Intramolecular Se Research Articles

Topochemical, Single-Crystal-to-Single-Crystal [2+2] Photocycloadditions Driven by Chalcogen-Bonding Interactions.

The face‐to‐face association of (E)‐1,2‐di(4‐pyridyl)ethylene (bpen) molecules into rectangular motifs stabilized for the first time by chalcogen bonding (ChB) interactions is shown to provide photoreactive systems leading to cyclobutane formation through single‐crystal‐to‐single‐crystal [2+2] photodimerizations. The chelating chalcogen bond donors are based on original aromatic, ortho‐substituted bis(selenocyanato)benzene derivatives 1–3, prepared from ortho‐diboronic acid bis(pinacol) ester precursors and SeO2 and malononitrile in 75–90 % yield. The very short intramolecular Se⋅⋅⋅Se distance in 1–3 (3.22–3.24 Å), a consequence of a strong intramolecular ChB interaction, expands to 3.52–3.54 Å in the chalcogen‐bonded adducts with bpen, a distance (<4 Å) well adapted to the face‐to‐face association of the bpen molecules into the reactive position toward photochemical dimerization.

Topochemical, Single‐Crystal‐to‐Single‐Crystal [2+2] Photocycloadditions Driven by Chalcogen‐Bonding Interactions

The face-to-face association of (E)-1,2-di(4-pyridyl)ethylene (bpen) molecules into rectangular motifs stabilized for the first time by chalcogen bonding (ChB) interactions is shown to provide photoreactive systems leading to cyclobutane formation through single-crystal-to-single-crystal [2+2] photodimerizations. The chelating chalcogen bond donors are based on original aromatic, ortho-substituted bis(selenocyanato)benzene derivatives 1–3, prepared from ortho-diboronic acid bis(pinacol) ester precursors and SeO2 and malononitrile in 75–90 % yield. The very short intramolecular Se⋅⋅⋅Se distance in 1–3 (3.22–3.24 Å), a consequence of a strong intramolecular ChB interaction, expands to 3.52–3.54 Å in the chalcogen-bonded adducts with bpen, a distance (<4 Å) well adapted to the face-to-face association of the bpen molecules into the reactive position toward photochemical dimerization.

Tetravalent Spiroselenurane Catalysts: Intramolecular Se···N Chalcogen Bond-Driven Catalytic Disproportionation of H2O2 to H2O and O2 and Activation of I2 and NBS.

Chalcogen-bonding interactions have recently gained considerable attention in the field of synthetic chemistry, structure, and bonding. Here, three organo-spiroselenuranes, having a Se(IV) center with a strong intramolecular Se···N chalcogen-bonded interaction, have been isolated by the oxidation of the respective bis(2-benzamide) selenides derived from an 8-aminoquinoline ligand. Further, the synthesized spiroselenuranes, when assayed for their antioxidant activity, show disproportionation of hydrogen peroxide into H2O and O2 with first-order kinetics with respect to H2O2 for the first time by any organoselenium molecules as monitored by 1H NMR spectroscopy. Electron-donating 5-methylthio-benzamide ring-substituted spiroselenurane disproportionates hydrogen peroxide at a high rate of 15.6 ± 0.4 × 103 μM min-1 with a rate constant of 8.57 ± 0.50 × 10-3 s-1, whereas 5-methoxy and unsubstituted-benzamide spiroselenuranes catalyzed the disproportionation of H2O2 at rates of 7.9 ± 0.3 × 103 and 2.9 ± 0.3 × 103 μM min-1 with rate constants of 1.16 ± 0.02 × 10-3 and 0.325 ± 0.025 × 10-3 s-1, respectively. The evolved oxygen gas from the spiroselenurane-catalyzed disproportion of H2O2 has also been confirmed by a gas chromatograph-thermal conductivity detector (GCTCD) and a portable digital polarographic dissolved O2 probe. Additionally, the synthesized spiroselenuranes exhibit thiol peroxidase antioxidant activities for the reduction of H2O2 by a benzenethiol co-reductant monitored by UV-visible spectroscopy. Next, the Se···N bonded spiroselenuranes have been explored as catalysts in synthetic oxidation iodolactonization and bromination of arenes. The synthesized spiroselenurane has activated I2 toward the iodolactonization of alkenoic acids under base-free conditions. Similarly, efficient chemo- and regioselective monobromination of various arenes with NBS catalyzed by chalcogen-bonded synthesized spiroselenuranes has been achieved. Mechanistic insight into the spiroselenuranes in oxidation reactions has been gained by 77Se NMR, mass spectrometry, UV-visible spectroscopy, single-crystal X-ray structure, and theoretical (DFT, NBO, and AIM) studies. It seems that the highly electrophilic nature of the selenium center is attributed to the presence of an intramolecular Se···N interaction and a vacant coordination site in spiroselenuranes is crucial for the activation of H2O2, I2, and NBS. The reaction of H2O2, I2, and NBS with tetravalent spiroselenurane would lead to an octahedral-Se(VI) intermediate, which is reduced back to Se(IV) due to thermodynamic instability of selenium in its highest oxidation state and the presence of a strong intramolecular N-donor atom.

