Integrated Circular Dichroism and Circularly Polarized Luminescence Measurements.

Circularly polarized luminescent (CPL) systems have a plethora of potential applications owing to their interesting excited-state properties. However, the progress in developing new chiral luminescence systems is significantly hindered by the lack of available instrumentation for the broader chemistry and materials science community to perform routine, reproducible measurements of chiral spectroscopies. In this work, we present data from an easy-to-use custom-built instrument based on a Jasco circular dichroism (CD) spectropolarimeter coupled with a CPL emission monochromator (CD/CPL hybrid system). The hybrid system measures CPL, fluorescence, CD, and absorbance on the same part of the sample without the need to move between the CD and CPL measurements. The instrument uses a xenon arc lamp as the light source, enabling a wide range of excitation wavelengths to support flexible development of new molecules and materials. Data obtained and presented for camphor, ruthenium metal complexes, the peptide gramicidin, and a DNA-ligand (4',6-diamidino-2-phenylindole, DAPI) system in this work highlight the ease of use and reproducibility of the results. The g-factors for CD and CPL obtained for the different compounds are shown to be the same for isolated transitions and some examples of how to use variations of g-factors with wavelength are demonstrated. The reliable and excellent benchmark results obtained from a custom-built commercial wavelength scanning CPL/CD hybrid instrument open up new avenues for the broader chemical and materials science community to intensify research on chiral luminescent systems.

Equilibrium and Kinetic Study of l- and d-Valine Adsorption in Supramolecular-Templated Chiral Mesoporous Materials.

Adsorption kinetic studies are conducted to investigate the potential to use chiral mesoporous materials nanoporous guanosine monophosphate material-1 (NGM-1) and nanoporous folic acid material-1 (NFM-1) for the enantiomeric separation of l- and d-valine. A pseudo-second-order (PSO) kinetic model is applied to test the experimental adsorption equilibrium isotherms, according to both the Langmuir and Freundlich models and the characteristic parameters for each model are determined. The calcined versions of both NGM-1 and NFM-1 fit the Langmuir model with maximum sorption capacities of 0.36 and 0.26 g/g for the preferred adsorption enantiomers, d-valine and l-valine, respectively. Experimental results and the analysis of adsorption models suggest a strong adsorbate-adsorbent interaction, and the formation of a monolayer of tightly packed amino acid on the internal mesopore surface for the preferred enantiomers.

Chiral Resolution using Supramolecular-Templated Mesostructured Materials.

Chiral resolution using non-functionalized mesoporous particles is demonstrated for a variety of enantiomeric pairs. This is achieved through the use of supramolecular templated silica materials prepared with guanosine monophosphate (NGM-1) and folic acid (NFM-1) which enable direct chiral transcription onto the surface of the mesopores after solvent extraction and post calcination of the template. The chiral selectivity and kinetics of the mesoporous materials are measured by circular dichroism (CD) spectroscopy on adsorbed molecules with different affinities for the pore surface. NGM-1 and NFM-1 have opposite enantiomeric selectivity for enantiomeric pairs. These results significantly increase the potential of mesoporous materials for chiral separation and enantiomeric catalysis.

Dispersed Uniform Nanoparticles from a Macroscopic Organosilica Powder.

A colloidal dispersion of uniform organosilica nanoparticles could be produced via the disassembly of the non-surfactant-templated organosilica powder nanostructured folate material (NFM-1). This unusual reaction pathway was available because the folate and silica-containing moieties in NFM-1 are held together by noncovalent interactions. No precipitation was observed from the colloidal dispersion after a week, though particle growth occurred at a solvent-dependent rate that could be described by the Lifshitz-Slyozov-Wagner equation. An organosilica film that was prepared from the colloidal dispersion adsorbed folate-binding protein from solution but adsorbed ions from a phosphate-buffered saline solution to a larger degree. To our knowledge, this is the first instance of a colloidal dispersion of organosilica nanoparticles being derived from a macroscopic material rather than from molecular precursors.

Non-absorbable mesoporous silica for the development of protein sequestration therapies.

