The hydrolysis and condensation reactions of monomeric alkoxysilanes and organylalkoxysilanes utilized in sol-gel processing are reviewed. Both reactions occur by acid or base-catalyzed bimolecular displacement reactions. The acid-catalyzed mechanisms are preceded by protonation of OH or OR substituents attached to Si, whereas under basic conditions hydroxyl or silanolate anions attack Si directly. Many of the observed structural trends are understood on the basis of the pH and [H20 ] dependence of the hydrolysis, condensation, and dissolution reactions.

intermediate frequencies, T u (q) interpolates smoothly between these two limiting behaviours 12 .The behaviour seen in Fig. 2 is consistent with KTB dynamics, if we identify the crossover with T KTB of an isolated bilayer. Above T KTB , the conductivity is predicted to scale according to 13±15 :The scaling function S(q/) is constrained by the physics of the high-and low-frequency limits. As q= !`, S must approach i/q in order for j to assume its superconducting form, equation (1). At low frequencies, S approaches a real constant S 1 (0) which characterizes the d.c. conductivity of the normal state. By comparing the measured complex conductivity to equation (2), we can extract both the phase stiffness and correlation time at each temperature. To analyse the experimental data in terms of equation (2), we note that the phase angle of the complex conductivity, J [ tan 2 1 j 2 =j 1 , equals the phase angle of S(q/). Therefore J depends only on the single parameter , and is independent of T 0 u . With the appropriate choice of (T), all the measured values of J should collapse to a single curve when plotted as a function of the normalized frequency q/. Knowing (T), T 0 u is obtained from a collapse of the normalized conductivity magnitude, (~=k B T 0 v jjqj=j Q , to jSq=j. Figure 3 shows the collapse of the data to the phase angle and magnitude of S. As anticipated, S approaches a real constant in the limit q= ! 0, and approaches i/q as q= !`.When analysed further, the data reveal a con®rmation of thermal generation of vortices in the normal state. In the KTB picture we expect that the d.c. conductivity will equal k B T/n f D© 2 0 , which is thè¯u x-¯ow' conductivity of n f free vortices with quantized¯ux © 0 , and diffusivity D (ref. 16). Together with equation (2), this implies that is a linear function of n f , that is, 0 n f a vc =£, where a vc is the area of a vortex core, £ [ T=T 0 u is the reduced temperature, and 0 [ p 2 S 1 0D=a vc . Moreover, we expect that n f will be a thermally activated function, except for T very close to T KTB . The activation energy is simply Ck B T 0 u , where C is a non-universal constant of order unity. It follows that the¯uctuation frequency depends exponentially on the reciprocal of the reduced temperature, 0 =£exp 2 2C=£. The inset to Fig. 3 is a plot of log(£) versus 1/£ which shows that the exponential relation is observed over nearly four orders of magnitude. This is direct evidence that vanishing of phase coherence in our samples re¯ects the dynamics of thermally generated vortices. From the slope and intercept of a straight-line ®t we obtain C 2:23 and 0 1:14 3 10 14 s 2 1 .In Fig. 4 we present the behaviour of the bare stiffness and phasecorrelation time obtained from our measurement and modelling of j(q). The main panel contrasts T 0 u with the dynamical stiffness T u (q) measured at 150 and 400 GHz. The inset shows t as a function of temperature together with hatching that highlights the region where t ,~=k B T.The parameters displayed in Fig. 4 suggest that while phase ...

The study of ordered mesoporous silica materials has exploded since their discovery by Mobil researchers 20 years ago. The ability to make uniformly sized, porous, and dispersible nanoparticles using colloidal chemistry and evaporation-induced self-assembly has led to many applications of mesoporous silica nanoparticles (MSNPs) as “nanocarriers” for delivery of drugs and other cargos to cells. The exceptionally high surface area of MSNPs, often exceeding 1000 m2/g, and the ability to independently modify pore size and surface chemistry, enables the loading of diverse cargos and cargo combinations at levels exceeding those of other common drug delivery carriers such as liposomes or polymer conjugates. This is because noncovalent electrostatic, hydrogen-bonding, and van der Waals interactions of the cargo with the MSNP internal surface cause preferential adsorption of cargo to the MSNP, allowing loading capacities to surpass the solubility limit of a solution or that achievable by osmotic gradient loading. The ability to independently modify the MSNP surface and interior makes possible engineered biofunctionality and biocompatibility. In this Account, we detail our recent efforts to develop MSNPs as biocompatible nanocarriers (Figure ) that simultaneously display multiple functions including (1) high visibility/contrast in multiple imaging modalities, (2) dispersibility, (3) binding specificity to a particular target tissue or cell type, (4) ability to load and deliver large concentrations of diverse cargos, and (5) triggered or controlled release of cargo. Toward function 1, we chemically conjugated fluorescent dyes or incorporated magnetic nanoparticles to enable in vivo optical or magnetic resonance imaging. For function 2, we have made MSNPs with polymer coatings, charged groups, or supported lipid bilayers, which decrease aggregation and improve stability in saline solutions. For functions 3 and 4, we have enhanced passive bioaccumulation via the enhanced permeability and retention effect by modifying the MSNP surfaces with positively charged polymers. We have also chemically attached ligands to MSNPs that selectively bind to receptors overexpressed in cancer cells. We have used encapsulation of MSNPs within reconfigurable supported lipid bilayers to develop new classes of responsive nanocarriers that actively interact with the target cell. Toward function 4, we exploit the high surface area and tailorable surface chemistry of MSNPs to retain hydrophobic drugs. Finally, for function 5, we have engineered dynamic behaviors by incorporating molecular machines within or at the entrances of MSNP pores and by using ligands, polymers, or lipid bilayers. These provide a means to seal-in and retain cargo and to direct MSNP interactions with and internalization by target cells. Application of MSNPs as nanocarriers requires biocompatibility and low toxicity. Here the intrinsic porosity of the MSNP surface reduces the extent of hydrogen bonding or electrostatic interactions with cell membranes as does surface coati...

Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability, and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma (HCC) exhibit a 10,000-fold greater affinity for HCC than for hepatocytes, endothelial cells, and immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, siRNA, and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer allow a single protocell loaded with a drug cocktail to kill a drug-resistant HCC cell, representing a 106-fold improvement over comparable liposomes.

This review discusses two classes of organic template-derived amorphous silicas distinguished by the nature of template-matrix interactions and the extent to which subsequent processing dictates the final pore morphology. First we discuss surfactant-templated silicas where the template-matrix interaction is via non-covalent bonding mechanisms and the pore structure is established in the solution stage. We then discuss silicas templated by organic ligands covalently bonded to the siloxane network where subsequent processing strongly influences the final pore structure.

We have developed structure/toxicity relationships for amorphous silica nanoparticles (NPs) synthesized through low temperature, colloidal (e.g. Stöber silica) or high temperature pyrolysis (e.g. fumed silica) routes. Through combined spectroscopic and physical analyses, we have determined the state of aggregation, hydroxyl concentration, relative proportion of strained and unstrained siloxane rings, and potential to generate hydroxyl radicals for Stöber and fumed silica NPs with comparable primary particle sizes (16-nm in diameter). Based on erythrocyte hemolytic assays and assessment of the viability and ATP levels in epithelial and macrophage cells, we discovered for fumed silica an important toxicity relationship to post-synthesis thermal annealing or environmental exposure, whereas colloidal silicas were essentially non-toxic under identical treatment conditions. Specifically, we find for fumed silica a positive correlation of toxicity with hydroxyl concentration and its potential to generate reactive oxygen species (ROS) and cause red blood cell hemolysis. We propose fumed silica toxicity stems from its intrinsic population of strained three-membered rings (3MRs) along with its chain-like aggregation and hydroxyl content. Hydrogen-bonding and electrostatic interactions of the silanol surfaces of fumed silica aggregates with the extracellular plasma membrane cause membrane perturbations sensed by the Nalp3 inflammasome, whose subsequent activation leads to secretion of the cytokine IL-1β. Hydroxyl radicals generated by the strained 3MRs in fumed silica but largely absent in colloidal silicas may contribute to the inflammasome activation. Formation of colloidal silica into aggregates mimicking those of fumed silica had no effect on cell viability or hemolysis. This study emphasizes that not all amorphous silica is created equal and that the unusual toxicity of fumed silica compared to colloidal silica derives from its framework and surface chemistry along with its fused chain-like morphology established by high temperature synthesis (>1300°C) and rapid thermal quenching.

Simple and efficient methods of organizing materials are key to the realization of a nanotech world. These authors report on recent developments in simple evaporation‐induced self‐assembly processes, which enable the rapid production of patterned porous or nanocomposite materials. The Figure shows a calcined particle exhibiting vesicular mesophase, which was generated by aerosol self‐assembly of the tri‐block copolymer P123.

Nanocomposite materials are widespread in biological systems. Perhaps the most studied is the nacre of abalone shell, an orientated coating composed of alternating layers of aragonite (CaCO 3 ) and a biopolymer. Its laminated structure simultaneously provides strength, hardness and toughness: containing about 1 vol. % polymer, nacre is twice as hard and 1,000 times as tough as its constituent phases 1 . Such remarkable properties have inspired chemists and materials scientists to develop synthetic, 'biomimetic' nanocomposite assemblies 2-5 . Nonetheless, the efficient processing of layered organic-inorganic composites remains an elusive goal. Here we report a rapid, efficient selfassembly process for preparing nanolaminated coatings that mimic the structure of nacre. Beginning with a solution of silica, surfactant and organic monomers, we rely on evaporation during dip-coating to induce the formation of micelles and partitioning of the organic constituents into the micellar interiors 6 . Subsequent self-assembly of the silica-surfactant-monomer micellar species into lyotropic mesophases 7 simultaneously organizes the organic and inorganic precursors into the desired nanolaminated form. Polymerization fixes this structure, completing the nanocomposite assembly process. This approach may be generalized both to other composite architectures and to other materials combinations.Natural nanocomposites are formed by biomineralization 5 , a templated self-assembly process in which pre-organized organic surfaces regulate the nucleation, growth, morphology and orientation of inorganic crystals. Related synthetic, so-called 'biomimetic', approaches include crystallization beneath Langmuir monolayers 8 , crystallization on self-assembled monolayers 3,9 , supramolecular self-assembly 2,6,10 and sequential deposition 11 . Of these, only the last two offer the ability to introduce periodic microstructural and compositional changes needed for nanocomposite assembly. With regard to nanolaminated structures, supramolecular self-assembly has resulted in the formation of lamellar (silica/surfactant) films 12 or letters to nature 256