Halogen Bond-Assisted Supramolecular Dimerization of Pyridinium-Fused 1,2,4-Selenadiazoles via Four-Center Se2N2 Chalcogen Bonding.

The synthesis and structural characterization of α-haloalkyl-substituted pyridinium-fused 1,2,4-selenadiazoles with various counterions is reported herein, demonstrating a strategy for directed supramolecular dimerization in the solid state. The compounds were obtained through a recently discovered 1,3-dipolar cycloaddition reaction between nitriles and bifunctional 2-pyridylselenyl reagents, and their structures were confirmed by the X-ray crystallography. α-Haloalkyl-substituted pyridinium-fused 1,2,4-selenadiazoles exclusively formed supramolecular dimers via four-center Se···N chalcogen bonding, supported by additional halogen bonding involving α-haloalkyl substituents. The introduction of halogens at the α-position of the substituent R in the selenadiazole core proved effective in promoting supramolecular dimerization, which was unaffected by variation of counterions. Additionally, the impact of cocrystallization with a classical halogen bond donor C6F3I3 on the supramolecular assembly was investigated. Non-covalent interactions were studied using density functional theory calculations and topological analysis of the electron density distribution, which indicated that all ChB, XB and HB interactions are purely non-covalent and attractive in nature. This study underscores the potential of halogen and chalcogen bonding in directing the self-assembly of functional supramolecular materials employing 1,2,4-selenadiazoles derived from recently discovered cycloaddition between nitriles and bifunctional 2-pyridylselenyl reagents.

Facile Access to 2-Selenoxo-1,2,3,4-tetrahydro-4-quinazolinone Scaffolds and Corresponding Diselenides via Cyclization between Methyl Anthranilate and Isoselenocyanates: Synthesis and Structural Features.

A practical method for the synthesis of 2-selenoxo-1,2,3,4-tetrahydro-4-quinazolinone was reported. The latter compounds were found to undergo facile oxidation with H2O2 into corresponding diselenides. Novel organoselenium derivatives were characterized by the 1H, 77Se, and 13C NMR spectroscopies, high-resolution electrospray ionization mass spectrometry, IR, elemental analyses (C, H, N), and X-ray diffraction analysis for several of them. Novel heterocycles exhibited multiple remarkable chalcogen bonding (ChB) interactions in the solid state, which were studied theoretically.

Synthesis and Biological Activity of Unsymmetrical Monoterpenylhetaryl Disulfides.

New unsymmetrical monoterpenylhetaryl disulfides based on heterocyclic disulfides and monoterpene thiols were synthesized for the first time in 48-88% yields. Hydrolysis of disulfides with fragments of methyl esters of 2-mercaptonicotinic acid was carried out in 73-95% yields. The obtained compounds were evaluated for antioxidant, antibacterial, antifungal activity, cytotoxicity and mutagenicity.

Towards Anion Recognition and Precipitation with Water-Soluble 1,2,4-Selenodiazolium Salts: Combined Structural and Theoretical Study.

The synthesis and structural characterization of a series of supramolecular complexes of bicyclic cationic pyridine-fused 1,2,4-selenodiazoles with various anions is reported. The binding of trifluoroacetate, tetrachloroaurate, tetraphenylborate, perrhenate, and pertechnetate anions in the solid state is regarded. All the anions interact with selenodiazolium cations exclusively via a pair of "chelating" Se⋯O and H⋯O non-covalent interactions, which make them an attractive, novel, non-classical supramolecular recognition unit or a synthon. Trifluoroacetate salts were conveniently generated via novel oxidation reaction of 2,2'-dipyridyl diselenide with bis(trifluoroacetoxy)iodo)benzene in the presence of corresponding nitriles. Isolation and structural characterization of transient 2-pyridylselenyl trifluoroacetate was achieved. X-ray analysis has demonstrated that the latter forms dimers in the solid state featuring very short and strong Se⋯O and Se⋯N ChB contacts. 1,2,4-Selenodiazolium trifluoroacetates or halides show good solubility in water. In contrast, (AuCl4)-, (ReO4)-, or (TcO4)- derivatives immediately precipitate from aqueous solutions. Structural features of these supramolecular complexes in the solid state are discussed. The nature and energies of the non-covalent interactions in novel assembles were studied by the theoretical methods. To the best of our knowledge, this is the first study that regards perrhenate and pertechnetate as acceptors in ChB interactions. The results presented here will be useful for further developments in anion recognition and precipitation involving cationic 1,2,4-selenodiazoles.

