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A novel fluorescently labelled synthetic ionophore, based on a cyclic phosphate-linked disaccharide (CyPLOS) backbone and decorated with four tetraethylene glycol tails carrying dansyl units, has been synthesised in 12 steps in 26% overall yield. The key intermediate in the synthetic strategy is a novel glucoside building block, serving through its 2- and 3-hydroxy groups as the anchor point for flexible tetraethylene glycol tentacles with reactive azido moieties at their ends. To test the versatility of this glucoside scaffold, it was preliminarily functionalised with a set of diverse probes--as fluorescent, redox-active or hydrophobic tags--either by reduction of the azides followed by condensation with activated carboxylic acid derivatives, or by a direct coupling with a terminal alkyne in a Cu(I)-promoted 1,3-dipolar cycloaddition. Tagging of the monomeric building block with dansyl residues allowed us to prepare a fluorescent, amphiphilic macrocycle, which was investigated for its propensity to self-aggregate in CDCl(3)--studied by means of concentration-dependent (31)P NMR spectroscopy experiments--and in aqueous solution, in which combined dynamic light scattering (DLS) and small-angle neutron scattering (SANS) measurements provided a detailed physico-chemical analysis of the self-assembled systems, mainly organised in the form of large vesicles. Its ion-transport properties through phospholipid bilayers, determined by HPTS fluorescence assays, showed this compound to be more active than the previously synthesised CyPLOS congeners. Solvent-dependent fluorescence changes for the labelled ionophore in liposome suspension established that the dansyl moieties are dispersed in environments with polarity intermediate between those of CH(2)Cl(2) and propan-2-ol, suggesting that the CyPLOS tentacles infiltrate the mid-polar region of the membranes.

The nine mutual diffusion coefficients D ij (i, j=1-3) of the quaternary system α-cyclodextrin (0.02 M)-L-phenylalanine (0.06 M)-monobutylurea (0.06 M)-H 2 O have been determined at 25 o C. Eight reliable experiments were performed at these mean concentrations by the free-diffusion method with a Gouy optical interferometer. A minimum of three experiments is required to obtain the nine diffusion coefficients

The four diffusion coefficients describing the isothermal interdiffusion transport in the three-component system BaCl2(1)-KCl(2)-H2O(3) at one concentration were measured. The conditions for the growth of convection inside the diffusion boundary (double diffusive convection) were computed according to the theory proposed by McDougall and compared with the experimental results. Good agreement was found between theory and experimental results. In this system, convection at the borders of the boundary grows even if the heavier components BaCl2 and KCl are more concentrated at the bottom of the diffusion boundary.

A rapid new procedure is described for getting the total number of fringes J from Gouy fringe pattern data. This PQ method is exact and the results excellent (within 0.01–0.03 fringe) for ideal systems (Ωj=0 for all j, Q0=0). Such systems include most binaries; for these, the diffusion coefficient is either constant or a polynomial function of concentration with small concentration differences. For multicomponent systems and some binaries, Q0 can be significantly different from 0. In these cases, the PQ method unambiguously gives the integer number of fringes. If in addition Q0/Q1 is larger than 2.0, then J obtained from a second extrapolation procedure is also good.

Two gemini surfactants, [C18CysL5CCK8](2) and [C18CysDTPAGlu](2), containing, respectively, the CCK8 peptide and the DTPAGlu chelating agent or its gadolinium complex have been prepared by linking lipophilic chains through a disulfide bond between two cysteine residues. The two surfactants aggregate in water solution forming pure or mixed micelles, with a critical micellar concentration in the 5 x 10(-6)-5 x 10(-5) mol kg(-1) range, as measured by fluorescence spectroscopy. As indicated by small-angle neutron scattering, the shape and size of the micelles are influenced by the temperature: increasing temperature leads to progressive reduction of the size of the supramolecular aggregates. Cylindrical structures found at lower temperatures (10-40 degrees C) evolve into ellipsoidal micelles at 50-80 degrees C. Furthermore, the surface-exposed CCK8 peptide changes its conformation above a transition temperature of approximately 45 degrees C, going from a beta-sheet to a random-coil structure, as indicated by circular dichroism measurements. The mixed aggregate obtained by coaggregation of the two gemini-based amphiphilic compounds, [C18CysDTPAGlu(Gd)](2) and [C18CysL5CCK8](2) in 70:30 molar ratio, represents the first example of a peptide-containing gemini surfactant as a potential target-selective contrast agent in MRI. In fact, it presents a high relaxivity value of the gadolinium complex, 21.5 mM(-1) s(-1), and the CCK8 bioactive peptide exposed on the external surface is therefore capable of selective targeting of the cholecystokinin receptors.

This article highlights our recent achievements on the development and upgrade of new potential tumor-specific contrast agents for magnetic resonance imaging (MRI) based on gadolinium complexes and peptides, assemblied in amphiphilic supramolecular aggregates. The physico–chemical characterization of these aggregates provides novel and interesting opportunities to investigate surfactant aggregation properties, that may be exploited in several applications such as in medical diagnostics or in drug and gene delivery.

