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The preparation of a series of novel homochiral atropisomeric sulfanyl- and sulfoxide-substituted naphthyltriazoles is described. The triazolization methodology used presents a new way towards novel and highly stable 1,2,3-triazole-based atropisomers, and introduces a new and complementary synthetic pathway towards 4-sulfanyl substituted 1,2,3-triazoles. Starting from sulfanyl-substituted naphthyl ketones, enantiopure amines, and 4-nitrophenyl azide, a collection of 16 sulfanyl-substituted naphthyltriazoles were obtained via the triazolization reaction in which the homochiral diastereomers are readily isolated. Subsequent monooxidation results in the preparation of several sulfoxide-substituted naphthyltriazoles. The absolute configuration of a set of diastereomeric sulfanyl- and sulfoxide-appended naphthyltriazoles was deduced via X-ray crystallography. Furthermore, the conformational stability of the atropisomers was determined experimentally, and further confirmed and analyzed with the aid of computational DFT calculations. ispartof: ORGANIC & BIOMOLECULAR CHEMISTRY vol:19 issue:29 pages:6521-6526 ispartof: location:England status: published

The phenyl-quinoxaline moiety in the title compound is not planar. In the crystal, C—H⋯O hydrogen bonds between neighboring quinoxaline rings form chains along the a axis direction., In the title mol­ecule, C23H28N2O, the phenyl ring is inclined to the quinoxaline ring system at a dihedral angle of 20.40 (9)°. In the crystal, C—H⋯O inter­actions between neighbouring mol­ecules form chains along the a-axis direction. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H⋯H (70.6%), H⋯C/C⋯H (15.5%) and H⋯O/O⋯H (4.6%) inter­actions. The optimized structure calculated using density functional theory at the B3LYP/6–311 G(d,p) level is compared with the experimentally determined structure in the solid state. The calculated highest occupied mol­ecular orbital (HOMO) and lowest unoccupied mol­ecular orbital (LUMO) energy gap is 3.8904 eV. Part of the n-nonyl chain attached to one of the nitro­gen atoms of the quinoxaline ring system shows disorder and was refined with a double conformation with occupancies of 0.604 (11) and 0.396 (11).

We report, herein, a palladium‐catalyzed cascade comprising carbopalladation, migratory insertion of isocyanide and triple bond activation followed by a nucleophilic attack (OR‐) to construct difunctionalized acyl indoles. The process involves multiple bond formations via key palladium‐chemistry steps, to construct these bis‐heterocycles containing two privileged scaffolds (indole and oxindole) in a single operational step, along with attempts to generate enantioselectivity at a quaternary carbon center. The methodology also demonstrates a continuous‐flow process to synthesize aryl isocyanides within minutes and using them in a telescopic manner. ispartof: Advanced Synthesis & Catalysis vol:363 issue:13 pages:3220-3226 status: published

We have developed a novel palladium-catalyzed arylative dearomatization and subsequent aromatization/dearomatization/aza-Michael addition process of Ugi adducts, enabling the rapid construction of diverse zephycarinatine and zephygranditine scaffolds containing two adjacent quaternary carbon stereocenters with excellent chemoselectivity and stereoselectivity in a rapid, step-economical, and highly efficient manner. This approach shows broad substrate scope and excellent functional-group tolerance with diverse electron-rich and electron-deficient aromatic substrates. The synthetic utility of this method is further demonstrated by versatile transformations of the products.

A highly selective ruthenium-catalyzed C–H activation/annulation of alkyne-tethered N-alkoxybenzamides has been developed. In this reaction, diverse products from inverse annulation can be obtained in moderate to good yields with high functional group compatibility. Insightful experimental and theoretical studies indicate that the reaction to the inverse annulation follows the Ru(ii)–Ru(iv)–Ru(ii) pathway involving N–O bond cleavage prior to alkyne insertion. This is highly different compared to the conventional mechanism of transition metal-catalyzed C–H activation/annulation with alkynes, involving alkyne insertion prior to N–O bond cleavage. Via this pathway, the in situ generated acetic acid from the N–H/C–H activation step facilitates the N–O bond cleavage to give the Ru-nitrene species. Besides the conventional mechanism forming the products via standard annulation, an alternative and novel Ru(ii)–Ru(iv)–Ru(ii) mechanism featuring N–O cleavage preceding alkyne insertion has been proposed, affording a new understanding of transition metal-catalyzed C–H activation/annulation., A highly selective ruthenium-catalyzed C–H activation/annulation through a pathway involving N–O bond cleavage prior to alkyne insertion is developed.

The field of peptide derivatization by metal-catalyzed C-H activation has been mostly directed to modify the side chains, but poor attention has been given to the peptide backbone. Here we report a ruthenium-catalyzed C-H activation/annulation process that can chemoselectively modify the peptide backbone producing functionalized isoquinolone scaffolds with high regioselectivity in a rapid and step-economical manner. This strategy is characterized by racemization-free conditions and the production of fluorescent peptides, and peptide conjugates to drugs, natural products and other peptide fragments, providing a chemical approach for the construction of novel peptide-pharmacophore conjugates. Mechanistic studies suggest that amide bonds of peptide backbone act as the bidentate directing group to promote the C-H activation/annulation process. This report provides an unprecedented example of peptide backbone diversification and bioorthogonal ligation exploiting the power of ruthenium-catalyzed C-H activation.

ispartof: Advanced Synthesis & Catalysis vol:361 issue:19 pages:4442-4447 status: published