Exploring Supramolecular Assembly Space of Cationic 1,2,4-Selenodiazoles: Effect of the Substituent at the Carbon Atom and Anions.

Chalcogenodiazoles have been intensively studied in recent years in the context of their supramolecular chemistry. In contrast, the newly discovered cationic 1,2,4-selenodiazole supramolecular building blocks, which can be obtained via coupling between 2-pyridylselenyl halides and nitriles, are virtually unexplored. A significant advantage of the latter is their facile structural tunability via the variation of nitriles, which could allow a fine tuning of their self-assembly in the solid state. Here, we explore the influence of the substituent (which derives from the nitrile) and counterions on the supramolecular assembly of cationic 1,2,4-selenodiazoles via chalcogen bonding.

Correction: Novel cationic 1,2,4-selenadiazoles: synthesis via addition of 2-pyridylselenyl halides to unactivated nitriles, structures and four-center Se⋯N contacts.

Correction for 'Novel cationic 1,2,4-selenadiazoles: synthesis via addition of 2-pyridylselenyl halides to unactivated nitriles, structures and four-center Se⋯N contacts' by Victor N. Khrustalev et al., Dalton Trans., 2021, 50, 10689-10691, DOI: 10.1039/D1DT01322J.

Novel cationic 1,2,4-selenadiazoles: synthesis via addition of 2-pyridylselenyl halides to unactivated nitriles, structures and four-center SeN contacts.

2-Pyridylselenyl halides undergo facile coupling with a triple CN bond of unactivated nitriles. Unprecedented heterocyclization allowed the preparation of a novel class of cationic 1,2,4-selenadiazoles in remarkably high yields. Cationic 1,2,4-selenadiazoles form supramolecular dimers in the crystal via SeN chalcogen bonding, which was studied theoretically.

Towards multi-target antidiabetic agents: Discovery of biphenyl-benzimidazole conjugates as AMPK activators.

Type 2 diabetes mellitus is a complex metabolic disorder requiring polypharmacology approaches for effective treatment. Combinatorial library of fifteen new tricyclic benzimidazole derivatives have been designed and synthesized to combine fragments commonly found in allosteric AMPK activators and AT1 receptor antagonists. It was found that 2'-cyanobiphenyl serves as the pharmacophore of AMPK-activating activity, which also increases with the expansion of the external hydrogenated cycle. Also, pronounced antiplatelet activity is characteristic of the studied compounds. One of derivatives was identified as a potent inhibitor of the formation of advanced protein glycation end-products with reactive dicarbonyl scavenging activity. Two submicromolar AMPK activators 2b and 3b prevents inflammatory activation of murine macrophages. Along with good water solubility and synthetic availability, these results render biphenyl derivatives of fused benzimidazoles as a valuable starting point for the development of AMPK activators with multi-target antidiabetic activity.

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds.

The unexpectedly uncatalyzed reaction between 2-amino-4-arylimidazoles, aromatic aldehydes and Meldrum's acid has selectively led to the corresponding Knoevenagel-Michael adducts containing a free amino group in the imidazole fragment. The adducts derived from Meldrum's acid have been smoothly converted into 1,7-diaryl-3-amino-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-ones and 3-(2-amino-4-aryl-1H-imidazol-5-yl)-3-arylpropanoic acids. The interaction of 2-amino-4-arylimidazoles with aromatic aldehydes or isatins and acyclic methylene active compounds has led to the formation of pyrrolo[1,2-c]imidazole-6-carbonitriles, pyrrolo[1,2-с]imidazole-6-carboxylates and spiro[indoline-3,7'-pyrrolo[1,2-c]imidazoles], which can be considered as the analogues of both 3,3'-spirooxindole and 2-aminoimidazole marine sponge alkaloids.

