Dual mechanism of zinc-proline catalyzed aldol reactions in water

The aldol reaction of acetone with aldehydes in aqueous medium under catalysis by zinc-proline (Zn(L-Pro)2) and secondary amines such as proline, (2S,4R)-4-hydroxyproline (Hyp) and (S)-(+)-1-(2-pyrrolidinomethyl)pyrrolidine (PMP) is shown to proceed by an enamine mechanism, as evidenced by reductive trapping of the iminium intermediate, while the aldol reaction of dihydroxyacetone (DHA) under catalysis by zinc-proline and by general bases such as N-methylmorpholine (NMM) is shown to occur under rate-limiting deprotonation of the alpha-carbon and formation of an enolate intermediate.     

On the nature of metallic nanoparticles obtained from molecular Co3Ru-carbonyl clusters in mesoporous silica matrices

We report on the impregnation of THF solutions of the low-valent heterometallic cluster NEt(4)[Co(3)Ru(CO)(12)] into two mesoporous silica matrices, amorphous xerogels and ordered MCM-41, and a study of its thermal decomposition into metallic nanoparticles by X-ray diffraction, transmission electron microscopy and in situ magnetic measurements under controlled atmospheres. The decomposition of the cluster was monitored as a function of temperature by examining the chemical composition of the particles, their size distributions and their structures as well as their magnetic properties. Treatment under inert atmosphere (i.e. argon) at temperatures below 200 degrees C resulted in the formation of segregated spherical particles of hcp-ruthenium (2.3 +/- 1.0 nm) and hcp-cobalt (3.1 +/- 0.9 nm). The latter is transformed to fcc-cobalt (3.2 +/- 1.0 nm) above 270 degrees C. At higher temperatures, Co-Ru alloying takes place and the Ru content of the particles increases with increasing temperature to reach the nominal composition of the molecular precursor, Co(3)Ru. The particles are more evenly distributed in the MCM-41 framework compared to the disordered xerogel and also show a narrower size distribution. Owing to the different magnetic anisotropy of hcp- and fcc-cobalt, which results in different blocking temperatures, we were able to clearly identify the products formed at the early stages of the thermal decomposition procedure.     

Neomycin-capped aromatic platforms: quadruplex DNA recognition and telomerase inhibition

A series of aminoglycoside-capped macrocyclic structures has been prepared using intramolecular bis-tethering of neomycin on three aromatic platforms (phenanthroline, acridine, quinacridine). Based on NMR and calculations studies, it was found that the cyclic compounds adopt a highly flexible structure without conformational restriction of the aminoglycoside moiety. FRET-melting stabilization measurements showed that the series displays moderate to high affinity for the G4-conformation of human telomeric repeats, this effect being correlated with the size of the aromatic moiety. In addition, a FRET competition assay evidenced the poor binding ability of all macrocycles for duplex DNA and a clear binding preference for loop-containing intramolecular G4 structures compared to tetramolecular parallel G4 DNA. Finally, TRAP experiments demonstrated that the best G4-binder (quinacridine ) is also a potent and selective telomerase inhibitor with an IC(50) in the submicromolar range (200 nM).     

DNA nanomachines and nanostructures involving quadruplexes

DNA is an attractive component for molecular recognition, because of its self-assembly properties. Its three-dimensional structure can differ markedly from the classical double helix. For example, DNA or RNA strands carrying guanine or cytosine stretches associate into four-stranded structures called G-quadruplexes or i-DNA, respectively. Since 2002, several groups have described nanomachines that take advantage of this structural polymorphism. We first introduce the unusual structures that are involved in these devices (i.e., i-DNA and G-quadruplexes) and then describe the opening and closing steps that allow cycling. A quadruplex-duplex molecular machine is then presented in detail, together with the rules that govern its formation, its opening/closing kinetics and the various technical and physico-chemical parameters that play a role in the efficiency of this device. Finally, we review the few examples of nanostructures that involve quadruplexes.     

Effects of structural modification on gene transfection and self-assembling properties of amphiphilic dendrimers

A library of novel amphiphilic, self-assembling dendrimers was designed and synthesised to evaluate the effects of structural changes on transfection efficiency.     

Insights into the self-directed structuring of hybrid organic-inorganic silicas through infrared studies

Fourier transform infrared (FTIR) spectroscopy has been used to probe the organization of the organic fragments in lamellar bridged silsesquioxanes with organic substructures based on alkylene chains of various lengths and urea groups [O1.5Si(CH2)3NHCONH(CH2)nNHCONH(CH2)3SiO1.5] (n = 6, 8-12). The structure and intermolecular interactions (hydrophobic and H-bonding) of these well-defined self-structured hybrid silicas are discussed in relation to their powder X-ray diffraction patterns. The degree of structural order is determined by the length and parity of the alkylene spacer. A concomitant enhancement in the degree of condensation of the inorganic component and a decrease in the strength of the hydrophobic interactions between the organic components are demonstrated. The strength and directionality of the H-bonding are directly correlated to the crystalllinity of the organic-inorganic hybrid materials.     