Visible Light‐Mediated Functionalization of Selenocystine‐Containing Peptides

AbstractA straightforward and atom‐economic method for the functionalization of short selenocystine‐containing peptides is presented. This method is shown to be tolerant to unprotected peptides. The detailed protocol is based on the generation of a selenium radical via visible light‐initiated reaction in the presence of transition metal‐free photocatalyst. The selenium radical is further oxidized to an electrophile and trapped by N‐heterocycles. The mechanism is confirmed by NMR, HRMS, UV, EPR and cyclic voltammetry (CV) experiments and photocatalyst emission quenching studies. A visible light‐initiated reaction is employed for the synthesis of selenocysteine‐containing indole‐based macrocycles via intramolecular Se−C bond formation.magnified image

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes.

3-Aryl-1-(trifluoromethyl)prop-2-yn-1-iminium triflate salts represent a novel, highly reactive class of acetylenic iminium salts. Herein we present several reactions which are based on the electron-poor acetylenic bond and on the high electrophilicity of the CF3-substituted iminium group. These salts were found to be highly reactive dienophiles in Diels–Alder reactions with cyclopentadiene, 2,3-dimethylbutadiene and even anthracene. At higher temperature, the cycloadducts undergo an intramolecular SE(Ar) reaction leading to condensed carbocycles incorporating a 1-(trifluoromethyl)-1-(dimethylamine)indene ring system. With styrenes and some substituted styrenes, cascade reactions take place, which likely include cyclobutene and several cationic intermediates and mainly yield 2-(1-phenylvinyl)indenes. In a similar reaction cascade, a fulvene derivative was obtained with 1,4-diphenylbutadiene as the substrate.

Conformation dynamics of cyclic disulfides and selenosulfides in CXXC(U) (X=Gly, Ala) tetrapeptide redox motifs.

Thioredoxin fold proteins often contain a Cys-(Xxx)n -Cys(Sec) or CXn C(U) motif, where the active cysteine (C) or selenocysteine (U) is bridged by X residues, which vary with protein function. The effect of the X residues on the conformation space of the oxidized disulfide and selenosulfide forms of the CXXC(U) motif has been investigated using molecular dynamics (MD) and density functional theory. Multi-microsecond-length MD simulations of the CGGC, CGAC, and CAGC cyclic peptides show that CGGC rings readily exchange between several conformations over the course of the simulation, but steric interactions with the methyl group of Ala limit the conformation space available to the cyclic peptide, especially for CGAC. The potential for the motif to be reduced, as measured by the energy of the lowest unoccupied molecular orbitals, is dependent upon the ring conformation. These results suggest that control of available conformations by the bridging residues and the protein tertiary structure may be important for defining the function of the CXXC motif. Theoretical 77 Se chemical shifts of the selenosulfide moiety are dependent upon the conformation and/or intramolecular Se···O interactions with the backbone carbonyl group of the C-terminal U residue.

Intramolecular SE Ar Reactions of Phosphorus Compounds: Computational Approach to the Synthesis of π-Extended Heterocycles.

