Anti Isomers Research Articles

Unusually high Deca-BDE concentrations and new flame retardants in a Canadian Arctic top predator, the glaucous gull

Despite a sustained effort in surveying flame retardants (FRs) in wildlife from industrialized regions, their occurrence in birds or any other wildlife species spanning the Arctic regions, particularly in North America, has received limited attention. This study investigated in the top predator glaucous gull (Larus hyperboreus) breeding in the Eastern Canadian Arctic (Cape Dorset, Nunavut) a comprehensive suite of FRs including unstudied halogenated and non-halogenated FRs of potential health concern, along with legacy organochlorines and mercury. The influence of diet acquired locally and in wintering areas on the tissue contaminant profiles was also investigated using δ15N and δ13C signatures in liver and feathers. The principal constituent in the Deca-brominated diphenyl ether (BDE) mixture, BDE-209, was remarkably the most concentrated PBDE congener determined in liver samples of Eastern Canadian Arctic glaucous gulls. This suggests dietary exposure from the local marine food web and perhaps also from nearby community landfills. Moreover, this study revealed for the first time the presence of 16 emerging halogenated and non-halogenated FRs in glaucous gulls from this Arctic region including HBB, DDC-CO (anti and syn isomers), PBEB, EHTBB, BEHTBP as well as a series of organophosphate esters (OPEs) (TCEP, TCIPP, TPP, TDCIPP, TDBPP, TBNP, TBOEP, TBEP, TCrP, EHDPP, and TEHP). With the exception of BDE-209, concentrations of other halogenated FRs and organochlorines were found to be in the lower range in liver of Eastern Canadian Arctic glaucous gulls compared to individuals from other circumpolar populations (Svalbard and Greenland). Mercury and methylmercury concentrations, however, were greater than reported elsewhere for glaucous gull populations.

Diastereospecific Bis‐alkoxycarbonylation of 1,2‐Disubstituted Olefins Catalyzed by Aryl α‐Diimine Palladium(II) Catalysts

AbstractReadily synthesized aryl α‐diimine derivatives have been used as efficient ligands for the palladium‐catalyzed oxidative bis‐alkoxycarbonylation reaction of 1,2‐disubstituted olefins. The most active catalyst A was formed in situ from bis‐(2,6‐dimethylphenyl)‐2,3‐dimethyl‐1,4‐diazabutadiene and Pd(TFA)2 (TFA=trifluoroacetate). This catalytic system was able to selectively convert 1,2‐disubstituted olefins into 2,3‐disubstituted‐succinic diesters with total diastereospecificity, in good yields (up to 97%) with 2 mol% of catalyst loading, under mild reaction conditions (4 bar of CO at 20 °C in presence of p‐ toluenesulfonic acid as additive and p‐benzoquinone as oxidant). The optimized reaction conditions could be successfully applied to 1,2‐disubstituted aromatic, aliphatic, cyclic olefins and to unsaturated fatty acid methyl esters, employing methanol or benzyl alcohol as nucleophiles. The use of the bulky, less reactive isopropyl alcohol has allowed to better understand the mechanisms involved in the catalytic process. The geometry of the carbonylated products can be explained as a consequence of a concerted syn addition of the Pd‐alkoxycarbonyl moiety to the olefin C=C bond. Catalyst A was isolated, characterized and analyzed by single crystal X‐ray diffraction analysis.magnified image

Syn and anti conformers of di-ammonium aqua-bis(malonato)oxidovanadate(IV) in an anhydrate crystal.

The asymmetric unit of the title anhydrate compound, (NH4)2[VO(C3H2O4)2(H2O)], consists of two independent complex anions and four ammonium cations. In the complex anions, the VIV atoms are each coordinated by two malonate ligands, one water mol-ecule and one oxide O atom in a distorted octa-hedral geometry. The equatorial plane is formed by the malonate O atoms, while the axial positions are occupied by water and oxide O atoms. The difference between the two independent complexes is the relative conformation of the malonate ligands. The two ligands in one complex anion are in a syn conformation, while in the other they adopt an anti conformation. In the crystal, the complex anions inter-act with the counter-cations and adjacent anions through O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds. Stacks of alternating layers consisting of either anti or syn isomers, formed with the aid of the hydrogen bonding, are observed. DFT calculations for the anti and syn isomers show a similar thermodynamic stability to each other. The crystal used for this analysis was an inversion twin with the ratio of the twin components being 0.270 (13):0.730 (13).