Large unilamellar liposomes formed by the Re LPS (from here below named LOS) from Salmonella enterica serotype minnesota strain 595 (Re mutant) have been prepared by the extrusion techniques. The physico-chemical investigation of these systems has been performed by a combined experimental strategy, which has allowed a characterization at different observation scales, from the morphological to the micro-structural level. Particularly, dynamic light scattering (DLS) measurements have revealed the formation of liposomes with a narrow dimension distribution; small-angle neutron scattering (SANS) measurements have led to an estimation of the thickness of the LOS bilayer, which is consistent with an extended conformation of the acyl chains; electron paramagnetic resonance (EPR) measurements have allowed to investigate the bilayer fluidity, as determined by LOS acyl chain conformation and packing; Pulsed-field-gradient stimulated echo nuclear magnetic resonance (PGSTE-NMR) measurements have shown that water permeability through the LOS bilayer is low. The effect of temperature has been considered. Liposome dimension does not change; however, centered at 30-35 degrees C, a progressive transition of the acyl chain self-organization from a gel to a liquid crystalline phase is detected. Above this temperature, the water permeability through the bilayer increases. The effect of introducing the zwitterionic phospholipid dilauroyl phosphatidylcholine (DLPC) in the liposome formulation have been also analysed. A comparative analysis of the results points out a clear relation between the microstructure of LOS molecules in the bilayer and liposome functional properties.

New nanocarriers are obtained by assembling two amphiphilic monomers: one containing the bioactive peptide CCK8 spaced, by a polydisperse poly(ethylene glycol), from two hydrophobic tails ((C18)2PEG2000CCK8), and the other containing a chelating agent able to give stable radiolabeled indium-111 complexes linked to the same hydrophobic moiety ((C18)2DTPAGlu). The size and shape of the supramolecular aggregates were structurally characterized by dynamic light scattering, small-angle neutron scattering, and cryogenic transmission electronic microscopy. Under the experimental conditions we investigated (pH 7.4 and molar ratio between monomers 30:70), there is the presence of high polydisperse aggregates: rod-like micelles with a radius of approximately 40 A and length >700 A, open bilayer fragments with thickness approximately 65 A, and probably vesicles. The presence of the bioactive peptide well exposed on the external surface of the aggregate allows selective targeting of nanocarriers towards the cholecystokinin receptors overexpressed by the cancerous cells. In vitro binding assays and in vivo biodistribution studies by nuclear medicine experiments using indium-111 are reported. Moreover, preliminary data concerning the drug loading capability of the aggregates and their drug efficiency on the target cells is reported by using the cytotoxic drug doxorubicin. Incubation of receptor-positive and control cells with peptide-containing aggregates filled with doxorubicin shows significantly lower cell survival in receptor-expressing cells relative to the control, for samples incubated in the presence of doxorubicin.

Two novel amphiphilic unimers containing an aliphatic hydrophobic chain (PDA) with two C≡C triple bonds and hydrophilic heads presenting the chelating agent DTPAGlu and the CCK8 bioactive peptide, respectively, have been prepared by solid phase synthesis. Aggregates obtained by mixing together PDA-DTPAGlu, or its Gd(III) complex, and PDA-L2-CCK8 in 70/30 molar ratio before and after a polymerization process carried out by UV irradiation have been structurally characterized by means of small angle neutron scattering. The relaxivity properties of aggregates containing Gadolinium complexes have also been investigated. Elongated mixed micelles have been observed, in which the relaxivity value r 1p for each Gadolinium complex, measured at 20 MHz and 298 K, is around 12 mM–1 s–1.

Diffusion coefficients, densities, and viscosities were measured on the systems (D,L)Norleucine-water and (L)Phenylalanine-water, at 25°C as a function of the amino-acid concentration. For the system (L)Phenylalanine-water enthalpies of dilution were also measured. The experimental results are discussed and compared with some literature data available for the amino-acid series.

Diffusion coefficients in the ternary system {alpha}-cyclodextrin (at one concentration)-L-phenylalanine (at four concentrations)-water have been measured by using the Gouy interferometric technique. The effect of the inclusion equilibrium on the cross-term diffusion coefficients was observed. The measured diffusion coefficients in the ternary systems were used to calculate values of the binding constants. These values are in good agreement with the value obtained from calorimetric studies.

Diffusion coefficients in the ternary system α-cyclodextrin (at one concentration)-(DL) norleucine (at three concentrations)-water have been measured using the Gouy interferometric technique. ― The effect of the inclusion equilibrium on the cross-term diffusion coefficients was observed. ― The measured diffusion coefficients in the ternary systems were used to calculate values of the binding constant. These values are in good agreement with that obtained from calorimetric studies

Diffusion, density, and viscosity data are collected for the systems α-cyclodextrin and β-cyclodextrin in water. Frictional coefficients were computed with the help of literature activity data and a qualitative discussion of their concentration dependence was attempted.

Surface tension, fluorescence quenching, and intradiffusion measurements have been performed on sodium decyl sulfonate and sodium decyl sulfate aqueous solutions in the presence and in the absence of poly(vinylpyrrolidone). Despite their chemical similarity, these two surfactants show differences in their behavior even in binary aqueous solution. In fact, the cmc values are different as are their aggregation numbers. Furthermore, the overall picture of the properties we have studied suggests the presence of a preferential interaction of poly (vinylpyrrolidone) toward sodium decyl sulfate with respect to sodium decyl sulfonate, for which no complex formation has been detected. The aqueous poly(vinylpyrrolidone)sodium decyl sulfate system has been extensively studied in order to obtain details on the micellar aggregates bound on the polymer. This includes an estimation of the number of micellelike clusters per polymer molecule and the number of surfactant molecules present in these micelles.

