Effect of Molecular Architecture and Composition on the Aggregation Pathways of POEGMA Random Copolymers in Water.

Understanding of the temperature-induced phase transition of poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) random copolymers with varied composition remains largely incomplete. Upon heating they can form either macroscopically phase-separated aggregates or micelles. We examined the effect of polymer architecture by rationally designing and synthesizing various POEGMA copolymer structures via atom transfer radical polymerization using OEGMA monomers of different EO lengths. Micelle formation occurred for copolymers with a small fraction of long side chains counterbalanced by an appropriate number of short side chains, while macroscopic phase separation occurred for other copolymer compositions. In some copolymer compositions and architectures, micelle formation followed by macroscopic phase separation occurred, and the temperature of these phase transitions could be tailored accordingly. This new strategy allows the control over the microstructure and specific transition temperatures enabling, for instance, the preparation of nanocarriers for encapsulating hydrophobic compounds.

Binucleating Hydrazonic Ligands and Their µ-Hydroxodicopper(II) Complexes as Promising Structural Motifs for Enhanced Antitumor Activity.

Very few inorganic antineoplastic drugs have entered the clinic in the last decades, mainly because of toxicity issues. Because copper is an essential trace element of ubiquitous occurrence, decreased side effects could be expected in comparison with the widely used platinum anticancer compounds. In the present work, two novel hydrazonic binucleating ligands and their µ-hydroxo dicopper(II) complexes were prepared and fully characterized. They differ by the nature of the aromatic group present in their aroylhydrazone moieties: while H3L1 and its complex, 1, possess a thiophene ring, H3L2 and 2 contain the more polar furan heterocycle. X-ray diffraction indicates that both coordination compounds are very similar in structural terms and generate dimeric arrangements in the solid state. Positive-ion electrospray ionization mass spectrometry analyses confirmed that the main species present in a 10% dimethyl sulfoxide (DMSO)/water solution should be [Cu2(HL)(OH)]+ and the DMSO-substituted derivative [Cu2(L)(DMSO)]+. Scattering techniques [dynamic light scattering (DLS) and small-angle X-ray scattering] suggest that the complexes and their free ligands interact with bovine serum albumin (BSA) in a reversible manner. The binding constants to BSA were determined for the complexes through fluorescence spectroscopy. Moreover, to gain insight into the mechanism of action of the compounds, calf thymus DNA binding studies by UV-visible and DLS measurements using plasmid pBR322 DNA were also performed. For the complexes, DLS data seem to point to the occurrence of DNA cleavage to Form III (linear). Both ligands and their dicopper(II) complexes display potent antiproliferative activity in a panel of four cancer cell lines, occasionally even in the submicromolar range, with the complexes being more potent than the free ligands. Our data on cellular models correlate quite well with the DNA interaction experiments. The results presented herein show that aroylhydrazone-derived binucleating ligands, as well as their dinuclear µ-hydroxodicopper(II) complexes, may represent a promising structural starting point for the development of a new generation of highly active potential antitumor agents.

Formation and assembly of amphiphilic Janus nanoparticles promoted by polymer interactions.

Almost three decades after de Gennes have introduced the term Janus for particles possessing two faces with different chemical nature, Janus particles are currently a hot topic in itself. Although de Gennes was not concerned with the size of particles, due to the advent and perspectives of nanotechnology, nanosized Janus particles have particularly received great attention. The capacity of having two antagonistic properties within the same particle has attracted interest on Janus nanoparticles for innumerous potential applications. It took some years for the studies about Janus nanoparticles to finally see great advances, mainly due to the progress in nanoparticle synthesis. What de Gennes might have not predicted (or at least he did not mention it during his speech) is that intermolecular interactions between polymers would be of immense importance to the actual achievement of Janus nanoparticles. Moreover, these interactions can also have large effects on the assembly process of amphiphilic Janus nanoparticles, which is important to form hierarchical structures and new materials at different scales. Hence, it is interesting to notice that de Gennes' contribution for the polymer field has been influencing the preparation and the controlled assembly of Janus nanoparticles. This article attempts to summarize empirical studies where noncovalent forces between polymers played a role, either on the production of Janus nanoparticles or on their assembly.

Stabilization of spherical nanoparticles of iron(III) hydroxides in aqueous solution by wormlike micelles.

HYPOTHESIS: The low Ksp value of Fe(OH)3 (3 × 10-38 at 298 K) explain the immediate coagulation when the pH of a solution of Fe(III) is adjusted to 7. However, stable dispersions of Fe(OH)3 can be formed when the pH is adjusted to 7 in the presence of wormlike micelles formed by cetyltrimethylammonium bromide and sodium salicylate. The formation of a structure containing Fe(OH)3 nanoparticles decorating wormlike micelles is responsible for the high stability of the dispersions. EXPERIMENTS: Fe(OH)3 nanoparticles were obtained by increasing the pH of solutions of cetyltrimethylammonium bromide and Fe(III), previously complexed with salicylate at pH 3. The interaction between nanoparticles and the chains of wormlike micelles was investigated by DLS, SAXS, TEM and Cryo-TEM. FINDINGS: DLS revealed higher scattering contrast and slower diffusion for wormlike micelles in the presence of nanoparticles. These results were interpreted as the decoration of the chains of wormlike micelles by nanoparticles of Fe(OH)3. A pearl-necklace model was successfully used to adjust SAXS curves, revealing nanoparticles with ∼3 nm of diameter, spaced ∼2 nm apart along the string. This result agrees with TEM and Cryo-TEM images. The formed structure prevents the coagulation of nanoparticles, assuring high stability to the dispersion.

