Dioxygenase-catalysed cis-dihydroxylation of meta-substituted phenols to yield cyclohexenone cis-diol and derived enantiopure cis-triol metabolites

cis-Dihydroxylation of meta-substituted phenol (m-phenol) substrates, to yield the corresponding cyclohexenone cis-diol metabolites, was catalysed by arene dioxygenases present in mutant and recombinant bacterial strains. The presence of cyclohexenone cis-diol metabolites and several of their cyclohexene and cyclohexane cis-triol derivatives was detected by LC-TOFMS analysis and confirmed by NMR spectroscopy. Structural and stereochemical analyses of chiral ketodiol bioproducts, was carried out using NMR and CD spectroscopy and stereochemical correlation methods. The formation of enantiopure cyclohexenone cis-diol metabolites is discussed in the context of postulated binding interactions of the m-phenol substrates at the active site of toluene dioxygenase (TDO).     

Dissociation kinetics of macrocyclic trivalent lanthanide complexes of 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (DO2A)

The [H(+)]-catalyzed dissociation rate constants of several trivalent lanthanide (Ln) complexes of 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (LnDO2A(+), Ln = La, Pr, Eu, Er and Lu) have been determined in two pH ranges: 3.73-5.11 and 1.75-2.65 at four different temperatures (19-41.0 °C) in aqueous media at a constant ionic strength of 0.1 mol dm(-3) (LiClO(4)). For the study in the higher pH range, i.e. pH 3.73-5.11, copper(II) ion was used as the scavenger for the free ligand DO2A in acetate/acetic acid buffer medium. The rates of Ln(III) complex dissociation have been found to be independent of [Cu(2+)] and all the Ln(III) complexes studied show [H(+)]-dependence at low acid concentrations but become [H(+)]-independent at high acid concentrations. Influence of the acetate ion content in the buffer on the dissociation rate has also been investigated and all the complexes exhibit a first-order dependence on [Acetate]. The dissociation reactions follow the rate law: k(obs) = k(Ac)[Acetate] + K'k(lim)[H(+)]/(1 + K'[H(+)]) where k(AC) is the dissociation rate constant for the [Acetate]-dependent pathway, k(lim) is the limiting rate constant, and K' is the equilibrium constant for the reaction LnDO2A(+) + H(+) ? LnDO2AH(2+). In the lower pH range, i.e. pH 1.75-2.65, the dye indicator, cresol red, was used to monitor the dissociation rate, and all the Ln(III) complexes also show [H(+)]-dependence dissociation pathways but without the rate saturation observed at higher pH range. The dissociation reactions follow the simple rate law: k(obs) = k(H)[H(+)], where k(H) is the dissociation rate constant for the pathway involving monoprotonated species. The absence of an [H(+)]-independent pathway in both pH ranges indicates that LnDO2A(+) complexes are kinetically rather inert. The obtained k(AC) values follow the order: LaDO2A(+) > PrDO2A(+) > EuDO2A(+) > ErDO2A(+) > LuDO2A(+), whereas the k(lim) and k(H) values follow the order: LaDO2A(+) > PrDO2A(+) > ErDO2A(+) > EuDO2A(+) > LuDO2A(+), mostly consistent with their thermodynamic stability order, i.e. the more thermodynamically stable the more kinetically inert. In both pH ranges, activation parameters, ΔH*, ΔS* and ΔG*, for both acetate-dependent and proton-catalyzed dissociation pathways have been obtained for most of the La(III), Pr(III), Eu(III), Er(III) and Lu(III) complexes, from the temperature dependence measurements of the rate constants in the 19-41 °C range. An isokinetic (linear) relationship is found between ΔH* and ΔS* values, which supports a common reaction mechanism.     

An investigation of paint from a mural in the church of Sainte Madeleine, Manas, France

The pigment in brown paint samples taken from a church in the Drôme region of France has been shown to be almost pure 6‐bromoindigo and 6,6′‐dibromoindigo. The composition of the pigment was established by comparison with 6‐bromoindigo and 6,6′‐dibromoindigo standards using atmospheric pressure photoionization combined with liquid chromatography and tandem mass spectrometry. The brown paint samples were taken from a frieze of ca 20 brown images having symmetric tree‐like forms composed of five overlapping filled circles representing foliage. The tree‐like images, simple rather than artistic, had a metallic luster. The molar ratio of 6‐bromoindigo and 6,6′‐dibromoindigo in the brown paint pigment (98:2) is remarkably similar to that of shellfish purple from the Mediterranean Murex brandaris (96.5:3.5) thus, it is possible that the origin of the indigoid compounds in the brown paint pigment is the eastern coast of the Mediterranean Sea. As the production of Tyrian purple ended with the fall of Byzantium in 1453, purple pigment had to have been produced prior to this time. We have conjectured about the circumstances that may account for the use of ‘purple’ in this manner in the Drôme region and how the pigment was transported there from the eastern coast of the Mediterranean Sea during the time of the Crusades. Copyright © 2011 John Wiley & Sons, Ltd.     