A series of 3-(3-phenyl­prop-1-ene-3-one-1-yl)thio­phene derivatives containing –OH, –OCH3, –OCH2CH3 and –Br at the para-position of the phenyl ring have been synthesized and their mol­ecular and crystal structures are reported., The synthesis, spectroscopic data and crystal and mol­ecular structures of four 3-(3-phenyl­prop-1-ene-3-one-1-yl)thio­phene derivatives, namely 1-(4-hydroxy­phen­yl)-3-(thio­phen-3-yl)prop-1-en-3-one, C13H10O2S, (1), 1-(4-meth­oxy­phen­yl)-3-(thio­phen-3-yl)prop-1-en-3-one, C14H12O2S, (2), 1-(4-eth­oxy­phen­yl)-3-(thio­phen-3-yl)prop-1-en-3-one, C15H14O2S, (3), and 1-(4-­bromophen­yl)-3-(thio­phen-3-yl)prop-1-en-3-one, C13H9BrOS, (4), are described. The four chalcones have been synthesized by reaction of thio­phene-3-carbaldehyde with an aceto­phenone derivative in an absolute ethanol solution containing potassium hydroxide, and differ in the substituent at the para position of the phenyl ring: –OH for 1, –OCH3 for 2, –OCH2CH3 for 3 and –Br for 4. The thio­phene ring in 4 was found to be disordered over two orientations with occupancies 0.702 (4) and 0.298 (4). The configuration about the C=C bond is E. The thio­phene and phenyl rings are inclined by 4.73 (12) for 1, 12.36 (11) for 2, 17.44 (11) for 3 and 46.1 (6) and 48.6 (6)° for 4, indicating that the –OH derivative is almost planar and the –Br derivative deviates the most from planarity. However, the substituent has no real influence on the bond distances in the α,β-unsaturated carbonyl moiety. The mol­ecular packing of 1 features chain formation in the a-axis direction by O—H⋯O contacts. In the case of 2 and 3, the packing is characterized by dimer formation through C—H⋯O inter­actions. In addition, C—H⋯π(thio­phene) inter­actions in 2 and C—H⋯S(thio­phene) inter­actions in 3 contribute to the three-dimensional architecture. The presence of C—H⋯π(thio­phene) contacts in the crystal of 4 results in chain formation in the c-axis direction. The Hirshfeld surface analysis shows that for all four derivatives, the highest contribution to surface contacts arises from contacts in which H atoms are involved.

A modular and streamlined synthetic strategy for the generation of bridged indole alkaloid-like heterocycles from easily available building blocks is elaborated. This approach utilizes an Ugi four-component reaction, establishing diversity, followed by an efficient cationic gold-triggered intramolecular cascade non-oxidative dearomative spirocarbocyclization/concerted [4 + 2] cyclization cascade, furnishing these architecturally complex and distinct bridged heterocyclic scaffolds with good diastereoselectivity. ispartof: Organic Letters vol:21 issue:12 pages:4469-4474 ispartof: location:United States status: published

A novel synthetic strategy toward N-acyl sulfamates was developed. Interestingly, fluorosulfates, a new emerging class of electrophiles, were used to construct the sulfamate core. This precludes handling of chlorosulfonyl isocyanate and sulfamoyl chloride. In combination with amides, a wide and diverse set of N-acyl sulfamates was synthesized, including functionalized bioactive compounds. Furthermore, initial results showed that this method is also amenable to access N-thioacyl sulfamates.

Anisotropic environments can drastically alter the spectroscopy and photochemistry of molecules, leading to complex structure-function relationships. We examined this using fluorescent proteins as easy-to-modify model systems. Starting from a single scaffold, we have developed a range of 27 photochromic fluorescent proteins that cover a broad range of spectroscopic properties, including the determination of 43 crystal structures. Correlation and principal component analysis confirmed the complex relationship between structure and spectroscopy, but also allowed us to identify consistent trends and to relate these to the spatial organization. We find that changes in spectroscopic properties can come about through multiple underlying mechanisms, of which polarity, hydrogen bonding and presence of water molecules are key modulators. We anticipate that our findings and rich structure/spectroscopy dataset can open opportunities for the development and evaluation of new and existing protein engineering methods. We are grateful to Gerrit Groenhof (University of Jyvaskyla), Jeremy Harvey (KU Leuven), Raffaele Vitale (Universite de Lille), and Dominique Bourgeois (Institut de Biologie Structurale) for critical insights and discussion. E.D.Z. and L.V.M. thank the beamline staff from X06DA at the Swiss Light Source (Villigen, Switzerland), Proxima1 and Proxima2A at synchrotron Soleil (Gif-sur-Yvette, France), XRD1 at Elettra (Trieste, Italy) and I03 at Diamond Light Source (Oxfordshire, UK) for assistance during X-ray diffraction data collection. E.D.Z., S.H., and S.D. thank the Research Foundation Flanders (FWO) for a doctoral fellowship and postdoctoral fellowships (12X7919N and 12R2817N). This work was supported through funding from the Research Foundation Flanders through grants 1514319 N, G090819N, G0B8817N, and the European Research Council through grant 714688 NanoCellActivity. Dedecker, P (corresponding author), Katholieke Univ Leuven, Dept Chem, Celestijnenlaan 200G Box 2403, B-3001 Leuven, Belgium. peter.dedecker@kuleuven.be

The isoxazolyl-benzimidazole moiety is not planar. In the crystal, N—H⋯N hydrogen bonds between neighboring benzimidazole rings form chains along the a-axis direction., In the title mol­ecule, C13H13N3O, the isoxazole ring is inclined to the benzimidazole ring at a dihedral angle of 69.28 (14)°. In the crystal, N—H⋯N hydrogen bonds between neighboring benzimidazole rings form chains along the a-axis direction. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H⋯H (48.8%), H⋯C/C⋯H (20.9%) and H⋯N/N⋯H (19.3%) inter­actions. The optimized structure calculated using density functional theory at the B3LYP/6–311 G(d,p) level is compared with the experimentally determined structure in the solid state. The calculated highest occupied mol­ecular orbital (HOMO) and lowest unoccupied mol­ecular orbital (LUMO) energy gap is 4.9266 eV.