Bromination of bis-(pyridin-2-yl) diselenide in methyl-ene chloride: the reaction mechanism and crystal structures of 1H-pyridine-2-selenenyl dibromide and its cyclo-adduct with cyclo-pentene (3aSR,9aRS)-2,3,3a,9a-tetra-hydro-1H-cyclo-penta-[4,5][1,3]selenazolo[3,2-a]pyridinium bromide.

1H-Pyridine-2-selenenyl dibromide, C5H5NSeBr2, 1, is a product of the bromination of bis-(pyridin-2-yl) diselenide in methyl-ene chloride recrystallization from methanol. Compound 1 is essentially zwitterionic: the negative charge resides on the SeBr2 moiety and the positive charge is delocalized over the pyridinium fragment. The C-Se distance of 1.927 (3) Šis typical of a single bond. The virtually linear Br-Se-Br moiety of 178.428 (15)° has symmetrical geometry, with Se-Br bonds of 2.5761 (4) and 2.5920 (4) Å, and is twisted by 63.79 (8)° relative to the pyridinium plane. The Se atom forms an inter-molecular Se⋯Br contact of 3.4326 (4) Å, adopting a distorted square-planar coordination. In the crystal, mol-ecules of 1 are linked by inter-molecular N-H⋯Br and C-H⋯Br hydrogen bonds, as well as by non-covalent Se⋯Br inter-actions, into a three-dimensional framework. (3aSR,(9aRS)-2,3,3a,9a-Tetra-hydro-1H-cyclo-penta[4,5][1,3]selenazolo[3,2-a]pyridinium-9 bromide, C10H12NSe+·Br-, 2, is a product of the cyclo-addition reaction of 1 with cyclo-pentene. Compound 2 is a salt containing a selenazolopyridinium cation and a bromide anion. Both five-membered rings of the cation adopt envelope conformations. The dihedral angle between the basal planes of these rings is 62.45 (11)°. The Se atom of the cation forms two additional non-covalent inter-actions with the bromide anions at distances of 3.2715 (4) and 3.5683 (3) Å, attaining a distorted square-planar coordination. In the crystal, the cations and anions of 2 form centrosymmetric dimers by non-covalent Se⋯Br inter-actions. The dimers are linked by weak C-H⋯Br hydrogen bonds into double layers parallel to (001).

Synthesis and biological evaluation of 3-substituted 2-oxindole derivatives as new glycogen synthase kinase 3ß inhibitors.

Glycogen synthase kinase 3ß (GSK-3ß) is a widely investigated molecular target for numerous diseases including Alzheimer's disease, cancer, and diabetes mellitus. Inhibition of GSK-3ß activity has become an attractive approach for treatment of diabetes and cancer. We report the discovery of novel GSK-3ß inhibitors of 3-arylidene-2-oxindole scaffold with promising activity. The most potent compound 3a inhibits GSK-3ß with IC50 4.19 nM. In a cell-based assay 3a shows no significant leucocyte toxicity at 10 µM and is moderately cytotoxic against A549 cells. Compound 3a demonstrated high antidiabetic efficacy in obese streptozotocin-treated rats improving glucose tolerance at a dose of 50 mg/kg body weight thus representing an interesting lead for further optimization.

The synthesis and crystal structure of 2-(chloro-selan-yl)pyridine 1-oxide: the first monomeric organoselenenyl chloride stabilized by an intra-molecular secondary Se⋯O inter-action.

The title compound, C5H4ClNOSe, is the product of the reaction of sulfuryl chloride and 2-selanyl-1-pyridine 1-oxide in di-chloro-methane. The mol-ecule has an almost planar geometry (r.m.s. deviation = 0.012 Å), and its mol-ecular structure is stabilized by an intra-molecular secondary Se⋯O inter-action of 2.353 (3) Å, closing a four-membered N-C-Se⋯O ring. The title compound represents the first monomeric organoselenenyl chloride stabilized intra-molecularly by an inter-action of this type. The non-valent attractive Se⋯O inter-action results in a substantial distortion of the geometry of the ipso-carbon atom. The endo-cyclic N-C-Se [102.1 (3)°] and exo-cyclic C-C-Se [136.9 (3)°] bond angles deviate significantly from the ideal value of 120° for an sp2-hybridized carbon atom, the former bond angle being much smaller than the latter. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds, forming zigzag chains propagating along [010]. The chains, which stack along the a-axis direction, are linked by offset π-π inter-actions [inter-centroid distance = 3.960 (3) Å], forming corrugated sheets parallel to the ab plane.

