Tetra-µ-acetato-κ8 O:O'-bis-[(3-chloro-pyridine-κN)ruthenium(II,III)](Ru-Ru) hexa-fluorido-phosphate 1,2-di-chloro-ethane monosolvate.

The title compound, [Ru2(µ-O2CCH3)4(C5H4ClN)2]PF6·C2H4Cl2, was obtained via a rapid substitution reaction of 3-chloro-pyridine for water in [Ru2(µ-O2CCH3)4(H2O)2]PF6 in 2-propanol and subsequent crystallization from a di-chloro-ethane solution. The cationic diruthenium(II,III) tetra-acetate core lies on a crystallographic inversion center with Ru-Ru and Ru-N bond lengths of 2.2738 (3) and 2.2920 (17) Å, respectively. The Ru-Ru-N bond angle is close to linear at 176.48 (4)°, and a significant π-stacking inter-action of 3.5649 (16) Šis seen between overlapping pyridine rings of adjacent cations.

Deuteration and tautomeric reactivity of the 1-methyl functionality of free-base dipyrrins.

Regioselective reactivity of the 1-methyl group of free-base dipyrrins is explored, including discussion of tautomerism to provide exocyclic alkenyl reactivity. Deuterium is installed so as to generate dipyrrins substituted with deuterated methyl groups. Furthermore, the 1-methyl group reacts to become involved in C-C bonds involving only sp3-hybridised carbon atoms. The isolation of an elusive framework featuring a dipyrrin substituted with a pyrrole in a non-vinylogous fashion is also reported. The use of asymmetric dipyrrins featuring an electron-withdrawing group on one of the pyrrolic units results in regioselective reaction of the alpha-methyl group distal to the electron-withdrawing group.

Au-Catalyzed Synthesis of Thiopyrano[2,3-b]indoles Featuring Tandem Rearrangement and Hydroarylation.

Gold(III)-catalyzed synthesis of 14-π electron heteroaromatic thiopyrano[2,3-b]indole is reported using conjugated enyne tethered indole sulfides, featuring skeletal rearrangement conjoined with intramolecular hydroarylation (via C3-H functionalization of the indole core) and oxidative aromatization. Subsequent Pd-catalyzed C-C coupling resulted in a 16-π electron heteroaromatic isothiochromeno[1,8,7-bcd]indole.

Synthesis and Photobiological Activity of Ru(II) Dyads Derived from Pyrrole-2-carboxylate Thionoesters.

The synthesis and characterization of a series of heteroleptic ruthenium(II) dyads derived from pyrrole-2-carboxylate thionoesters are reported. Ligands bearing a conjugated thiocarbonyl group were found to be more reactive toward Ru(II) complexation compared to analogous all-oxygen pyrrole-2-carboxylate esters, and salient features of the resulting complexes were determined using X-ray crystallography, electronic absorption, and NMR spectroscopy. Selected complexes were evaluated for their potential in photobiological applications, whereupon all compounds demonstrated in vitro photodynamic therapy effects in HL-60 and SK-MEL-28 cells, with low nanomolar activities observed, and exhibited some of the largest photocytotoxicity indices to date (>2000). Importantly, the Ru(II) dyads could be activated by relatively soft doses of visible (100 J cm-2, 29 mW cm-2) or red light (100 J cm-2, 34 mW cm-2), which is compatible with therapeutic applications. Some compounds even demonstrated up to five-fold selectivity for malignant cells over noncancerous cells. These complexes were also shown to photocleave, and in some cases unwind, DNA in cell-free experiments. Thus, this new class of Ru(II) dyads has the capacity to interact with and damage biological macromolecules in the cell, making them attractive agents for photodynamic therapy.

Synthesis, Characterization, and Properties of Weakly Coordinating Anions Based on tris-Perfluoro-tert-Butoxyborane.

A convenient method for the preparation of strongly Lewis acidic tris-perfluoro-tert-butoxyborane B(ORF)3 (1), (ORF = OC(CF3)3) was developed, and its X-ray structure was determined. 1 was used as a precursor, guided by density functional theory (DFT) calculations and volume-based thermodynamics, for the synthesis of [NEt4][NCB(ORF)3] (3) and [NMe4][FB(ORF)3] (5) and the novel large and weakly coordinating anion salts [Li 15-Crown-5][B(ORF)4] (2) and [NEt4][CN{B(ORF)3}2] (4). The stability of [B(ORF)4]- was compared with that of some related known weakly coordinating anions by appropriate DFT calculations.

