Versatile Tetrablock Copolymer Scaffold for Hierarchical Colloidal Nanoparticle Assemblies: Synthesis, Characterization, and Molecular Dynamics Simulation.

A unique combination of molecular dynamics (MD) simulation and detailed size exclusion chromatography-multiangle light scattering (SEC-MALS) analysis is used to provide important a priori insights into the solution self-assembly of a well-defined and symmetric tetrablock copolymer with two acrylic acid (AA) outer blocks, two polystyrene (PS) inner blocks, and a trithiocarbonate (TTC) central group, prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. SEC-MALS experiments show that the copolymer forms aggregates in both tetrahydrofuran and N,N-dimethylformamide (DMF), even in the presence of different salts, but not in 1,4-dioxane (dioxane). Combined with MD simulations, these results indicate that the AA units are the main cause of aggregation through intermolecular hydrogen bonding, with additional stabilization by the central TTC. The block copolymer chains self-assemble in dioxane by adding cadmium acetate, originating flowerlike inverse micelles with a cadmium acrylate core and the TTC groups in the outer surface of the PS corona. The micelles were used as nanoreactors in the templated synthesis of a single cadmium selenide (CdSe) quantum dot (QD) in the core of each micelle, whereas the shell TTC groups can be converted into thiol functions for further use of these units in hierarchical nanostructures. Only in dioxane where simulations and SEC-MALS suggest an absence of copolymer aggregates prior to cadmium acetate addition do well-dispersed and highly luminescent CdSe QDs form by templated synthesis. These results provide valuable insights into the self-assembly of RAFT copolymers in different solvent systems as it relates to the preparation of emissive QDs with polymer-spaced thiol functionality for binding to gold nanostructures.

Interaction of gold nanoparticles with Doxorubicin mediated by supramolecular chemistry.

A copolymer containing ß-cyclodextrin, catechol and polyethylene glycol groups in its side chain was designed for the in situ synthesis and coating of gold nanoparticles (Au@PEG-CD NPs). These platforms were designed as a smart carrier and traceable delivery probe of the chemotherapeutic Doxorubicin drug (Dox). The coated polymer forms stable complexes with Dox in water with a high binding constant (K=2.3×10(4) M(-1) at 25°C), which is one hundred times greater than those reported for its complexation with native ßCD. Therefore, Au@PEG-CD NPs were able to load 0.01 mg of the drug per mg of NP and to release up to 60% of it in 48 h at 37°C. In addition, Au@PEG-CD NPs had the capacity to act as a quencher of Dox fluorescence when it was complexed with ßCD in the NP organic shell. This feature allows the Dox release to be tracked by monitoring the recovery of its fluorescence in real time. Therefore, the Dox release kinetics and the influence of temperature on the thermal stability of Dox/CD complexes on Au@PEG-CD NP were investigated. The increase in temperature favors the dissociation of the complexes and subsequent Dox release from the NP. The first order rate constant for drug releasing was 1.1×10(-2) min(-1) with a half-life time of 63 min at 37°C. Finally, the great potential of the carrier/probe double nature of Au@PEG-CD NPs was demonstrated in real time inside HeLa cells.

Twisted morphologies and novel chiral macroporous films from the self-assembly of optically active helical polyphosphazene block copolymers.

A series of optically active helical polyphosphazene block copolymers of general formula R-[N=P(O2C20H12)]n-b-[N=PMePh]m (R-7 a-c) was synthesized and characterized. The polymers were prepared by sequential living cationic polycondensation of N-silylphosphoranimines using the mono-end-capped initiator [Ph3 P=N=PCl3][PCl6] (5) and exhibit a low polydispersity index (ca. 1.3). The temperature dependence of the specific optical activity ([α]D) of R-7 a,b relative to that for the homopolymers R-[N=P(O2C20H12)]n (R-8 a) and the R/S analogues (R/S-7 a,b), revealed that the binaphthoxy-phosphazene segments induce a preferential helical conformation in the [N=PMePh] blocks through a "sergeant-and-soldiers" mechanism, an effect that is unprecedented in polyphosphazenes. The self-assembly of drop-cast thin films of the chiral block copolymer R-7 b (bearing a long chiral and rigid R-[N=P(O2C20H12)] segment) evidenced a transfer of helicity mechanism, leading to the formation of twisted morphologies (twisted "pearl necklace"), not observed in the nonchiral R/S-7 b. The chiral R-7 a and the nonchiral R/S-7 a, self-assemble by a nondirected morphology reconstruction process into regular-shaped macroporous films with chiral-rich areas close to edge of the pore. This is the first nontemplate self-assembly route to chiral macroporous polymeric films with pore size larger than 50 nm. The solvent annealing (THF) of these films leads to the formation of regular spherical nanostructures (ca. 50 nm), a rare example of nanospheres exclusively formed by synthetic helical polymers.