Highly Selective Syn Addition of 1,3‐Diones to Internal Ynamides Catalyzed by Zinc Iodide

1,3‐Diones are already established as nucleophiles to perform additions to ynamides; the highly selective hydroalkoxylation of internal ynamides is now described. Several catalytic systems have been compared to perform this transformation, including transition‐metal‐based catalysts and Lewis acids. ZnI2 was found to be both very active and highly selective providing only E adducts through a syn addition. Investigation of the scope and limitations showed that this catalyst was compatible with various functional groups. In addition to seventeen examples of ynamide hydroalkoxylation, one example of ynamide hydroarylation is reported.

Synthesis of NN palladium complexes and six-membered CN palladacycles from 1-N- and 2-N-benzylindazoles

The reaction of 1-N-benzylindazole (1) and 2-N-benzylindazole (1a) with Na2PdCl4 in MeOH afforded the NN coordinated complexes Pd(1)2Cl2 (2) as the only trans-isomer and Pd(1a)2Cl2 (2a) as the 1:1 mixture of cis and trans isomers. Direct palladation of 1 and 1a using Pd(OAc)2 in AcOH led to the corresponding μ-acetato-dimeric complexes (3 and 3a) with six-membered palladacycles as the mixtures of syn and anti isomers. The reaction of 3 and 3a with LiCl in aqueous acetone gave the μ-Cl-dimeric complexes 5 and 5a where the acetate groups were replaced by Cl. The following addition of PPh3 to the solution of 5 and 5a in CH2Cl2 generated the mononuclear adducts 7 and 7a. NMR spectroscopy data supported the proposed structures of all complexes. The solid-state structure of 7 and 7a was determined by the single-crystal X-ray diffraction methods and indicated a boat conformation of both 6-membered palladacycles.

Postsynthetic Addition of Ligand Struts in Metal-Organic Frameworks: Effect of Syn/Anti Addition on Framework Structures with Distinct Topologies.

For the parent metal-organic framework (MOF) of UiO-type 1, postsynthetic bromination (anti addition) was readily carried out on the stilbene-ligand struts by directly adding excess bromine, whereas successful hydrogenation (syn addition) can only be achieved by slowing the reaction rate; otherwise, the crystalline structure of 1 will be irreversibly damaged. Meanwhile, Kagomé-like MOF 2 can be smoothly modified by both postsynthetic bromination and hydrogenation. This study of the structural conversion not only represents the first example that adopts postsynthetic hydrogenation for modifying MOFs but also reveals various factors such as the reaction manner of syn/anti, framework topology, and reaction rate that can influence postsynthetic modification on the ligand struts of MOFs.

Regio‐ and Stereoselective Chlorocyanation of Alkynes

AbstractA variety of terminal and internal alkynes were converted regio‐ and stereoselectively into (Z)‐3‐chloroacrylonitriles by treatment with BCl3 in the presence of stoichiometric amounts of imidazolium thiocyanates. These products could be readily functionalized to provide useful building blocks, thus demonstrating the synthetic value of the method. Preliminary mechanistic studies suggest initial activation of the cationic thiocyanate by the Lewis acid, followed by electrophilic attack of the alkyne. The syn addition of a chloride to the vinyl cation intermediate and final elimination of the thiourea unit afford the desired chloroacrylonitriles.

Regio- and Stereoselective Chlorocyanation of Alkynes.