Crystal structure of rac-(3aR*,9aS*)-4,4,4-tri-chloro-1,2,3,3a,4,9a-hexa-hydro-4λ(5),9λ(4)-cyclo-penta-[4,5][1,3]tellurazolo[3,2-a]pyridine.

The title compound, C10H12Cl3NTe, crystallizes with two crystallographically independent mol-ecules (A and B) in the asymmetric unit. In each case, the coordination around the Te atom is distorted square-pyramidal, with the equatorial plane composed of the three Cl atoms and the C atom of the pyridinium ring. The Te atom is displaced from the mean-square plane by 0.1926 (7) and 0.1981 (8) Å, in mol-ecules A and B, respectivly, away from the apical C atom. The bond lengths from the Te atom to the two Cl atoms arranged trans to each other [2.5009 (7)/2.5145 (7) and 2.5184 (7)/2.5220 (8) Šin mol-ecules A and B, respectivly] are substan-ti-ally shorter than the third Te-Cl distance [2.8786 (7) and 2.8763 (7) Šin mol-ecules A and B, respectivly]. The 1,3-tellurazole ring is almost planar (r.m.s. deviations of 0.042 and 0.045 Šin mol-ecules A and B, respectivly). The cyclopentane rings in both molecules A and B adopt envelope conformations with the carbon atom opposed to the (Te)C-C(N) bond as the flap. In the crystal, mol-ecules form centrosymmetric 2 + 2 associates via Te⋯Cl inter-actions [3.3993 (7) and 3.2030 (7) Å]. As a result of these secondary inter-actions, the Te atom attains a strongly distorted 5 + 1 octa-hedral environment. Further, the 2 + 2 associates are bound by weak C-H⋯Cl hydrogen bonds into a three-dimensional framework.

Dichloridobis(pyridine-2-seleno-lato-κ(2) N,Se)tin(IV).

The title compound, [SnCl2(C5H4NSe)2], is the product of a reaction of 2,2'-dipyridyl diselenide with tin tetra-chloride. The mol-ecule is located about a twofold rotation axis. The coordination environment of the Sn(IV) atom is a distorted octa-hedron, with two bidentate 2-pyridine-seleno-late ligands inclined to each other at an angle of 83.96 (7)°. The two Sn-Cl and two Sn-N bonds are in cis configurations, while the two Sn-Se bonds of 2.5917 (3) Šare in a trans configuration, with an Se-Sn-Se angle of 157.988 (15)°. In the crystal, π-π inter-actions between the pyridine rings [centroid-to-centroid distance of 3.758 (3) Å] and weak inter-molecular C-H⋯Cl hydrogen bonds link the mol-ecules into chains along the c axis.

3-(4-Meth-oxy-phen-yl)-1,3-selenazolo[2,3-b][1,3]benzo-thia-zol-4-ium hydrogen sulfate.

The title compound, C16H12NOSSe(+)·HSO4 (-), was obtained from a mixture of 3-(4-meth-oxy-phen-yl)[1,3]selenazolo[2,3-b][1,3]benzo-thia-zol-4-ium chloride and potassium hydrogen sulfate. In the cation, the benzene ring is twisted by 71.62 (7)° from the tricycle mean plane. In the crystal, O-H⋯O hydrogen bonds link the anions into chains along [100]. The anions in adjacent chains are linked via weak C-H⋯O hydrogen bonds. The crystal packing exhibits short inter-molecular contacts between the chalcogen unit and the O atoms: Se⋯O(anion) 2.713 (3), Se⋯O(cation) 2.987 (3) and S⋯O(anion) 2.958 (3) Å.

The synthesis of low molecular weight pyrrolo[2,3-c]pyridine-7-one scaffold.

A facile method for the synthesis of substituted pyrrolo[2,3-c]pyridine-7-ones is developed that applies an acid-promoted intramolecular cyclization of 2-pyrrolecarboxylic acid amidoacetals as key step. The synthesis is easily scaled up to 1.5 mol quantity with no yield decrease. The alkylation/arylation reaction of the pyrrolo[2,3-c]pyridine-7-ones proceeds regioselectively giving N6-substituted derivatives.