The reaction mechanism associated with the synthesis of phosphorus-based heteropolyaromatic architectures was investigated by DFT calculations at the B3LYP-D3/6-311+G(D) level of theory. The aim of this study is to provide essential information for the future development of improved polycyclic organophosphorus materials. To that end, the impact of the structure of the initial reactant and/or the intermediates structure on the mechanistic features and energetic profiles of the phosphorus cyclization process was studied. Moreover, the reactivity parameters were analyzed in detail in a conceptual DFT framework and the underlying reactivity trends were extracted. Thus, these findings provide important insights for a rational design of polycyclic phosphorus compounds.

New organoselenium compounds with intramolecular Se⋯O/ Se⋯H interactions: NMR and theoretical studies

New 1,3-bis(phenylselanylmethyl)benzene (1, 2 and 4) and butyl phenylselane derivatives (3 and 5) are synthesized and full heteronuclear NMR characterization of these compounds are reported. Interestingly, NMR spectrum of compounds 2–5 show coupling of 1H and 13C signals of groups involved in intramolecular nonbonding interactions with 77Se. The coupling constants JH-Se and JC-Se are in the range 13.6–21.6 Hz and 28–49 Hz, respectively. For compounds 4 and 5, JH-Se coupling constants of formyl proton are smaller than their respective acetal CH protons for compounds 2 and 3. However, this trend is opposite for JC-Se coupling constants, indicating that in formyl group containing compounds 4 and 5, Se⋯O interactions are present while in compounds 2 and 3 with acetal fragments, Se⋯H interactions also could be present because of steric constraints. To confirm these interactions, quantum chemical analyses were performed for 2, 4 and 5. The minimal energy conformation for these compounds present Se⋯O/Se⋯H interactions and are at lower energy in comparison to different conformers which do not show any interaction. For compounds 4 and 5, minimal energy conformation present Se⋯O interactions and for compound 2, Se⋯H is the favored conformation. These results are in accordance with the NMR data for these compounds. X-ray crystal structure of compound 1,3-bis(phenylselanylmethyl)benzene (1) was also determined during this work. In order to understand the effect of the Se⋯O/Se⋯H interactions and the position of phenylselanylmethyl groups, quantum chemical analyses were also carried out for 1,4-bis(phenylselanylmethyl)benzene derivatives (6 and 7). Interestingly, minimal energy conformers of 1,3-bis(phenylselanylmethyl)benzene derivatives 2 and 4 are more stable than their corresponding conformers of 1,4-bis-(phenylselanylmethyl)benzene derivatives 6 and 7.1,3-bis[{(2-(diethoxymethyl)phenyl)selanyl}methyl]benzene (2) with an energy barrier of 16.22 kcal/mol is more stable than corresponding 1,4-bis [{(2-(diethoxymethyl)phenyl)selanyl}methyl]benzene (7), while molecule 4 is 1.79 kcal/mol more stable than its corresponding 2'-[{1,4-phenylenebis(methylene)}bis(selanediyl)]dibenzaldehyde (6).

2-[(4-Chloro-phen-yl)selan-yl]-3,4-di-hydro-2H-benzo[h]chromene-5,6-dione: crystal structure and Hirshfeld analysis.

The title organoselenium compound, C19H13ClO3Se {systematic name: 2-[(4-chloro-phen-yl)selan-yl]-2H,3H,4H,5H,6H-naphtho-[1,2-b]pyran-5,6-dione}, has the substituted 2-pyranyl ring in a half-chair conformation with the methyl-ene-C atom bound to the methine-C atom being the flap atom. The dihedral angle between the two aromatic regions of the mol-ecule is 9.96 (9)° and indicates a step-like conformation. An intra-molecular Se⋯O inter-action of 2.8122 (13) Å is noted. In the crystal, π-π contacts between naphthyl rings [inter-centroid distance = 3.7213 (12) Å] and between naphthyl and chloro-benzene rings [inter-centroid distance = 3.7715 (13) Å], along with C-Cl⋯π(chloro-benzene) contacts, lead to supra-molecular layers parallel to the ab plane, which are connected into a three-dimensional architecture via methyl-ene-C-H⋯O(carbon-yl) inter-actions. The contributions of these and other weak contacts to the Hirshfeld surface is described.

