Blueprint for a self-sustained European Centre for service provision in safe and sustainable innovation for nanotechnology.

The coming years are expected to bring rapid changes in the nanotechnology regulatory landscape, with the establishment of a new framework for nano-risk governance, in silico approaches for characterisation and risk assessment of nanomaterials, and novel procedures for the early identification and management of nanomaterial risks. In this context, Safe(r)-by-Design (SbD) emerges as a powerful preventive approach to support the development of safe and sustainable (SSbD) nanotechnology-based products and processes throughout the life cycle. This paper summarises the work undertaken to develop a blueprint for the deployment and operation of a permanent European Centre of collaborating laboratories and research organisations supporting safe innovation in nanotechnologies. The proposed entity, referred to as "the Centre", will establish a 'one-stop shop' for nanosafety-related services and a central contact point for addressing stakeholder questions about nanosafety. Its operation will rely on significant business, legal and market knowledge, as well as other tools developed and acquired through the EU-funded EC4SafeNano project and subsequent ongoing activities. The proposed blueprint adopts a demand-driven service update scheme to allow the necessary vigilance and flexibility to identify opportunities and adjust its activities and services in the rapidly evolving regulatory and nano risk governance landscape. The proposed Centre will play a major role as a conduit to transfer scientific knowledge between the research and commercial laboratories or consultants able to provide high quality nanosafety services, and the end-users of such services (e.g., industry, SMEs, consultancy firms, and regulatory authorities). The Centre will harmonise service provision, and bring novel risk assessment and management approaches, e.g. in silico methodologies, closer to practice, notably through SbD/SSbD, and decisively support safe and sustainable innovation of industrial production in the nanotechnology industry according to the European Chemicals Strategy for Sustainability.

Propofol adsorption at the air/water interface: a combined vibrational sum frequency spectroscopy, nuclear magnetic resonance and neutron reflectometry study.

Propofol is an amphiphilic small molecule that strongly influences the function of cell membranes, yet data regarding interfacial properties of propofol remain scarce. Here we consider propofol adsorption at the air/water interface as elucidated by means of vibrational sum frequency spectroscopy (VSFS), neutron reflectometry (NR), and surface tensiometry. VSFS data show that propofol adsorbed at the air/water interface interacts with water strongly in terms of hydrogen bonding and weakly in the proximity of the hydrocarbon parts of the molecule. In the concentration range studied there is almost no change in the orientation adopted at the interface. Data from NR show that propofol forms a dense monolayer with a thickness of 8.4 Å and a limiting area per molecule of 40 Å2, close to the value extracted from surface tensiometry. The possibility that islands or multilayers of propofol form at the air/water interface is therefore excluded as long as the solubility limit is not exceeded. Additionally, measurements of the 1H NMR chemical shifts demonstrate that propofol does not form dimers or multimers in bulk water up to the solubility limit.

Interactions between model cell membranes and the neuroactive drug propofol.

Vibrational sum frequency spectroscopy (VSFS) complemented by surface pressure isotherm and neutron reflectometry (NR) experiments were employed to investigate the interactions between propofol, a small amphiphilic molecule that currently is the most common general anaesthetic drug, and phospholipid monolayers. A series of biologically relevant saturated phospholipids of varying chain length from C18 to C14 were spread on either pure water or propofol (2,6-bis(1-methylethyl)phenol) solution in a Langmuir trough, and the change in the molecular structure of the film, induced by the interaction with propofol, was studied with respect to the surface pressure. The results from the surface pressure isotherm experiments revealed that propofol, as long as it remains at the interface, enhances the fluidity of the phospholipid monolayer. The VSF spectra demonstrate that for each phospholipid the amount of propofol in the monolayer region decreases with increasing surface pressure. Such squeeze out is in contrast to the enhanced interactions that can be exhibited by more complex amphiphilic molecules such as peptides. At surface pressures of 22-25 mN m-1, which are relevant for biological cell membranes, most of the propofol has been expelled from the monolayer, especially in the case of the C16 and C18 phospholipids that adopt a liquid condensed phase packing of its alkyl tails. At lower surface pressures of 5 mN m-1, the effect of propofol on the structure of the alkyl tails is enhanced when the phospholipids are present in a liquid expanded phase. Specifically, for the C16 phospholipid, NR data reveal that propofol is located exclusively in the head group region, which is rationalized in the context of previous studies. The results imply a non-homogeneous distribution of propofol in the plane of real cell membranes, which is an inference that requires urgent testing and may help to explain why such low concentration of the drug are required to induce general anaesthesia.

Surface structure of a "non-amphiphilic" protic ionic liquid.

The nanostructure of the ethanolammonium nitrate (EtAN)-air surface has been investigated using X-ray reflectometry (XRR), vibrational sum frequency spectroscopy (VSFS) and neutral impact collision ion scattering spectroscopy (NICISS). The XRR data decays more rapidly than expected for a perfectly sharp interface, indicating a diffuse electron (scattering length) density profile. Modelling of the XRR data using three different fitting routines produced consistent interfacial profiles that suggest the formation of interfacial EtAN clusters. Consistent with this, VSFS reveals that the EtAN surface is predominantly covered by -CH(2)- moieties, with the -NH(3)(+) and -OH groups of the cation buried slightly deeper in the interface. The elemental profiles determined using NICISS also show enrichment of carbon relative to nitrogen and oxygen in the outermost surface layer, which is consistent with the surface cation orientation deduced from VSFS, and with the presence of EtAN aggregates at the liquid surface.