This article is part of the themed collection: Editor’s Choice: Single-atom and nanocluster catalysis., One of the hallmarks of microwave irradiation is its selective heating mechanism. In the past 30 years, alternative designs of chemical reactors have been introduced, where the microwave (MW) absorber occupies a limited reactor volume but the surrounding environment is MW transparent. This advantage results in a different heating profile or even the possibility to quickly cool down the system. Simultaneous cooling–microwave heating has been largely adopted for organic chemical transformations. However, to the best of our knowledge there are no reports of its application in the field of nanocluster synthesis. In this work, we propose an innovative one-pot procedure for the synthesis of Cu nanoclusters. The cluster nucleation was selectively MW-activated inside the pores of a highly ordered mesoporous substrate. Once the nucleation event occurred, the crystallization reaction was instantaneously quenched, precluding the growth events and favoring the production of Cu clusters with a homogenous size distribution. Herein, we demonstrated that Cu nanoclusters could be successfully adopted for radical cascade annulations of N-alkoxybenzamides, resulting in various tricyclic and tetracyclic isoquinolones, which are widely present in lots of natural products and bioactive compounds. Compared to reported homogeneous methods, supported Cu nanoclusters provide a better platform for a green, sustainable and efficient heterogeneous approach for the synthesis of tricyclic and tetracyclic isoquinolones, avoiding a variety of toxic waste/byproducts and metal contamination in the final products., Liangliang Song appreciates the Postdoctoral Mandate (PDM) of KU Leuven. This project has received funding from the European Union's Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement no. 721290. This publication reflects only the author's view, exempting the Community from any liability. Project website: http://cosmic-etn.eu/. LVM thanks the Hercules Foundation for supporting the purchase of the diffractometer through project AKUL/09/0035. We acknowledge the FWO [Fund for Scientific Research-Flanders (Belgium)] and the Research Council of KU Leuven (BOF) for financial support. We acknowledge the support of RUDN University Program 5-100. The microscopy works have been conducted in the Laboratorio de Microscopias Avanzadas at Instituto de Nanociencia de Aragón-Universidad de Zaragoza. Authors acknowledge the LMA-INA for offering access to their instruments and expertise.

The controlled formation of protein supramolecular assemblies is challenging but it could provide an important route for the development of hybrid biomaterials. In this work, we demonstrate formation of well-defined complexes formed between the 8-fold symmetrical designer protein Tako8 and soluble metal-oxo clusters from the family of Anderson-Evans, Keggin and ZrIV- substituted Wells-Dawson polyoxometalates. A combination of x-ray crystallography and solution studies showed that metal-oxo clusters are able to serve as linker nodes for the bottom-up creation of protein based supramolecular assemblies. Our findings indicate that clusters with larger size and negative charge are capable of modulating the crystal packing of the protein, highlighting the need for a size and shape complementarity with the protein node for optimal alteration of the crystalline self-assembly.

The development of a rapid and diverse access to complex natural product-like 3,4-fused indole scaffolds has always attracted considerable attention from synthetic and medicinal communities. We herein disclose a modular and straightforward protocol to prepare the densely substituted polycyclic azepino[5,4,3

ispartof: MOLECULAR CATALYSIS vol:522 status: published

Photochromic fluorescent proteins have become versatile tools in the life sciences, though our understanding of their structure-function relation is limited. Starting from a single scaffold, we have developed a range of 27 photochromic fluorescent proteins that cover a broad range of spectroscopic properties, yet differ only in one or two mutations. We also determined 43 different crystal structures of these mutants. Correlation and principal component analysis of the spectroscopic and structural properties confirmed the complex relationship between structure and spectroscopy, suggesting that the observed variability does not arise from a limited number of mechanisms, but also allowed us to identify consistent trends and to relate these to the spatial organization around the chromophore. We find that particular changes in spectroscopic properties can come about through multiple different underlying mechanisms, of which the polarity of the chromophore environment and hydrogen bonding of the chromophore are key modulators. Furthermore, some spectroscopic parameters, such as the photochromism, appear to be largely determined by a single or a few structural properties, while other parameters, such as the absorption maximum, do not allow a clear identification of a single cause. We also highlight the role of water molecules close to the chromophore in influencing photochromism. We anticipate that our dataset can open opportunities for the development and evaluation of new and existing protein engineering methods.

Five 2-aroyl-5-bromobenzo[b]furan-3-ol compounds (two of which are new) and four new 2-aroyl-5-iodobenzo[b]furan-3-ol compounds were synthesized starting from salicylic acid. The compounds were characterized by mass spectrometry and 1H NMR and 13C NMR spectroscopy. Single-crystal X-ray diffraction studies of four compounds, namely, (5-bromo-3-hydroxybenzofuran-2-yl)(4-fluorophenyl)methanone, C15H8BrFO3, (5-bromo-3-hydroxybenzofuran-2-yl)(4-chlorophenyl)methanone, C15H8BrClO3, (5-bromo-3-hydroxybenzofuran-2-yl)(4-bromophenyl)methanone, C15H8Br2O3, and (4-bromophenyl)(3-hydroxy-5-iodobenzofuran-2-yl)methanone, C15H8BrIO3, were also carried out. The compounds were tested for their in vitro cytotoxicity on the four human cancer cell lines KB, Hep-G2, Lu-1 and MCF7. Six compounds show good inhibiting abilities on Hep-G2 cells, with IC50 values of 1.39–8.03 µM.

