Synthesis and structural characterization of integrally oxidized, metal-free phthalocyanine compounds: [H(2)(pc)][IBr(2)] and [H(2)(pc)](2)[IBr(2)]Br.C(10)H(7)Br

The first integrally oxidized metal-free phthalocyanine compounds have been synthesized by chemical oxidation. Phthalocyanine (H(2)(pc), pc = phthalocyaninato) was oxidized with IBr to afford the compounds [H(2)(pc)][IBr(2)] (1) and [H(2)(pc)](2)[IBr(2)]BrAC(10)H(7)Br (2), whose structures were determined by means of single-crystal X-ray diffraction methods: [H(2)(pc)][IBr(2)], P2(1)/c, a = 8.0272(9) A, b = 21.258(2) A, c = 18.1439(2) A, beta = 113.975(2) degrees, V = 2828.8(5) A(3), T = 153 K, Z = 4; [H(2)(pc)](2)[IBr(2)]Br.C(10)H(7)Br, P, a = 8.4724(6) A, b = 13.5794(10) A, c = 13.8403(10) A, alpha = 90.854(1) degrees, beta = 103.417(1) degrees, gamma = 97.049(1)E degrees, V = 1535.61(19) A(3), T = 153 K, Z = 1. The extended structure of [H(2)(pc)][IBr(2)] comprises slipped columns of pc rings stacked along the a axis in adjacent columns at approximately 70 degrees to one another. IBr(2-) ions occupy the interstitial columns. The extended structure of [H(2)(pc)](2)[IBr(2)]Br.C(10)H(7)Br comprises slant stacks of pc rings along the crystallographic a axis with IBr(2-) ions, Br(-) ions, and disordered 1-bromonaphthalene molecules in the adjacent, parallel columns. The overall reaction for the formation of 1 is 2H(2)(pc) + 4IBr --> 2[H(2)(pc)][IBr(2)] + I(2), and the overall reaction for the formation of 2 (not including solvent) is 2H(2)(pc) + 3IBr --> [H(2)(pc)](2)Br[IBr(2)] + I(2).     

Conjugate acid structure for oxaziridines bearing primary and secondary 2-alky 1 groups

The protonation of five representative oxaziridines is reported for inert solvents (deuterio-chloroform or carbon tetrachloride) where conjugate acid formation may be effected by the addition of about 20% (v/v) TFA. Comparison of the ¹H nmr chemical shifts for neutral and conjugate acid forms suggests that oxaziridines usually undergo protonation on the N-atom under these conditions. For one compound studied, 2-ethyl-3-p-nitrophenyloxaziridine, there is a possibility that protonation occurs on the alternative O-atom. The relevance of these findings to the mechanism of the acid-catalysed hydrolysis of oxaziridines is discussed.     

Pro-domain removal in ASP-2 and the cleavage of the amyloid precursor are influenced by pH

Background

One of the signatures of Alzheimer's disease is the accumulation of aggregated amyloid protein, Aβ, in the brain. Aβ arises from cleavage of the Amyloid Precursor protein by β and γ secretases, which present attractive candidates for therapeutic targeting. Two β-secretase candidates, ASP-1 and ASP-2, were identified as aspartic proteases, both of which cleave the amyloid precursor at the β-site. These are produced as immature transmembrane proteins containing a pro-segment.

Results

ASP-2 expressed in HEK293-cells cleaved the Swedish mutant amyloid precursor at different β-sites at different pHs in vitro. Recent reports show that furin cleaves the pro-peptide of ASP-2, whereas ASP-1 undergoes auto-catalysis. We show that purified recombinant ASP-2 cleaves its own pro-peptide at ph 5 but not pH 8.5 as seen by mass spectrometry, electrophoresis and N-terminal sequencing.

Conclusion

We suggest that ASP-2 processing as well as activity are influenced by pH, and hence the cellular localisation of the protein may have profound effects on the production of Aβ. These factors should be taken into consideration in the design of potential inhibitors for these enzymes.     

Electronic structure of unstable intermediates

The geometry of the linear molecule HBO, has been investigated within the restricted Hartree-Fock LCAO-MO-SCF approximation. The calculated bond lengths for the near Hartree-Fock calculation were R(H-B)=2.1913 bohr, R(B-O)=2.2284 bohr. Several one electron properties have been calculated for the minimum energy configuration.     

Lewis-Base Adducts of Group 11 Metal(I) Compounds. LXXVI Structural Studies in the Copper(I) Halide : Norbornadiene System

The structural characterizations of some copper(I) halide (CuX) adducts with norbornadiene (nbd) are recorded. CuCl : nbd (1:1)₄ (a redetermination), (2:1)_2(|), are systems both based around Cu₄Cl₄ cubane-type cluster arrays. CuBr : nbd (7:3)_(|)( 0.5 MeOH), a complex polymer with 3-symmetry, is believed to be the complex previously described as an adduct of 2:1 stoichiometry. Attempts to obtain an iodide counterpart have resulted in the definition of an ephemeral adduct CuI : MeCN (3:2)_(|). 0.5 C₇H₈ in which, remarkably, the nbd is uncoordinated; the complex is a polymer, related to the [AgX(quinoline)]_(|) (X = Cl, Br) saddle polymer.     

