Streamlined synthesis of phosphatidylinositol (PI), PI3P, PI3,5P2, and deoxygenated analogues as potential biological probes

Highly direct total syntheses of phosphatidylinositol (PI), phosphatidylinositol-3-phosphate (PI3P), phosphatidylinositol-3,5-bisphosphate (PI3,5P2), and a range of deoxygenated versions are reported. Each synthesis is carried out to deliver the target in optically pure form. The key step for each synthesis is a catalytic asymmetric phosphorylation reaction that affects desymmetrization of an appropriate myo-inositol precursor. Elaboration to each target compound is then carried out employing a diversity-oriented strategy from the common precursors. In addition to three natural products, several additional streamlined total syntheses of deoxygenated PI analogues are reported. These syntheses set the stage for high-precision biological investigations of polar headgroup/biological target interactions of these membrane-associated signaling molecules.     

Thermodynamically self-consistent liquid state theories for systems with bounded potentials

The mean spherical approximation (MSA) can be solved semianalytically for the Gaussian core model (GCM) and yields exactly the same expressions for the energy and the virial equations. Taking advantage of this semianalytical framework, we apply the concept of the self-consistent Ornstein-Zernike approximation (SCOZA) to the GCM: a state-dependent function K is introduced in the MSA closure relation which is determined to enforce thermodynamic consistency between the compressibility route and either the energy or virial route. Utilizing standard thermodynamic relations this leads to two differential equations for the function K that have to be solved numerically. Generalizing our concept we propose an integrodifferential-equation-based formulation of the SCOZA which, although requiring a fully numerical solution, has the advantage that it is no longer restricted to the availability of an analytic solution for a particular system. Rather it can be used for an arbitrary potential and even in combination with other closure relations, such as a modification of the hypernetted chain approximation.     

Formation of polymorphic cluster phases for a class of models of purely repulsive soft spheres

We present results from density functional theory and computer simulations that unambiguously predict the occurrence of first-order freezing transitions for a large class of ultrasoft model systems into cluster crystals. The clusters consist of fully overlapping particles and arise without the existence of attractive forces. The number of particles participating in a cluster scales linearly with density, therefore the crystals feature density-independent lattice constants. Clustering is accompanied by polymorphic bcc-fcc transitions, with fcc being the stable phase at high densities.     

Generalized time-dependent conditional linear models under left truncation and right censoring

Consider the model f(S(z|X)){\phi(S(z|X))} = \pmbb(z) [(X)\vec]{\pmb{\beta}(z) {\vec{X}}}, where f{\phi} is a known link function, S(·|X) is the survival function of a response Y given a covariate X, [(X)\vec]{\vec{X}} = (1, X, X ² , . . . , X ^p ) and \pmbb(z){\pmb{\beta}(z)} is an unknown vector of time-dependent regression coefficients. The response is subject to left truncation and right censoring. Under this model, which reduces for special choices of f{\phi} to e.g. Cox proportional hazards model or the additive hazards model with time dependent coefficients, we study the estimation of the vector \pmbb(z){\pmb{\beta}(z)} . A least squares approach is proposed and the asymptotic properties of the proposed estimator are established. The estimator is also compared with a competing maximum likelihood based estimator by means of simulations. Finally, the method is applied to a larynx cancer data set.     

Silver(I) complexation of linked 2,2'-dipyridylamine derivatives. Synthetic, solvent extraction, membrane transport and X-ray structural studies

Synthesis of the 2,2'-dipyridylamine derivatives di-2-pyridylaminomethylbenzene 1, 1,2-bis(di-2-pyridylaminomethyl)benzene 2, 1,3-bis(di-2-pyridylaminomethyl)benzene 3, 2,6-bis(di-2-pyridylaminomethyl)pyridine 4, 1,4-bis(di-2-pyridylaminomethyl)benzene 5, and 1,3,5-tris(di-2-pyridylaminomethyl)benzene 6 are reported together with the single-crystal X-ray structures of 2, 3, and 5. Reaction of individual salts of the type AgX (where X = NO(3)(-), PF(6)(-), ClO(4)(-), or BF(4)(-)) with the above ligands has led to the isolation of thirteen Ag(I) complexes, nine of which have also been characterised by X-ray diffraction. In part, the inherent flexibility of the respective ligands has resulted in the adoption of a range of coordination arrangements. A series of liquid-liquid (H(2)O/CHCl(3)) extraction experiments of Ag(I) with varying concentrations of 1-6 in the organic phase have been undertaken, with the counter ion in the aqueous phase being respectively picrate, perchlorate and nitrate. In general, extraction efficiencies for a given ionophore followed the Hofmeister order of picrate > perchlorate > nitrate; in each case the tris-dpa derivative 6 acting as the most efficient extractant of the six systems investigated. Competitive seven-metal bulk membrane transport experiments (H(2)O/CHCl(3)/H(2)O) employing the above ligands as the ionophore in the organic phase and equimolar concentrations of Co(II), Ni(II), Zn(II), Cu(II), Cd(II), Pb(II) and Ag(I) in the aqueous source phase were also undertaken, with transport occurring against a pH gradient. Under the conditions employed 1 and 5 yielded negligible transport of any of the metals present in the source phase while sole transport selectivity for Ag(I) was observed for 2-4 and 6.     