Controlling the phase structures of polymer/surfactant complexes by changing macromolecular architecture and adding n-alcohols.

Phase behavior of complex salts formed by a cationic surfactant and different ethoxylated polyions was investigated in water and with addition of two n-alcohols of different chain lengths: n-butanol and n-decanol. The polyion possesses a main chain of methacrylic acid randomly grafted with oligo(ethylene oxide) chains. Strong electrostatic interaction between the anionic main chain and the cationic surfactant hexadecyltrimethylammonium (C16TA) leads to the formation of C16TAP(MA-MAEO(n)) x:y complex salts. Modifications in polyion structure, such as changes in the proportion of grafted comonomers and in the side chain length caused differences in the overall balance of interactions with water and n-alcohols, altering the complex salt solubility and, consequently, the formed liquid-crystalline structures. The role of n-decanol as a cosurfactant was verified, but the hydrophilic side chains expanded the capacity of the formed liquid crystalline phases to incorporate water. Additionally, a novel structure, probably cubic bicontinuous (Pn3m), was observed coexisting with lamellar phases at low water concentration. Because n-butanol is known for being a good solvent for poly(ethylene oxide), these side chains intensified the role of this short chain n-alcohol as cosolvent for C16TAP(MA-MAEO(n)) x:y complex salts, favoring the formation of disordered solutions, including a bicontinuous microemulsion.

How does the ethoxylated grafting of polyelectrolytes affect the self-assembly of polyanion-cationic surfactant complex salts?

A cationic surfactant and different anionic copolymers randomly grafted with side chains of ethylene oxide were used to prepare stoichiometric complex salts. Variations in the length or proportion of side chains were shown to be responsible for affecting the surfactant phase behavior in water, resulting in the observation of a number of structures characterized by small angle X-ray scattering measurements, including a hierarchical micellar system and different liquid-crystalline phases. Additionally, although aqueous mixtures of stoichiometric complex salts usually phase separate, the presence of a sufficiently high weight fraction of ethylene oxide side chains can enhance the solubility of the complex salt aggregates in water over a wide range of concentration. Moreover, a dispersion of an isotropic concentrated solution of complex salts is formed at higher temperatures in a reversible process. In summary, this study proves the importance of the polyion structure for tuning the properties of systems of complex salts.

Polyion-surfactant ion complex salts formed by a random anionic copolyacid at different molar ratios of cationic surfactant: phase behavior with water and n-alcohols.

The presence of acid groups with different pK(a) values in the anionic copolymer poly(4-styrene sulfonic acid-co-maleic acid), P(SS-Ma), allowed the preparation of complex salts with a variable fraction of anionic groups neutralized by cationic surfactant in the copolymer via controlled titration with hexadecyltrimethylammonium hydroxide, C(16)TAOH. Two new complex salts were selected for detailed phase studies, C(16)TA(2)P(SS-Ma) and C(16)TA(3)P(SS-Ma), where both had 100% charged styrene sulfonate groups, but the fraction of charged carboxylate groups on the polyion was 50% or 100%, respectively. These complex salts thus contained both hydrophobic (styrene sulfonate) and hydrophilic (carboxylate) charged groups, and the ratio between the two could be altered by titration. These features were found to have consequences for the phase behavior in water and in ternary mixtures with water and n-alcohols for the two complex salts, which differed compared to complex salts containing homo- or copolyions with only carboxylate or styrene sulfonate charged groups. For both complex salts, binary mixtures with water produced, in the dilute region, two isotropic phases in equilibrium, the bottom (concentrated) one displaying increasing viscosity with increasing concentration. For the complex salt C(16)TA(2)P(SS-Ma), there was evidence of micellar growth to form anisometric aggregates at high concentrations. For the C(16)TA(3)P(SS-Ma) complex salt, this was not observed, and the isotropic phase was followed by a narrow region of cubic phase. In both cases, concentrations above ca. 60 wt % produced a hexagonal phase. For ternary mixtures with n-alcohols, the general trend was that a short-chain alcohol such as n-butanol acted as a cosolvent dissolving the aggregates, whereas with n-decanol, a cosurfactant effect was observed, inducing the formation of lamellar phases. Visual inspection (also between crossed polarizers), small angle X-ray scattering (SAXS) and diffusion nuclear magnetic resonance (NMR) were used in these studies.