pH-Responsive Membranes from Self-Assembly of Poly(2-(dimethylamino)ethyl methacrylate) Brush Silica Nanoparticles.

We have prepared novel pH-responsive nanoporous membranes by the self-assembly of silica nanoparticles carrying poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes with a degree of polymerization (DP) in the 100-450 range. The nanoparticles were prepared by surface-initiated ARGET-ATRP, and the membranes were assembled by pressure-driven deposition onto porous supports. The permeability and pore size of the resulting robust membranes were studied using water and hexane flux and filtration cutoff experiments. The pore size of the PDMAEMA "hairy" silica nanoparticle (HNP) membranes measured by water flux was ca. 22 nm and was mostly independent of the polymer brush length. We attributed this to a combination of the PDMAEMA brushes swelling and their permeability to water. In contrast, the pore size measured by hexane flux strongly depended on the DP. The flux and pore size of these membranes in water strongly depended on the pH. The pore size decreased by a factor of 1.6 when the pH was changed from neutral to acidic. pH-Responsive HNP membranes combine many attractive properties, including control over the filtration cutoff, responsive permeability, and high flux at low pressure. The reversible self-assembly of the PDMAEMA HNP membranes may help not only in their facile preparation but also in material recycling if biofouling occurs. The key features of the PDMAEMA HNP assemblies are attractive in membrane separations, molecular valves, and biosensors, where having precise control over the pore size and pore gating is highly desirable.

Temperature-Responsive Nanoporous Membranes from Self-Assembly of Poly(N-isopropylacrylamide) Hairy Nanoparticles.

Nanoporous membranes play a critical role in numerous separations on laboratory and industrial scales, ranging from water treatment to biotechnology. However, few strategies exist that allow for the preparation of mechanically robust nanoporous membranes whose separation properties can be easily tuned. Here, we introduce a new family of tunable nanoporous membranes based on nanoparticles decorated with temperature-responsive polymer brushes. We prepared mechanically robust membranes from hairy nanoparticles (HNPs) carrying PNIPAM polymer brushes. We assembled the HNPs into thin films through pressure-driven deposition of nanoparticle suspensions and measured the permeability and filtration cutoff of these membranes at different temperatures. The membrane pore diameter at room temperature varied between 10 and 30 nm depending on the polymer length. The water permeability of these membranes could be controlled by temperature, with the effective pore diameter increasing by a factor of 3-6 (up to 100 nm) when the temperature was increased to 60 °C. The size selectivity of these membranes in the filtration of nanoparticles could also be attenuated by temperature. Molecular dynamics computer simulations of a coarse-grained HNP model show that temperature-sensitive pores sizes are consistent with our experimental results and reveal the polymer configurations responsible for the observed filtration membrane permeability. We expect that these membranes will be useful for separations and in the preparation of responsive microfluidic devices.

Flow Reduction in Pore Networks of Packed Silica Nanoparticles: Insights from Mesoscopic Fluid Models.

A modified many-body dissipative particle dynamics (mDPD) model is rigorously calibrated to achieve realistic fluid-fluid/solid interphase properties and applied for mesoscale flow simulations to elucidate the transport mechanisms of heptane liquid and water, respectively, through pore networks formed by packed silica nanoparticles with a uniform diameter of 30 nm. Two million CPU core hours were used to complete the simulation studies. Results show reduction of permeability by 54-64% in heptane flow and by 88-91% in water flow, respectively, compared to the Kozeny-Carman equation. In these nanopores, a large portion of the fluids are in the near-wall regions and thus not mobile due to the confinement effect, resulting in reduced hydraulic conductivity. Moreover, intense oscillations in the calculated flow velocities also indicate the confinement effect that contests the external driven force to flow. The generic form of Darcy's law is considered valid for flow through homogeneous nanopore networks, while permeability depends collectively on pore size and surface wettability. This fluid-permeability dependency is unique to flow in nanopores. In addition, potential dependence of permeability on pore connectivity is observed when the porosity remains the same in different core specimens.

Medium controlled aggregative growth as a key step in mesoporous silica nanoparticle formation.

