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LL-III is an anticancer peptide and has the ability to translocate across tumor cell membranes, which indicates that its action mechanism could be non-membranolytic. However, the exact mechanism through which the peptide gains access into the cell cytoplasm is still unknown. Here, we use a plethora of physico-chemical techniques to characterize the interaction of LL-III with liposomes mimicking the lipid matrix of the tumor cell membrane and its effect on the microstructure and thermotropic properties of the membrane. Furthermore, the effect of the presence of Ca

The ternary system water–pentaethyleneglycol monooctyl ether (C8E5)–octyltrimethyl ammonium bromide (C8TAB) has been studied at 25 °C. Accurate c.m.c. values have been determined through spectrofluorimetric measurements, by using DL-tryptophan as a molecular probe. The surfactant intradiffusion coefficients have been measured through the PGSE-NMR technique. Experimental data show the formation of mixed micelles. The compositions of the aqueous and micellar pseudo-phase have been computed over the whole micellar composition range; they indicate that C8E5 has a larger tendency to form aggregates than C8TAB. The aggregation number and the Gibbs energy of mixed micelle formation are calculated and interpreted in terms of interactions among the surfactants in the micellar aggregates. The experimental results have been compared with those predicted by the regular solution model finding reasonable agreement.

The micellization process of three sulfonate surfactants [CH3(CH2)n−1SO3Na (n = 6,8,10), CnSO3Na] has been studied by electron paramagnetic resonance (EPR) spectroscopy by employing TEMPO-choline [4-(N,N-dimethyl-N-(2-hydroxyethyl))ammonium-2,2,6,6-tetramethylpiperidine-1-oxyl chloride, TC) as a spin label. The dependence of both the nitrogen isotropic hyperfine coupling constant (〈AN〉) and the correlation time (τC) of the label on the surfactant molality have been analysed. In order to allow a correct interpretation of the experimental evidence a preliminary study on the factors influencing the EPR spectrum of TC in solution has been performed. EPR spectra of TC in various solvents show that the 〈AN〉 value increases with increasing the solvent polarity and, especially, H-bonding ability. The experimental values have been compared with those obtained by a composite ab initio computational approach, in which 〈AN〉 is determined by a suitable combination of post-Hartree–Fock and density functional calculations. Solvent effects are modelled by using the polarizable continuum model (PCM) and, for solvents with H-bonding ability, by including a few explicit solvent molecules. The experimental and computed values are in good agreement, confirming the reliability of the adopted computational strategy. The effect of the ionic strength on the EPR spectrum of TC in NaCl and Na2SO4 aqueous solution has been also investigated, finding that the 〈AN〉 value is almost constant, whereas τC increases with the electrolyte molality. In surfactants' aqueous solution, both 〈AN〉 and τC of TC, plotted as a function of the surfactant molality, show a slope change, corresponding to the critical micellar composition (c.m.c.). The τC increase can be interpreted in terms of a reduction of the label mobility determined by the strong electrostatic interaction between the TC positive charge and the anionic micelles' surface. The 〈AN〉 decrease can be ascribed to the embedding of the NO moiety of TC in the outer part of the micellar hydrophobic core. By comparing the data collected for the different surfactants, it can be seen that the variation of both τC and 〈AN〉 upon micellization increases with the surfactant chain length. This evidence can be interpreted in terms of an increasing strength of the TC-micelle surface interaction, and of an increasing hydrophobic behaviour of the outer part of the micellar core in which the NO moiety of TC is solubilized. The TC affinity for the micellar pseudo-phase has been estimated by evaluating the distribution coefficient, Kd, of the spin label between the micelles and the aqueous medium. The Kd value increases with the length of the surfactant hydrophobic chain.

A simple mathematical model based on bistationary autocatalytic kinetics is proposed to describe a possible progression of prion disease. The model accounts for both the sporadic and the infectious manifestation of the disease. Peculiarly, it shows how the disease grows if the concentration of the infectious agent (the prion PrPSc) is added to the metabolic system over a threshold concentration, while for a lower concentration the disease cannot grow.