The effect of the polymer molecular weight on the interaction between pentaethylene glycol n-octyl ether (C8E5) and poly(acrylic acid) (PAA) has been investigated by a combined experimental strategy including tensiometry, potentiometry, calorimetry, fluorescence quenching and intradiffusion (pulsed gradient spin echo-NMR) measurements. PAA samples with an average molecular weight varying in a wide range ( M ¯ w = 2000 , 100,000, 250,000, and 450,000) have been considered. The measurements have been performed at constant polymer concentration (0.1% w/w) with varying surfactant molality. In all the considered systems, at low surfactant concentration, adsorption of surfactant monomers onto the polymer chain has been detected. At a C8E5 molality ( T 1 ) independent of the PAA M ¯ w , surfactant molecules start to aggregate, forming clusters to which the polymer co-participates. Above this concentration, the behavior of the system depends on M ¯ w . In fact, if polymer samples with high molecular weight ( M ¯ w ⩾ 100 , 000 ) are employed, all the added surfactant aggregates onto the polymer leading to the polymer saturation and, subsequently, to free micelles formation. Both saturation and free micellization occur at surfactant concentrations which are independent of the polymer molecular weight. C8E5 aqueous mixtures containing PAA with low molecular weight ( M ¯ w = 2000 ) behaves differently, in that, above T 1 , only a fraction ( ∼ 20 % ) of the added surfactant molecules interact with the polymer, forming aggregates to which more than one PAA chain participate. In this case, C8E5 free micellization occurs before polymer saturation. The experimental evidences have been interpreted in terms of the subtle balance between the various molecular interactions driving the surfactant–polymer aggregation.

The relaxivity behaviour and the structural characterization of new supramolecular aggregates (bilayer structures and micelles) obtained by combining two different amphiphilic monomers are reported. One monomer, (C18)(2)DTPAGlu-Gd, contains a very stable gadolinium complex, and the other, DSPE-PEG(2000)-CCK8, contains the bioactive CCK8 peptide. Samples that contained only DSPE-PEG(2000)-CCK8, or up to 50 % (C18)(2)DTPAGlu-Gd, aggregated as double-layer structures (lamellar aggregates) with a thickness of approximately 80-100 A, as evaluated by SANS measurement and Cryo-TEM imaging. A transition to micelle formation was observed when the amount of (C18)(2)DTPAGlu-Gd in the aggregate was increased. These were rod-like micelles approximately 40 A in radius and >200 A in length. The proton relaxivities for both lamellar aggregates and rod-like micelles were the same (17.2 mM(-1) s(-1)), although the values were the results of different combinations of local and global contributions. The in vitro target selectivity of aggregates that contained the CCK-8 peptide was demonstrated by using nuclear medicine techniques.

The structure of chemically-crosslinked chitosan and chitosan-poly(vinylpyrrolidone) (PVP) hydrogels is investigated by means of the combined use of small-angle neutron scattering (SANS), electron paramagnetic resonance spectroscopy (EPR), intradiffusion, and swelling degree measurements. These hydrogels may be described in terms of an inhomogeneous structure composed by polymer-rich and polymer-poor regions. The polymer-rich regions, whose correlation distance zeta is ranged between approximately 600 and approximately 850 A, are, in turn, characterized by the presence of a network formed by the chemical crosslinks, with a mean correlation distance xi approximately 90 A. The structures of chitosan and chitosan-PVP hydrogels have also been analyzed in the presence of sodium decylsulfate micelles that could provide a multidomain system useful, in principle, for drug delivery applications. Both SANS and EPR measurements show that sodium decylsulfate micelles do not significantly interact with both the gels. Finally, intradiffusion and swelling degree measurements show an improved hydrophilicity of chitosan-PVP gels, even further magnified by the presence of C10OS surfactant.

The structure of poly(vinyl alcohol) (PVA) hydrogels formed as a result of freeze/thaw treatments of aqueous solutions of the polymer (11 wt % PVA) in the freshly prepared state is analyzed through the combined use of small (SANS) and ultrasmall (USANS) angle neutron scattering techniques. The structure of these hydrogels may be described in terms of polymer rich regions, with dimensions of the order of 1-2 microm, dispersed in a water rich phase, forming two bicontinuous phases. The PVA chains in the polymer rich phase form a network where the cross-linking points are mainly crystalline aggregates of PVA having average dimensions of approximately 45 A. The structural organization of freeze/thaw PVA hydrogel membranes does not change either after rehydration of dried gels or in the presence of a tensile force. Finally, addition of surfactant micelles inside the gel provides a formulation with both hydrophobic and hydrophilic regions, which demonstrates the potential of the system for drug delivery. Both SANS and EPR measurements show that sodium decylsulfate (C10OS) micelles do not significantly interact with the PVA gel. Variation of the gel structure by the number of freeze/thaw cycles should modulate the rate of release of an active constituent, for example, in a dermal patch.

The aggregation behavior of an amphiphilic supramolecular system, with potential application as a tumor-specific magnetic resonance imaging contrast agent, has been studied in detail by dynamic light scattering, small-angle neutron scattering and cryotransmission electron microscopy. The system was constituted of mixed aggregates formed by an anionic unimer containing the DTPAGlu, a chelating agent for the paramagnetic Gd3+ ion, and an uncharged unimer containing the bioactive peptide CCK8, capable of directing the assembly toward tumor cells. Mixed aggregates formed by both unimers, and in the case of the DTPAGlu unimer with the chelating agent as free base or as Gd3+ complex, have been investigated. A number of interesting features of the aggregation behavior were revealed: at physiological pH, micelles and bilayer structures were present, whereas upon decreasing solution pH or increasing ionic strength, the formation of bilayer structures was favored. On the basis of the above observations, the aggregating mechanism has been elucidated by considering the screening effect on intra- and interaggregate electrostatic repulsions.

We report the four diffusion coefficients for the lysozyme-MgCl2-water ternary system at 25 degrees C and pH 4.5. The comparison with previous results for the lysozyme-NaCl-water ternary system is used to examine the effect of salt stoichiometry on the transport properties of lysozyme-salt aqueous mixtures. We find that the two cross-diffusion coefficients are very sensitive to salt stoichiometry. One of the cross-diffusion coefficients is examined in terms of common-ion, excluded-volume, and protein-preferential hydration effects. We use the four ternary diffusion coefficients to extract chemical-potential cross-derivatives and protein-preferential interaction coefficients. These thermodynamic data characterize the protein-salt thermodynamic interactions. We demonstrate the presence of the common-ion effect (Donnan effect) by analyzing the dependence of the preferential-interaction coefficient not only with respect to salt concentration but also with respect to salt stoichiometry. We conclude that the common-ion effect and the protein-preferential hydration are both important for describing the lysozyme-MgCl2 thermodynamic interaction.