A gold(I)-catalyzed cascade transformation of

The 3-(4-(methoxycarbonyl)phenyl)triazapentalene is a highly fluorescent small molecule which is readily accessible via a two-step synthesis. In the search for postfunctionalization methods, a radical CH-arylation with diazonium salts was attempted. However, azo coupling resulted in a ring-degenerate rearrangement toward a 2-aryl-4-azotriazapentalene, which was confirmed via crystallographic analysis. A mechanism involving the generation of a nitrilimine is proposed. In addition, reduction of the azo group led to cleavage of the triazapentalene core. The present results further demonstrate the sensitivity of the triazapentalene fluorophore. ispartof: The Journal of Organic Chemistry vol:84 issue:14 pages:9434-9439 ispartof: location:United States status: Published online

Nucleosides with a bi(hetero)aryl nucleobase have unique potential applications as antiviral drugs and molecular probes. The need for transition metal catalysis to synthesize these nucleosides from pre-functionalized building blocks and the use of nucleobase protection groups results in expensive and tedious syntheses. Herein we report that 5-imidazolyl-uracil can be obtained by scalable Van Leusen imidazole synthesis and regioselectively introduced on ribose to obtain the desired nucleoside in a 5 step synthesis (total yield 55 %). The 5-imidazolyl moiety leads to improved fluorescence properties. The only side-product formed was characterized by 2D-NMR and X-ray crystallography and could be suppressed during synthesis in favor of the desired product.

New easily functionalisable and highly fluorescent BOPAHY chromophores are synthesised via a one-pot two-step reaction starting from commercially available pyrrole-2-carbaldehydes and respective acyl hydrazides in the presence of BF

A highly selective ruthenium-catalyzed C-H activation/annulation of alkyne-tethered N-alkoxybenzamides has been developed. In this reaction, diverse products from inverse annulation can be obtained in moderate to good yields with high functional group compatibility. Insightful experimental and theoretical studies indicate that the reaction to the inverse annulation follows the Ru(ii)-Ru(iv)-Ru(ii) pathway involving N-O bond cleavage prior to alkyne insertion. This is highly different compared to the conventional mechanism of transition metal-catalyzed C-H activation/annulation with alkynes, involving alkyne insertion prior to N-O bond cleavage. Via this pathway, the in situ generated acetic acid from the N-H/C-H activation step facilitates the N-O bond cleavage to give the Ru-nitrene species. Besides the conventional mechanism forming the products via standard annulation, an alternative and novel Ru(ii)-Ru(iv)-Ru(ii) mechanism featuring N-O cleavage preceding alkyne insertion has been proposed, affording a new understanding of transition metal-catalyzed C-H activation/annulation. ispartof: CHEMICAL SCIENCE vol:11 issue:42 pages:11562-11569 ispartof: location:England status: published

The dinuclear platinacyclic complex [Pt2Cl2(Eug-1H)2] (1) (Eug-1H = deprotonated eugenol) has been synthesized. Reaction of 1 with amines afforded [PtCl(Eug-1H)(pyridine)] (2), [PtCl(Eug-1H)(4-Me-pyridine)] (3), [PtCl(Eug-1H)(piperidine)] (4), [PtCl(Eug-1H)(quinoline)] (5), [PtCl(Eug-1H)(NH3)] (6), [PtCl(Eug-1H)(4-Me-aniline)] (7), [PtCl(Eug-1H)(4-Cl-aniline)] (8), [Pt(Eug-1H)(8-O-quinoline)] (9) and [Pt(Eug-1H)(8-O-2-Me-quinoline)] (10). X-ray diffraction and NMR analysis show that in complexes 1–10 the chelating eugenol ligand is bound with the Pt(II) ion both through the ethylenic double bond of the allyl group and at a benzene carbon atom; in 2–10 the donor N atom of the amine is in the cis-position with respect to the ethylenic double bond. For complexes 2 and 3, two types of relatively strong highly directional intermolecular interactions are observed in the crystal packing: O–H…ClPt(II) hydrogen bonds and C–H…π interactions, in 3 further complemented by C–H…Cl interactions. The crystal packing of 7 is dominated by dimer formation through O–H…O, N–H…Cl, C–H…Cl and C–H…π interactions. In a d-chloroform solution of 2–5 two types of strong intermolecular interactions were detected: a Cl3C-D…ClPt(II) hydrogen bond and Cl2DC-Cl…Pt(II) halogen bond. Complex 9 exhibits significant activities on the human cancer cells KB, Hep-G2, MCF-7 and Lu, with IC50 values of 8.7, 10.8, 9.9 and 10.4 µM respectively.

We herein report an expeditious synthetic strategy to access diverse (spiro)polyheterocycles from easily available starting materials in two operational steps including an Ugi four-component reaction and a cationic gold(I)-catalyzed cascade bicyclization. Divergent synthesis of these structurally complex pyrido[2,1-a]isoindol-4(6H)-ones and spiroisoquinoline-pyrrole-3,5′-diones via a cascade nucleophilic cyclization/intramolecular 1,3-migration/1,5-enyne cycloisomerization process and a tandem hydroamination/Michael addition sequence, respectively, was controlled by substituents, where the electronic effect on the migrating groups and steric effect of the secondary amide moieties play crucial roles.

