A Water Molecule Triggers Guest Exchange at a Mono-Zinc Centre Confined in a Biomimetic Calixarene Pocket: a Model for Understanding Ligand Stability in Zn Proteins

In this study, the ligand exchange mechanism at a biomimetic Zn^II centre, embedded in a pocket mimicking the possible constrains induced by a proteic structure, is explored. The residence time of different guest ligands (dimethylformamide, acetonitrile and ethanol) inside the cavity of a calix[6]arene-based tris(imidazole) tetrahedral zinc complex was probed using 1D EXchange SpectroscopY NMR experiments. A strong dependence of residence time on water content was observed with no exchange occurring under anhydrous conditions, even in the presence of a large excess of guest ligand. These results advocate for an associative exchange mechanism involving the transient exo-coordination of a water molecule, giving rise to 5-coordinate Zn^II intermediates, and inversion of the pyramid at the Zn^II centre. Theoretical modelling by DFT confirmed that the associative mechanism is at stake. These results are particularly relevant in the context of the understanding of kinetic stability/lability in Zn proteins and highlight the key role that a single water molecule can play in catalysing ligand exchange and controlling the lability of Zn^II in proteins.     

Chemical Synthesis and Biological Activities of Amaryllidaceae Alkaloid Norbelladine Derivatives and Precursors

Amaryllidaceae alkaloids (AAs) are a structurally diverse family of alkaloids recognized for their many therapeutic properties, such as antiviral, anti-cholinesterase, and anticancer properties. Norbelladine and its derivatives, whose biological properties are poorly studied, are key intermediates required for the biosynthesis of all ~650 reported AAs. To gain insight into their therapeutic potential, we synthesized a series of O-methylated norbelladine-type alkaloids and evaluated their cytotoxic effects on two types of cancer cell lines, their antiviral effects against the dengue virus (DENV) and the human immunodeficiency virus 1 (HIV-1), and their anti-Alzheimer’s disease (anti-cholinesterase and -prolyl oligopeptidase) properties. In monocytic leukemia cells, norcraugsodine was highly cytotoxic (CC₅₀ = 27.0 μM), while norbelladine was the most cytotoxic to hepatocarcinoma cells (CC₅₀ = 72.6 μM). HIV-1 infection was impaired only at cytotoxic concentrations of the compounds. The 3,4-dihydroxybenzaldehyde (selectivity index (SI) = 7.2), 3′,4′-O-dimethylnorbelladine (SI = 4.8), 4′-O-methylnorbelladine (SI > 4.9), 3′-O-methylnorbelladine (SI > 4.5), and norcraugsodine (SI = 3.2) reduced the number of DENV-infected cells with EC₅₀ values ranging from 24.1 to 44.9 μM. The O-methylation of norcraugsodine abolished its anti-DENV potential. Norbelladine and its O-methylated forms also displayed butyrylcholinesterase-inhibition properties (IC₅₀ values ranging from 26.1 to 91.6 μM). Altogether, the results provided hints of the structure–activity relationship of norbelladine-type alkaloids, which is important knowledge for the development of new inhibitors of DENV and butyrylcholinesterase.     

IndecomposableA-module summands inH * V which are unstable algebras

Letp be a prime and denote byA the modp Steenrod algebra. We determine the indecomposableA-module summands ofH*((ℤ/p)) ^d ;F _p which admit the structure of an unstableA-algebra. In fact, it turns out that this is equivalent to the problem of determining those indecomposableA-module summands which arise as the modp cohomology of a space (or even a classifying space of a finite group). We reduce this problem to one in modular representation theory, namely for whichd andp is the projective cover of the trivial one dimensional GL(d,F _p ) representationF _p a permutation module. Our solution of this latter problem makes use of the classification of subgroups of GL(d,F _p ) acting transitively on (F _p ) ^d \{0} and hence depends on the classification of finite simple groups (on Feit-Thompson's odd order theorem ifp=2).     