Identification of polymorphism in ethylone hydrochloride: synthesis and characterization.

Ethylone, a synthetic cathinone with psychoactive properties, is a designer drug which has appeared on the recreational drug market in recent years. Since 2012, illicit shipments of ethylone hydrochloride have been intercepted with increasing frequency at the Canadian border. Analysis has revealed that ethylone hydrochloride exists as two distinct polymorphs. In addition, several minor impurities were detected in some seized exhibits. In this study, the two conformational polymorphs of ethylone hydrochloride have been synthesized and fully characterized by FTIR, FT-Raman, powder XRD, GC-MS, ESI-MS/MS and NMR ((13) C CPMAS, (1) H, (13) C). The two polymorphs can be distinguished by vibrational spectroscopy, solid-state nuclear magnetic resonance spectroscopy and X-ray diffraction. The FTIR data are applied to the identification of both polymorphs of ethylone hydrochloride (mixed with methylone hydrochloride) in a laboratory submission labelled as 'Ocean Snow Ultra'. The data presented in this study will assist forensic scientists in the differentiation of the two ethylone hydrochloride polymorphs. This report, alongside our recent article on the single crystal X-ray structure of a second polymorph of this synthetic cathinone, is the first to confirm polymorphism in ethylone hydrochloride. © 2015 Canada Border Services Agency. Drug Testing and Analysis published by John Wiley & Sons, Ltd. © 2015 Canada Border Services Agency. Drug Testing and Analysis published by John Wiley & Sons, Ltd.

Access to Substituted Dihydrothiopyrano[2,3-b]indoles via Sequential Rearrangements During S-Alkylation and Au-Catalyzed Hydroarylation on Indoline-2-thiones.

An efficient methodology for the synthesis of indole-fused dihydrothiopyrans has been developed from indoline-2-thiones. The protocol involves the synthesis of conjugated ene-yne-substituted indole-sulfides, a gold(III)-catalyzed rearrangement of the ene-yne side chain followed by intramolecular hydroarylation via C3-H functionalization of the indole core. This new synthesis of functionalized tricyclic indole derivatives through sequential rearrangements is quite general in nature.

Inversion twinning in a second polymorph of the hydrochloride salt of the recreational drug ethylone.

A second polymorph of the hydrochloride salt of the recreational drug ethylone, C12H16NO3(+)·Cl(-), is reported [systematic name: (±)-2-ethylammonio-1-(3,4-methylenedioxyphenyl)propane-1-one chloride]. This polymorph, denoted form (A), appears in crystallizations performed above 308 K. The originally reported form (B) [Wood et al. (2015). Acta Cryst. C71, 32-38] crystallizes preferentially at room temperature. The conformations of the cations in the two forms differ by a 180° rotation about the C-C bond linking the side chain to the aromatic ring. Hydrogen bonding links the cations and anions in both forms into similar extended chains in which any one chain contains only a single enantiomer of the chiral cation, but the packing of the ions is different. In form (A), the aromatic rings of adjacent chains interleave, but pack equally well if neighbouring chains contain the same or opposite enantiomorph of the cation. The consequence of this is then near perfect inversion twinning in the structure. In form (B), neighbouring chains are always inverted, leading to a centrosymmetric space group. The question as to why the polymorphs crystallize at slightly different temperatures has been examined by density functional theory (DFT) and lattice energy calculations and a consideration of packing compactness. The free energy (ΔG) of the crystal lattice for polymorph (A) lies some 52 kJ mol(-1) above that of polymorph (B).

Design, synthesis and bioevaluation of novel 6-(4-Hydroxypiperidino)naphthalen-2-ol-based potential Selective Estrogen Receptor Modulators for breast cancer.

In a study directed towards development of novel Selective Estrogen Receptor Modulators (SERMs), 1-(4-(2-(dialkylamino)ethoxy)benzyl)-6-(4-hydroxypiperidin-1-yl)-2-naphthol and corresponding aryl methyl ethers were synthesized and bioevaluated against the estrogen-responsive human MCF-7 breast cancer cell line. The phenolic analogs displayed little or no activity, but aryl methyl ether analogs showed significant cytotoxic potency. Also, representative compounds from the aryl methyl ether series showed significant binding and antagonistic activity against ERα. Two representative compounds were also evaluated for in vitro membrane permeability, plasma stability as well as in-vivo toxicity in mice. The compounds displayed well-acceptable drug-like in vitro membrane permeability as well as plasma stability and were well-tolerated in experimental mice at 300 mg/kg dose.