Mixed supramolecular aggregates, obtained by assembling together two amphiphilic monomers (C(18)H(37))(2)NCO(CH(2))(2)CO(AdOO)(5)-G-CCK8 (AdOO is 8-amino-3,6-dioxaoctanoic acid, CCK8 is C-terminal octapeptide of cholecystokinin) and (C(18)H(37))(2)NCO(CH(2))(2)COLys(DTPAGlu)CONH(2) (DTPAGlu is N,N-bis[2-[bis(carboxyethyl)amino]ethyl]-L-glutamic acid), are characterized for their structural parameters by dynamic light scattering and for their relaxometric properties, in the absence and in the presence of 0.9 wt% NaCl. Two different aggregates (micelles and bilayer structures) are present in the absence of NaCl, while only bilayer structures are observed at physiological ionic strength. The presence of NaCl increases the ionic strength, promoting a decrease in the repulsions between the polar heads and among the aggregates in solution, thus supporting the formation of large-curvature aggregates such as bilayer structures like vesicles. In these conditions the closed, vesicular shape and the large size (hydrodynamic radius of about 300 A) of the aggregates allow a high number of paramagnetic gadolinium complexes and bioactive peptides to be accommodated on the inner and external surfaces . The presence of the salt causes a variation in the structural arrangement of the molecules and a partial rigidification of the assembled Gd(III) complexes on the surface vesicles, reducing their internal motions and giving an approximately 15% higher relaxivity value (r (1p) = 21.0 and 18.6 Mm(-1) s(-1) in the presence and in the absence of NaCl, respectively). The vesicles obtained, for the high relaxivity of each gadolidium complex and for the presence of a surface-exposed bioactive peptide, are very promising candidates as target-selective MRI contrast agents.

In this paper, we present the development of a new potential blood pool contrast agent for magnetic resonance imaging applications (MRA/MRI) based on gadolinium complexes containing amphiphilic supramolecular aggregates. A novel amphiphilic unimer, containing the DTPAGlu chelating agent covalently bound to two C18 alkylic chains, has been synthesized. DTPAGlu is a well-known chelating agent for a wide number of ions such as the paramagnetic metal ion Gd3+ used as contrast agent in MRA/MRI. The wide aggregation behavior of this surfactant, as free base or as gadolinium complex, has been studied and compared by means of dynamic light scattering, small-angle neutron scattering and cryogenic transmission electron microscopy techniques. Near neutral pH in both cases, the dominant aggregates are micelles. The high negative actual charge of the surfactant headgroup causes a strong headgroups repulsion, promoting the formation of large and high curvature aggregates. By decreasing pH and less markedly increasing the ionic strength, we observe a micelle-to-vesicle transition driven by a decreased electrostatic repulsion. A straightforward switch between different aggregation states can be particularly useful in the development of pH-responsive MRA/MRI contrast agents.

The interaction in aqueous solution between either the normal block copolymer poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide): Pluronic PE6200 [(EO)(11)-(PO)(28)-(EO)(11)], or the reverse block copolymer poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide): Pluronic 25R4 [(PO)(19)-(EO)(33)-(PO)(19)] and the surfactants sodium decylsulfate, C(10)OS, decyltrimethyl ammonium bromide, C(10)TAB, and pentaethylene glycol monodecyl ether, C(10)E(5), was investigated and the aggregation behavior of these surfactants with Pluronics was compared. Surface tension measurements show that Pluronics in their non-aggregated state better interact with the anionic surfactant C(10)OS than with cationic and non-ionic ones. The presence of the two Pluronics induces the same lowering of the aggregation number of C(10)OS as shown by fluorescence quenching measurements. The number of polymer chains necessary to bind each C(10)OS aggregate has been estimated to be approximately 6 for PE6200 and approximately 2 for 25R4. Furthermore, this surfactant also induces the same increment in the gyration radius of the polymers as revealed by viscosimetry. Calorimetric results have been reasonably reproduced by applying a simple equilibrium model to the aggregation processes.

Mutual diffusion in a multicomponent system at high level of macromolecular crowding has been investigated for a solution containing a protein and a polymeric precipitant. Specifically, precise mutual diffusion coefficients for the ternary system lysozyme (component 1)-PEG2000 (component 2)-water (component 0) up to 25% in volume of PEG have been determined via Gouy interferometry. Experimental diffusion data, Dij, are compared to those predicted by two semiemprirical equations, which are discussed according to the physics behind them. Dij values are used to analyze the gravitational stability of the protein-polymer aqueous solution, and, in combination with the Onsager reciprocal relations, to evaluate the lysozyme salting out coefficient for addition of PEG (í12). Experimental í12 are in good agreement with those predicted by Lekkerkerker's equation. All the results have been compared to those corresponding, previously determined, for a companion system containing a PEG sample at a different molecular weight, PEG400. The influence of PEG-induced crowding on proteins in physiological or in crystallization media has been discussed.