A variety of terminal and internal alkynes were converted regio- and stereoselectively into (Z)-3-chloroacrylonitriles by treatment with BCl3 in the presence of stoichiometric amounts of imidazolium thiocyanates. These products could be readily functionalized to provide useful building blocks, thus demonstrating the synthetic value of the method. Preliminary mechanistic studies suggest initial activation of the cationic thiocyanate by the Lewis acid, followed by electrophilic attack of the alkyne. The syn addition of a chloride to the vinyl cation intermediate and final elimination of the thiourea unit afford the desired chloroacrylonitriles.

Expanding the Family of Hoveyda–Grubbs Catalysts Containing Unsymmetrical NHC Ligands

A series of Hoveyda–Grubbs second-generation catalysts containing N-alkyl/N′-aryl N-heterocyclic carbene (NHC) ligands were synthesized and investigated in representative olefin metathesis reactions. Steric perturbations of unsymmetrical NHCs were achieved through modulation of the hindrance of alkyl (neopentyl, neophyl, cyclohexyl) and aryl (2-isopropylphenyl, mesityl) substituents at the nitrogen atoms in combination with different backbone configurations (syn and anti). The NHC substitution patterns strongly influence the stability and reactivity of the corresponding complexes. In general, complexes bearing an anti NHC backbone are more stable and more active than their corresponding syn isomers. In both the series, the presence of bulky, highly branched N-alkyl groups tends to give reduced catalytic differences between syn and anti isomers, whereas the nature of the N′-aryl substituent (2-isopropylphenyl or mesityl) gives rise to different activity and/or selectivity. Of note, an N′-mesityl catalyst w...

Synthesis of an ortho‐Methyl‐N,N′‐bis(triptycenyl) N‐Heterocyclic Carbene Ligand and Its Metal Complexes

A new N,N′‐bis(triptycenyl)‐NHC ligand with methyl groups in the ortho position has been synthesized starting from 2,3‐dimethyltriptycene‐1,4‐quinone. The respective metal complexes [ML(NHC)] [ML = CuBr, AuCl, PdCl(allyl), RhCl(cod), IrCl(cod), RhCl(CO)2, IrCl(CO)2, and RuCl2(=CHC6H4OiPr)] were obtained by standard procedures. All the complexes were initially mixtures of syn and anti isomers. The ruthenium complex was separated into the syn and anti isomers. The crystal structure of the anti complex [RhCl(cod)(8)] has been determined.

Trans-Mutation at Gold(III): A Mechanistic Study of a Catalytic Acetylene Functionalization via a Double Insertion Pathway

The Au(III) complex Au(tpy)(OAcF)2 (OAcF = OCOCF3; tpy = 2-(p-tolyl)pyridine) catalyzes the anti addition of trifluoroacetic acid (HOAcF) to acetylene to furnish vinyl trifluoroacetate. The Au(III) vinyl complex Au(tpy)(OAcF)(CH═CHOAcF) (vinyl group bonded trans to tpy-N) is formed during the early stage of the reaction. The vinyl complex, which has been isolated and structurally characterized, resists protolytic cleavage of the vinyl group, and therefore catalysis does not proceed by a simple formal insertion (i.e., coordination-nucleophilic attack-protolysis at the site trans to tpy-N) mechanism. Experimental evidence, including isotopic labeling, rather suggests that a double-insertion process is operative. The unobserved Au(III) divinyl complex Au(tpy)(CH═CHOAcF)2 is a crucial intermediate for which the true catalytic activity, comprising a coordination-nucleophilic attack-protolysis sequence, occurs at the site trans to tpy-C. The overall mechanism is in full agreement with DFT calculations and is a result of the considerable differences in the kinetic and thermodynamic trans effects of tpy-N versus tpy-C on each reaction step. The computational data provide a rationale for the catalytic functionalization of acetylene trans to tpy-C, whereas ethylene (previously reported) only undergoes a stoichiometric insertion, and then comes to a full stop, trans to tpy-N.