Activation and deprotection of F-BODIPYs using boron trihalides.

The activation of F-BODIPYs with boron trihalides, followed by treatment with a nucleophile, effects facile substitution at boron; using water as the nucleophile promotes deprotective removal of the -BF2 moiety and thereby production of the corresponding parent dipyrrin salt in quantitative yield under extremely mild conditions.

Aza-Diels-Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome.

The synthesis of 5-substituted 6,6a-dihydroisoindolo[2,1-a]quinolin-11(5H)-ones via [4 + 2] imino-Diels-Alder cyclization from N-aryl-3-hydroxyisoindolinones and N-vinyl lactams under Lewis acid-catalysed anhydrous conditions is reported. Reactions of N-(2-substituted-aryl)-3-hydroxyisoindolinones with N-vinylpyrrolidone under identical conditions resulted in the formation of 2-(2-substitued-aryl)-3-(2-(2-oxopyrrolidin-1-yl)vinyl)isoindolin-1-one analogues indicating steric hinderance as the cause of deviation. The probable mechanism of the reaction based on the results from X-ray crystallography and molecular modelling is discussed.

Bronsted acid-catalyzed rapid enol-ether formation of 2-hydroxyindole-3-carboxaldehydes.

A one-step Bronsted acid-catalyzed synthetic methodology leading to 3-(alkoxymethylene)indolin-2-ones was developed starting from easily accessible 2-hydroxyindole-3-carboxaldehydes. The procedure simply involves a treatment of differently substituted 2-hydroxyindole-3-carboxaldehydes with various alcohols (primary/secondary/tertiary/allyl/propargyl/benzyl) in the presence of a catalytic amount of Bronsted acids such as [Formula: see text]-toluenesulfonic acid and trifluroacetic acid. A series of 19 indolin-2-one-based enol-ethers were synthesized in excellent yields, which implies the general character of our methodology. The enol-ethers produced could be used as a useful building block for the synthesis of indole-based heterocycles.

Reactions of a cyclodimethylsiloxane (Me2SiO)6 with silver salts of weakly coordinating anions; crystal structures of [Ag(Me2SiO)6][Al] ([Al] = [FAl{OC(CF3)3}3], [Al{OC(CF3)3}4]) and their comparison with [Ag(18-crown-6)]2[SbF6]2.

Two silver-cyclodimethylsiloxane cation salts [AgD6][Al] ([Al] = [Al(ORF)4](1) or [FAl(OR(F))3](2), R(F) = C(CF3)3, D = Me2SiO) were prepared by the reactions of Ag[Al] with D6 in SO2(l). For a comparison the [Ag(18-crown-6)]2[SbF6]2(3) salt was prepared by the reaction of Ag[SbF6] and 18-crown-6 in SO2(l). The compounds were characterized by IR, multinuclear NMR, and single crystal X-ray crystallography. The structures of 1 and 2 show that D6 acts as a pseudo crown ether toward Ag(+). The stabilities and bonding of [MDn](+) and [M(18-crown-6)](+) (M = Ag, Li, n = 4-8) complexes were studied with theoretical calculations. The calculations predicted that D6 adopts a puckered C(i) symmetric structure in the gas phase in contrast to previous reports. 18-Crown-6 was calculated to bind more strongly to Li(+) and Ag(+) than D6. (29)Si[(1)H] NMR results in solution, and calculations in the gas phase established that a hard Lewis acid Li(+) binds more strongly to D6 than Ag(+). A comparison of the [MD(n)](+) complex stabilities showed D7 to form the most stable metal complexes in the gas phase and the solid state and explained why [AgD7][SbF6] was isolated in a previous reaction where ring transformations resulted in an equilibrium of [AgD(n)](+) complexes. In contrast, the isolations of 1 and 2 were possible because the corresponding equilibrium of [AgD(n)](+) complexes was not observed with [Al](-) anions. The formation of the dinuclear complex salt 3 instead of the corresponding mononuclear complex salt was shown to be driven by the gain in lattice enthalpy in the solid state. The bonding to Li(+) in D6 and 18-crown-6 metal complexes was described by a quantum theory of atoms in molecules (QTAIM) analysis to be mostly electrostatic while the bonding to Ag(+) also had a significant charge transfer component. The charge transfer from both D6 and 18-crown-6 to Ag(+) and Li(+) metal ions was depicted by the QTAIM analysis to be of similar strength, and the difference in the stabilities of the complexes was attributed mostly to more attractive electrostatic interactions between 18-crown-6 and the metal ions despite the more negative oxygen atomic charges calculated for D6.

