NH+···N hydrogen bonding. That the CNC angles in imidazoles and 1,2,4-triazoles are sensitive to protonation, the cationic forms having larger (approximately 4.4 degrees) values than comparable neutral rings, was used as a parameter to distinguish between protonated and neutral azole rings. Our results indicate that ICCs based upon azolium-azole supramolecular heterosynthons are viable targets, which has implications for the development of new azole drug substances with improved properties.

RESUMEN

We describe a series of new chalcogen-bonded cocrystals featuring 1,2-bis(selenocyanatomethyl)benzene (DSN) and 1,2,4,5-tetrakis(selenocyanatomethyl)-benzene (TSN) as the donor moieties and a variety of Lewis bases such as onium halides, N-oxides, and pyridine-containing heterocycles as the acceptors. Single-crystal X-ray diffraction demonstrates that, in every case, the selenocyanates consistently interact with the acceptor molecules through strong and directional Se···X chalcogen-bonds (ChBs) (X = halides, oxygen, and nitrogen). 77Se solid-state nuclear magnetic resonance spectroscopy was applied to measure selenium chemical shift tensor magnitudes and to explore potential correlations between these tensor elements and the local ChB geometry. In every case, the isotropic 77Se chemical shift decreases, and the chemical shift tensor span increases upon cocrystallization of DSN with the various ChB acceptors. This work contributes to a growing body of knowledge concerning the predictability and robustness of chalcogen bonds in crystal engineering as well as the NMR response to the establishment of chalcogen bonds. In particular, among the systems studied here, highly linear chalcogen bonds are formed exclusively at the stronger σ-hole of each and every selenium atom regardless of the size, charge, or denticity of the electron donor moiety.

RESUMEN

We report a multifaceted experimental and computational study of three self-complementary chalcogen-bond donors as well as a series of seven chalcogen bonded cocrystals. Bis(selenocyanatomethyl)benzene derivatives were cocrystallized with various halide salts (Bu4NCl, Bu4NBr, Bu4NI) and nitrogen-containing Lewis bases (4,4'-bipyridine and 1,2-di(4-pyridyl)ethylene). Three new single-crystal X-ray structures are reported. 77Se solid-state nuclear magnetic resonance spectroscopic study of a series of cocrystals establishes correlations between the NMR parameters of selenium and the local ChB geometry. For example, the 77Se isotropic chemical shift generally decreases on cocrystal formation. Diagnostic 13C chemical shifts are also described. In addition, all the chalcogen bonded cocrystals and pure tectons are investigated by Raman and IR spectroscopy techniques. Characteristic red shifts of the NC-Se stretching band upon cocrystal formation on the order of 10 to 20 cm-1 are observed, which provides a distinct signature of the chalcogen bond involving selenocyanates. The 125Te chemical shift tensor and X-ray structure of chalcogen-bonded tellurocyanatomethylbenzene are also reported. Insights into the connection between the electronic structure of the chalcogen bond and the experimentally measured 77Se chemical shift tensors are afforded through a natural localized molecular orbital density functional theory analysis. For the systems studied here, the lack of a very strong a correlation between experimental and DFT-computed 77Se chemical shift tensors leads to the conclusion that many structural features likely influence their ultimate values; however, computations on model systems reveal that the ChB alone produces consistent and predictable effects (e.g., the chalcogen chemical shift decreases as the chalcogen bond is shortened).

RESUMEN

Group 16 chalcogens potentially provide Lewis-acidic σ-holes, which are able to form attractive supramolecular interactions with electron rich partners through chalcogen bonds. Here, a multifaceted experimental and computational study of a large series of novel chalcogen-bonded cocrystals, prepared using the principles of crystal engineering, is presented. Single-crystal X-ray diffraction studies reveal that dicyanoselenadiazole and dicyanotelluradiazole derivatives work as promising supramolecular synthons with the ability to form double chalcogen bonds with a wide range of electron donors including halides and oxygen- and nitrogen-containing heterocycles. Extensive 77 Se and 125 Te solid-state nuclear magnetic resonance spectroscopic investigations of cocrystals establish correlations between the NMR parameters of selenium and tellurium and the local chalcogen bonding geometry. The relationships between the electronic environment of the chalcogen bond and the 77 Se and 125 Te chemical shift tensors were elucidated through a natural localized molecular orbital density functional theory analysis. This systematic study of chalcogen-bond-based crystal engineering lays the foundations for the preparation of the various multicomponent systems and establishes solid-state NMR protocols to detect these interactions in powdered materials.