Thermodynamics of complexation of monovalent metal cations by the ionophore monensin free acid in acetonitrile

The standard Gibbs functions, enthalpies, and entropies for the formation of the complexes of monensin acid with monovalent metal cations in acetonitrile were obtained using various methods (conductometry, potentiometry, and calorimetry). Complexation is appreciable (from 2.0 to 4.5 in terms of association constant logarithm) and controlled mainly by the enthalpic effect. Comparison with formation of the corresponding neutral complexes permits a comparison to the process of monensin mediated transport of cation in membranes. A two-step process involving first the formation of the acidic complex is suggested.     

A roe-type Riemann solver for hyperbolic systems with relaxation based on time-dependent wave decomposition

Summary. The paper is devoted to the construction of a higher order Roe-type numerical scheme for the solution of hyperbolic systems with relaxation source terms. It is important for applications that the numerical scheme handles both stiff and non stiff source terms with the same accuracy and computational cost and that the relaxation variables are computed accurately in the stiff case. The method is based on the solution of a Riemann problem for a linear system with constant coefficients: a study of the behavior of the solutions of both the nonlinear and linearized problems as the relaxation time tends to zero enables to choose a convenient linearization such that the numerical scheme is consistent with both the hyperbolic system when the source terms are absent and the correct relaxation system when the relaxation time tends to zero. The method is applied to the study of the propagation of sound waves in a two-phase medium. The comparison between our numerical scheme, usual fractional step methods, and numerical simulation of the relaxation system shows the necessity of using the solutions of a fully coupled hyperbolic system with relaxation terms as the basis of a numerical scheme to obtain accurate solutions regardless of the stiffness. Received October 7, 1994 / Revised version received September 27, 1995     

Highly ordered metal oxide nanopatterns prepared by template-assisted chemical solution deposition

TiO₂, Al₂O₃, and ZrO₂ patterns composed of ordered nano motifs of various morphologies (i.e. perforations (craters), rings, canyons, wires, dots, or channels) with typical lateral dimensions of less than 40 nm and thickness below 15 nm are presented. Simple chemical solution deposition (CSD) of molecular inorganic precursors and commercial block copolymers was used to create patterns on several substrate surfaces (bare, hydrophobized or gold covered silicon wafers and ITO). Self-assembly during evaporation and subsequent stabilization at 500 °C leads to the various nanostructures. Compared to other techniques for surface nano patterning, the present method has the advantage of being cheap, reproducible and easy to scale up and does not require specialized equipment. The type, dimension, and organization of these motifs were assessed by AFM, FE-SEM, spectroscopic ellipsometry, and GI-SAXS and are shown to depend on the conditions of preparation. Usage as model surfaces for modelling of wetting properties and as nanoelectrode arrays were investigated.     

Low temperature raman evidence for two crystalline phases of methylcyclohexane

Comparison of the lattice mode region of the low-temperature Raman spectrum of MCH and MCH-d₁₄ under various cooling rates shows that there are two crystalline modifications. The molecular mode region frequencies however, remain invariant to cooling rate suggesting a single molecular conformation for both crystalline phases.     

1H and 13C NMR of platinum porphyrins—III. Platinum deuteroporphyrin IX dimethyl ester

¹H and ¹³C NMR spectra of the title compound are reported and peaks assigned by comparison with the free-base porphyrin. Long-range spin—spin coupling is observed between platinum and the macrocyclic protons and carbon atoms. Meso-protons are assigned from line-broadening observed for three of the peaks, possibly caused by residual coupling of these protons to the pyrrole β-protons. Allylic coupling of the pyrrole β-protons to adjacent methyl groups is also noted, and supports the tautomeric model of an 18-atom delocalisation pathway around the macrocycle. The ¹H NMR spectrum of the title compound is more concentration-dependent than that of the free-base porphyrin and probably reflects additional macrocyclic interactions via the platinum atoms.     

Limiting distributions of homogeneous functions of sample spacings for distributions approaching the uniform distribution

Summary X ₁,...,X _n are independent random variables, identically distributed over the unit interval, with common probability density function 1 + r(x)/n for all sufficiently large n, where is a positive constant, and |r(x)| <D. V ₁, ..., V _n+1 are the sample spacings generated by X ₁,..., X _n . It is shown that in many cases, the asymptotic joint distribution of homogeneous functions of V ₁,..., V _n+1 can be found directly from the asymptotic joint distribution of homogeneous functions of independent exponential random variables.Research supported by NSF Grant GP 3783.