Copper(II), nickel(II) and cobalt(III) complexes of the macrocyclic ligand C-meso-7,14-diphenyl-5,6-butano-12,13-butano-1,4,8,11-tetraazacyclotetradeca-4,11-diene

Summary Metal complexes of the macrocyclic tetraaza ligand C-meso-7,14-diphenyl-5,6-butano-12,13-butano-1,4,8,11-tetraazacyclotetradeca-4,11-diene (L) are described. The copper(II) and nickel(II) complexes, isolated as their perchlorate salts, are 4-coordinate species. Several cobalt(III) complexes,trans-[CoLX₂]⁺(X = Cl^–, Br^–, NO ₂ ^– or N ₃ ^– have also been characterised. The most probable stereochemistry of the ligand in the metal complexes is the C-meso-N-meso arrangements of the chiral centres. The N-meso stereochemistry leads to the bulky phenyl groups lying in equatorial positions. I.r. and d-d spectra are reported for the various complexes described.     

Kinetics and mechanism of the base hydrolysis of thecis-chlorobis(ethylenediamme)(benzimidazole)cobalt(III) cation

Summary The hydrolysis ofcis-[CoCl(en)₂(bzmH)]²⁺ (en=ethylenediamine, bzmH=benzimidazole) has been studied over the pH range 8.31–11.58 at I=0.1 mol dm^–3 and 25°. Potentiometric titration of aqueous solutions of the [Co(en)₂(bzmH)OH₂]³⁺ complex obtained by silver(I) catalysed aquation of the chloro-complex give pK₁=5.81 and pK₂ = 8.84 for Equilibria (1) and (2) at 25° and I=0.1 mol dm^–3. Spectrophotometric titration of the hydroxy complex also gives a value of pK₂=8.88 for the ionisation of the coordinated benzimidazole. The kinetic data can be interpreted in terms of base hydrolysis ofcis-[CoCl(en)₂(bzmH)]²⁺ (k_OH=220 dm³ mol^–1s^–1) andcis-[CoCl(en)₂(bzm)]⁺ (k_OH=14.9 dm³ mol^–1s^–1). Comparisons with the corresponding imidazole and pyridine complexes are made.     

Vanadium bromoperoxidase-catalyzed biosynthesis of halogenated marine natural products

Marine red algae (Rhodophyta) are a rich source of bioactive halogenated natural products. The biogenesis of the cyclic halogenated terpene marine natural products, in particular, has attracted sustained interest in part because terpenes are the biogenic precursors of many bioactive metabolites. The first enzymatic asymmetric bromination and cyclization of a terpene, producing marine natural products isolated from red algae, is reported. Vanadium bromoperoxidase (V-BrPO) isolated from marine red algae (species of Laurencia, Plocamium, Corallina) catalyzes the bromination of the sesquiterpene (E)-(+)-nerolidol producing alpha-, beta-, and gamma-snyderol and (+)-3beta-bromo-8-epicaparrapi oxide. alpha-Snyderol, beta-snyderol, and (+)-3beta-bromo-8-epicaparrapi oxide have been isolated from Laurencia obtusa, and each have also been isolated from other species of marine red algae. gamma-Snyderol is a proposed intermediate in other bicyclo natural products. Single diastereomers of beta-snyderol, gamma-snyderol, and mixed diastereomers of (+)-3beta-bromo-8-epicaparrapi oxide (de = 20-25%) are produced in the enzyme reaction, whereas two diastereomers of these compounds are formed in the synthesis with 2,4,4,6-tetrabromocyclohexa-2,5-dienone (TBCO). V-BrPO likely functions by catalyzing the two-electron oxidation of bromide ion by hydrogen peroxide producing a bromonium ion or equivalent in the active site that brominates one face of the terminal olefin of nerolidol. These results establish V-BrPO's role in the biosynthesis of brominated cyclic sesquiterpene structures from marine red algae for the first time.     