Characterizing matchings as the intersection of matroids

This paper deals with the problem of representing the matching independence system in a graph as the intersection of finitely many matroids. After characterizing the graphs for which the matching independence system is the intersection of two matroids, we study the function (G), which is the minimum number of matroids that need to be intersected in order to obtain the set of matchings on a graph G, and examine the maximal value, (n), for graphs with n vertices. We describe an integer programming formulation for deciding whether (G)k. Using combinatorial arguments, we prove that (n)(log logn). On the other hand, we establish that (n)O(logn/ log logn). Finally, we prove that (n)=4 for n=5,,12, and sketch a proof of (n)=5 for n=13,14,15.An earlier version appears as an extended abstract in the Proceedings of COMB01 [5]. Supported by the Gerhard-Hess-Forschungs-Förderpreis (WE 1462) of the German Science Foundation (DFG) awarded to R. Weismantel.     

Nonenzymatic peptide-based catalytic asymmetric phosphorylation of inositol derivatives

The ability to use small peptides as catalysts for asymmetric phosphorylation provides opportunities for rapid syntheses of phosphate-containing compounds and natural products. This short review outlines the genesis of this concept and its reduction to practice in the context of concise syntheses of the enantiomeric D-I-1P and D-I-3P targets. The implications for the development of additional site-selective catalysts are discussed.     

Intelligent control of surface hydrophobicity.

Switchable surfaces are highly useful materials with surface properties that change in response to external stimuli. These surfaces can be employed in both research and industrial applications, where the ability to actively control surface properties can be used to develop smart materials and intelligent surfaces. Herein, we review a range of surfaces in which hydrophobicity can be controlled. We present the principal ideas of surface switching, discuss recent developments, explore experimental issues and examine factors that influence surface switching, including the nature of the stimuli, the underlying material, the morphology of the surface and the surrounding environment. We have categorised switchable surfaces according to the stimuli that trigger changes in surface hydrophobicity. These are electrically, electrochemically, thermally, mechanically, photo- and environmentally inducible surfaces. In addition, we review the use of chemical reactions to modify the properties of switchable surfaces and produce changes in the molecular structure and nanoscale features of the surface.     

Selective self-organization of guest molecules in self-assembled molecular boxes

This article describes the synthesis and binding properties of highly selective noncovalent molecular receptors 1(3).(DEB)6 and 3(3).(DEB)6 for different hydroxyl functionalized anthraquinones 2. These receptors are formed by the self-assembly of three calix[4]arene dimelamine derivative molecules (1 or 3) and six diethylbarbiturate (DEB) molecules to give 1(3).(DEB)6 or 3(3).(DEB)6. Encapsulation of 2 occurs in a highly organized manner; that is, a noncovalent hydrogen-bonded trimer of 2 is formed within the hydrogen-bonded receptors 1(3).(DEB)6 and 3(3).(DEB)6. Both receptors 1(3).(DEB)6 and 3(3).(DEB)6 change conformation from staggered to eclipsed upon complexation to afford a better fit for the 2(3) trimer. The receptor selectivity toward different anthraquinone derivatives 2 has been studied using 1H NMR spectroscopy, X-ray crystallography, UV spectroscopy, and isothermal microcalorimetry (ITC). The pi-pi stacking between the electron-deficient center ring of the anthraquinone derivatives 2a-c and 2e-g and the relatively electron-poor melamine units of the receptor is the driving force for the encapsulation of the guest molecules. The selectivity of the hydrogen-bonded host for the anthraquinone derivatives is the result of steric interactions between the guest molecules and the calix[4]arene aromatic rings of the host.