The phase behavior (temperature vs composition) and microstructure for the two binary systems Pluronic 25R4 [(PO)(19)(EO)33(PO)(19)]-water and Pluronic 25R2 [PO)(21)(EO)(14)(PO)(21)]-water have been studied by a combined experimental approach in the whole concentration range and from 5 to 80 degreesC. The general phase behavior has been identified by inspection under polarized light. Precise phase boundaries have been determined by analyzing H-2 NMR line shape. The identification and microstructural characterization of the liquid crystalline phases have been achieved using small-angle X-ray scattering (SAXS). The isotropic liquid Solution phases have been investigated by self-diffusion measurements (PGSE-NMR method). 25R2 does not form liquid crystals and is miscible with water in the whole concentration range; with increasing temperature, the mixtures split into water-rich and a copolymer-rich solutions in equilibrium. 25R4 shows rich phase behavior, passing. with increasing copolymer concentration, from a water-rich solution to a lamellar and copolymer-rich solution. A small hexagonal phase, completely encircled in the stability region of the water-rich solution, is also present. In water-rich solutions, at low temperatures and low copolymer concentrations, the copolymers are dissolved as independent macromolecules. With increasing copolymer concentrations an interconnected network of micelles is formed in which micellar cores of hydrophobic poly(propylene oxide) are interconnected by poly(ethylene oxide) strands. In copolymer-rich solutions water is molecularly dissolved in the copolymer. The factors influencing the self-aggregation of Pluronic R copolymers (PPO-PEO-PPO sequence) are discussed, and their behavior in water is compared to that of Pluronic copolymers (PEO-PPO-PEO sequence). (C) 2004 Elsevier Inc. All rights reserved.

A detailed structural investigation on mixed micelle aggregates as target-specific contrast agents for magnetic resonance imaging technique has been carried out by way of small angle neutron scattering measurements. These mixed micelles are formed by two new amphiphilic molecules formed by a bioactive peptide and a claw moiety. The first molecule, C18H37CONH(AdOO)(x)-G-CCK8 (C18LxCCK8, x = 2, 5), contains an 18-carbon-atom alkylic chain bound to the C-terminal of the cholecystokinin octapeptide amide (CCK 26-33 or CCK8) and is able to bind to the overexpressed CCK receptor of some tumor cells. The second molecule, C(18)H(37)CONHLys(DTPAGlu)CONH25- (C18DTPAGlu) or its gadolinium complex [C(18)H(37)CONHLys(DTPAGlu)CONH2Gd](2-), C18DTPAGlu(Gd),contains the same 18-carbon-atom alkylic chain bound, through a lysine residue, to the DTPAGlu chelating agent. Small angle neutron scattering measurements have been performed on ternary systems at different total concentrations and at various ratios of the two molecules. The effect of the concentration on the aggregation number as well as on the shape of the micelle has been investigated. Furthermore in order to optimize the exposure of the peptide on the micelle surface, C18LxCCK8 having the spacer L of different length has been used. The pure binary systems of the synthesized molecules are also presented.

Multicomponent diffusion properties for the tetra(ethylene glycol) (PEG4)-sodium chloride-water ternary system are investigated at constant salt concentration (0.5 mol dm-3) and a wide range of PEG4 concentration approaching 3.0 mol dm-3 (60% volume fraction). Cross-velocity correlation (counterflows) for any pair of components in this ternary system is determined. Comparison between the exact multicomponent approach and the pseudobinary approximation, which is based on the assumption that the PEG4-water mixed solvent can be treated as one component, shows how the latter approach is misleading in describing the electrolyte diffusion properties in mixed solvents. Our results show strong coupling between the fluxes of NaCl and PEG4, which is attributed to the NaCl-PEG4 nonpreferential interactions in water. Moreover, the behavior of the NaCl and PEG4 chemical potentials as a function of the system composition can be quantitatiVely extracted from our diffusion measurements with the help of some interesting observations about the viscosity and conductivity properties of the system.

The interaction between pentaethylene glycol n-octyl ether (C8E5) and low-molecular-weight poly(acrylic acid) (PAA, M(w)=2000) in aqueous solution has been investigated by various experimental techniques at constant polymer concentration (0.1% w/w) with varying surfactant molality. Spectrofluorimetry, using pyrene as molecular probe, shows (i) the formation of surfactant-polymer aggregates at a surfactant molality (T(1)) lower than the critical micelle concentration (cmc) of C8E5 in water and (ii) the formation of free micelles at a surfactant molality (T(2)) slightly higher than the cmc. Fluorescence quenching measurements indicate that the presence of PAA induces a lowering of the C8E5 aggregation number. Calorimetry confirms spectrofluorimetric evidence; in addition, it shows the presence of weak interactions below T(1) between monomeric surfactant molecules and the polymer chains. Tensiometry shows that, above T(1), only a low fraction of surfactant molecules interact with the polymer and that free micelle formation occurs before polymer saturation. The peculiarities of the interaction between surfactants and low-molecular-weight polymers have been discussed.

The common approach of neglecting the effect of polydispersity on matter transport leads, in multicomponent systems, to thermodynamic inconsistency at infinite dilution of all of the solutes. Furthermore such an approximation could cause an incorrect determination of the diffusion coefficients if the standard calculation procedures are applied. We present a novel approach to correct for the effect of the polydispersity of a solute on the values of the basic Gouy parameters D A "the reduced height-area ratio" and Q 0 "the area under the Ω graph" used in the Fujita-Gosting procedure to compute the four diffusion coefficients of a ternary system containing a polydisperse component. The proposed procedure satisfies the thermodynamic requirements at infinite solute dilution. To verify the reliability of our method, a series of simulations on the ternary aqueous system containing poly(ethyleneglicol) 200 and poly(ethyleneglicol) 400 in the presence of a monodisperse solute have been performed. For the polymeric sample, Poisson and Zimm - Schultz distributions have been considered. In both cases, our procedure has been applied successfully up to dilute concentration of components present in the system.