Dichloridobis(pyridine-2-thiol-ato-κ²N,S)tin(IV): a new polymorph.

The title compound, [SnCl2(C5H4NS)2], is the product of reaction of 2,2'-dipyridyl disulfide with tin tetra-chloride. The Sn(IV) atom adopts a distorted octa-hedral geometry, with the two bidentate pyridine-2-thiol-ate ligands forming two planar four-membered chelate rings. The two Sn-Cl, two Sn-N and two Sn-S bonds are in cis, cis and trans configurations, respectively. The crystal grown from acetonitrile represents a new monoclinic polymorph in space group C2/c with the mol-ecule having twofold rotational symmetry, the Sn(IV) atom lying on the twofold axis. The mol-ecular structure of the monoclinic polymorph is very close to that of the triclinic polymorph studied previously in space group P-1, the mol-ecule occupying a general position [Masaki & Matsunami (1976 ▶). Bull. Chem. Soc. Jpn, 49, 3274-3279; Masaki et al. (1978 ▶). Bull. Chem. Soc. Jpn, 51, 3298-3301]. Apparently, the formation of the two polymorphs is determined by the different systems of inter-molecular inter-actions. In the crystal of the monoclinic polymorph, mol-ecules are bound into ribbons along the c axis by C-H⋯Cl hydrogen bonds, whereas in the crystal of the triclinic polymorph, mol-ecules form chains along the a axis by attractive S⋯S inter-actions. The crystal studied was a pseudo-merohedral twin; the refined BASF value is 0.221 (1).

[Bis(pyridin-2-yl) selenide-κ(2)N,N']tetra-chloridotin(IV).

The title compound, [SnCl(4)(C(10)H(8)N(2)Se)], was obtained by the reaction of 2,2'-dipyridyl diselenide with tin tetra-chloride. The Sn(IV) ion is coordinated by two N atoms [Sn-N = 2.266 (2) and 2.274 (2) Å] from the bis-(2-pyrid-yl)selenide ligand and four chloride anions [Sn-Cl = 2.3717 (6)-2.3939 (6) Å] in a distorted octa-hedral geometry. The central six-membered chelate ring has a boat conformation with the Se and Sn atoms deviating by 0.692 (3) and 0.855 (3) Å, respectively, from the mean plane through the remaining four ring atoms. The pyridine rings are inclined to each other by a dihedral angle of 49.62 (8)°. The crystal packing exhibits short inter-molecular Se⋯Cl contacts [3.5417 (7) and 3.5648 (7) Å], weak C-H⋯Cl hydrogen bonds and π-π stacking inter-actions between the pyridine rings with a centroid-centroid distance of 3.683 (3) Å.

1-Methyl-2,3-dihydro-1H-benzimidazole-2-selone.

The title compound C(8)H(8)N(2)Se, is the product of the reaction of 2-chloro-1-methyl-benzimidazole with sodium hydro-selenide. The mol-ecule is almost planar (r.m.s. deviation = 0.041 Å) owing to the presence of the long chain of conjugated bonds (Se=C-NMe-C=C-C=C-C=C-NH). The C=Se bond length [1.838 (2) Å] corresponds well to those found in the close analogs and indicates its pronounced double-bond character. In the crystal, mol-ecules form helicoidal chains along the b axis by means of N-H⋯Se hydrogen bonds.

(7aR*,12bS*)-8,12b-Dihydro-7aH-indeno-[1',2':5,6][1,4]selenazino[2,3,4-ij]quinolin-13-ium hydrogen sulfate.

In the title compound, C(18)H(14)NSe(+)·HSO(4) (-), the cyclo-pentene ring in the cation has an envelope conformation while the central six-membered 1,4-selenazine ring adopts a sofa conformation. The dihedral angle between the planes of the terminal benzene rings is 68.08 (11)°. In the crystal, the anions form chains along the c axis through O-H⋯O hydrogen bonds. Weak C-H⋯O and C-H⋯π hydrogen bonds, as well as attractive Se⋯Se [3.5608 (8) Å] inter-actions, further consolidate the crystal structure.