In this work, three new quinolone derivatives were prepared by alkylation of 2-oxo-1,2-dihydroquinoline-4-carboxylic acid with ethyl 2-bromoacetate. The synthesized compounds 2-4 were characterized by using FT-IR, 1H NMR, 13C NMR and mass spectrometry. Crystal structure of 4 was determined by single crystal X-ray diffraction. The optimized structures of 2-4 in gas phase, 1H and 13C NMR chemical shifts, molecular electrostatic potential (MEP), frontier orbitals and non-linear properties (NLO) have been investigated by using the B3LYP/6-311++G(d,p) method. All compounds were evaluated in vitro for their antibacterial activities against Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC4157, Streptococcus faecalis ATCC 29212 and Staphylococcus aureus ATCC 25923 bacterial strains. The tested compounds exhibited a good to moderate antibacterial activity with MIC values between 6.25 and 50 μg/mL, when compared to references Ampicillin and Chloramphenicol. Among the three compounds, compound 4 showed the most potent antibacterial activity against S. aureus with MIC value of 6.25 μg/mL. In addition, molecular docking studies of compounds 2-4 were performed within the active site of PDB: 2ZCQ protein to analyze the binding interactions responsible for their activities.

Electrolytes consisting of sodium bis(fluorosulfonyl)imide (NaFSI) dissolved in glymes (monoglyme, diglyme, and triglyme) were characterized by FT-Raman spectroscopy and 13C, 17O, and 23Na NMR spectroscopy. The glyme:NaFSI molar ratio was varied from 50:1 to 1:1, and it was observed that, in the dilute electrolytes, the sodium salt is completely dissociated into solvent separated ion pairs (SSIPs). However, contact ion pairs (CIPs) and aggregates (AGGs) become the predominant species in more concentrated solutions. Some of the electrolytes with the highest concentrations can be classified as solvate ionic liquids (SILs), where all of the solvent molecules are coordinated to sodium cations. Therefore, these electrolytes are fundamentally different from more dilute electrolytes which are typically used in commercially available secondary batteries. The melting point or glass transition temperature, dynamic viscosity, density, sodium concentration, and ionic conductivity of these solvate ionic liquids are reported as well as the crystal structures of [Na(G3)][FSI] and [Na(G3)2][FSI]. Galvanostatic cycling experiments were performed in coin-type cells with a Na2/3[Mn0.55Ni0.30Co0.15]O2 cathode to study the influence of these electrolytes on the electrochemical stability and charge/discharge behavior. ispartof: Journal of Physical Chemistry B vol:122 issue:1 pages:275-289 ispartof: location:United States status: published

We report herein an efficient gold(I)-catalyzed post-Ugi domino dearomatization/ipso-cyclization/Michael sequence that enables access to libraries of diverse (hetero)arene-annulated tricyclic heterocycles. This process affords novel complex polycyclic scaffolds in moderate to good yields from readily available acyclic precursors with excellent chemo-, regio-, and diastereoselectivity. The power of this strategy has been demonstrated by the rapid synthesis of 40 highly functionalized polyheterocycles bearing indole, pyrrole, (benzo)furan, (benzo)thiophene, pyrazole, and electron-rich arene groups in two operational steps. ispartof: Angewandte Chemie - International Edition vol:57 issue:1 pages:272-276 ispartof: location:Germany status: published

An excellent chemo- and regioselective palladium-catalyzed cascade intermolecular N-arylation/aryl-aryl coupling process has been developed. Employing Pd(TFA)2, PCy3•HBF4, K2CO3 and 1,4-dioxane in an oil bath at 100°C for 12 h, diverse C4-substituted phenanthridinones are synthesized from o-bromobenzamides in 42-92% yield. Broad substrate scope and excellent functional group tolerance are observed. The synthetic utility of this method is illustrated by the further derivatization to prepare multiple-substituted phenanthridinones in 30-75% yield.

The synthesis and crystal structure of a new thio­phene monomer containing an additional 1,2,4-triazole ring are reported. The compound has a V-shaped conformation with the thio­phene ring disordered over two positions by a rotation of approximately 180°., In the title compound, C7H8N4S2, the thio­phene ring shows rotational disorder over two orientations in a 0.6957 (15):0.3043 (15) ratio. The plane of the 1,2,4-triazole ring makes a dihedral angle of 75.02 (17)° with the major-disorder component of the thiophene ring. In the crystal, two types of inversion dimers, described by the graph-set motifs R 2 2(8) and R 2 2(10), are formed by N—H⋯S inter­actions. Chains of mol­ecules running in the [101] direction are linked by weaker N—H⋯N inter­actions. The thio­phene ring is involved in π–π and C—H⋯π inter­actions.

The synthesis and crystal structure of a new thio­phene monomer containing an additional rhodanine heterocycle are reported. The crystal packing is sustained by N—H⋯O, C—H⋯O, C—H⋯S and C—H⋯π inter­actions., The title compound, C9H8N2O2S3, crystallizes with two mol­ecules (A and B) in the asymmetric unit. Both have similar conformations (overlay r.m.s. deviation = 0.209 Å) and are linked by an N—H⋯O hydrogen bond. In both mol­ecules, the thio­phene rings show orientational disorder, with occupancy factors of 0.6727 (17) and 0.3273 (17) for mol­ecule A, and 0.7916 (19) and 0.2084 (19) for mol­ecule B. The five-membered rings make an angle of 79.7 (2)° in mol­ecule A and an angle of 66.8 (2)° in mol­ecule B. In the crystal, chains of mol­ecules running along the a-axis direction are linked by N—H⋯O hydrogen bonds. The inter­action of adjacent chains through N—H⋯O hydrogen bonds leads to two types of ring structures containing four mol­ecules and described by the graph-set motifs R 4 4(18) and R 4 2(14).