Cinchona-Alkaloids Based Isoselenazolones: Synthesis and Their Catalytic Reactivity in Asymmetric Bromolactonization of Alkenoic Acid

A series of chiral isoselenazolones have been synthesized and characterized by multinuclear (1H, 13C, and 77Se) NMR, mass spectrometry, and single crystal X-ray crystallography. Catalytic reactivity of synthesized chiral isoselenazolones was studied in the enantioselective bromolactonization of alkenoic acids using N-bromosuccinimide as a source of bromine. A series of alkenoic acid underwent bromolactonization successfully in the presence of 10 mol% of chiral isoselenazolone catalyst and excellent yields of bromolactones were obtained with high diastereoselectivity and moderate enantioselectivity. Isoselenazolone catalyst derived from quininamine afforded bromolactones in 82–94 % yield with 1−47 % enantioselectivity while rest of the isoselenazolones derived from simple chiral (S)-phenylethyl, and (S)-naphthylethyl, quinidin, and cinchonidin-amine afforded poor enantioselectivity in the bromolactonization reaction. Furthermore, isoselenazolone having Se–N bond gave best enantioselectivity in the bromolactonization of 5-phenyl-4-pentenoic acid as compared to the isothiazolone having S–N bond. Also isoselenazolone gave best enantioselectivity than the corresponding methyl selenide and diselenide bearing the same quininamine auxiliary in the organoselenium catalyst. Crystal structure and enantioselectivity outcome in bromolactonization on similar isoselenazolone catalysts; quininamine based (intramolecular Se…N distance 3.56 A, ee 47 %); cinchonidinamine based (Se…N distances 3.80 A, ee 17 %), and 7-methyl-amide and quininamine based (Se…N distances 3.72 A, ee 28 %) suggests that intramolecular Se…N interaction could be the crucial parameter for the enantioselectivity outcome of the reaction.

Effect of a Bromo Substituent on the Glutathione Peroxidase Activity of a Pyridoxine-like Diselenide.

In search for better mimics of the glutathione peroxidase enzymes, pyridoxine-like diselenides 6 and 11, carrying a 6-bromo substituent, were prepared. Reaction of 2,6-dibromo-3-pyridinol 5 with sodium diselenide provided 6 via aromatic nucleophilic substitution of the 2-bromo substituent. LiAlH4 caused reduction of all four ester groups and returned 11 after acidic workup. The X-ray structure of 6 showed that the dipyridyl diselenide moiety was kept in an almost planar, transoid conformation. According to NBO-analysis, this was due to weak intramolecular Se···O (1.1 kcal/mol) and Se···N-interactions (2.5 kcal/mol). That the 6-bromo substituent increased the positive charge on selenium was confirmed by NPA-analysis and seen in calculated and observed (77)Se NMR-shifts. Diselenide 6 showed a more than 3-fold higher reactivity than the corresponding des-bromo compound 3a and ebselen when evaluated in the coupled reductase assay. Experiments followed for longer time (2 h) confirmed that diselenide 6 is a better GPx-catalyst than 11. On the basis of (77)Se-NMR experiments, a catalytic mechanism for diselenide 6 was proposed involving selenol, selenosulfide and seleninic acid intermediates. At low concentration (10 μM) where it showed only minimal toxicity, it could scavenge ROS produced by MNC- and PMNC-cells more efficiently than Trolox.

Crystal structure of 4-phenyl-1-{2-[(2,4,6-tri-methyl-phen-yl)selan-yl]phen-yl}-1H-1,2,3-triazole.

In the title compound, C23H21N3Se, the C-bound phenyl ring is almost coplanar with the central five-membered ring [dihedral angle = 2.84 (10)°], but the N-bound benzene ring is inclined [dihedral angle = 47.52 (10)°]. The dihedral angle between the Se-bound rings is 69.24 (9)°. An intra­molecular Se⋯N inter­action of 3.0248 (15) Å is noted. In the crystal, C—H⋯π inter­actions connect mol­ecules into double layers that stack along the a axis with no directional inter­actions between them.

Crystal structure of 1-{2-[(2-meth-oxy-phen-yl)selan-yl]phen-yl}-4-phenyl-1H-1,2,3-triazole.

In the title compound, C21H17N3OSe, the dihedral angles between the central five-membered ring and the C- and N-bound rings are 17.89 (10) and 42.35 (10)°, respectively, indicating the mol­ecule is twisted. The dihedral angle between the Se-bound rings is 85.36 (10)°. A close intra­molecular Se⋯O contact of 2.8507 (13) Å is noted. In the crystal, C—H⋯O, C—H⋯N and C—H⋯π inter­actions lead to the formation of supra­molecular layers parallel to (011); these stack with no specific inter­molecular inter­actions between them.