The reactions of [(μ-H)M3(CO)9(CCSiMe3)] (M=Fe, Ru) with thiols: Cleavage of M-M and formation of M-S bonds in isomeric structures

The reactions of the acetylide trinuclear derivatives [(μ-H)M3(CO)9(CCSiMe3)] (M=Fe, Ru) with the thiols C6H5SH and C6F5SH were carried out. Both reactions lead to the formation of products where cleavage of M-M bonds have occurred. In the case of the iron complex, two products are obtained in the reactions with both thiols: a trinuclear complex of formula [Fe3(CO)9(CCSiMe3)(SR)] (R=C6H5 and C6F5) and a dinuclear compound [Fe2(CO)6(CCSiMe3)(SR) (R=C6H5 and C6F5) which is found as anti and syn isomers in the case of C6H5 and only as the anti isomer in the fluorinated thiol. The reaction with the ruthenium complex under the same conditions gives only decomposition products, but when the reaction with pentafluorothiophenol is carried out in the presence of trimethylamine oxide, total cleavage of M-M bonds takes place to form a mononuclear complex [Ru(CO)3(SC6F5)3]. Spectroscopic and structural characterization of the iron complexes is given. Two isomeric crystal structures were obtained for the trinuclear fluorinated complex.

Tolvaptan-Type Vasopressin Receptor Ligands: Important Role of Axial Chirality in the Active Form.

The anti and syn isomers of tolvaptan-type compounds, N-benzoyl-5-hydroxy-1-benzazepines (5a-c), were prepared in a stereocontrolled manner by biasing the conformation with a methyl group at C9 and C6, respectively, and the enantiomeric forms were separated. Examination of the affinity at the human vasopressin receptors revealed that the axial chirality (aS) plays a more important role than the central chirality at C5 in receptor recognition, and the most preferable form was shown to be (E,aS,5S).

Dechlorane Plus induces oxidative stress and decreases cyclooxygenase activity in the blue mussel

Dechlorane Plus (DP) is a chlorinated flame retardant used mainly in electrical wire and cable coating, computer connectors, and plastic roofing materials. Concentrations of DP (syn and anti isomers) are increasingly being reported in aquatic ecosystems worldwide. However, there is exceedingly little information on the exposure-related toxicity of DP in aquatic organisms, especially in bivalves. The objective of this study was to investigate the in vivo and in vitro effects of DP exposure on histopathology, lipid peroxidation (LPO) levels, cyclooxygenase (COX) activity, phagocytosis capacity and efficiency, and DNA strand breakage in the blue mussel (Mytilus edulis) following a 29days exposure (0.001, 0.01, 0.1 and 1.0μg DP/L). Blue mussels accumulated DP in muscle and digestive gland in a dose-dependent manner. LPO levels in gills were found to increase by 82% and 67% at the 0.01 and 1.0μg DP/L doses, respectively, while COX activity in gills decreased by 44% at the 1μg/L dose. No histopathological lesion was found in gonads following DP exposure. Moreover, no change in hemocyte DNA strand breakage, phagocytosis rate, and viability was observed following DP exposure. Present study showed that toxicity of DP may occur primarily via oxidative stress in the blue mussel and potentially other bivalves, and that gills represent the most responsive tissue to this exposure.

Understanding the Crystal Packing and Organic Thin-Film Transistor Performance in Isomeric Guest-Host Systems.

In order to understand how additives influence the structure and electrical properties of active layers in thin-film devices, a compositionally identical but structurally different guest-host system based on the syn and anti isomers of triethylsilylethynyl anthradithiophene (TES ADT) is systematically explored. The mobility of organic thin-film transistors (OTFTs) comprising anti TES ADT drops with the addition of only 0.01% of the syn isomer and is pinned at the mobility of OTFTs having pure syn isomer after the addition of only 10% of the isomer. As the syn isomer fraction increases, intermolecular repulsion increases, resulting in a decrease in the unit-cell density and concomitant disordering of the charge-transport pathway. This molecular disorder leads to an increase in charge trapping, causing the mobility of OTFTs to drop with increasing syn-isomer concentration. Since charge transport is sensitive to even minute fractions of molecular disorder, this work emphasizes the importance of prioritizing structural compatibility when choosing material pairs for guest-host systems.