Solventless synthesis of monodisperse Cu2S nanorods, nanodisks, and nanoplatelets

Cu(2)S nanocrystals with disklike morphologies were synthesized by the solventless thermolysis of a copper alkylthiolate molecular precursor. The nanodisks ranged from circular to hexagonal prisms from 3 to 150 nm in diameter and 3 to 12 nm in thickness depending on the growth conditions. High resolution transmission electron microscopy (HRTEM) revealed the high chalcocite (hexagonal) crystal structure oriented with the c-axis ([001] direction) orthogonal to the favored growth direction. This disk morphology is thermodynamically favored as it allows the extension of the higher energy [100] and [110] surfaces with respect to the [001] planes. The hexagonal prism morphology also appears to relate to increased C-S bond cleavage of adsorbed dodecanethiol along the more energetic [100] facets relative to [001] facets. Monodisperse Cu(2)S nanodisks self-assemble into ribbons of stacked platelets. This solventless approach provides a new technique to synthesize anisotropic metal chalcogenide nanostructures with shapes that depend on both the face-sensitive thermodynamic surface energy and the surface reactivity.     

An efficient synthesis of acetylide/trimetal/acetylide molecular wires

Efficient syntheses are reported for incorporating trimetal units of the type M(3)(dpa)(4)(2+) (M = Cr, Co, Ni, and dpa = 2,2'-dipyridylamide) into polyalkynyl assemblies to give the prototypical bis-phenylacetylide complexes M(3)(dpa)(4)(CCPh)(2). Reactions of M(3)(dpa)(4)Cl(2) with LiCCPh have led only to mixtures of products which cocrystallize forming materials of the composition M(3)(dpa)(4)(CCPh)(x)()Cl(2)(-)(x)(). Here we report that acetonitrile complexes [M(3)(dpa)(4)(NCCH(3))(2)](PF(6))(2) react cleanly with LiCCPh in MeCN to afford the desired target molecules in 40-60% yield and in excellent purity. Isolation of the mixed ligand complex [Co(3)(dpa)(4)(NCCH(3))(CCPh)]PF(6) has been accomplished, which suggests that these reactions are stepwise and that it will be possible to synthesize mixed acetylide complexes (i.e., M(3)(dpa)(4)(CCR)(CCR')) via this method.     

An investigation into causes and effects of high cyanide levels in the palladium-catalyzed cyanation reaction

[reaction: see text] The palladium-catalyzed cyanation reaction is known to be sensitive to dissolved cyanide. Investigation into some causes of high levels of dissolved cyanide is presented here, along with a robust solution to this problem.     

Computational and experimental studies of the effect of substituents on the singlet-triplet energy gap in phenyl(carbomethoxy)carbene

The effect of aromatic substitution on the singlet-triplet energy gap in substituted phenyl(carbomethoxy)carbene (X-Ph-C-CO(2)CH(3), PCC) has been explored by time-resolved infrared (TRIR) spectroscopy and gas-phase computational methods. The ground state of para-substituted PCC is calculated to change from the triplet state in p-NO(2)-PCC (Delta G(ST) = 6.1 kcal/mol) to the singlet state in p-NH(2)-PCC (Delta G(ST) = -2.8 kcal/mol). The absence of solvent perturbation in the TRIR spectra of p-N(CH(3))(2)-PCC (which should have electronic properties similar to p-NH(2)-PCC) and parent PCC is consistent with their ground states lying > +/-2 kcal/mol from the next available electronic state, in line with the computational results. The observation of solvent perturbation in the TRIR spectra of p-OCH(3)-PCC and p-CH(3)-PCC implies that their ground states lie < +/-1 kcal/mol from their next available electronic state. This is in agreement with our computational results, which predict a gas-phase Delta G(ST) of -0.8 and 1.6 kcal/mol for p-OCH(3)-PCC and p-CH(3)-PCC as compared to Delta G(ST) values of -3.9 and -1.3 kcal/mol from polarizable continuum model (PCM) calculations with acetonitrile as a solvent. Gas-phase computational results for the meta- and ortho-substituted PCC species are also presented, along with selected linear free energy (LFE) relationships for the para and meta species.     

Efficient synthesis of 3H-imidazo[4,5-b]pyridines from malononitrile and 5-amino-4-(cyanoformimidoyl)imidazoles

1-Aryl-5-amino-4-(cyanoformimidoyl)imidazoles 2 were reacted with malononitrile under mild experimental conditions and led to 3-aryl-5,7-diamino-6-cyano-3H-imidazo[4,5-b]pyridines 5, when the reaction was carried out in the presence of DBU, or to 3-aryl-5-amino-6,7-dicyano-3H-imidazo[4,5-b]pyridines 3, in its absence. Both reactions evolved from the adduct formed by nucleophilic attack of the malononitrile anion to the carbon of the cyanoformimidoyl substituent. A 5-amino-1-aryl-4-(1-amino-2,2-dicyanovinyl)imidazole 4 was isolated when this reaction was carried out in the presence of DBU. The structure of compound 4 was confirmed by spectroscopic methods and by reaction with triethyl orthoformate and with acetic anhydride, leading respectively to 9-aryl-6-(cyanomethylidene)purines 11 and 12. Imidazole 2b was also reacted with ethyl acetoacetate, a carbon acid with a pK(a) comparable to that of malononitrile. Similar reaction conditions were used and the product isolated was a 6-carbamoyl-1,2-dihydropurine 10, showing that a different mechanism was operating in this case.