In the present work the mixtures water - sodium decylsulfate (C10OS)- poly(vinylpyrrolidone) (PVP) and water - sodium decylsulfonate (C10S) - PVP have been investigated by electron paramagnetic resonance (EPR) spectroscopy employing 4-(N, N-dimethyl-N-(2-hydroxyethyl)) ammonium-2,2,6,6-tetramethyl-piperidine-1-oxyl chloride (TEMPO-choline, TC) as spin probe. TC cations condense on the surface of the aggregates formed by anionic surfactants, acting as counterions, and fit their NO moiety in the outer shell of the hydrophobic core. In water - C10OS - PVP mixtures the nitrogen isotropic hyperfine coupling constant of TC ([A(N)]), reported as a function of the surfactant molality at constant PVP composition, shows two breakpoints: the former ( critical aggregation concentration, c. a. c.) corresponds to the formation of surfactant - polymer clusters while the latter (c(2)) corresponds to the formation of free surfactant micelles. The trend of the correlation time (tau(C)) of the nitroxides in the same system shows that the electrostatic repulsion among the clusters formed onto the PVP macromolecules favours a broadening of the polymer coil and a stiffening of its chain. In contrast, in water - C10S - PVP mixtures no surfactant - polymer interaction could be detected. The effect of the molecular structure of the surfactant headgroup on the surfactant - polymer interaction has been discussed in terms of charge density distribution. In order to further highlight the importance of the headgroup molecular structure on the surfactant association behaviour, the micellisation process of the sodium alkylsulfates (CnOS, n = 6,8,10) has been investigated by the same experimental approach, and the results have been compared with those, previously reported (A. M. Tedeschi, G. D'Errico, E. Busi, R. Basosi and V. Barone, Phys. Chem. Chem. Phys., 2002, 4, 2180, ref. 46), relative to the sodium alkylsulfonates (CnS). CnOS micelles are more ordered and compact with respect to the CnS ones. For the former class of surfactants the electrostatic interaction with TC is stronger and the hydrophobic behaviour of the TC solubilization site is higher.

The interactions in aqueous solution between poly(vinylpyrrolidone) (PVP) and sodium nonanoate (C8COONa), sodium octylsulfonate (C8SNa), lithium perfluorononanoate ( C8FCOOLi), respectively, were investigated. In all the studied systems, the presence of PVP induces a lowering of the aggregation number of the surfactant as evidenced by fluorescence quenching measurements. However, no direct surfactant-polymer interaction has been found for the systems C8COONa PVP and C8SNa PVP. Strong hydrophobic interaction in the system C8FCOOLi PVP has been shown by the fluorescent behavior of pyrene used as a probe. The presence of the fluorinated surfactant induces an increment of similar to14% of the polymer gyration radius, as shown by viscosimetry. Calorimetry confirms the experimental results obtained through fluorescence and shows that the adsorption of C8FCOOLi on PVP is an endothermic process.

The effect of the molecular size of components on preferential solvation analysis has been investigated by studying aqueous solutions of the poly(ethylene glycol) (PEG) homologous chemical series. Precise density data are analyzed for some PEG–water systems, for polymers of molecular weight up to 3400 at 25 °C, at the highest practicable concentrations. The combination of density, activity, and compressibility data allows the evaluation of Kirkwood–Buff integrals for these systems. Data were discussed in terms of preferential solvation, showing that co-operativity takes part to some extent in the PEG–PEG interaction, depending on PEG concentration and molecular weight. The size mismatch between solvent and solute requires a proper reference state, the Matteoli–Shulgin–Ruckenstein state, which takes into account the excluded volume effect. This correction must be applied when considering macromolecular systems, otherwise physically meaningless analyses are developed. Density data at high concentration have been analyzed in order to evaluate progressive aggregation up to network formation, recently proposed for PEG–water systems. The study provides a new picture of aqueous PEG solutions useful for the interpretation of protein precipitation induced by this uncharged polymer. Comparisons with a preferential solvation analysis of the PEG oligomers and with a recent velocity-correlation analysis of PEG polymers have been also made. This paper provides a new picture of PEG–water media, useful to interpret the colloidal stability in the presence of PEG.

The first multicomponent diffusion data ever determined in protein-polymer systems are presented for the system lysozyme(1)-PEG 400(2)-water. Although there are no specific interactions between protein and polymer, the cross-term diffusion coefficient D 21, that links the PEG flow to the protein concentration gradient, is up to 35 times the main-term diffusion coefficient of the protein. This observation can only be due to a "crowding effect" and not to specific interactions, such as electrostatic ones. The exclusion effect is also qualitatively confirmed by the measured counter-flow associated with the protein motion. On the base of a hard core potential, our recent predictive equations are used to predict diffusion coefficients in this ternary system, and a good agreement with the experimental D 21 is obtained. The PEG concentration dependence of the main-term diffusion coefficient of the protein cannot be interpreted exclusively by the excluded volume effect. Some dielectric effect or aggregation phenomena must be invoked to completely describe diffusive behavior in protein-PEG systems. A strong dielectric constant decrease and an anomalous pH dependence on PEG concentration in this system have been observed. We have extended to this nonelectrolyte system a recent procedure for extracting thermodynamic data from ternary diffusion coefficients that uses the Onsager reciprocal relations and the coupling of D ij and second virial coefficient data. Thus we obtained the change of the lysozyme chemical potential with increasing PEG concentration. We emphasize that it is incorrect to neglect the nonideality of PEG-water systems, as was done in some previous preferential solvation analyses.

