Lanthanoid/Alkali Metal β‐Triketonate Assemblies: A Robust Platform for Efficient NIR Emitters

The reaction of hydrated lanthanoid chlorides with tribenzoylmethane and an alkali metal hydroxide consistently resulted in the crystallization of neutral tetranuclear assemblies with the general formula [Ln(Ae ? HOEt)( L )₄]₂ (Ln=Eu³⁺, Er³⁺, Yb³⁺; Ae=Na⁺, K⁺, Rb⁺). Analysis of the crystal structures of these species revealed a coordination geometry that varied from a slightly distorted square antiprism to a slightly distorted triangular dodecahedron, with the specific geometrical shape being dependent on the degree of lattice solvation and identity of the alkali metal. The near‐infrared (NIR)‐emitting assemblies of Yb³⁺ and Er³⁺ showed remarkably efficient emission, characterized by significantly longer excited‐state lifetimes (τ_obs≈37–47 μs for Yb³⁺ and τ_obs≈4–6 μs for Er³⁺) when compared with the broader family of lanthanoid β‐diketonate species, even in the case of perfluorination of the ligands. The Eu³⁺ assemblies show bright red emission and a luminescence performance (τ_obs≈0.5 ms, ${{\Phi}{{{\rm L}\hfill \atop {\rm Ln}\hfill}}}$ ≈35–37 %, η_sens≈68–70 %) more akin to the β‐diketonate species. The results highlight that the β‐triketonate ligand offers a tunable and facile system for the preparation of efficient NIR emitters without the need for more complicated perfluorination or deuteration synthetic strategies.     

Rheological and photophysical investigations of chromonic-like supramolecular mesophases formed by luminescent iridium(III) ionic complexes in water

Luminescent complexes with general formula [(C^N)₂Ir(N^N)]OCOCH₃, where C^N = 2-phenylpyridine (ppy) and N^N = 2,2?-bipyridine (bpy), self-assemble into ordered ‘soft’ viscous mesophases of chromonic type. By changing the ancillary ligand with 1,10-phenanthroline (phen), a new mesomorphic complex was obtained. The self-assembly into ordered liquid crystalline phases of chromonic type in water was investigated by comprehensive rheological and photophysical studies. By changing the ancillary ligand bpy with phen, assembly into smaller, more symetric aggregates is favoured, resulting in lower viscosity and more dynamic mesophase.     

Modulation of ionization and structural properties of weak polyelectrolytes due to 1D, 2D,and 3D confinement

What is the impact of reducing the space available to molecules onto their properties is a fundamental question for capillary systems, molecular biology and transport, protein and material sciences. Possibly influenced by space restriction, ionization degree has rarely been studied for confined polyelectrolytes; Monte Carlo titrations and coarse‐grained models are thus used to investigate structural and ionization changes induced on a single polyelectrolyte chain by confinement into slit (1D), cylindrical (2D), or spherical (3D) cavities. Four polyelectrolyte models differing in chain stiffness and the possible formation of charged hydrogen bonds (c? H? bonds) are studied. Low pH effective ionization constants (pK_a ) of confined chains are lower than for the free species if c? H? bonds can be formed. This is especially evident for 3D‐confined stiff chains, a finding rationalized by the impact of global compression onto chain conformations. If no c? H? bonds are allowed, chain ionization is largely unaffected by 1D or 2D confinement, while it is depressed by 3D. Chain confinement Helmholtz energy (ΔA _conf) was computed as a function of both pH and confining width (W) to gauge the impact of ionization‐induced stiffening onto ΔA _conf versus W behavior, the partition coefficient governing absorption, and the average number of c? H? bond formed. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017 , 55 , 1088–1102     

Mean-Field Pontryagin Maximum Principle

This paper provides a characterization of the optimal average cost function, when the long-run (risk-sensitive) average cost criterion is used. The Markov control model has a denumerable state space with finite set of actions, and the characterization presented is given in terms of a system of local Poisson equations, which gives as a by-product the existence of an optimal stationary policy.     