Q-band EPR spectroscopy of photogenerated quartet state organic nitreno radicals

Q-band 34 GHz EPR spectra are reported for quartet state 2-(para-nitrenophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl and 3-(para-nitrenophenyl)-1,5,6-triphenylverdazyl reactive intermediates generated from the corresponding azido precursors under frozen matrix photochemical conditions, in situ in a Q-band resonator. Comparison of the Q-band spectra to those generated under conventional X-band (9-10 GHz) conditions shows the much superior resolution of transitions in the g > 2 region of the former. Spectral transitions assigned by line shape simulation yield the zero field splittings for the nitreno-radical species.     

A cross-over inhibitor of the botulinum neurotoxin light chain B: a natural product implicating an exosite mechanism of action

Clostridium botulinum produces the most lethal toxins known to man, as such they are high risk terrorist threats, and alarmingly there is no approved therapeutic. We report the first cross-over small molecule inhibitor of these neurotoxins and propose a mechanism by which it may impart its inhibitory activity.     

Colour coding the co-conformations of a [2]rotaxane flip-switch

Fine-tuning the charge transfer chromophores in a series of [2]rotaxane flip-switches yields a unique optical signal (purple colour) for one of the interactions allowing for facile determination of the position of the flip-switch equilibrium.     

The structure and dynamics of hydrated and hydroxylated magnesium oxide nanoparticles

An understanding of the structure of water on metal oxide nanoparticles is important due to its involvement in a number of surface processes, such as in the modification of transport near surfaces and the resulting impact on crystal growth and dissolution. However, as direct experimental measurements probing the metal oxide-water interface of nanoparticles are not easily performed, we use atomistic simulations using experimentally derived potential parameters to determine the structure and dynamics of the interface between magnesium oxide nanoparticles and water. We use a simple strategy to generate mineral nanoparticles, which can be applied to any shape, size, or composition. Molecular dynamics simulations were then used to examine the structure of water around the nanoparticles, and highly ordered layers of water were found at the interface. The structure of water is strongly influenced by the crystal structure and morphology of the mineral and the extent of hydroxylation of the surface. Comparison of the structure and dynamics of water around the nanoparticles with their two-dimensional flat surface counterparts revealed that the size, shape, and surface composition also affects properties such as water residence times and coordination number.     

Understanding the interfacial properties of nanostructured liquid crystalline materials for surface-specific delivery applications

Nonlamellar liquid crystalline dispersions such as cubosomes and hexosomes have great potential as novel surface-targeted active delivery systems. In this study, the influence of internal nanostructure, chemical composition, and the presence of Pluronic F127 as a stabilizer, on the surface and interfacial properties of different liquid crystalline particles and surfaces, was investigated. The interfacial properties of the bulk liquid crystalline systems with coexisting excess water were dependent on the internal liquid crystalline nanostructure. In particular, the surfaces of the inverse cubic systems were more hydrophilic than that of the inverse hexagonal phase. The interaction between F127 and the bulk liquid crystalline systems depended on the internal liquid crystalline structure and chemical composition. For example, F127 adsorbed to the surface of the bulk phytantriol cubic phase, while for monoolein cubic phase, F127 was integrated into the liquid crystalline structure. Last, the interfacial adsorption behavior of the dispersed liquid crystalline particles also depended on both the internal nanostructure and the chemical composition, despite the dispersions all being stabilized using F127. The findings highlight the need to understand the specific surface characteristics and the nature of the interaction with colloidal stabilizer for understanding and optimizing the behavior of nonlamellar liquid crystalline systems in surface delivery applications.     

Study of the lanthanide-catalyzed, aqueous, asymmetric Mukaiyama aldol reaction

The development of efficient methods for the asymmetric Mukaiyama aldol reaction in aqueous solution has received great attention. We have developed a new series of chiral lanthanide-containing complexes that produce Mukaiyama aldol products with outstanding enantioselectivities. In this paper, we describe an optimized ligand synthesis, trends in stereoselectivity that result from changing lanthanide ions, and an exploration of substrate scope that includes aromatic and aliphatic aldehydes and silyl enol ethers derived from aromatic and aliphatic ketones.