Near monodisperse mesoporous silica nanoparticles (MSN) represent a promising and rapidly developing type of mesoporous silica materials; however, the vast data on their synthesis remains unorganized and ill-understood. We systematically studied the formation of MSN under basic and neutral conditions using various temperatures, CTAB concentrations, hydrolyzing agents (triethanolamine, ammonia, phosphate buffers), and media with different colloidal stabilization properties (with ethanol as a cosolvent and monovalent salts). In the typical conditions for the preparation of stable MSN colloids, the particle size was controlled by colloidal stabilization by the medium (solvent type, ionic strength, and surfactant concentration) in agreement with the "aggregative growth" mechanism, rather than by solely the hydrolysis and condensation rates conventionally used for data interpretation in the classical nucleation theory. Medium properties (pH, ion types and concentration, polarity) also defined the efficiency of silica-surfactant cooperative self-assembly, which directly affected the porosity, mesopore size and pore wall thickness. Interestingly, this traditional silica-surfactant route showed a limited effect on the particle size, emphasizing the dominating role of colloidal stabilization in the studied reaction conditions. In situ pH measurements showed that every reaction medium has unique pH evolution profiles depending on the buffer capacity, hydrolysis and condensation rates. Reaction systems that fail to maintain the working pH can lead to non-porous products or undesired particle morphology and size distribution. The established particle formation mechanism allowed us to formulate comprehensive guidelines for preparing relatively concentrated colloids of near monodisperse (PDI 5-15%) mesoporous 30-700 nm silica spheres with variable porosity and mesopore size. These findings will be particularly useful in designing new mesoporous silica-containing materials for biomedical applications.

Percolation analysis for estimating the maximum size of particles passing through nanosphere membranes.

Percolation theory can be used to study the flow-related properties of various porous systems. In particular, recently developed membranes from silica nanoparticles with surface grafted polymer brushes represent a quintessential hard-sphere soft-shell system for which fluid-flow behavior can be illuminated via a percolation framework. However, a critical parameter in membrane design involves the maximum pass-through size of particles. While percolation theory considers path connectedness of a system, little explicit consideration is given to the size of the paths that traverse the space. This paper employs a hard-sphere soft-shell percolation model to investigate maximum particle pass-through size of membranes. A pixelated (as opposed to continuous) representation of the geometry is created, and combined with readily available homology software to analyze percolation behavior. The model is validated against previously published results. For a given sphere volume fraction, the maximum diameter of a percolating path is determined by applying iterative dilations to the spheres until the percolation threshold is reached. A simple approximate relationship between maximum particle size and sphere volume fraction is derived for application to membrane design. Experimental particle cutoff size results for the polymer modified silica nanoparticle membranes were used as a partial verification of the model created in this paper. The presence of a distribution of sphere sizes (naturally created by the manufacturing process) is found to have negligible effect, compared to results for a single sphere size.

Porous Structure of Silica Colloidal Crystals.

We prepared silica colloidal crystals with different pore sizes using isothermal heating evaporation-induced self-assembly in quantities suitable for nitrogen porosimetry and studied their porous structure. We observed pores of two types in agreement with the description of silica colloidal crystals as face-centered cubic packed structures containing octahedral and tetrahedral voids. We calculated the sizes of these pores using the Derjaguin-Broekhoff-de Boer theory of capillary condensation for spherical pores. We also described the pore geometry mathematically and showed that the octahedral pore radii measured experimentally matches closely the radii of the spheres of the same volume. In the case of the tetrahedral pores, the proposed approach underestimated the pore radius by ca. 40%. Overall, this simple geometrical description provides a good representation of the porous system in silica colloidal crystals.

Responsive Nanoporous Membranes with Size Selectivity and Charge Rejection from Self-Assembly of Polyelectrolyte "Hairy" Nanoparticles.

We report the preparation and characterization of charged nanoporous membranes by self-assembly of "hairy" silica nanoparticles (HNPs) functionalized with polyelectrolyte copolymer brushes. We show that HNP membranes possess high water flux, have well-defined pore sizes, and rejection up to 80% of charged species in solution. The properties of these membranes can be tuned by controlling the length and composition of polymer brushes and the electrolyte concentration in solution. We demonstrate that membrane pore sizes undergo changes of up to 40% in response to changes in the ionic strength of the salt solution. Using MD computer simulations of a coarse-grained model, we link these tunable properties to the conformations of polymer chains in the spaces between randomly packed HNPs. As polymer length increases, the polymers fill the interparticle gaps, and the pore size decreases markedly. On the basis of their straightforward fabrication and tunable properties, HNP membranes may find applications in size- and charge-selective separations, water desalination, and responsive devices.