An improved method for the synthesis of F-BODIPYs from dipyrrins and bis(dipyrrin)s.

An improved methodology for the synthesis of F-BODIPYs from dipyrrins and bis(dipyrrin)s is reported. This strategy employs lithium salts of dipyrrins as intermediates that are then treated with only 1 equiv of boron trifluoride diethyletherate to obtain the corresponding F-BODIPYs. This scalable route to F-BODIPYs renders high yields with a facile purification process involving merely filtration of the reaction mixture through Celite in many cases.

Use of F-BODIPYs as a protection strategy for dipyrrins: optimization of BF(2) removal.

We recently reported the first general method for the deprotection of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (F-BODIPYs) involving a microwave-assisted procedure for the removal of the BF(2) moiety, and liberation of the corresponding free-base dipyrrin. Further optimization of the reaction has resulted in a more convenient and accessible protocol. The availability of this new methodology enables BF(2)-complexation to be used as a dipyrrin protection strategy. Herein lies a detailed examination of the deprotection reaction, with a view to optimization and gaining mechanistic insight, and its application in facilitating a multistep synthesis of pyrrolyldipyrrins.

(1,5-Diphenyl-thio-carbazonato-κS)trimethyl-tin(IV).

In the title compound, [Sn(C13H11N4S)(CH3)3], the Sn(IV) atom is coordinated by an S atom from the 1,5-diphenyl-thio-carbazonato (L) ligand [Sn-S 2.4710 (6) Å] and by three methyl groups [Sn-C 2.123 (3)-2.130 (2) Å] in a distorted tetra-hedral geometry. The aromatic rings of the L ligand form a dihedral angle of 2.1 (1)°.

Selective formation of angular tricyclic compounds by ruthenium-mediated ring-rearrangement metathesis.

Unsaturated spirocyclic substrates bearing two alkenyl chains underwent ruthenium-mediated ring-rearrangement metathesis through relaying cyclohexene and cycloheptene moieties to give angularly fused tricyclics. In some instances where two products were expected, high degrees of selectivity were observed. In one instance the structural parameter leading to selectivity was very subtle; in others the transformation favoured the formation of products with a cis-fused cyclohexene moiety. An unusual transformation involving ring-opening, double-bond migration, and then ring-closing was observed.

Cl-BODIPYs: a BODIPY class enabling facile B-substitution.

Cl-BODIPYs, synthesized in high yields from dipyrrins under air- and moisture-free conditions, are extremely facile to substitution at boron compared to their corresponding F-BODIPYs, opening up a new route to BODIPYs functionalized at boron.

Chiral induction via the disassembly of diruthenium(II,III) tetraacetate by chiral diphosphines.

[Ru(2)(µ-O(2)CCH(3))(4)(MeOH)(2)](PF(6)) reacts with chiral diphosphines (R,R)- and (S,S)-chiraphos, leading to disassembly and production of the enantiomers Λ-[Ru(η(2)-O(2)CCH(3))(η(2)-(R,R)-chiraphos)(2)](PF(6)) and Δ-[Ru(η(2)-O(2)CCH(3))(η(2)-(S,S)-chiraphos)(2)](PF(6)) in high yield and purity. X-ray crystallography and solid-state circular dichroism (CD) show that only the indicated isomers are present in the solid state. Solution CD measurements also indicate their predominance in solution.

One-pot synthesis of asymmetric annulated bis(pyrrole)s.

Condensation of activated functionalized pyrroles with acetone results in asymmetric bis(pyrrole)s, formed via ring annulation. The methodology is somewhat general and can be applied to a variety of ketones, as well as to a range of pyrrolic substrates that do not bear electron-withdrawing groups directly adjacent to the pyrrole ring.