Fragment‐Based Discovery of a Dual pan‐RET/VEGFR2 Kinase Inhibitor Optimized for Single‐Agent Polypharmacology

Oncogenic conversion of the RET (rearranged during transfection) tyrosine kinase is associated with several cancers. A fragment‐based chemical screen led to the identification of a novel RET inhibitor, Pz‐1. Modeling and kinetic analysis identified Pz‐1 as a type II tyrosine kinase inhibitor that is able to bind the “DFG‐out” conformation of the kinase. Importantly, from a single‐agent polypharmacology standpoint, Pz‐1 was shown to be active on VEGFR2, which can block the blood supply required for RET‐stimulated growth. In cell‐based assays, 1.0 nM of Pz‐1 strongly inhibited phosphorylation of all tested RET oncoproteins. At 1.0 mg kg^?1 day^?1 per os, Pz‐1 abrogated the formation of tumors induced by RET‐mutant fibroblasts and blocked the phosphorylation of both RET and VEGFR2 in tumor tissue. Pz‐1 featured no detectable toxicity at concentrations of up to 100.0 mg kg^?1, which indicates a large therapeutic window. This study validates the effectiveness and usefulness of a medicinal chemistry/polypharmacology approach to obtain an inhibitor capable of targeting multiple oncogenic pathways.     

Modulus of continuity of the coefficients and (non)quasianalytic solutions in the strictly hyperbolic Cauchy problem

In the strictly hyperbolic Cauchy problem, we investigate the relation between the modulus of continuity in the time variable of the coefficients and the well-posedness in Beurling-Roumieu classes of ultradifferentiable functions and functionals. We find well-posedness in nonquasianalytic classes assuming that the coefficients have modulus of continuity tω(1/t) such that . This condition is sharp because, in the case , we provide examples of Cauchy problems which are well-posed only in quasianalytic classes.     

Gradient estimates for the Perona–Malik equation

We consider the Cauchy problem for the Perona–Malik equation

A Real Analyticity Result for Symmetric Functions of the Eigenvalues of a Domain-Dependent Neumann Problem for the Laplace Operator

Let Ω be an open connected subset of for which the imbedding of the Sobolev space W ^1,2(Ω) into the space L ²(Ω) is compact. We consider the Neumann eigenvalue problem for the Laplace operator in the open subset (Ω) of , where is a Lipschitz continuous homeomorphism of Ω onto (Ω). Then we prove a result of real analytic dependence for symmetric functions of the eigenvalues upon variation of . This paper represents an extension of a part of the work performed by P.D. Lamberti in his PhD Thesis at the University of Padova under the guidance of M. Lanza de Cristoforis.     

Rapid determination of short chain carnitines in human plasma by electrospray ionisation-ion trap mass spectrometry using capillary electrophoresis instrument as sampler

A capillary electrophoresis apparatus was used as sampler for flow injection analysis (FIA) in tandem mass spectrometry of L-carnitine and its acetyl- and propionyl-metabolites in human plasma. The capillary electrophoresis instrument was coupled to the ion trap mass spectrometer by an electrospray ionization coaxial sheath liquid interface. The electrophoresis capillary introduced the sample directly into the source by applying a prolonged sample injection. The use of the capillary electrophoresis apparatus miniaturised the FIA procedure, substantially reducing the quantities of solvents and samples used, and allowed rapid automated sequential analyses. The method was optimised and validated using a dialyzed human plasma matrix. The plasma samples were analysed after a simple, rapid deproteinisation procedure with acetonitrile and diluted 70 times before direct injection into the mass spectrometer for product ion scan MS/MS analysis in positive ionisation. The total analysis time was 5 min, including capillary preconditioning and acquisition time (3 min). The method was sensitive, allowing the determination of L-, L-acetyl- and L-propionyl-carnitines at 140, 14 and 3.6 nM concentrations (injected values) corresponding to lower limit of quantitation values in plasma of 10, 1 and 0.25 microM, respectively. The method was processed for full validation and applied to the analysis of L-carnitine and its short chain derivatives in human plasma samples.