Synthesis of water-degradable silica nanoparticles from carbamate-containing bridged silsesquioxane precursor.

Silica nanoparticles (SNPs) are attractive for applications for the delivery of drugs and as imaging agents due to their ease of synthesis and scale up, robust structure, and controllable size and composition. Degradability is one important factor that limits biomedical applications of SNPs. With this in mind, we designed, prepared and characterized novel hydrolysable organosilica nanoparticles (ICPTES-Sorbitol SNPs). These particles were prepared by co-condensation of tetraethoxysilane with a bridged sorbitol-based silsesquioxane precursor containing carbamate linkages. The non-porous spherical ICPTES-Sorbitol SNPs became porous after they were placed in an aqueous environment as a result of the hydrolysis of carbamate bonds and were completely degraded upon prolonged exposure to water. The rate of degradation depended on the pH of the solution, with nanoparticles degrading slower at pH 2 than at pH 4 or pH 7. The degradation was demonstrated by transmission electron microscopy, nitrogen desorption analysis and solution analytical techniques such as ICP-MS and molybdenum blue assay, which was also used to follow the dissolution of ICPTES-Sorbitol SNPs.

Diffusion of Proteins across Silica Colloidal Crystals.

We studied the diffusion of three model proteins, lysozyme (Lz), bovine hemoglobin (BHb), and bovine serum albumin (BSA), normal to the (111) plane of sintered silica colloidal crystals with three different pore "radii" (7.5, 19, and 27 nm). We demonstrated that these colloidal crystals exhibit size selectivity when the nanopores are sufficiently small (7.5 and 19 nm). Because these nanopores are still larger than the diffusing proteins, the observed size selectivity can be attributed to the tortuosity of the colloidal nanopores. Larger (27 nm) nanopores led to higher transport rates but at the cost of selectivity. In addition to the size selectivity, we also demonstrated that 19 nm nanopores possess shape selectivity for the proteins of comparable molecular weights. We showed that the high temperature sintering required for the preparation of sintered colloidal crystals reduces the extent of interactions between the proteins and the nanopore surface, which appear to play a minor role in the diffusion, and that transport selectivity is decided solely by protein size and shape. Taken together, our observations suggest that sintered silica colloidal crystals constitute promising nanoporous membranes for protein separations, with easily controllable pore size, size and shape selectivity, and minimal surface fouling.

Identification of Position-Specific Correlations between DNA-Binding Domains and Their Binding Sites. Application to the MerR Family of Transcription Factors.

The large and increasing volume of genomic data analyzed by comparative methods provides information about transcription factors and their binding sites that, in turn, enables statistical analysis of correlations between factors and sites, uncovering mechanisms and evolution of specific protein-DNA recognition. Here we present an online tool, Prot-DNA-Korr, designed to identify and analyze crucial protein-DNA pairs of positions in a family of transcription factors. Correlations are identified by analysis of mutual information between columns of protein and DNA alignments. The algorithm reduces the effects of common phylogenetic history and of abundance of closely related proteins and binding sites. We apply it to five closely related subfamilies of the MerR family of bacterial transcription factors that regulate heavy metal resistance systems. We validate the approach using known 3D structures of MerR-family proteins in complexes with their cognate DNA binding sites and demonstrate that a significant fraction of correlated positions indeed form specific side-chain-to-base contacts. The joint distribution of amino acids and nucleotides hence may be used to predict changes of specificity for point mutations in transcription factors.

Functional membranes via nanoparticle self-assembly.

This article summarizes a recently developed approach for the preparation of membrane materials by the self-assembly of inorganic, polymeric or hybrid nanoparticles, with the focus on functional membranes possessing permselectivity. Two types of such membranes are discussed, those possessing size and charge selectivity suitable for ultra- and nanofiltration and chemoselective separation, and those possessing proton or lithium transport properties suitable for fuel cell and lithium battery applications, respectively. This article describes the preparation methods of nanoparticle membranes, as well as their mechanical, molecular, and ionic transport properties.

Tumor targeting, trifunctional dendritic wedge.