The structure of an oxazolonaphthyridinone derivative unexpectedly formed during the synthesis of pyridodiazepinediones is reported., The title compound, C17H12BrN3O2, was unexpectedly isolated during an attempt to synthesize pyridodiazepinediones and identified as an oxazolonaphthyridinone derivative. The almost planar oxazolonaphthyridinone ring (r.m.s. deviation = 0.016 Å) makes a dihedral angle of 61.6 (2)° with the phenyl ring. In the crystal, columns of mol­ecules stacked along the a axis are formed by π–π inter­actions between the six-membered rings of the oxazolonaphthyridone moieties [centroid-to-centroid distances = 3.494 (2)–3.906 (3) Å], which further inter­act through C—H⋯π contacts with the phenyl rings.

Cu2ZnSnSe4-based solar cells with 5.5% power conversion efficiency were fabricated from Cu/Sn/Zn stacks electrodeposited from liquid metal salts. These electrolytes allow metal deposition rates one order of magnitude higher than those of other deposition methods. crosscheck: This document is CrossCheck deposited related_data: Supplementary Information related_data: Crystal Structure Data identifier: Luc Van Meervelt (ORCID) identifier: Phillip J. Dale (ORCID) identifier: Phillip J. Dale (ResearcherID) copyright_licence: The Royal Society of Chemistry has an exclusive publication licence for this journal history: Received 18 November 2016; Accepted 20 December 2016; Accepted Manuscript published 20 December 2016; Advance Article published 23 December 2016; Version of Record published 10 January 2017 ispartof: Chemical Communications vol:53 issue:5 pages:913-916 ispartof: location:England status: published

The design and synthesis of oligoamide α-helix peptidomimetics is reported. The oligoamide type systems are prepared in a modular fashion by coupling the monomers using palladium-catalyzed carbonylation chemistry. This enabled us to use substrates with a low nucleophilicity, leading to previously unreported pyrazine based oligoamide α-helix mimetics. The proof of principle is given by synthesizing a small set of compounds. Various end-capping groups were introduced and also a mixed multimer was successfully prepared. crosscheck: This document is CrossCheck deposited related_data: Supplementary Information related_data: Crystal Structure Data identifier: Philippe Gilles (ORCID) identifier: Cedrick Veryser (ORCID) identifier: Cedrick Veryser (ResearcherID) identifier: Luc Van Meervelt (ORCID) identifier: Wim M. De Borggraeve (ORCID) identifier: Wim M. De Borggraeve (ResearcherID) copyright_licence: The Royal Society of Chemistry has an exclusive publication licence for this journal copyright_licence: This article is freely available. This article is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported Licence (CC BY-NC 3.0) history: Received 30 October 2016; Accepted 29 November 2016; Accepted Manuscript published 29 November 2016; Advance Article published 2 December 2016; Version of Record published 4 January 2017 ispartof: ORGANIC & BIOMOLECULAR CHEMISTRY vol:15 issue:2 pages:373-378 ispartof: location:England status: published

A rapid approach for the diversity-oriented synthesis of complex bridged polycyclic N-heterocycles from readily available starting materials in two operational steps has been developed. This strategy firstly introduces molecular diversity by an Ugi four-component reaction, and then achieves these bridged N-heterocycles via an efficient gold-triggered chemo- and diastereoselective cascade non-oxidative ortho-dearomative spirocarbocyclization/Diels–Alder reaction sequence. The application of microwave irradiation for this cascade process efficiently shortens the reaction time to 10 minutes and improves the diastereoselectivity.

A series of bay-substituted thiaza[5]helicenes was synthesized to investigate the effect of different substituents on the properties of these helicenes. These thiaza[5]helicenes with different substituents were prepared in a straightforward manner through indole- and benzo[b]thiophene synthesis, palladium-catalyzed Suzuki coupling, oxidative cyclization, and functional group interconversion reactions. We investigated the impact of these different bay area substituents compared to the unsubstituted thiaza[5]helicene on the structural parameters and studied the steady-state electronic spectroscopy of these thiaza[5]helicenes in toluene and acetonitrile. We found that different functional groups influence the solid state structure and spectroscopic properties, but a single substituent in the bay area of a thiaza[5]helicene was not enough to prevent enantiomerization at room temperature. ispartof: JOURNAL OF ORGANIC CHEMISTRY vol:84 issue:21 pages:13528-13539 ispartof: location:United States status: published

© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Twelve new organoplatinum(II) complexes: [PtCl(Saf)(2-Me-8-OquiN)] (1), [PtCl(Saf)(5,7-Cl 2 -8-OquiN)] (2), [PtCl(Saf)(5,7-Cl 2 -2-Me-8-OquiN)] (3), [PtCl(Meteug)(5,7-Cl 2 -8-OquiN)] (4), [PtCl(Meteug)(5,7-Cl 2 -2-Me-8-OquiN)] (5), [Pt(Saf-1H)(2-Me-8-OquiN)] (6), [Pt(Saf-1H)(5,7-Cl 2 -8-OquiN)] (7), [Pt(Saf-1H)(5,7-Cl 2 -2-Me-8-OquiN)] (8), [Pt(Eteug-1H)(2-Me-8-OquiN)] (9), [Pt(Eteug-1H)(2-OHC-8-OquiN)] (10), [Pt(Eteug-1H)(5,7-Cl 2 -8-OquiN)] (11) and [Pt(Eteug-1H)(5,7-Cl 2 -2-Me-8-OquiN)] (12) (Saf: Safrole, Meteug: Methyl eugenoxyacetate, Saf-1H: Deprotonated safrole, Eteug-1H: Deprotonated ethyl eugenoxyacetate, OquiN: substituted quinolin-8-olate) were synthesized. These complexes were characterized by elemental analyses, IR, 1 H NMR, for several also by NOESY, MS spectra and 9 by single-crystal X-ray diffraction. It is shown that in 1-5 the Pt(II) ion is surrounded by a Cl ion and the ethylenic double bond of the aryl olefin, and by N and O atoms of the 8-OquiN, its donor N is in trans-position in comparison with the ethylenic double bond. In 6-12 the Pt(II) ion is surrounded by an aromatic C atom and the ethylenic C = C double bond of the aryl olefin, and by N and O atoms of the 8-OquiN resulting in a slightly distorted square-planar coordination environment; the donor N is in cis-position in comparison with the ethylenic double bond. Complexes 2, 4 and 7 exhibit high activities on human cancer cells KB, Hep-G2, Lu and MCF-7 with most IC 50 values lower than those of cisplatin. ispartof: JOURNAL OF COORDINATION CHEMISTRY vol:72 issue:10 pages:1637-1651 status: published