Crystal structure of a fluorescent C-shaped molecule containing closely stacked bithiophene-substituted quinoxaline rings.

Molecules with well-defined structures that feature closely stacked aromatic rings are important for understanding π-π interactions. A previously reported C-shaped molecule with bithiophene-substituted quinoxaline rings suspended from an aliphatic bridge that holds the aromatic rings in close proximity exists as a pair of syn and anti diastereomers. The anti isomer, namely (1α,2β,4β,5α,16α,17β,19β,20α)-1,5,16,20-tetrachloro-31,31,32,32-tetramethoxy-11,26-bis[5-(thiophen-2-yl)thiophen-2-yl]-7,14,22,29-tetraazanonacyclo[18.10.1.15,16.02,19.04,17.06,15.08,13.021,30.023,28]dotriaconta-6(15),7,9,11,13,21(30),22,24,26,28-decaene chloroform monosolvate, C48H36Cl4N4O4S4·CHCl3, whose X-ray structure is described herein, has cofacial quinoxaline rings with bithiophene rings attached on opposite sides. The molecular structure is approximately C-shaped and consists of an aliphatic spacer with a boat-shaped cyclohexane ring in the middle. The centroid-to-centroid distance between the quinoxaline rings is 3.950 (1) Å, with ring-offset distances of 0.354 (3) and 0.816 (2) Å. The pendant bithiophene rings are oriented parallel to one another, which results from the thiophene rings connected to the quinoxaline rings being oriented such that their S atoms are rotated inward toward one another, but are not overlapped. Intermolecular packing is largely governed by van der Waals forces and a few weak C-H...X (X = N or O) interactions.

Electrophilic addition/substitution of an alkynyl methyl ketone with tellurium tetrahalides: A novel synthetic approach to telluracyclopentenones

The interaction of tellurium tetrahalides, TeX4 (X = Cl. Br) with 4-(trimethylsilyl)but-3-yn-2-one under dry nitrogen gives novel crystalline 1,1,3-trihalo-2-(trimethylsilyl)telluracyclopent-2-en-4-ones (X = Cl, 1a and X = Br, 2b) as the major products. In a tandem reaction, the trisubstituted vinyltellurium trihalide formed initially by the anti addition of a tellurium tetrahalide across the polar triple bond of the 1,2-disubstituted acetylene, instantly undergoes intramolecular electrophilic substitution of the carbonyl activated methyl protons to eliminate a molecule of hydrogen halide. These tellurium(IV) derivatives can be reduced safely with aqueous sodium meta bisulphite to give tellurium(II) heterocyles, 3-halo-2-(trimethylsilyl)telluracyclopent-2-en-4-ones as fairly stable viscous oils. Molecular geometry of 1a as substantiated from the single-crystal X-ray diffraction data has Cs symmetry and resembles a see-saw with a pentagonal stand that supports the Cl─Te─Cl beam at the Te atom as its fulcrum.

Conformational and electronic effects on the formation of anti cyclobutane pyrimidine dimers in G-quadruplex structures

Cyclobutane pyrimidine dimers (CPDs) are the most commonly formed photochemical products when nucleic acids interact with UV radiation. In duplex DNA, the relative inflexible structure allows for only the cis, syn CPD isomer to be formed. G-quadruplex structures, however, have loops that are more flexible and allow for different orientations of the bases to interact. As a result, the highly unusual formation of an anti CPD has been observed in these structures. Due to the close proximity between two opposing loops containing the TTA sequence in two G-quadruplex structures (called "form-3" and "basket"), a high yield of anti CPD formation was expected in these structures. However, while significant yields of anti CPDs are observed in form-3, the anti CPD is hardly observed in the basket structure. To account for this inconsistency, we examine the process of anti CPD formation in form-3 and basket structures using simulations at the atomistic level. Here, we consider the conformational effect using MD simulations, which show whether the formation of the anti CPD is structurally feasible. Quantum mechanical/molecular mechanical (QM/MM) calculations of excited states are also used to consider the electronic effect by an adjacent guanine base which can quench the formation of the anti CPD through charge transfer (CT). Our results are in qualitative agreement with the experimental results, predicting a significant yield of the anti CPD in the form-3 structure and a negligible yield in the basket structure, while they also predict the formation of the cis, syn CPD between two opposing loops in form-3. Most importantly, our simulation results show that the yields of the anti CPD in the G-quadruplex are affected significantly by both conformational and electronic effects.