RESUMEN

Classical examples of supramolecular recognition units or synthons are the ones formed by hydrogen bonds. Here, we report the ubiquity of a S⋅⋅⋅O chalcogen bonded synthon observed in a series of supramolecular complexes of the amyotrophic lateral sclerosis drug riluzole. Although the potential of higher chalcogens such as Se and Te to form robust and directional chalcogen bonded motifs is known, intermolecular sulfur chalcogen bonding is considered to be weak owing to the lower polarizability of S atoms. Here, the robustness and electronic nature of a S⋅⋅⋅O chalcogen bonding non-classical synthon, and the origin of its exceptional directionality have been explored. Bond orders of the drug-coformer chalcogen bonding are found to be as high as one third of a single bond, and they are largely ionic in nature. The contribution of the S⋅⋅⋅O chalcogen bonded motifs to the lattice energies of a series of crystals from the Cambridge Structural Database has been analyzed, showing they can be indeed significant, especially in molecules devoid of strong hydrogen bond donor groups.

RESUMEN

Modeling indicates the presence of a region of low electronic density (a "σ-hole") on group 14 elements, and this offers an explanation for the ability of these elements to act as electrophilic sites and to form attractive interactions with nucleophiles. While many papers have described theoretical investigations of interactions involving carbon and silicon, such investigations of the heavier group 14 elements are relatively scarce. The purpose of this review is to rectify, to some extent, the current lack of experimental data on interactions formed by germanium and tin with nucleophiles. A survey of crystal structures in the Cambridge Structural Database is reported. This survey reveals that close contacts between Ge or Sn and lone-pair-possessing atoms are quite common, they can be either intra- or intermolecular contacts, and they are usually oriented along the extension of the covalent bond formed by the tetrel with the most electron-withdrawing substituent. Several examples are discussed in which germanium and tin atoms bear four carbon residues or in which halogen, oxygen, sulfur, or nitrogen substituents replace one, two, or three of those carbon residues. These close contacts are assumed to be the result of attractive interactions between the involved atoms and afford experimental evidence of the ability of germanium and tin to act as electrophilic sites, namely tetrel bond (TB) donors. This ability can govern the conformations and the packing of organic derivatives in the solid state. TBs can therefore be considered a promising and robust tool for crystal engineering. Graphical abstract Intra- and intermolecular tetrel bonds involving organogermanium and -tin derivatives in crystalline solids.

RESUMEN

Bis(trimethylammonium) alkane diiodides dynamically encapsulate dicarboxylic acids through intermolecular hydrogen bonds between the I- anions of the hosts and the carboxylic OH groups of the guests. A selective recognition is realized when the size of the I- ⋅⋅⋅HOOC(CH2 /CF2 )n COOH⋅⋅⋅I- superanion matches the dication alkyl chain length. Dynamic recognition is also demonstrated in solution, where the presence of the size-matching organic salt boosts the acid solubility profile, thus allowing efficient mixture separation.

RESUMEN

A library of supramolecular anionic networks showing Borromean interpenetration has been prepared by self-assembly of crypt-222, several metal or ammonium halides, and five bis-homologous α,ω-diiodoperfluoroalkanes. Halogen bonding has driven the formation of these anionic networks. Borromean entanglement has been obtained starting from all the four used cations, all the three used anions, but only two of the five used diiodoperfluoroalkanes. As the change of the diiodoperfluoroalkane, the cation, or the anion has a different relative effect on the metrics and bondings of the self-assembled systems, it can be generalized that bonding, namely energetic, features play here a less influential role than metric features in determining the topology of the prepared tetra-component cocrystals. This conclusion may hold true for other multi-component systems and may function as a general heuristic principle when pursuing the preparation of multi-component systems having the same topology but different composition.

RESUMEN

Experimental observations and modeling data are reported on the solid-state structural features of crypt- 111⋅HI (1) and the three-component co-crystals that 1 forms with α,ω-diiodoperfluoroalkanes 2 a-d. X-ray analyses indicate that, in all five systems and at low temperature, the caged proton is covalently bonded to a single nitrogen atom and is involved in a network of intramolecular hydrogen bonds. In contrast, room-temperature, solid-state 15 N NMR spectroscopy suggests magnetic equivalency of the two N atoms of crypt-111 in both 1 and co-crystals of 1 with diiodoperfluoroalkanes. Computational modelling confirms that the acidic hydrogen inside the cavity preferentially sits along the internitrogen axis and is covalently bonded to one nitrogen. The computed energy barriers suggest that the hopping of the encapsulated proton between the two N atoms of the cage can occur in the halogen-bonded co-crystals of 1⋅2, but it is hardly possible in the pure H+ ⊂crypt-111 iodide 1. These different pictures of the proton position and dynamics obtained by using different techniques and conditions confirm the unique characteristics of the confined space within the cavity of crypr-111 and the distinctive features of processes occurring therein.