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Four Wells–Dawson type metal-substituted polyoxometalates (MSPs), 1:2 ZrIV-Wells–Dawson [ZrIV(α2-P2W17O61)]8– (1), 1:1 CoII-Wells–Dawson [CoII(α2-P2W17O61)]10– (2), 1:1 NiII-Wells–Dawson [NiII(α2-P2W17O61)]10– (3) and 1:1 CuII-Wells–Dawson [CuII(α2-P2W17O61)]10– (4), which differ in the nature of the imbedded metal ion, were examined in co-crystallization experiments with a protein Hen Egg White Lysozyme (HEWL). Single crystal X-ray structures of four noncovalent complexes between POMs and HEWL have been determined, and the influence of the type of substituted metal on the mode of POM binding to a protein was investigated. All crystal structures exhibited a high degree of similarity, suggesting that the interaction is largely independent on the nature of substituted metal within the same polyoxometalate (POM) archetype. The main driving force for the formation of the noncovalent complex is electrostatic attraction between POM and HEWL surface regions. Stabilization is further provided by direct and water mediated hydrogen bonding between terminal oxygen atoms of the POM framework and flexible HEWL residues. ispartof: EUROPEAN JOURNAL OF INORGANIC CHEMISTRY vol:2019 issue:3-4 pages:506-511 status: published

Two artificial β-propeller proteins with eight identical blades were designed, purified and crystallized. X-ray crystallography confirmed the perfectly symmetrical structures of these highly stable proteins., β-Propeller proteins form one of the largest families of protein structures, with a pseudo-symmetrical fold made up of subdomains called blades. They are not only abundant but are also involved in a wide variety of cellular processes, often by acting as a platform for the assembly of protein complexes. WD40 proteins are a subfamily of propeller proteins with no intrinsic enzymatic activity, but their stable, modular architecture and versatile surface have allowed evolution to adapt them to many vital roles. By computationally reverse-engineering the duplication, fusion and diversification events in the evolutionary history of a WD40 protein, a perfectly symmetrical homologue called Tako8 was made. If two or four blades of Tako8 are expressed as single polypeptides, they do not self-assemble to complete the eight-bladed architecture, which may be owing to the closely spaced negative charges inside the ring. A different computational approach was employed to redesign Tako8 to create Ika8, a fourfold-symmetrical protein in which neighbouring blades carry compensating charges. Ika2 and Ika4, carrying two or four blades per subunit, respectively, were found to assemble spontaneously into a complete eight-bladed ring in solution. These artificial eight-bladed rings may find applications in bionanotechnology and as models to study the folding and evolution of WD40 proteins.

© 2018 A novel intramolecular cascade annulation of O-substituted N-hydroxybenzamides for the synthesis of indolizinones triggered by rhodium(III)-catalyzed sequential C(sp 2 )-H activation and C(sp 3 )-H amination is developed. This method features air as the oxidant, a broad substrate scope and excellent functional-group tolerance, including various heterocyclic substrates. The applicaton of indolizinone products with aminal functionality is demonstrated by further derivatization. Mechanistic studies and DFT calculations indicate that two pathways are involved in the formation of indolizinones via rhodium hydride intermediate. ispartof: MOLECULAR CATALYSIS vol:463 pages:30-36 status: published

Grignard reactions were applied to synthesize 2-ethynyl-2-hydroxylallobetulin 5 from 2-oxoallobetulin 4. The compound plays an important role as starting material to synthesize heterocyclic triterpenes using the click reaction. A series of new 1,2,3-triazole derivatives derived from 2-oxoallobetulin were successfully obtained. Under similar reaction conditions, only one compound 6 kept the hydroxyl functional group, while in the other compounds 7, 8 and 9, water was eliminated. The structures of obtained compounds were confirmed by 2D-NMR spectroscopy. The X-ray analysis of 5 indicated that only one isomer was obtained and in this compound, the hydroxyl group is situated on the same side as the ether group, the ethynyl group being situated at the opposite side. All products were also evaluated for their cytostatic activity in cell culture including L1210, CEM and Hela. Several compounds showed measurable cytostatic activity in the micromolar range.