We report in vitro and in vivo evaluation of a newly designed trifunctional theranostic agent for targeting solid tumors. This agent combines a dendritic wedge with high boron content for boron neutron capture therapy or boron MRI, a monomethine cyanine dye for visible-light fluorescent imaging, and an integrin ligand for efficient tumor targeting. We report photophysical properties of the new agent, its cellular uptake and in vitro targeting properties. Using live animal imaging and intravital microscopy (IVM) techniques, we observed a rapid accumulation of the agent and its retention for a prolonged period of time (up to 7 days) in fully established animal models of human melanoma and murine mammary adenocarcinoma. This macromolecular theranostic agent can be used for targeted delivery of high boron load into solid tumors for future applications in boron neutron capture therapy.

Reversible assembly of tunable nanoporous materials from "hairy" silica nanoparticles.

Membranes with 1-100 nm nanopores are widely used in water purification and in biotechnology, but are prone to blockage and fouling. Reversibly assembled nanoporous membranes may be advantageous due to recyclability, cleaning, and retentate recovery, as well as the ability to tune the pore size. We report the preparation and characterization of size-selective nanoporous membranes with controlled thickness, area, and pore size via reversible assembly of polymer brush-grafted ("hairy") silica nanoparticles. We describe membranes reversibly assembled from silica particles grafted with (1) polymer brushes carrying acidic and basic groups, and (2) polymer brushes carrying neutral groups. The former are stable in most organic solvents and easily disassemble in water, whereas the latter are water-stable and disassemble in organic solvents.

Nanoporous membranes with tunable pore size by pressing/sintering silica colloidal spheres.

We prepared robust nanoporous membranes with controlled area and uniform thickness by pressing silica colloidal spheres into disks followed by sintering. Three different diameters of silica particles, 390, 220, and 70 nm, were used to prepare the membranes with different pore size. In order to evaluate their size-selectivity, we measured the diffusion of polystyrene particles through these membranes. Although pressed silica colloidal membranes do not possess visible order or uniform pore size, they showed size-selective transport. We also demonstrated that pressed silica colloidal membranes can be functionalized via pore-filling. Sulfonated polymer brushes were grown inside the pores via surface-initiated atom transfer radical polymerization, which resulted in a material with high proton conductivity suitable for fuel cell applications.

Surface-modified silica colloidal crystals: nanoporous films and membranes with controlled ionic and molecular transport.

Nanoporous membranes are important for the study of the transport of small molecules and macromolecules through confined spaces and in applications ranging from separation of biomacromolecules and pharmaceuticals to sensing and controlled release of drugs. For many of these applications, chemists need to gate the ionic and molecular flux through the nanopores, which in turn depends on the ability to control the nanopore geometry and surface chemistry. Most commonly used nanoporous membrane materials are based on polymers. However, the nanostructure of polymeric membranes is not well-defined, and their surface is hard to modify. Inorganic nanoporous materials are attractive alternatives for polymers in the preparation of nanoporous membranes. In this Account, we describe the preparation and surface modification of inorganic nanoporous films and membranes self-assembled from silica colloidal spheres. These spheres form colloidal crystals with close-packed face centered cubic lattices upon vertical deposition from colloidal solutions. Silica colloidal crystals contain ordered arrays of interconnected three dimensional voids, which function as nanopores. We can prepare silica colloidal crystals as supported thin films on various flat solid surfaces or obtain free-standing silica colloidal membranes by sintering the colloidal crystals above 1000 °C. Unmodified silica colloidal membranes are capable of size-selective separation of macromolecules, and we can surface-modify them in a well-defined and controlled manner with small molecules and polymers. For the surface modification with small molecules, we use silanol chemistry. We grow polymer brushes with narrow molecular weight distribution and controlled length on the colloidal nanopore surface using atom transfer radical polymerization or ring-opening polymerization. We can control the flux in the resulting surface-modified nanoporous films and membranes by pH and ionic strength, temperature, light, and small molecule binding. When we modify the surface of the colloidal nanopores with ionizable moieties, they can generate an electric field inside the nanopores, which repels ions of the same charge and attracts ions of the opposite charge. This allows us to electrostatically gate the ionic flux through colloidal nanopores, controlled by pH and ionic strength of the solution when surface amines or sulfonic acids are present or by irradiation with light in the case of surface spiropyran moieties. When we modify the surface of the colloidal nanopores with chiral moieties capable of stereoselective binding of enantiomers, we generate colloidal films with chiral permselectivity. By filling the colloidal nanopores with polymer brushes attached to the pore surface, we can control the ionic flux through the corresponding films and membranes electrostatically using reversibly ionizable polymer brushes. By filling the colloidal nanopores with polymer brushes whose conformation reversibly changes in response to pH, ionic strength, temperature, or small molecule binding, we can control the molecular flux sterically. There are various potential applications for surface-modified silica colloidal films and membranes. Due to their ordered nanoporous structure and mechanical durability, they are beneficial in nanofluidics, nanofiltration, separations, and fuel cells and as catalyst supports. Reversible gating of flux by external stimuli may be useful in drug release, in size-, charge-, and structure-selective separations, and in microfluidic and sensing devices.