RESUMEN

The synthesis and self-assembly capabilities of a new halogen-bond donor ligand, 2,3,5,6-tetrafluoro-4-iodophenyl 5-(1,2-dithiolan-3-yl)pentanoate (1), are reported. The crystal structure of ligand (1) and the formation of a cocrystal with 1,2-di(4-pyridyl)ethylene, (1)·(2), both show halogen bonds involving the 4-iodotetrafluorobenzene moiety. Ligand (1), being a self-complementary unit, forms an infinite halogen-bonded chain driven by the S...I synthon, while the cocrystal (1)·(2) self-assembles into a discrete trimeric entity driven by the N...I synthon. Ligand (1) was also successfully used to functionalize the surface of gold nanoparticles, AuNP-(1). Experiments on the dispersibility profile of AuNP-(1) demonstrated the potential of halogen bonding in facilitating the dispersion of modified NPs with halogen-bond donors in pyridine.

RESUMEN

Bioactive compounds comprising secondary metabolites produced by endophytic fungi have wide applications in pharmacology and agriculture. Isolation, characterisation and evaluation of biological activities of secondary metabolites were carried out from Cochliobolus kusanoi an endophytic fungus of Nerium oleander L. The fungus was identified based on 18S rDNA sequence analysis. There are no reports available on the compounds of C.kusanoi hence, antimicrobial metabolite produced by this fungus was extracted and purified by fractionation using hexane, diethyl ether, dichloromethane, ethyl acetate and methanol. Out of all the solvent fractions, the methanol fraction exhibited better antimicrobial activity which was further purified and characterised as oosporein. Oosporein from C.kusanoi exhibited broad spectrum in vitro antimicrobial, antioxidant and cytotoxic activities. The characterisation and antioxidant activity of oosporein from C. kusanoi are reported for the first time.

Asunto(s)

Antiinfecciosos/aislamiento & purificación , Antiinfecciosos/farmacología , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Ascomicetos/química , Benzoquinonas/farmacología , Nerium/microbiología , Animales , Antiinfecciosos/química , Antineoplásicos/química , Antioxidantes/química , Benzoquinonas/química , Cricetinae , Ensayos de Selección de Medicamentos Antitumorales , Hongos/efectos de los fármacos , Humanos

RESUMEN

In the current communication, we report the synthesis, spectroscopic, crystal structure, DFT and photophysical studies of a new nicotinonitrile derivative, viz. 2-methoxy-6-(4-methoxy-phenyl)-4-p-tolyl-nicotinonitrile (2) as a potential blue light emitting material. The compound 2 was synthesized in good yield via a simple route. The acquired spectral and elemental analysis data were in consistent with the chemical structure of 2. The single crystal study further confirms its three dimensional structure, molecular shape, and nature of short contacts. Its DFT calculations reveal that compound 2 possesses a non-planar structure and its theoretical IR spectral data are found to be in accordance with experimental values. In addition, its UV-visible and fluorescence spectral measurements prove that the compound exhibits good absorption and fluorescence properties. Also, it shows positive solvatochromic effect when the solvent polarity was varied from non-polar to polar.

Asunto(s)

Luz , Luminiscencia , Modelos Moleculares , Nitrilos/química , Nitrilos/síntesis química , Teoría Cuántica , Cristalografía por Rayos X , Electricidad , Espectrometría de Masas , Conformación Molecular , Espectroscopía de Protones por Resonancia Magnética , Solventes/química , Espectrometría de Fluorescencia , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier

RESUMEN

In the title compound, C14H12ClNO4S, the dihedral angle between the chloro- and meth-oxy-substituted benzene rings is 87.40 (1)°. In the crystal, adjacent mol-ecules form inversion-related dimers through strong N-H⋯O hydrogen bonds, generating R 2 (2)(8) loops. The dimers are further connected through two C-H⋯O inter-actions that form C(11) chains and R 2 (2)(14) loops. Aromatic π-π stacking inter-actions [centroid-centroid separation = 3.8574 (1) Å] are also observed.

RESUMEN

In the title compound, C15H15NO4S, the dihedral angle between the methyl- and meth-oxy-substituted benzene rings is 88.99 (12)°. An intra-molecular C-H⋯O hydrogen bond occurs. In the crystal, adjacent mol-ecules form inversion-related dimers through strong N-H⋯O hydrogen bonds, generating R 2 (2)(8) loops. The dimers are further connected through C-H⋯O inter-actions that form C(8) chains parallel to (001). Mol-ecules are also connected through other C-H⋯O hydrogen bonds along the b axis, forming additional C(8) chains. Two aromatic π-π stacking inter-actions [centroid-centroid separations = 3.6150 (1) and 3.6837 (1) Å] generate a three-dimensional architecture.