Crown ethers at the aqueous solution-air interface. Part 2. Electrolyte effects, ethylene oxide hydration and temperature behaviour.

Vibrational Sum Frequency Spectroscopy (VSFS) was employed to study adsorbing films of 4-Nitro Benzo-15-Crown-5 (NB15C5) and Benzo-15-Crown-5 (B15C5) at the aqueous solution-air interface. The surface of the solution is strongly influenced by the presence of crown ether species. Changes in the orientation of NB15C5 were monitored as a function of solution concentration, by targeting the ratio of peak intensities of the CN and NO(2) vibrational modes. The water of hydration has also been probed as a function of crown concentration, salt concentration, and temperature. The latter study strongly suggests that the surface can be treated as a charged interface, and that the associated ordered water decreases with increasing ionic strength of the bulk solution.

Crown ethers at the aqueous solution-air interface: 1. Assignments and surface spectroscopy.

The surface of aqueous solutions of 4-Nitro Benzo-15-Crown-5 (NB15C5) and Benzo-15-Crown-5 (B15C5) has been studied using the surface sensitive technique vibrational sum frequency spectroscopy (VSFS). The NO, CN, COC and CH vibrational modes of these compounds at the air-water interface as well as OH vibrational modes of the surface water hydrating this compound have been targeted in order to obtain molecular information about arrangement and conformation of the adsorbed crown ether molecules at the air-water interface. The CH(2) vibrational modes of crown ethers have been identified and found to be split due to interaction with ether oxygen. The spectra provide evidence for the existence of a protonated crown complex moiety at the surface leading to the appearance of strongly ordered water species. The interfacial water species are influenced by the resulting charged interface and by the strong Zundel polarizability due to tunneling of the proton species between equivalent sites within the crown ring.

Molecular structure upon compression and stability toward oxidation of Langmuir films of unsaturated fatty acids: a vibrational sum frequency spectroscopy study.

Vibrational sum frequency spectroscopy (VSFS) has been used to determine the stability toward oxidation in air of a series of unsaturated fatty acids, measuring as a function of time the changes in the chemical structure and conformational order of films spread on a Langmuir trough. The fatty acids studied consisted of a 20-carbon backbone with increasing numbers of cis double bonds in the chain: 11c-eicosenoic acid (20:1 EA, omega-9), 11c,14c-eicosadienoic acid (20:2 EA, omega-6), and 11c,14c,17c-eicosatrienoic acid (20:3 EA, omega-3). Measurements at constant surface pressure show that double bonds are lost from the surface region and that drops in intensity of the vinyl CH stretch are detectable within a few minutes of spreading the monolayer. The results are consistent with the fatty acid peroxidation free radical mechanism. The sum frequency spectra also reveal that what remains on the surface is conformationally more disordered with a larger number of gauche defects. The oxidation kinetics are found to be strongly dependent on the packing density of the monolayer, being more stable at higher pressures. Oxidation can be avoided by purging the system in an inert atmosphere. Finally, the molecular structure upon compression was tracked in unoxidized monolayers. The results suggest that the packing and orientation of the double bond sections of all three unsaturated fatty acids show remarkable similarities, with the direction of the double bonds approximately parallel to each other irrespective of the number of unsaturations in the chain, with the 20:3 EA probably forming "iron-angle" structures. The possibility of unsaturated chains in a "hairpin" configuration is discarded for area per molecules smaller than approximately 50 A(2), which corresponds to the lowest surface pressure measured with VSFS.

Structure of the ethylammonium nitrate surface: an X-ray reflectivity and vibrational sum frequency spectroscopy study.

X-ray reflectivity and vibrational sum frequency spectroscopy are used to probe the structure of the ethylammonium nitrate (EAN)-air interface. X-ray reflectivity reveals that the EAN-air interface is structured and consists of alternating nonpolar and charged layers that extend 31 A into the bulk. Vibrational sum frequency spectroscopy reveals interfacial cations have their ethyl moieties oriented toward air, with the CH(3) C(3) axis positioned approximately 36.5 degrees from interface normal. This structure is invariant between 15 and 51 degrees C. On account of its molecular symmetry, the orientation of the nitrate anion cannot be determined with certainty.

Nonionic surfactant adsorption at the ethylammonium nitrate surface: a neutron reflectivity and vibrational sum frequency spectroscopy study.

The adsorbed layers of polyoxyethylene n-alkyl ether surfactants C(12)E(4), C(14)E(4), and C(16)E(4) at the EAN surface have a headgroup layer that is thin and compact (only approximately 30 vol % EAN). The headgroups do not adopt a preferred orientation and are disordered within the ethylene oxide layer. Alkyl tails contain a significant number of gauche defects indicating a high degree of conformational disorder. The thickness of the tail layer increases with increasing alkyl chain length, while the headgroup layer shows little change. Lowering the C(12)E(4) concentration from 1 to 0.1 wt % decreases the adsorbed amount, and the headgroup layer becomes thinner and less solvated, whereas C(14)E(4) and C(16)E(4) adsorbed layers are unaffected by dilution over the same concentration range. The C(16)E(4) layer thickness increases and area per molecule decreases on warming to 60 degrees C, but the adsorbed layer structures of C(12)E(4) and C(14)E(4) are unchanged. Both effects are attributed to surfactant solubility.