Hydrophobic distal pocket affects NO-heme geminate recombination dynamics in dehaloperoxidase and H64V myoglobin

The recombination dynamics of NO with dehaloperoxidase (DHP) from Amphitrite ornata following photolysis were measured by femtosecond time-resolved absorption spectroscopy. Singular value decomposition (SVD) analysis reveals two important basis spectra. The first SVD basis spectrum reports on the population of photolyzed NO molecules and has the appearance of the equilibrium difference spectrum between the deoxy and NO forms of DHP. The first basis time course has two kinetic components with time constants of tau(11) approximately 9 ps and tau(12) approximately 50 ps that correspond to geminate recombination. The fast geminate process tau(11) arises from a contact pair with the heme iron in a bound state with S = 3/2 spin. The slow geminate process tau(12) corresponds to the recombination from a more remote docking site >3 A from the heme iron with the greater barrier corresponding to a S = 5/2 spin state. The second SVD basis spectrum represents a time-dependent Soret band shift indicative of heme photophysical processes and protein relaxation with time constants of tau(21) approximately 3 ps and tau(22) approximately 17 ps, respectively. A comparison between the more rapid rate constant of the slow geminate phase in DHP-NO and horse heart myoglobin (HHMbNO) or sperm whale myoglobin (SWMbNO) suggests that protein interactions with photolyzed NO are weaker in DHP than in the wild-type MbNOs, consistent with the hydrophobic distal pocket of DHP. The slower protein relaxation rate tau(22) in DHP-NO relative to HHMbNO implies less effective trapping in the docking site of the distal pocket and is consistent with a greater yield for the fast geminate process. The trends observed for DHP-NO also hold for the H64V mutant of SWMb (H64V MbNO), consistent with a more hydrophobic distal pocket for that protein as well. We examine the influence of solution viscosity on NO recombination by varying the glycerol content in the range from 0% to 90% (v/v). The dominant effect of increasing viscosity is the increase of the rate of the slow geminate process, tau(12), coupled with a population decrease of the slow geminate component. Both phenomena are similar to the effect of viscosity on wild-type Mb due to slowing of protein relaxation resulting from an increased solution viscosity and protein surface dehydration.     

Anion exchange liquid chromatography--inductively coupled plasma-mass spectrometry detection of the Co2+, Cu2+, Fe3+ and Ni2+ complexes of mugineic and deoxymugineic acid

Phytosiderophores, such as mugineic and deoxymugineic acid, are produced by graminaceous plant species in response to Fe deficiency conditions normally experienced in calcareous and alkaline non-calcareous soils. As these phytosiderophores have the ability to form thermodynamically stable complexes with other metal cations present in the growing medium, they have also been implicated in the transport and bioavailability of these metals in the environment. However, routine analytical methodology to detect the various metal complexes formed by these phytosiderophores is lacking. Therefore, as these complexes are negatively charged over a wide range of pH values, anion exchange liquid chromatography (AE LC) coupled to inductively coupled plasma-mass spectrometry (ICP-MS) was investigated as a means to separate and quantify these complexes. The metal-phytosiderophore complexes were prepared at pH 7 and separated by NaOH or NH4NO3 gradient elution on a Dionex AS11 anion exchange column. Of the metals tested only the Co2+ and Ni2+ complexes of mugineic and deoxymugineic acid were detected when using a 0-20mM NaOH gradient elution profile. However, the phytosiderophore complexes of Cu2+ and Fe3+ were also detected when using NH4NO3 as the mobile phase at pH 7. Base-assisted hydrolysis of the latter two complexes is proposed to explain their apparent 'instability' in the high pH NaOH mobile phase. The absolute detection limits of the developed methodologies for these metal complexes ranged from 0.1 to 2.8pmol. As phytosiderophore complexes with Cd2+ and Zn2+ were not detected, it was concluded that the dissociation kinetics of these metal-phytosiderophore complexes were too rapid for these complexes to be observed in the present chromatographic conditions.     

Characterization of UV-transparent capillaries for CEC and CE

This short communication describes features of UV-transparent capillaries employed for CEC and CE. A waveguide effect was observed when using UV-transparent capillaries. Through imaging with SEM, the UV-transparent coating was found to be highly porous unlike polyimide coating, which did not exhibit any porosity at all. Prolonged exposure to several commonly employed solvents with elevated pH caused abrasion of the coating at the capillary tip but no swelling of the UV-transparent coating was observed. Lastly, four different cutting techniques were compared to obtain smooth capillary tips.     

Communication: thermodynamic signatures of cluster formation in fluids with competing interactions

Convergent theoretical evidence, based on self-consistent integral equations for the pair structure and on Monte Carlo simulations, is presented for the existence of small simultaneous jump discontinuities of several thermodynamic and structural properties of systems of colloidal particles with competing short-range attractive and long-range repulsive interactions, under physical conditions close to the onset of particle clustering. The discontinuities thus provide a signature of the transition from a homogeneous fluid phase to a locally inhomogeneous cluster phase.