SiO2@Au core-shell nanospheres self-assemble to form colloidal crystals that can be sintered and surface modified to produce pH-controlled membranes.

We prepared colloidal crystals by self-assembly of gold-coated silica nanospheres, and free-standing nanoporous membranes by sintering these colloidal crystals. We modified the nanopore surface with ionizable functional groups, by forming a monolayer of L-cysteine or by surface-initiated polymerization of methacrylic acid. Diffusion experiments for the cationic dye Rhodamine B through L-cysteine-modified membranes showed a decrease in flux upon addition of an acid due to the nanopore surface becoming positively charged. Diffusion experiments for the neutral dye, ferrocenecarboxaldehyde, through the PMAA-modified membranes showed a 13-fold increase in flux upon addition of an acid resulting from the protonated polymer collapsing onto the nanopore surface leading to larger pore size. Our results demonstrate that SiO2@Au core-shell nanospheres can self-assemble into colloidal crystals and that transport through the corresponding surface-modified Au-coated colloidal membranes can be controlled by pH.

p-tert-Butyl thiacalix[4]arenes functionalized at the lower rim by amide, hydroxyl and ester groups as anion receptors.

New p-tert-butyl thiacalix[4]arenes differently substituted at the lower rim with amide, hydroxyl and ester groups were synthesized. Binding properties of the compounds toward some tetrabutylammonium salts n-Bu(4)NX (X = F(-), Cl(-), Br(-), I(-), CH(3)CO(2)(-), H(2)PO(4)(-), NO(3)(-)) were studied by UV spectroscopy. It was found that the stoichiometry of the complexes, generally, is 1 : 1, and the association constants are in the range of 10(3)-10(5) M(-1). The p-tert-butyl thiacalix[4]arenes containing secondary amide groups trisubstituted at the lower rim bind the studied anions most effectively. Selective receptors for fluoride and dihydrogen phosphate salts of tetrabutylammonium were found.

Size-selective molecular transport through silica colloidal nanopores.

Diffusion rate of dye-labelled PAMAM dendrimers through free-standing silica colloidal crystals was studied as a function of the dendrimer generation and nanopore size to determine the transport selectivity.

Biomimetic glass nanopores employing aptamer gates responsive to a small molecule.

We report the preparation of 20 and 65 nm radii glass nanopores whose surface is modified with DNA aptamers controlling the molecular transport through the nanopores in response to small molecule binding.

Free-standing silica colloidal nanoporous membranes.

We prepared robust free-standing 200 microm-thick colloidal membranes (nanofrits) with a relatively large area and no mechanical defects by sintering silica colloidal films. The silica spheres used to prepare the nanofrits were 338, 300, or 251 nm in diameter, leading to 25, 22.5, and 19 nm nanopore sizes, respectively. The room-temperature diffusional flux through these membranes is of the order of 3.6 x 10(-10) mol s(-1) cm(-2) for a Fe(bpy)32+ ion in acetonitrile test solution in the absence of applied pressure and is in good agreement with the calculated diffusional flux for colloidal crystals of the same thickness. To evaluate the feasibility of nanofrit surface modification, we treated them with 3-aminopropyltriethoxysilane after rehydroxylation. We found, by measuring the surface coverage for dansyl amide on the surface, that the number of the amines on the nanofrit surface is lower as compared to that observed for colloidal films not treated with heat. As a result, the selectivity for the transport of Fe(bpy)3(2+) through the aminated nanofrits in the presence of acid is lower than the selectivity observed for amine-modified colloidal films.