Dendritic metalloporphyrins with a distal H-bond donor as mimics of haemoglobin

We report the synthesis of iron(II) porphyrins functionalised with first- and second-generation dendrons as mimics of haemoglobin. The porphyrin core bears an ethynyl linker pointing towards the centre of the molecule, in an ideal position for the introduction of a series of distal ligands as potential H-bond donors by Pd0-catalysed Sonogashira cross-coupling.     

Surface vibrations of Na(001) and K(001) surfaces

We present the results of a theoretical study of the dynamics of the atom motion of Na(001) and K(001) surfaces. The total electronic energy is calculated using a pseudopotential approach with a confined electron gas as unperturbed system. With this theory the dynamical matrix can he derived without resorting to empirical parametrizations. Surface phonon dispersion curves are reported for the high symmetry directions of the two-dimensional Brillouin zone for ideal and relaxed configurations. The calculated spectra are compared with the results of semi-empirical force constant calculations. The effects of single and multilayer relaxations on the location and the nature of the main surface bands are examined.     

A Heterobimetallic Superoxide Complex formed through O2 Activation between Chromium(II) and a Lithium Cation

The reaction of 1,1,3,3‐tetraphenyl‐1,3‐disiloxandiol (LH₂) with n‐butyllithium and CrCl₂ results in a mononuclear chromium(II) complex ( 1 ) that further reacts with O₂ at low temperatures to yield a mononuclear chromium(III) superoxide complex [L₂CrO₂(THF)][Li₂(THF)₃] ( 2 ). The crystal structure revealed that the chromium superoxido entity is stabilized by the coordination to an adjacent lithium cation. Complex 2 thus contains an unprecedented heterobimetallic [Cr^III(μ‐O₂)Li⁺] core; beyond this it is the first chromium superoxide for which a temperature‐dependent magnetic characterization could be achieved, and the first structurally characterized representative with chromium in an exclusive O‐donor environment.     

Regioselective Pd‐Catalyzed Methoxycarbonylation of Alkenes Using both Paraformaldehyde and Methanol as CO Surrogates

In recent years, considerable effort has focused on the development of novel carbonylative transformations using CO surrogates. Consequently, toxic CO gas can be replaced by more convenient inorganic or organic carbonyl compounds. Herein, the first regioselective methoxycarbonylation of alkenes with paraformaldehyde and methanol as CO substitutes is reported. This new procedure is applicable to a series of alkenes in the presence of a palladium catalyst under relatively mild conditions and is highly atom efficient.     

Biomolecular Fishing for Calixarene Partners by a Chemoproteomic Approach

MS‐based chemical‐proteomics technology is introduced herein as a third general strategy to study the biomolecular recognition properties of given calixarene derivatives. In particular, we demonstrate that a simply designed calix[4]arene derivative 1 a bearing acetamido groups at the exo rim (pAC), when linked to a solid support, is able to fish out a specific protein (PDI protein) from a crude extract of HeLa cells. Western blot and surface plasmon resonance studies confirmed the direct interaction between PDI and the linker‐free pAC derivative 1 b with considerable affinity, and in vitro tests showed its inhibition of PDI chaperone activity. In accordance with the role of PDI in a variety of human cancers, biological tests showed that pAC 1 b was cytotoxic and cytostatic toward CAL‐27 and PC‐3 cancer cell lines in vitro. Docking studies showed that H bonds and hydrophobic interactions contribute to the stabilization of the PDI/pAC complex.     

Sensitivity enhancement in saturation transfer difference (STD) experiments through optimized excitation schemes

Investigation of ligand-protein interactions by the saturation transfer difference (STD) experiment has been well established in the drug discovery process through numerous examples. Thus, binding epitopes may be mapped by comparing signals of the ligand with and without saturation of the protein. Herein, it is shown that a less selective process allows more protons to assist in the saturation of the protein, thereby considerably enhancing the sensitivity of the STD experiment. Increasing the saturation power entails a greater risk of perturbing the ligand; however, an amplitude modulation of the waveform assists this procedure by distributing the applied energy in sidebands.     

Construction of hybrid 1D-0D networks for efficient and accurate blood flow simulations

The one-dimensional (1D) modeling of blood flow in complex networks of vessels and cardiovascular models can result in computationally expensive simulations. The complexity of such networks has significantly increased in the last years, in terms of both enhanced anatomical detail and modeling of physiological mechanisms and mechanical characteristics. To address such issue, the main goal of this work is to present a novel methodology to construct hybrid networks of coupled 1D and 0D vessels and to perform computationally efficient and accurate blood flow simulations in such networks. Departing from both the 1D and lumped-parameter (0D) nonlinear models for blood flow, we propose high-order numerical coupling strategies to solve the 1D, 0D, and hybrid coupling of vessels at junctions. To effectively construct hybrid networks, we explore different a-priori model selection criteria focusing in obtaining the best possible trade-off between computational cost of the simulations and accuracy of the computed solutions for the hybrid network with respect to the 1D network. The achievement of the expected order of accuracy is verified in several test cases. The novel methodology is applied to two different arterial networks, the 37-artery network and the reduced ADAN56 model, where, in order to identify the best performing a-priori model selection criteria, the quantitative assessment of CPU times and errors and the qualitative comparison between results are carried out and discussed.