Novel fluorinated poly(aryl ether ketone)s

Two novel fluorinated monomers were prepared and polymerized with biphenols to produce amorphous, thermally stable poly(aryl ether ketone)s. The properties of the fluorinated polymers are compared to those of unfluorinated, amorphous poly(aryl ether ketone)s. The presence of fluorine in the polymers was found to cause a decrease in glass transition temperature and Young's moduli, however, no increase in thermal stability was observed. The fluorinated polymers are soluble in common organic solvents such as chloroform and methylene chloride at room temperature, and also show solubility in solvents containing a ketonic moiety, such as acetone. Evidence of polymer branching through fluorines considered to be unreactive under the polymerization conditions was found. Efforts were made to evaluate the reactivity of fluorine atoms under the polymerization conditions using both molecular modeling and ¹⁹F-NMR to ascertain if such branching could be avoided. © 1995 John Wiley & Sons, Inc.     

Guest control of diol inclusion host lattices

A survey of the multimolecular inclusion compounds formed bysyn-2,syn-7-dihydroxy-2,7-dimethyltricyclo[4.3.1.1^3,8]undecane1 and 34 guest molecules shows that two inclusion crystal structures are commonly obtained, namely the helical tubulate inclusion lattice and the ellipsoidal clathrate structure type. Interactions between host and guest are necessarily weak since the host surface is hydrocarbon. Small differences in the guest molecules can tip the balance between alternative inclusion lattices, one of which is chiral. For the first time precise guest locations in the helical tubulate structure have been obtained by X-ray diffraction analysis. Crystal data:1·CCl₄: space groupP3 ₁21,a=13.2812(2),c=6.904(1) Å, unit cell contents 3(C₁₃H₂₂O₂) + 1.2CCl₄,R=0.044;1·BrCH₂CH₂CH₂Br: space groupP3 ₁21,a=13.206(2),c=6.915(2) Å, unit cell contents 3(C₁₃H₂₂O₂)+ BrCH₂CH₂CH₂Br,R=0.042;1.0- xylene: space groupP3 ₁21,a=13.380(2),c=6.905(1) Å, unit cell contents 3(C₁₃H₂₂O₂) + 1.2 C₈H₁₀,R=0.042.     

The preparation and characterisation of chromium(III) complexes of C-meso-5, 12-dimethyl-1, 4, 8, 11-tetraazacyclotetradecane (LM). Aquation and base hydrolysis kinetics ofcis- andtrans-[CrLMCl2]+

Summary The reaction of [CrCl₃(DMF)₃] with C-meso-5, 12-dimethyl-1, 4, 8, 11-tetra-azacyclotetradecane(L_M) in DMF gives a mixture ofcis-[CrL_MCl₂]Cl (ca. 90%) andtrans-[CrL_MCl₂]Cl (ca. 10%). These complexes are readily separated, as thecis-isomer is insoluble in warm methanol while thetrans-isomer is soluble. Using the dichlorocomplexes as precursors it has been possible to prepare a range ofcis-[CrL_MX₂]⁺ complexes (X=Br^–, NO ₃ ^– , N ₃ ^– , NCS^– and X₂=bidentate oxalate) and alsotrans-[CrL_MX₂]⁺ complexes (X=Br^–, H₂O or NCS^–). The spectroscopic properties and detailed stereochemistry of the complexes are discussed.The aquation and base hydrolysis kinetics ofcis- andtrans-[CrL_MCl₂]⁺ have been studied at 25° C. Base hydrolysis of thecis-complex is extremely rapid with K_OH =1.46×10⁵ dm³ mol^–1 at 25° C. This unusual reactivity appears to be associated with thetrans II stereochemistry of thesec-NH centres of the macrocycle. Base hydrolysis of thetrans complex with thetrans III chiral nitrogen stereochemistry is quite normal with k_OH =1.1 dm³ mol^–1 s^–1 at 25° C.     