Intradiffusion coefficients, D, of n-alkyltrimethylammonium bromides [CH(3)-(CH(2))(n-1)-N(CH(3))(3)Br, C(n)TAB] (n=6, 8, 10, 12) in mixtures with heavy water were measured by the PGSE-NMR technique at 25 degrees C. The experimental data permitted evaluation of the influence of the alkyl chain length on the surfactant self-aggregation process. For all the surfactants considered, the D trend showed a slope change corresponding to the critical micellar composition (cmc). In the premicellar composition range, D decreased linearly with the square root of the surfactant molality. The D values extrapolated at infinite dilution were related to the limiting mutual diffusion coefficients, determined through the Taylor dispersion technique. In the micellar composition range, solubilized tetramethylsilane (TMS) molecules were used to determine the micelle intradiffusion coefficient, D(M), from which the aggregate radii and the aggregation numbers were obtained. The decreasing trend of D(M) with increasing surfactant molality was interpreted in terms of interparticle electrostatic repulsion. D(M) values allowed evaluation of the Gouy-Chapman layer thickness. The solvent intradiffusion coefficient in the heavy water-C(n)TAB mixtures, D(w), was also measured. It decreased with increasing surfactant molality. For n=8, 10, 12 the D(w) trend presented a slope change at the cmc, which could be ascribed to the strong decrease in hydration of surfactant molecules upon micellization. Because of its short hydrophobic tail, C(6)TAB exhibited peculiar aggregation behavior. Its cmc, which is poorly marked, is lower than the value predicted by extrapolating the cmc values obtained for the other terms of the series. The C(6)TAB aggregates do not solubilize TMS molecules; the estimated aggregation number is extremely low ( approximately 3). Finally, no abrupt slope change in the solvent intradiffusion coefficient trend was detected. This evidence suggests that C(6)TAB molecules do not micellize in aqueous solution, but form trimers in which the surfactant hydrophobic tails are not hidden from contact with water molecules. Copyright 2001 Academic Press.

The multicomponent approach in the description of molecular diffusion takes into account the correlation of motion between solutes. Here it is shown that this approach is necessary to describe correctly the flows of each component in concentrated solutions of macromolecules, defined `crowded solutions'. Microscopic intuitive considerations make clear this necessity also for hypothetical uncharged hard particles. We present precise measurements of mutual diffusion coefficients relative to five compositions of the ternary system poly(ethylene glycol) (PEG) 400-NaCl-water, changing both the PEG and salt concentrations. The values of the experimental diffusion coefficients for this system seem to be dominated by an excluded volume effect. Our recent predictive equations, proposed to evaluate the diffusion coefficients in a ternary systems of hard sphere solutes, have been tested on the experimental data with reasonable success. The thermodynamic and gravitational stability analysis on the collected data is also reported. By changing the choice of solvent constituent from water to PEG or NaCl, it is clear that the counter-flow related to the polymer flux in crowded solutions is due essentially to the water and not to other constituents.

Recently, some of us have proposed predictive equations for the four diffusion coefficients, Dij, in a ternary system of hard spheres. These equations have been tested successfully for some ternary systems of interest in protein crystallization: mixture of PEGs in aqueous solution, and the system lysozyme–NaCl–H2O. These equations supply the tools for a correct coupled analysis of the diffusion phenomena occurring in crystallization processes. Using the previous approach for the dependence of the four diffusion coefficients on the solute concentrations, a numerical analysis of transport phenomena in a model system that can simulate protein crystal growth has been carried out. The set of equations is based on the incompressible form of the two-dimensional and time dependent Navier–Stokes equations. The hypothesis of variable thermodynamic properties (diffusion and dynamical viscosity) and the Bousinnesq approximation for the momentum equation have been considered. The study has been performed by means of a numerical code based on a finite difference method. The influence of the coupled diffusion has been evaluated at different gravity levels.

The multicomponent approach for the description of liquid diffusion processes includes cross-term diffusion coefficients that describe the interaction between the flows of different solute components. We demonstrate that these cross-term diffusion coefficients can be large and thus necessary for the description of diffusion of polydisperse polymers. In this study, the four mutual diffusion coefficients have been measured at 25 °C for the ternary system PEG 2000 (1) [poly(ethylene glycol) 2000 g mol -1] + PEG 200 (2) [poly(ethylene glycol) 200 g mol -1] + water (0). Diffusion coefficients were measured at solute concentrations of 0.0827 mol dm -3 PEG 2000 and 0.076, 0.2293, and 0.4105 mol dm -3 PEG 200. One of the cross-terms, D 21, varies linearly with the concentration of PEG 200 at a constant concentration of PEG 2000 and, at the highest concentration of PEG 200, was larger than either of the main-diffusion coefficients D 11 and D 22. The diffusion coefficients have been qualitatively interpreted in terms of molecular interactions and the excluded volume effect. We also report binary diffusion coefficients, densities, and viscosities for binary solutions of both PEG 200 and PEG 2000 in water at 25 °C.

Clinical followup was performed in 73 neonates with a prenatal echographic suspicion of uropathy. Of 42 patients with a prenatal suspicion of unilateral hydronephrosis only 15 had pathological obstruction and 2 had multicystic dysplastic kidneys. Among 10 infants with a prenatal suspicion of bilateral hydronephrosis only 1 had true bilateral obstruction and 2 had unilateral obstruction. In 2 patients hydroureteronephrosis seen on prenatal echography was due to massive bilateral vesicoureteral reflux. In this group there was also a multicystic dysplastic kidney and 1 patient with bilateral cystic dysplasia. There was a prenatal suspicion of cystic disease in 8 infants. Postnatally, diagnosis was multicystic dysplastic kidney in 2 patients and a simple renal cyst in 4. The remaining 2 neonates had obstructive uropathy. Finally, of 13 neonates with a prenatal suspicion of anatomical-echo-structural abnormalities a definitive abnormality could be established in only 8. The predictive value of prenatal echography positive for obstructive uropathy was 34.6%.