Intradiffusion coefficients of binary mixtures, water-polyethyleneglycol (PEG) (molecular weight 200, 400, 2000, 3400, 10 000 Da), were measured by pulsed gradient spin echo (PGSE)-NMR to determine the mass and concentration effects. The properties of polydisperse samples are compared with those of oligomers, and the e†ect of polydispersity is discussed. The PEG diffusion coefficients approach a constant value at high concentration, indicating the formation of a dynamic network between water and PEG molecules. The stochiometry of this network is evaluated and compared with the result of a model derived from an extension of gelation theory. It was found that at infinite dilution limiting self and mutual diffusion coefficients are not equal : this has been interpreted as an effect of polydispersity.

Mutual diffusion coefficients have been measured, at 25 °C, for binary systems of some ethylene glycol oligomers in aqueous solution over the whole mole fraction range. The results have been combined with activity and intradiffusion data to calculate the velocity cross-correlation coefficients (VCCs). An attempt has been made to explain the results in terms of molecular interactions.

Viscosity, density, diffusion and self-diffusion data have been collected on the system N-methylpyrrolidone–water at 20 °C over the entire composition range. From density and vapour pressure data, affinities, Gαβ(α,β= 1, 2), were computed and compared with the velocity cross-correlation coefficients, fαβ. Good agreement was found between the interpretation of dynamic, fαβ, and thermodynamic, Gαβ, data. Both data are in favour of preferential solute–solvent interactions leading to short-lived hydration aggregates.

An amphiphilic ruthenium-based molecule (DOPURu) with potential antineoplastic activity has been synthesized, and its aggregation behavior in the presence of phospholipids has been investigated. A very rich variety of aggregates has been found, spanning from vesicles to cubic bicontinuous phases. Cubosomes here presented represent one of the first systems with potential use for medical therapy.

Lipid composition of viral envelopes is usually rich in sphingolipids and cholesterol (CHOL). These components have a stiffening effect on the membrane, thus enhancing the energetic barrier to be overcome for its fusion with the T-cell plasma membrane, a fundamental step of the infection process. In this work, we demonstrate that the octapeptide (C8) corresponding to the Trp770–Ile777 sequence of the Feline Immunodeficiency Virus gp36 is highly effective in inducing the fusion of palmitoyl oleoyl phosphatidylcholine (POPC)/sphingomyelin (SM)/CHOL membranes. We analyze the molecular mechanism of the C8–membrane interactions combining Neutron Reflectivity (NR) and Electron Spin Resonance (ESR) experiments, and molecular dynamics simulations. A strict interplay among the different lipids in the peptide-induced fusion mechanism is highlighted. Since CHOL preferentially locates close to SM, POPC molecules remain relatively free to interact with the peptide, driving its positioning at the membrane interface. Here, C8 comes in contact with CHOL-interacting SM molecules, causing a strong perturbation of acyl chain ordering, which is a necessary condition for membrane fusion. Our findings suggest that CHOL rules, by an indirect mechanism, the activity of viral fusion glycoproteins.

In continuation with our studies concerning the synthesis, characterization and biological evaluation of nucleolipidic Ru(III) complexes, a novel design for this family of potential anticancer agents is presented here. As a model compound, a new uridine-based nucleolipid has been prepared, named HoUrRu, following a simple and versatile synthetic procedure, and converted into a Ru(III) salt. Stable formulations of this highly functionalized Ru(III) complex have been obtained by co-aggregation with either the zwitterionic lipid POPC or the cationic DOTAP, which have been subjected to an in-depth microstructural characterization, including DLS, SANS and EPR measurements. The in vitro bioactivity profile of HoUrRu, as a pure compound or in formulation with POPC or DOTAP, reveals high antiproliferative activity against MCF-7 and WiDr human cancer cell lines.

Ruthenium complexes offer new perspectives in cancer therapy; towards this aim we have synthesized a new amphiphilic unimer able to coordinate ruthenium complexes and to form liposomes.