Green-to-red photoconvertible fluorescent proteins repeatedly enter dark states, causing interrupted tracks in single-particle-tracking localization microscopy (sptPALM). We identified a long-lived dark state in photoconverted mEos4b that results from isomerization of the chromophore and efficiently absorbs cyan light. Addition of weak 488-nm light swiftly reverts this dark state to the fluorescent state. This strategy largely eliminates slow blinking and enables the recording of longer tracks in sptPALM with minimum effort. ispartof: NATURE METHODS vol:16 issue:8 pages:707-+ ispartof: location:United States status: published

Crystallization experiments with the dinuclear chelate ring complex di-μ-chlorido-bis[(η2-2-allyl-4-methoxy-5-{[(propan-2-yloxy)carbonyl]methoxy}phenyl-κC1)platinum(II)], [Pt2(C15H19O4)2Cl2], containing a derivative of the natural compound eugenol as ligand, have been performed. Using five different sets of crystallization conditions resulted in four different complexes which can be further used as starting compounds for the synthesis of Pt complexes with promising anticancer activities. In the case of vapour diffusion with the binary chloroform–diethyl ether or methylene chloride–diethyl ether systems, no change of the molecular structure was observed. Using evaporation from acetonitrile (at room temperature), dimethylformamide (DMF, at 313 K) or dimethyl sulfoxide (DMSO, at 313 K), however, resulted in the displacement of a chloride ligand by the solvent, giving, respectively, the mononuclear complexes (acetonitrile-κN)(η2-2-allyl-4-methoxy-5-{[(propan-2-yloxy)carbonyl]methoxy}phenyl-κC1)chloridoplatinum(II) monohydrate, [Pt(C15H19O4)Cl(CH3CN)]·H2O, (η2-2-allyl-4-methoxy-5-{[(propan-2-yloxy)carbonyl]methoxy}phenyl-κC1)chlorido(dimethylformamide-κO)platinum(II), [Pt(C15H19O4)Cl(C2H7NO)], and (η2-2-allyl-4-methoxy-5-{[(propan-2-yloxy)carbonyl]methoxy}phenyl-κC1)chlorido(dimethyl sulfoxide-κS)platinum(II), determined as the analogue {η2-2-allyl-4-methoxy-5-[(ethoxycarbonyl)methoxy]phenyl-κC1}chlorido(dimethyl sulfoxide-κS)platinum(II), [Pt(C14H17O4)Cl(C2H6OS)]. The crystal structures confirm that acetonitrile interacts with the PtIIatomviaits N atom, while for DMSO, the S atom is the coordinating atom. For the replacement, the longest of the two Pt—Cl bonds is cleaved, leading to acisposition of the solvent ligand with respect to the allyl group. The crystal packing of the complexes is characterized by dimer formationviaC—H...O and C—H...π interactions, but no π–π interactions are observed despite the presence of the aromatic ring.

Crystallization of tacrine hydrochloride, an acetylcholinesterase inhibitor used during treatment of mild to moderate Alzheimer's disease, from a water:ethanol solution has resulted in an orthorhombic pseudopolymorph. This orthorhombic form which occurs as a dihydrate shows columns of stacking acridines together with continuous Cl—Owater—Owater—Cl chains and ladder-like ribbons composed of squares and hexagons.

Five new platinum(II) complexes bearing a eugenol and a quinoline derivative, namely [η2-4-allyl-2-methoxy-1-(propoxycarbonylmethoxy)benzene]-trans-dichlorido(quinoline-κN)platinum(II), [PtCl2(C15H20O4)(C9H7N)], (2), {η2-4-allyl-2-methoxy-1-[(propan-2-yloxy)carbonylmethoxy]benzene}-trans-dichlorido(quinoline-κN)platinum(II), [PtCl2(C15H19O4)(C9H7N)], (3), [η2-4-allyl-2-methoxy-1-(propoxycarbonylmethoxy)benzene]chlorido(quinolin-8-olato-κ2 N,O)platinum(II), [Pt(C9H6NO)Cl(C15H20O4)], (4), {η2-4-allyl-2-methoxy-1-[(propan-2-yloxy)carbonylmethoxy]benzene}chlorido(quinolin-8-olato-κ2 N,O)platinum(II), [Pt(C9H6NO)Cl(C15H20O4)], (5), and [η2-4-allyl-2-methoxy-1-(propoxycarbonylmethoxy)benzene]chlorido(quinolin-2-carboxylato-κ2 N,O)platinum(II), [Pt(C10H6NO2)Cl(C15H20O4)], (6), have been synthesized and fully characterized spectroscopically. A single-crystal X-ray diffraction study was carried out for complexes (2) and (4)–(6). PrEug [or 4-allyl-2-methoxy-1-(propoxycarbonylmethoxy)benzene] in (2), (4) and (6), and iPrEug (the propan-2-yloxy analogue of PrEug) in (3) and (5) coordinate with PtII at the ethylenic double bond of the allyl group. In (2)–(6), the donor N atom of the amine group occupies a trans position with respect to the double bond. A comparison of the IC50 values of 0.38–29.23 µM for (2)–(6) with cisplatin, as well as other platinum(II) complexes, indicates an excellent in vitro cytotoxicity against the KB, LU, Hep-G2 and MCF-7 cancer cell lines, with the highest cytotoxic effect (IC50 = 0.38–1.99 µM) being for complexes (4) and (5) bearing a quinolin-8-olate ligand.

In recent decades, considerable research attention has been devoted to new synthetic procedures for thiacyclophanes. Thiacyclophanes are widely used as host molecules for the molecular recognition of organic compounds as well as metals. Herein, we report the selective and high-yielding synthesis of novel alternate-linked-meta-para-thiacyclophanes. These novel thiacyclophanes are selectively synthesized in high-yielding procedures. Furthermore, post-functionalization of the phenolic moieties was successfully performed. The 3D structure of the alternate-linked-meta-para-[22.12]thiacyclophane was further elucidated via X-ray crystallographic analysis. ispartof: BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY vol:14 pages:2190-2197 ispartof: location:Germany status: published