Intradiffusion coefficients of sodium alkylsulfonates [CH3-(CH2)n-1SO-3 Na+, CnSNa] (n = 5-9, 11) in mixtures with heavy water were measured by the PGSE-NMR technique at 25 degrees C. A slope change in the experimental trends permits the determination of the critical micelle concentration (CMC). In the micellar composition range, solubilized TMS molecules were used to determine the micelle intradiffusion coefficient, from which the micelle radii were obtained. Both the monomer surfactant and the micelle intradiffusion coefficients show a sharp decrease above the CMC. These results can be interpreted in terms of the obstruction effect due to the micelles. The electrostatic repulsion among charged particles strongly enhances this effect. A simple approach that permits the computation of the Gouy-Chapman layer thickness from the experimental coefficients has been proposed and the results are briefly discussed. Copyright 1999 Academic Press.

Isothermal mutual diffusion coefficients (D) have been measured for binary aqueous solutions of sodium alkylsulfonates at 25 degrees C. The diffusion coefficient values drop as the concentration of micelles in the system increases. As the length of the hydrocarbon chain increases, the observed drop in D becomes increasingly sharp and shifts to lower concentrations. When the micellization process is treated as a chemical equilibrium, diffusion coefficients lead to the calculation of the thermodynamic parameters association number, n, and the equilibrium constant, K. These parameters are briefly discussed in connection with the alkyl chain length of the surfactants. Copyright 1999 Academic Press.

Accurate models of protein diffusion are important in a no. of applications, including liq.-liq. phase sepn. and growth of protein crystals for X-ray diffraction studies. In concd. multicomponent protein systems, significant deviations from pseudobinary behavior can be expected. Rayleigh interferometry is used to measure the four elements (Dij)v of the ternary diffusion coeff. matrix for the extensively investigated protein, hen egg-white lysozyme (component 1) in aq. NaCl (component 2) at pH 4.5 and 25 °C. These are the first multicomponent diffusion coeffs. measured for any protein system at concns. high enough to be relevant to modeling and prediction of crystal growth or other phase transitions, and the first for a system involving lysozyme at any concn. The four ternary diffusion coeffs. for the system lysozyme chloride/NaCl/water are reported for lysozyme chloride at 0.60 mM (8.6 mg/mL) and NaCl at concns. of 0.25, 0.50, 0.65, 0.90, and 1.30 M (1.4, 2.8, 3.7, 5.1, and 7.2 wt %), with the latter two compns. being supersatd. One cross-term, (D21)v, is 80-259 times larger than the main term (D11)v and 7-18 times larger than (D22)v. Std. interferometric diagnostic tests indicate that aggregation is unimportant in our expts. We also present binary diffusion coeffs. Dv for lysozyme chloride/water at concns. from 0.43 to 3.08 mM (6.2-44.1 mg/mL), at the same pH and temp. The precision of the results is about 0.1% for the binary diffusion coeffs. and diagonal ternary diffusion coeffs., and about 1-2% for the cross-terms. For the ternary systems investigated, we show that a single pseudobinary diffusion coeff. does not accurately describe diffusive transport, and predictions by simple models such as the Nernst-Hartley equations are inaccurate at the higher concns. considered here. Finally, dynamic light-scattering diffusion coeffs., differing from both our interferometrically measured (Dij)v and a theor. prediction of light-scattering diffusion coeffs. in multicomponent systems, are reported for the same solns. used for the ternary expts. at 1.30 M.

Diffusion coefficients have been measured in the ternary system α-cyclodextrin−sodium benzenesulfonate−water at 25 °C. The higher mobility of the inclusion complex, compared to that of free cyclodextrin, proves that in the presence of binding complexes between solutes it is possible to measure positive cross diffusion coefficients. Previously only negative cross terms have been measured in systems containing cyclodextrin−ligand complexes. A discussion of the concentration dependence of the four diffusion coefficients and of the sign of cross terms is given.

Apparent enthalpies of mixing were measured for various surfactants of the general formula CH3-(CH2)n-1-(OCH2-CH2)mOH(CnEm) in aqueous solution at 25 degreesC. From the experimental data the enthalpies of micellization were obtained. The results are briefly discussed. Copyright 1998 Academic Press.

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.

Diffusion in a boundary between a polymer+solvent solution and non-solvent was treated by accounting for the presence of the four diffusion coefficients that describe the isothermal transport process in a three component system. Diffusion equations were integrated assuming a concentration dependence of diffusion coefficients that account for the thermodynamic conditions on the cross diffusion terms of Eq. (1). The presence of non-zero cross terms promotes an incongruent diffusion of polymer whose concentration increases at the boundary between the polymer+solvent solution and the non-solvent. Although our model describes diffusion in the range of homogeneous solution, this incongruent polymer diffusion is a process similar to that promoted by the solvent evaporation from the polymer+solvent film that some authors suggested as an intermediate step before the film immersion into the coagulation bath to obtain good asymmetric membranes.

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.

Among 8,579 neonates born between February 1, 1981 and March 31, 1987, and cleared by prenatal sonography for significant urinary tract abnormality 158 subsequently were hospitalized because of signs or symptoms of urinary tract disease, predominantly urinary tract infection. Evaluation of these 158 patients revealed 24 with vesicoureteral reflux, 7 with duplicated systems (2 of which showed reflux), 1 with the syndrome of Fraley, 1 with pyelectasis and 5 with mild hydronephrosis (3 secondary to reflux and 2 with diethylenetriaminepentaacetic acid renal scans considered to be nonobstructed). There was no incidence of significant obstructive uropathy that had been missed by the previous prenatal sonography and that surfaced subsequently to cause morbidity in this series. The principal disorder of the urinary tract that may fail prenatal investigation is vesicoureteral reflux.