Determination of molecular parameters of hydroxyethyl and hydroxypropyl celluloses by chromatography with dual detection.

Hydroxyethylcellulose (HEC) and hydroxypropylcellulose (HPC) were studied by means of size exclusion chromatography with dual detection, i.e. employing simultaneously a refractive index (concentration sensitive) and a multiangle light scattering (molecular weight sensitive) detectors. The eluent was water and water solutions containing different concentrations of ionic salts. Molecular weight distributions and averages, coefficients of the scaling law of molecular dimensions and unperturbed dimensions were thus obtained from a single polydisperse sample of each polymer. Measurements were performed at 25 degrees C and the anomalous chromatographic behaviour, due to a combination of ion and size exclusion mechanisms, found when using pure water as eluent is transformed into a size exclusion mechanism by the addition of ionic salts. However, the two polymers behave on a different way in presence of salts. Thus, HEC, which is of low degree of substitution (DS), is close to theta conditions in the aqueous salt solutions (i.e. the q exponent of the scaling law has a value close to 0.5), whereas in the case of HPC the addition of salt improves the quality of the solvent up to a value of q around 0.6. Unperturbed dimensions are also calculated for both celluloses.

Unperturbed dimensions of Carrageenans in different salt solutions.

Commercial samples of kappa-, iota-, and lambda-carrageenans were studied by means of Size Exclusion Chromatography with dual detection, i.e. employing a Refractive Index (concentration sensitive) and Multiangle Light Scattering (size sensitive) detectors. The eluent was water containing 0.1 M concentration of different ionic salts, namely LiCl, NaCl, KCl and NaI, with the exception of kappa-carrageenan that aggregates in presence of KCl. Molecular weight distributions and averages, coefficients of the scaling law of molecular dimensions and unperturbed dimensions were thus obtained from a single polydisperse sample of each polymer. Measurements were performed at 25 degrees C and all the systems were above theta conditions with values of the q exponent of the scaling law ranging from 0.51 to 0.59. Extrapolation to unperturbed conditions provides values of the characteristic ratio C(N)=56+/-1 and 40+/-5 respectively for lambda- and iota-carrageenans regardless of the ionic salt employed. However, kappa-carrageenan gives C(N)=31, 35 and 59, respectively, in presence of LiCl, NaCl and NaI, which clearly indicates that this polymer behaves on a different way in presence of NaI than with the other two salts. A tentative explanation of this difference is provided.

Combination of SEC/MALS experimental procedures and theoretical analysis for studying the solution properties of macromolecules.

Size-exclusion chromatography (SEC) with dual detection, i.e., employing refractive index (RI) and multiangle light-scattering (MALS) detectors, has been applied to study the solution properties of two very different polymer-solvent systems at 25 degrees C: poly(N-vinylcarbazole) (PVCz) in an organic solvent THF that is a very good solvent and a system under theta conditions that is formed by polyvinylpyrrolidone (PVP) in water containing a 0.1 M concentration of NaNO(3). In both cases, the analysis of a single highly polydisperse sample obtained by free radical polymerization is enough for obtaining molecular weight and radius of gyration calibration curves, molecular weight distributions (MWD) (and thus, molecular weight averages), molecular dimensions, scaling laws coefficients and unperturbed dimensions. Extrapolation to theta conditions produces values of the characteristic ratio of the unperturbed dimensions C(n)=(o)/nl(2)=15.9 and 14, respectively, for PVCz and PVP. Unperturbed dimensions are also theoretically calculated with different models such as Kuhn equivalent chain, worm-like chain and rotational isomeric states model. Conformational parameters required for this last model were taken from the literature in the case of PVCz; however, they are calculated by molecular dynamics simulations in the case of PVP. Theoretical values obtained with the RIS model are in good agreement with the experimental results.