A mechanistic investigation of anti-elimination in (Z)-1,2-bis(arylseleno)-1-alkenes and their sulfur analogs.

The oxidation of (Z)-1,2-bis(arylseleno)-1-alkenes is known to afford alkynyl selenoxides via a unique selenoxide anti-elimination mechanism; however, to date, there have been no mechanistic studies of this reaction. During our studies of this transformation, monoselenoxides 6 and 7 were unexpectedly isolated as stable reaction intermediates. In addition, (77)Se NMR studies of the reaction mixture revealed the presence of an intramolecular Se···O interaction and the formation of alkynyl selenoxides. Meanwhile, even at higher temperatures, the reaction of a (Z)-1,2-bis(arylsulfinyl)-1-alkene, the sulfur analog of (Z)-1,2-bis(arylseleninyl)-1-alkenes, did not proceed via sulfoxide elimination but proceeded via isomerization and disproportionation. Therefore, the intramolecular Se···O interaction can be concluded to play a pivotal role in the anti-elimination reaction.

Pyridoxine-derived organoselenium compounds with glutathione peroxidase-like and chain-breaking antioxidant activity.

One of the vitamin B6 vitamers, pyridoxine, was modified to incorporate selenium in various oxidation states in place of the methyl group in position 2. Such compounds were conveniently accessed by treatment of bis-4,5-(carboethoxy)-2-iodo-3-pyridinol with disodium diselenide and LiAlH4 -reduction. After work-up, selone 7 was isolated in good yield as an air-stable crystalline material. Hydrogen bonding to the neighboring hydroxyl group, as revealed by the short intramolecular Se⋅⋅⋅H distance in the crystal structure is likely to provide extra stabilization to the compound. Computational studies showed that selone 7 is more stable than the corresponding selenol tautomer by 12.2 kcal mol(-1) . Hydrogen peroxide oxidation of the selone 7 afforded diselenide 12, and, on further oxidation, seleninic acid 13. Treatment of the seleninic acid with thiophenol provided an isolable selenosulfide 14. The glutathione peroxidase-like properties of the pyridoxine-derived compounds were assessed by using the coupled reductase method. Seleninic acid 13 was found to be twofold more active than ebselen. The chain-breaking capacity of the pyridoxine compounds were studied in a water/chlorobenzene membrane model containing linoleic acid as an oxidizable substrate and N-acetylcysteine as a thiol reducing agent. Diselenide 15 could match α-tocopherol when it comes to reactivity towards peroxyl radicals and inhibition time.

Synthesis, Characterization, and Structures of α-Substituted Selenenyl-Acetophenones

A series of α-substituted selenenyl acetophenone derivatives of the types, [PhC(OCH2CH2O)CH2Se]2, [PhC(OCH2CH2O)CH2SeR], (PhCOCH2Se)2, and [PhCOCH2SeR] have been prepared. These compounds have been characterized by elemental analyses, IR and NMR (1H, 13C, 77Se) spectroscopy. The compounds, [PhC(OCH2CH2)CH2Se]2 and (PhCOCH2Se)2 have been structurally characterized by single crystal X-ray diffraction analyses. The former shows intra-molecular Se‐ ‐ ‐O interaction, while the latter exhibits inter-molecular nonbonding Se‐ ‐ ‐O interaction. [Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text and figures.]

Crystal Structure Studies on Some of Benzamide Ring Substituted Isoselenazolones and Symmetric Diaryl Monoselenides Derived from Benzamides