RESUMEN

In the title compound, C15H15NO4S, the dihedral angle between the benzene rings is 88.87 (1)°. In the crystal, adjacent mol-ecules form inversion dimers through pairs of strong N-H⋯O hydrogen bonds, generating R 2 (2)(8) loops. Two C-H⋯π inter-actions and an aromatic π-π inter-action [centroid-centroid separation = 3.8191 (1) Å] are also observed.

RESUMEN

In our pursuit to develop new potential anticancer leads, we designed a combination of structural units of indole and substituted triazole; and a library of 1-{1-methyl-2-[4-phenyl-5-(propan-2-ylsulfanyl)-4H-1,2,4-triazol-3-yl]-1H-indol-3-yl}methanamine derivatives was synthesized and characterized. Cytotoxic evaluations of these molecules over a panel of three human cancer cell lines were carried out. Few molecules exhibited potent growth inhibitory action against the treated cancer cell lines at lower micro molar concentration. An in vitro assay investigation of these active compounds using recombinant human SIRT1 enzyme showed that one of the compounds (IT-14) inhibited the deacetylation activity of the enzyme. The in vivo study of IT-14 exemplified its promising action by reducing the prostate weight to the body weight ratio in prostate hyperplasia animal models. A remarkable decrease in the disruption of histoarchitecture of the prostate tissues isolated from IT-14 treated animal compared to that of the positive control was observed. The molecular interactions with SIRT1 enzyme were also supported by molecular docking simulations. Hence this compound can act as a lead molecule to treat prostatic hyperplasia.

Asunto(s)

Antineoplásicos/farmacología , Inhibidores de Histona Desacetilasas/farmacología , Hiperplasia/tratamiento farmacológico , Indoles/farmacología , Sirtuina 1/antagonistas & inhibidores , Bibliotecas de Moléculas Pequeñas/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HEK293 , Inhibidores de Histona Desacetilasas/síntesis química , Inhibidores de Histona Desacetilasas/química , Humanos , Hiperplasia/inducido químicamente , Indoles/síntesis química , Indoles/química , Células K562 , Masculino , Modelos Moleculares , Estructura Molecular , Ratas , Ratas Wistar , Sirtuina 1/metabolismo , Bibliotecas de Moléculas Pequeñas/síntesis química , Bibliotecas de Moléculas Pequeñas/química , Relación Estructura-Actividad , Testosterona

RESUMEN

In the title compound, C(20)H(19)FN(2)O(2), the dihedral angle between the aromatic rings is 62.1 (1)°, and those between the pyrazole ring and the fluoro-benzene and benzoic acid rings are 52.1 (1) and 53.1 (1)°, respectively. In the crystal, mol-ecules are linked into [010] C(7) chains by O-H⋯N hydrogen bonds.

RESUMEN

In the title compound, C(27)H(22)N(2)O(4), the dihedral angles between the central benzene ring and the cyano-benzene ring and the 2H-coumarin ring system (r.m.s. deviation = 0.014 Å) are 22.95 (11) and 75.59 (8)°, respectively. Both terminal C atoms of the pendant diethyl-amino group lie to the same side of the coumarin ring system [deviations = 1.366 (2) and 1.266 (2) Å]. In the crystal, mol-ecules are linked by C-H⋯O and C-H⋯N hydrogen bonds and a C-H⋯π inter-action, generating a three-dimensional network.

RESUMEN

In the title compound, C15H13F3N2O2·H2O, the dihedral angle between the benzene and pyridine rings is 74.97 (1)°. The -CF3 group attached to the benzene ring is syn to the C=O bond in the adjacent side chain. In the crystal, mol-ecules are linked to one another through the water mol-ecules by strong N-H⋯O, O-H⋯O and O-H⋯N hydrogen bonds, forming a ladder-type network. The benzamide mol-ecules are also linked to one another through C-H⋯F inter-actions, forming C(6) chains parallel to the b-axis direction. Aromatic π-π stacking inter-actions [centroid-centroid separations = 3.7150 (1) and 3.7857 (1) Å] between adjacent pairs of pyridine and benzene rings are also observed, resulting in a three-dimensional architecture are also observed.

RESUMEN

In the title compound, C15H14O4, the dihedral angle between the benzene rings is 67.18 (8)°. The Ca-Cm-O-Ca (a = aromatic and m = methyl-ene) torsion angle is 172.6 (3)° and an intra-molecular O-H⋯O hydrogen bond generates an S(6) ring. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds into zigzag chains propagating in [001] and C-H⋯π inter-actions also occur.