A new and convenient strategy for the preparation of metallosomes has been developed by mixing organometallic metallosurfactants and phospholipids. These aggregates show the characteristic properties of liposomes (stability upon dilution and low toxicity) and the toxicity is at least ten-fold lower than that of the metallosurfactant aggregates without phospholipids.The preparation and study of nanomaterials by self-assembly in aqueous medium is an increasingly relevant topic. Supramolecular structures for a wide range of applications can be obtained from simple molecules, which can be easily modified to modulate the properties of the aggregates in order to yield new materials with designed properties. Surfactants that contain a metal atom in the molecular structure are named metallosurfactants (MTSs) and they are attractive molecules due to the fact that they can lead to characteristic supramolecular aggregates (micelles, vesicles, etc.), and simultaneously they contain metallic atoms. The presence of the metal makes it possible to use these aggregates in a broad range of applications such as catalysis, optoelectronics, and biomedicine.1 Although in most of the reported MTS the metallic atom is located in the polar group of the molecule, we have recently reported organometallic MTSs wherein the metallic fragment is embedded in the hydrophobic part of the molecule. 2These MTSs render mostly unilamellar vesicles in water if the MTS concentration is higher than the critical value. However, dilution of these suspensions leads to disaggregation of the vesicles, which is a drawback of using them in in vivo applications. To circumvent this disadvantage we considered the possibility of obtaining mixed systems with phospholipids. In particular, we used soybean phosphatidylcholine (SPC), a natural non-toxic phospholipid that is known to form the so-called liposomes, that is, dilution-stable closed vesicles with entrapped water (Scheme 1), and which are used for several medical applications. 3 Our hypothesis is that mixed systems of MTS and phospholipids (Scheme 1) could lead to new supramolecular aggregates with a higher biocompatibility and with useful properties for biomedical applications. Since these new systems contain metallic atoms in the liposome membrane, they can be classified as a new kind of metallosome. 4 In this article, we report the study of the viability of the preparation of metallosomes by mixing SPC with two organometallic MTSs, the molybdenum pentacarbonyl Mo(CO) 5 L (PCO) or the molybdenum tetracarbonyl complex Mo(CO) 4 L 2 (TCO) (L = Ph 2 PCH 2 CH 2 SO 3 Na). It is known that the liposome membrane allows the inclusion of a wide variety of lipophilic or amphipathic substances such as, drugs and proteins. Thus, the incorporation of a bilayer-forming metallosurfactant into a phospholipid bilayer was considered to be a rational choice. The simplest procedure to obtain mixed vesicles involves the Scheme 1 Representation of vesicles obtained with a pure phospholipid or with a metallosurfactant, and when...

Two families of molybdenum carbonyl metallosurfactants, Mo(CO) 5 L and Mo(CO) 4 L 2 , were synthesized using the functionalized phosphines, Ph 2 P(CH 2 ) n SO 3 Na (n = 2, 6, 10) and characterized by the usual spectroscopic and spectrometric methods. The study of the supramolecular arrangements of these compounds in aqueous medium has been performed by surface tension, fluorescence, dynamic light scattering, cryo-TEM, and small angle X-ray scattering. All data points to the formation of medium and large vesicular structures with a membrane similar to the classical lipid bilayer, but it contains organometallic fragments instead of simple hydrophobic chains. Studies of CO releasing with these molybdenum carbonyl metallosurfactants have shown their viability as a promising CO releasing molecules.

a New supramolecular systems have been prepared by mixing molybdenum organometallic metallosurfactants M(CO) 5 L and M(CO) 4 L 2 {L = Ph 2 P(CH 2 ) 6 SO 3 Na} with the phospholipid phosphatidylcholine. The analysis of the resulting supramolecular structures using dynamic light scattering and cryo-transmission electron microscopy has shown the formation of different aggregates depending on the metallosurfactant/ phospholipid ratio, as well as a significantly different behaviour between the two studied metallosurfactants. Mixed vesicles, with properties very similar to liposomes, can be obtained with both compounds, and are called metallosomes. The formation of the mixed aggregates has also been studied by microfluidics using MeOH and EtOH as organic solvents, and it has been observed that the size of the aggregates is strongly dependent on the organic solvent used. In order to analyse the viability of these mixed systems as CO Releasing Molecules (CORMs) for biomedical applications, the CO release was studied by FT-IR spectroscopy, showing that they behave as photo-CORMs with visible and ultraviolet light. Toxicity studies of the different mixed aggregate systems have shown that metallosomes exhibit a very low toxicity, similar to liposomes that do not contain metallosurfactants, which is well below the results observed for pure metallosurfactants. Micro-FTIR microscopy using synchrotron radiation has shown the presence of metallosurfactants in cells. The results of this study show the influence of the length of the hydrocarbon chain on the properties of these mixed systems, compared with previously reported data. IntroductionThe first references to the concept "metallosurfactant" (MTS) were published in the 1990s and, in general, this term was used to refer to molecules that behave as surfactants and contain a metal atom in the molecular structure. Since surfactants are amphiphilic molecules that contain hydrophobic groups and a polar group, and considering that in a wide range of metal complexes the resulting coordinated metal atom is located in a polar region of the molecule, in a large number of the reported MTSs the metal atom is placed in the polar head group of the surfactants. This is the case for metallic complexes with alkyl amines or organic carboxylates that contain a long hydrophobic chain (which can be seen schematically in the drawing (a) of Scheme 1). Thus, a large number of the reported MTSs fit this representation in which the metal atom is located in the polar group of the amphiphilic molecule. However, other designs are possible, and exactly the opposite situation is shown in the drawing (b) View Article Online View Journal | View IssueScheme 1 (an MTS that contains the metal atom embedded in the hydrophobic tail). These kinds of compounds can be prepared by means of an organometallic approach, because it makes it possible to locate a metallic atom in a hydrophobic environment. Although these MTSs are much less common, some examples have been reported, such as the ferrocenyl surfactants.14 ...