In the present work, crystal structures of four benzamide ring substituted isoselenazolones and also crystal structures of thiophenamide and ortho-methoxy benzamide derived symmetric diaryl selenides studied. Diaryl selenides were obtained as unexpected product in the copper catalyzed Se-N bond forming reaction. Isos- elenazolones were synthesized by copper catalyzed reac- tion and have been reported earlier. Ebselen derivatives studied in this work were obtained from 2-halo-N-aryl- benzamides, selenium powder, potassium carbonate base in the presence of catalytic amount of copper iodide and 1, 10-phenanthroline. When 2-chloro-thiophenyl amide was subjected under identical reaction conditions, instead of Se-N bond formation, symmetrical monoselenide was obtained in excellent yield. Symmetric aryl selenides were characterized by multi-nuclear ( 1 H, 13 C and 77 Se) NMR spectroscopy, mass spectrometry and single crystal X-ray diffraction techniques. Crystal structure studies on diaryl selenides revealed interesting intramolecular Se_N/O interactions in which one nitrogen out of two and one oxygen out of two interacted with one selenium atom. Intramolecular non-bonding interaction of selenium with methoxy oxygen is observed in isoselenazolone bearing methoxy group ortho to selenium center while intermo- lecular Se_O interaction between two isoselenazolone molecules is present in fluoro group containing isos- elenazolones and therefore they exist as dimer in asym- metric unit.

Benzoselenadiazole Containing Donor–Acceptor–Donor Small Molecules: Nonbonding Interactions, Packing Patterns, and Optoelectronic Properties

Herein, we describe the fine-tuning of intermolecular Se···N interaction in benzoselenadiazole (BDS) derivatives to form head-to-head dimers in the solid state. The structures and photophysical properties of phenyl-, thiophene-, and selenophene-capped BDS (1–3, respectively) are studied here. Because of the presence of the strong intramolecular Se···N interaction, selenophene-capped BDS 3 showed syn arrangement of two capped selenophene rings, whereas two thiophene rings in 2 showed an anti orientation. Compounds 1 and 2 showed the tendency to form head-to-head dimers in the solid state through the intermolecular Se···N interactions. In contrast to compounds 1 and 2, compound 3 does not form a dimer in the solid state and, instead, shows strong intramolecular Se···N interactions. The tendency to form dimers largely depends on the nonbonding interactions and the steric effect of capped rings.

Synthesis, characterization, structures and antioxidant activity of nicotinoyl based organoselenium compounds

A series of nicotinoyl based organoselenium compounds, [2-NC5H3(3-COOH)Se]2 (1), [2-NC5H3(3-CO)Se–Se] (2), [2-NC5H3(3-CONH2)Se]2 (3), [2-NC5H3(3-CONHPh)Se]2 (4), [2-NC5H3(3-CONHpyrimidine)Se]2 (5), [2-NC5H3(3-CONHPh)SeBr] (6) and [2-NC5H3(3-CONHPh)SeI] (7) have been synthesized and characterized by absorption, IR, NMR (1H, 13C{1H}, 77Se{1H}) and mass spectrometry. The crystal structures of [2-NC5H3(3-CO)Se–Se] (2) and [2-NC5H3(3-CONHPh)Se]2 (4) have been determined. The structure of (4) revealed the existence of two intra-molecular Se⋯X (X = O and N) interactions, as a result of this, C–Se–Se–C torsion angle is unusually large (180°). The GPx mimicking activity of these compounds has been evaluated using methods based on 1H NMR spectroscopy and HPLC. Free radical scavenging ability of the compounds was examined by DPPH and deoxyribose assay. All these studies indicated that the compound (3) not only showed highest GPx activity but also has a very good free radical scavenging ability thus making it a novel structure for development of nicotine based antioxidants.

Effect of chelate ring and rigidity on Se⋯N interactions: a computational study

The intramolecular Se⋯N interactions between the selenium and the nitrogen atom in three series of o-substituted organoselenium compounds has been studied using density functional theory (DFT). The nature and the strength of these interactions and their dependence on substituents, the chelate ring size as well as the rigidity are predicted using a B3LYP/6-31G(d)/LanL2DZ method. The strength of the Se⋯N interactions is found to be dependent on the nature of Se–X (X = Cl, Br, I, SPh, CH2Ph; Ph: Phenyl) acceptor orbitals and follow the order I > Br > Cl > SPh > CH2Ph. The natural bond orbital (NBO) analysis using DFT methods points to nN→σ*Se–X electron delocalization as the key contributing factor towards Se⋯N nonbonding interactions. Both NBO and atoms in molecules (AIM) methods suggest that the intramolecular interaction in the organoselenium compounds is dominantly covalent in nature. Studies on the effect of solvent on the Se⋯N interaction show that a polar solvent stabilizes the Se⋯N interactions by shortening the Se⋯N distances.