Cyclic RGD peptidomimetics containing bifunctional diketopiperazine scaffolds as new potent integrin ligands

The synthesis of eight bifunctional diketopiperazine (DKP) scaffolds is described; these were formally derived from 2,3-diaminopropionic acid and aspartic acid (DKP-1-DKP-7) or glutamic acid (DKP-8) and feature an amine and a carboxylic acid functional group. The scaffolds differ in the configuration at the two stereocenters and the substitution at the diketopiperazinic nitrogen atoms. The bifunctional diketopiperazines were introduced into eight cyclic peptidomimetics containing the Arg-Gly-Asp (RGD) sequence. The resulting RGD peptidomimetics were screened for their ability to inhibit biotinylated vitronectin binding to the purified integrins α(v)β(3) and α(v)β(5), which are involved in tumor angiogenesis. Nanomolar IC(50) values were obtained for the RGD peptidomimetics derived from trans DKP scaffolds (DKP-2-DKP-8). Conformational studies of the cyclic RGD peptidomimetics by (1)H?NMR spectroscopy experiments (VT-NMR and NOESY spectroscopy) in aqueous solution and Monte Carlo/Stochastic Dynamics (MC/SD) simulations revealed that the highest affinity ligands display well-defined preferred conformations featuring intramolecular hydrogen-bonded turn motifs and an extended arrangement of the RGD sequence [Cβ(Arg)-Cβ(Asp) average distance ≥8.8??]. Docking studies were performed, starting from the representative conformations obtained from the MC/SD simulations and taking as a reference model the crystal structure of the extracellular segment of integrin α(v)β(3) complexed with the cyclic pentapeptide, Cilengitide. The highest affinity ligands produced top-ranked poses conserving all the important interactions of the X-ray complex.     

Functionalization of multiwalled carbon nanotubes and their pH-responsive hydrogels with amyloid fibrils

New biocompatible, pH-responsive, and fully fibrous hydrogels have been prepared based on amyloid fibrils hybridized and gelled by functionalized multiwalled carbon nanotubes (MWNTs) far below the gelling concentration of amyloid fibrils. Sulfonic functional groups were introduced on the surfaces of MWNTs either by a covalent diazonium reaction or by physical π-π interactions. The presence of the isoelectric point of amyloid fibrils allows a reversible gelling behavior through ionic interactions with functionalized MWNTs.     

Three-Dimensional Trajectories of Spheroidal Particles in Two-Dimensional Flow Fields

We investigate the motion of homogeneous, spheroidal particles immersed in an incompressible, viscous fluid. We assume the particles to be more dense than the surrounding fluid and small enough that inertia is negligible with respect to viscous forces. We give exact solutions for the motion of the particle’s center of mass for steady, linear flows, either irrotational or without strain. For a weakly strained, two-dimensional, rotational flow we give an asymptotic approximation to the solutions, and we compare it with numerical solutions. In the presence of vorticity we find that the spheroid moves along three-dimensional, non-planar paths. With pure strain the three-dimensionality of the paths is transient. If a two-dimensional rotational flow is perturbed by strain, then the generic path of a spheroid is an open curve, even if all the streamlines of the flow are closed. We conclude by speculating about the significance of these findings for the ecology of phytoplankton.     

Environment-mediated control of a quantum system

Recently, a new approach for the controllability of a two-dimensional quantum system S has been proposed, based on its interaction with an initially uncorrelated two-dimensional probe P whose initial state can be arbitrarily modified. Following this scheme and considering a particular model for the environment, we show that, in some specific cases, the environment-induced entanglement is rich enough to completely control the dynamics of S. Under suitable conditions on the interaction of S, P, and the environment, we prove that the state of S can be driven to an arbitrary target state by varying the initial state of P.     

Quantitative Pólya-Szegö principle for convex symmetrization

We study Pólya-Szegö inequality involving convex symmetrization of functions and anisotropic Dirichlet integrals. A quantitative estimate of the deviation of a function u from its convex symmetral in terms of the gap between their Dirichlet integrals is given.     

Influence of Intermolecular Vibrations on the Electronic Coupling in Organic Semiconductors: The Case of Anthracene and Perfluoropentacene

We have performed classical molecular dynamics simulations and quantum‐chemical calculations on molecular crystals of anthracene and perfluoropentacene. Our goal is to characterize the amplitudes of the room‐temperature molecular displacements and the corresponding thermal fluctuations in electronic transfer integrals, which constitute a key parameter for charge transport in organic semiconductors. Our calculations show that the thermal fluctuations lead to Gaussian‐like distributions of the transfer integrals centered around the values obtained for the equilibrium crystal geometry. The calculated distributions have been plugged into Monte‐Carlo simulations of hopping transport, which show that lattice vibrations impact charge transport properties to various degrees depending on the actual crystal structure.     