Density Functional Investigations on the Selective Binding of an endo-Functionalized Bis-urea Macrocycle.

The preferential binding of syn and anti configurational isomers of endo-functionalized bis-urea molecular receptor to 1,2-dinitrobenzene (G1) and 1,4-dioxane (G2) guests has been explained using dispersion-corrected M06-2X-based density functional theory. The host-guest binding is facilitated via hydrogen bonding, C-H···π, dipole-dipole, C···C and O···O (chalcogen-chalcogen) interactions. The formation of an inclusion complex is spontaneous and thermodynamically favorable. The molecular electrostatic potential and quantum theory of atoms in molecules in conjunction with the noncovalent interactions reduced density gradient have been employed to characterize the noncovalent interactions. The encapsulation of G1 or G2 within the π-electron-rich cavity of the bis-urea macrocycle reflects the frequency shift of the characteristic N-H and C-H vibrations of their vibrational spectra. It has also been shown that binding of the bis-urea isomers to G1 and G2 emerges with a signature in the upfield signals of the guest protons confined to the host cavity in 1H NMR spectra.

Synthesis and Evaluation of Molybdenum and Tungsten Monoaryloxide Halide Alkylidene Complexes for Z-Selective Cross-Metathesis of Cyclooctene and Z-1,2-Dichloroethylene.

Molybdenum complexes with the general formula Mo(NR)(CHR')(OR″)(Cl)(MeCN) (R = t-Bu or 1-adamantyl; OR″ = a 2,6-terphenoxide) recently have been found to be highly active catalysts for cross-metathesis reactions between Z-internal olefins and Z-1,2-dichloroethylene or Z-(CF3)CH═CH(CF3). In this paper we report methods of synthesizing new potential catalysts with the general formula M(NR)(CHR')(OR″)(Cl)(L) in which M = Mo or W, NR = N-2,6-diisopropylphenyl or NC6F5, and L is a phosphine, a pyridine, or a nitrile. We also test and compare all catalysts in the cross-metathesis of Z-1,2-dichloroethylene and cyclooctene. Our investigations indicate that tungsten complexes are inactive in the test reaction either because the donor is bound too strongly or because acetonitrile inserts into a W═C bond. The acetonitrile or pivalonitrile Mo(NR)(CHR')(OR″)(Cl)(L) complexes are found to be especially reactive because the 14e Mo(NR)(CHR')(OR″)Cl core is accessible through dissociation of the nitrile to a significant extent. Pivalonitrile can be removed (>95%) from Mo(NAr)(CHCMe2Ph)(OHMT)(Cl)(t-BuCN) (Ar = 2,6-diisopropylphenyl; OHMT = 2,6-dimesitylphenoxide) to give 14e Mo(NAr)(CHCMe2Ph)(OHMT)Cl in solution as a mixture of syn and anti (60:40 at 0.015 M) nitrile-free isomers, but these 14e complexes have not yet been isolated in pure form. The syn isomer of Mo(NAr)(CHCMe2Ph)(OHMT)Cl binds pivalonitrile most strongly. Other Mo(NR)(CHR')(OR″)(Cl)(L) complexes can be activated through addition of B(C6F5)3. High stereoselectivities (>98% Z,Z) of ClCH═CH(CH2)6CH═CHCl are not restricted to tert-butylimido or adamantylimido complexes; 96.2% Z selectivity is observed with boron-activated Mo(NC6F5)(CHR')(OHIPT)(Cl)(PPhMe2). So far no Mo═CHCl complexes, which are required intermediates in the test reaction, have been observed in NMR studies at room temperature.