Some observations on the systems Co2(CO)8/sodium amalgam and Hg[Co(CO)4]2/sodium amalgam,and the effect of added LiBr

Co₂(CO)₈ and Hg[Co(CO)₄]₂ react sodium amalgam and/or mercury in ethereal solvents to give a variety of products. On treatment with aqueous M(o-phen)₃Cl₂(M  Fe, Ni), the anions [Co(CO)₄^?, [Co₃(CO)₁₀]^?, {Hg[Co(CO)₄]₃}^? and {Hg[Co(CO)₄]₂Cl}^? could be isolated as their [M(o-phen)₃]²⁺ salts. The effect of LiBr on the reacting systems was also investigated and the anion {Hg[Co(CO)₄]₂Br}^? isolated.     

Bis[pyrrolyl Ru(ii)] triads: a new class of photosensitizers for metal–organic photodynamic therapy

A new family of ten dinuclear Ru(ii) complexes based on the bis[pyrrolyl Ru(ii)] triad scaffold, where two Ru(bpy)₂ centers are separated by a variety of organic linkers, was prepared to evaluate the influence of the organic chromophore on the spectroscopic and in vitro photodynamic therapy (PDT) properties of the compounds. The bis[pyrrolyl Ru(ii)] triads absorbed strongly throughout the visible region, with several members having molar extinction coefficients (ε) ≥ 10⁴ at 600–620 nm and longer. Phosphorescence quantum yields (Φ_p) were generally less than 0.1% and in some cases undetectable. The singlet oxygen quantum yields (Φ_Δ) ranged from 5% to 77% and generally correlated with their photocytotoxicities toward human leukemia (HL-60) cells regardless of the wavelength of light used. Dark cytotoxicities varied ten-fold, with EC₅₀ values in the range of 10–100 μM and phototherapeutic indices (PIs) as large as 5400 and 260 with broadband visible (28 J cm^–2, 7.8 mW cm^–2) and 625 nm red (100 J cm^–2, 42 mW cm^–2) light, respectively. The bis[pyrrolyl Ru(ii)] triad with a pyrenyl linker (5h) was especially potent, with an EC₅₀ value of 1 nM and PI > 27 000 with visible light and subnanomolar activity with 625 nm light (100 J cm^–2, 28 mW cm^–2). The lead compound 5h was also tested in a tumor spheroid assay using the HL60 cell line and exhibited greater photocytotoxicity in this more resistant model (EC₅₀ = 60 nM and PI > 1200 with 625 nm light) despite a lower dark cytotoxicity. The in vitro PDT effects of 5h extended to bacteria, where submicromolar EC₅₀ values and PIs >300 against S. mutans and S. aureus were obtained with visible light. This activity was attenuated with 625 nm red light, but PIs were still near 50. The ligand-localized ³ππ* state contributed by the pyrenyl linker of 5h likely plays a key role in its phototoxic effects toward cancer cells and bacteria.     

Methodological approaches for the study of GABA<Subscript>A</Subscript> receptor pharmacology and functional responses

Inhibitory GABA_A receptor ion channels are the target for a wide range of clinically-used therapeutic agents. The complex structural diversity of these ligand-gated channels, revealed by molecular cloning studies, together with increasing requirements for higher-throughput functional assays in drug discovery, has led to the development of a wide range of techniques to examine GABA_A receptor pharmacology and function. In the current article we review some of the methodologies which have contributed to the expansion of knowledge in this field. The techniques include: molecular approaches, immunoprecipitation, and immunopurification to study receptor assembly, structure, and functional expression; in situ hybridization, immunocytochemistry, and autoradiography to examine receptor distribution in native tissues; radioligand binding, site-directed mutagenesis, and electrophysiology to examine pharmacology and allosteric modulation; and patch clamp, ion flux, microphysiometry, and a variety of novel fluorescence-based technologies to examine ion-channel function. The use of gene targetting approaches in transgenic mice has also provided important insights into the role of specific GABA_A receptor subtypes in vivo. The continuing evolution of novel technologies and assay approaches with appropriate sensitivity and resolution to measure subtle modulation of GABA_A ion channels will facilitate ongoing investigation of the physiological functions of these important inhibitory receptors.