Majorana Solutions to the Two-Electron Problem

The two-electron atom is the simplest nontrivial quantum system not amenable to exact solutions. Today, its relevance in the development of quantum mechanics and its pedagogical value within the realm of atomic physics are widely recognized. In this work, an historical review of the known different methods and results devised to study such a problem is presented, with an emphasis to the calculations of the ground state energy of helium. Then we discuss several, related, unpublished results obtained around the same years by Ettore Majorana, which remained unknown till recent times. Among them a general variant of the variational method appears to be particularly interesting, even for current research in atomic and nuclear physics: it takes directly into account, already in the trial wavefunction, the action of the full Hamiltonian operator of a given quantum system. Further relevant contributions, specialized to the two-electron problem, include the introduction of the remarkable concept of an effective nuclear charge different for the two electrons (thus generalizing previous known results) and an application of the perturbative method, where the atomic number Z was treated effectively as a continuous variable. Finally a survey of results, relevant mainly for pedagogical reasons, is given; in particular we focus on simple broad range estimates of the helium ionization potential, obtained by suitable choices for the wavefunction, as well as on a simple alternative to Hylleraas’ method, which led Majorana to first order calculations comparable in accuracy with well-known order 11 results derived, in turn, by Hylleraas.     

Formamide and the origin of life

The complexity of life boils down to the definition: “self-sustained chemical system capable of undergoing Darwinian evolution” (Joyce, 1994) [1]. The term “self-sustained” implies a set of chemical reactions capable of harnessing energy from the environment, using it to carry out programmed anabolic and catabolic functions. We briefly present our opinion on the general validity of this definition.Running anabolic and catabolic functions entails complex chemical information whose stability, reproducibility and evolution constitute the core of what is dubbed genetics.Life as-we-know-it is made of the intimate interaction of metabolism and genetics, both built around the chemistry of the most common elements of the Universe (hydrogen, oxygen, nitrogen, carbon). Other elements like phosphorus and sulphur play important but ancillary and potentially replaceable roles.The reproducible interaction of metabolic and genetic cycles results in the hypercycles of organization and de-organization of chemical information that we consider living entities. In order to approach the problem of the origin of life it is therefore reasonable to start from the assumption that both metabolism and genetics had a common origin, shared a common chemical frame, were embedded in physical–chemical conditions favourable for the onset of both.The most abundant three-atoms organic compound in interstellar environment is hydrogen cyanide HCN, the most abundant three-atoms inorganic compound is water H₂O. The combination of the two results in the formation of formamide H₂NCOH. We have explored the chemistry of formamide in conditions compatible with the synthesis and the stability of compounds of potential pre-genetic and pre-metabolic interest. We discuss evidence showing (i) that all the compounds necessary for the build-up of nucleic acids are easily obtained abiotically, (ii) that essentially all the steps leading to the spontaneous generation of RNA are abiotically possible, (iii) that the key compounds of extant metabolic cycles are obtained in the same chemical frame, often in the same test tube.How close are these observations to a plausible scenario for the origin of life?     

Chain Conformations in the Crystalline Field of Syndiotactic Vinyl Polymers Deriving from 1,3‐Diene Monomers. Analysis by Molecular Mechanics

Summary: Conformational energy calculations on the chain conformation in the crystalline field have been performed for various syndiotactic vinyl polymers deriving from 1,3‐diene monomers. Energy maps as a function of the independent torsion angles have evidenced for all the polymers minima corresponding to highly extended and to helical chains. Energy minimizations as a function of all the internal parameters for the s(2/1)2 and t cm symmetries have allowed the evaluation of the energy differences between chains having the two symmetries and the prediction of the values of the conformational parameters for each polymer. The results have been compared with the experimental data reported in the literature for some of the studied polymers.

Conformational energy map of sPBD12.     

Fruits Vinegar: Quality Characteristics,Phytochemistry, and Functionality

The popularity of fruits vinegar (FsV) has been increased recently as a healthy drink wealthy in bioactive compounds that provide several beneficial properties. This review was designed in the frame of valorization of fruits vinegar as a by-product with high value added by providing overall information on its biochemical constituents and beneficial potencies. It contains a cocktail of bioactive ingredients including polyphenolic acids, organic acids, tetramethylperazine, and melanoidins. Acetic acid is the most abundant organic acid and chlorogenic acid is the major phenol in apple vinegar. The administration of fruits vinegar could prevent diabetes, hypercholesterolemia, oxidative stress, cancer, and boost immunity as well as provide a remarkable antioxidant ability. The production techniques influence the quality of vinegar, and consequently, its health benefits.