Practical Synthesis of Phosphinic Dipeptides by Tandem Esterification of Aminophosphinic and Acrylic Acids under Silylating Conditions

In this report, a synthetic protocol for the preparation of phosphinic dipeptides of type 5 is presented. These compounds serve as valuable building blocks for the development of highly potent phosphinopeptidic inhibitors of medicinally relevant Zn-metalloproteases and aspartyl proteases. The proposed method is based on the tandem esterification of α-aminophosphinic and acrylic acids under silylating conditions in order to subsequently participate in a P-Michael reaction. The scope of the transformation was investigated by using a diverse set of readily available acrylic acids and (R)-α-aminophosphinic acids, and high yields were achieved in all cases. In most examples reported herein, the isolation of biologically relevant (R,S)-diastereoisomers became possible by simple crystallization from the crude products, thus enhancing the operational simplicity of the proposed method. Finally, functional groups corresponding to acidic or basic natural amino acids are also compatible with the reaction conditions. Based on the above, we expect that the practicality of the proposed protocol will facilitate the discovery of pharmacologically useful bioactive phosphinic peptides.     

Liposome-gold nanorod hybrids for high-resolution visualization deep in tissues

The design of liposome-nanoparticle hybrids offers a rich toolbox for the fabrication of multifunctional modalities. A self-assembled liposome-gold nanorod hybrid vesicular system that consists of lipid-bilayer-associated gold nanorods designed to allow deep tissue detection, therapy, and monitoring in living animals using multispectral optoacoustic tomography has been fabricated and characterized in vitro and in vivo.     

Poly(amidoamine)-based dendrimer/siRNA complexation studied by computer simulations: effects of pH and generation on dendrimer structure and siRNA binding

In this work we report, compare and discuss the results obtained from fully atomistic molecular dynamics simulations of generations 4, 5, and 6 of PAMAM-based dendrimers having NH(3) and triethanolamine as cores, forming complexes with a short interfering RNA (siRNA) at different pH values and at physiological ionic strength. By employing a detailed analysis we demonstrate how features such as molecular size, structural details, and protonation level of this category of dendrimers affect the dendrimer/siRNA complexation. Properties like the conformational flexibility of the dendrimer, the effective charge distribution of the assembly, and the level of intra- and intermolecular hydrogen bonding between the two molecular entities are all found to play a significant role in the mutual interactions between the nucleic acid and the hyperbranched molecules. All these features are of key importance in the multifaceted mechanism of dendrimer/gene complexation, and their understanding can provide valuable insight toward the design of more efficient nucleic acid nanocarriers.     

Symmetry breaking and restoration for interacting scalar and gauge fields in Lifshitz type theories

We consider the one-loop effective potential at zero and finite temperature in field theories with anisotropic space–time scaling, with critical exponent z=2$z=2$, including both scalar and gauge fields. Depending on the relative strength of the coupling constants for the gauge and scalar interactions, we find that there is a symmetry breaking term induced at one loop at zero temperature and we find symmetry restoration through a first-order phase transition at high temperature.     

The bimodal theory of plasticity: A form-invariant generalisation

The bimodal plasticity model of fibre-reinforced materials is currently available and applicable only in association with thin-walled fibrous composites containing a family of straight fibres which are conveniently assumed parallel with the x₁-axis of an appropriately chosen Cartesian co-ordinate system. Based on reliable experimental evidence, the model suggests that plastic slip in the composite operates in two distinct modes; the so-called matrix dominated mode (MDM) which depends on a matrix yield stress, and the fibre dominated mode (FDM) which depends also on the fibre yield stress. Each mode is activated by different states of applied stress, has its own yield surface (or surfaces) in the stress space and has its own segment on the overall yield surface of the composite. This paper employs theory of tensor representations and produces a form-invariant generalisation of both modes of the model. This generalisation furnishes the model with direct applicability to relevant plasticity problems, regardless of the shape of the fibres or the orientation of the co-ordinate system. It thus provides a proper mathematical foundation that underpins important physical concepts associated with the model while it also elucidates several technical relevant issues. A most interesting of those issues is the revelation that activation of the MDM plastic regime is possible only if the applied stress state allows the fibres to act like they are practically inextensible. Moreover, activation of the more dominant, between the two MDM plastic slip branches is possible only if conditions of material incompressibility hold, in addition to the implied condition of fibre inextensibility. A direct mathematical connection is thus achieved between basic, experimentally verified concepts of the bimodal plasticity model and a relevant mathematical model originated earlier from the theory of ideal fibre-reinforced materials. An additional issue of discussion involves the number of independent yield stress parameters that the bimodal theory needs to take into consideration. Moreover, an analytical expression is provided of a relatively simple mathematical surface that possesses all known features of the FDM yield surface; currently captured with the aid of both experimental and computational means. The present study is guided by the existing relevant experimental evidence which, however, is principally associated with the plastic behaviour of solids reinforced by strong fibres. Nevertheless, several of the outlined developments are expected to be applicable to composite materials containing a single family of more compliant or even weak fibres.     

Characterization by gas chromatography-mass spectrometry of diterpenoid resinous materials in Roman-age amphorae from northern Greece

A combined gas chromatography-mass spectrometry approach has been used for the characterization of two lumps of resin and 17 adsorbed residues on Roman-age vessels, mainly amphorae, from northern Greece. The data show that a diterpenic resin from plants of the Pinacae family is the main component of the tarry material associated with the analyzed archaeological samples. The identification and mass spectrometric fragmentation of several characteristic diterpenoid biomarkers is discussed. The abundance of secondary products identified in the archaeological samples suggests that the oxidative degradation of abietic acid and dehydroabietic acid to aromatic products was the main pathway. Of particular interest is the presence of characteristic saturated abietane hydrocarbons in one sample, which indicate that a reductive process also occurred on a small scale. The overall similarity in the composition of the residues suggests the common use of pine tar as a waterproofing and sealing agent at different sites in northern Greece during the Roman period.     

Making carbon nanotubes biocompatible and biodegradable

Carbon nanotubes are promising nanomaterials with great potential in the field of nanomedicine for both therapeutic and diagnostic applications. Different approaches have been developed to render this material biocompatible and to modulate any ensuing toxic effects. In the context of medical use, although chemically functionalised carbon nanotubes display reduced toxicity, they are still considered with scepticism due to their perceived non-biodegradability. Recently, it has been demonstrated that functionalised carbon nanotubes can be degraded by oxidative enzymes. This finding is offering a new perspective for the development of carbon nanotubes in medicine. This article highlights recent advances that can act as paradigm-shifts towards the design of biocompatible and biodegradable functionalised carbon nanotubes and allow their translation into the clinic.