While our understanding of the molecular events leading to disease onset and progression have increased exponentially, our capacity to therapeutically intervene in these events with new chemical diversity has clearly fallen short of that pace. In the quest to readdress this situation, the drug discovery sector is slowly but increasingly exploring sources of alternative chemical matter, such as the ones provided by material science and nanotechnology. While new functional nano-sized materials hold great promise for the future, our lack of understanding of the long term safety implications associated with systemic exposure as well as the unclear regulatory path ahead hamper their present impact in drug development. Paradoxically, the exploitation of novel, functionally active micron-sized, synthetic, non-absorbable chemical matter, for the treatment or prevention of a number of epidemiologically significant conditions remains clearly underexplored. A combination of pre-existing evidence and future potential indicates that micron-sized mesoporous silica materials could be an untapped source of new drug candidates. These are free from both the dreaded high attrition associated with small molecule drug discovery and the uncertainties of nano-size technologies. This, together with the coming of age of synthetic methodologies to control particle size and shape; pore size and geometry; surface chemistry, bioconjugation and formulation, open up exciting possibilities to exploit this novel chemistry-biology therapeutic interface.

Supramolecular transcription of guanosine monophosphate into mesostructured silica.

There is large interest in replicating biological supramolecular structures in inorganic materials that are capable of mimicking biological properties. The use of 5-guanosine monophosphate in the presence of Na(+) and K(+) ions as a supramolecular template for the synthesis of well-ordered mesostructured materials is reported here. Mesostructured particles with the confined template exhibit high structural order at both meso- and atomic scales, with a lower structural symmetry in the columnar mesophase. Although a chiral space group can not be deduced from X-ray diffraction, analysis by electron microscopy and circular dichroism confirms a chiral stacking arrangement along the c-axis. Guanosine monophosphate based mesophases thus illustrate the possibility for specific molecular imprinting of mesoporous materials by genetic material and the potential for higher definition in molecular recognition.

Self-assembly mechanism of folate-templated mesoporous silica.

A method to form ordered mesoporous silica based on the use of folate supramolecular templates has been developed. Evidence based on in situ small-angle X-ray scattering (SAXS), electron microscopy, infrared spectroscopy, and in situ conductivity measurements are used to investigate the organic-inorganic interactions and synthesis mechanism. The behavior of folate molecules in solution differs distinctively from that of surfactants commonly used for the preparation of ordered mesoporous silica phases, notably with the absence of a critical micellar concentration. In situ SAXS studies reveal fluctuations in X-ray scattering intensities consistent with the condensation of the silica precursor surrounding the folate template and the growth of the silica mesostructure in the initial stages. High-angle X-ray diffraction shows that the folate template is well-ordered within the pores even after a few minutes of synthesis. Direct structural data for the self-assembly of folates into chiral tetramers within the pores of mesoporous silica provide evidence for the in register stacking of folate tetramers, resulting in a chiral surface of rotated tetramers, with a rotation angle of 30°. Additionally, the self-assembled folates within pores were capable of adsorbing a considerable amount of CO2 gas through the cavity space of the tetramers. The study demonstrates the validity of using a naturally occurring template to produce relevant and functional mesoporous materials.

Adjuvant properties of mesoporous silica particles tune the development of effector T cells.

Alum is the most frequently used adjuvant today, primarily inducing Th2 responses. However, Th1-type responses are often desirable within immune therapy, and therefore the development of new adjuvants is greatly needed. Mesoporous silica particles with a highly ordered pore structure have properties that make them very interesting for future controlled drug delivery systems, such as controllable particle and pore size; they also have the ability to induce minor immune modulatory effects, as previously demonstrated on human-monocyte-derived dendritic cells (MDDCs). In this study, mesoporous silica particles are shown to be efficiently engulfed by MDDCs within 2 h, probably by phagocytic uptake, as seen by confocal microscopy and transmission electron microscopy. A co-culture protocol is developed to evaluate the capability of MDDCs to stimulate the development of naïve CD4(+) T cells in different directions. The method, involving ELISpot as a readout system, demonstrates that MDDCs, after exposure to mesoporous silica particles (AMS-6 and SBA-15), are capable of tuning autologous naïve T cells into different effector cells. Depending on the size and functionalization of the particles added to the cells, different cytokine patterns are detected. This suggests that mesoporous silica particles can be used as delivery vehicles with tunable adjuvant properties, which may be of importance for several medical applications, such as immune therapy and vaccination.

Enhanced Antioxidant Effects of the Anti-Inflammatory Compound Probucol When Released from Mesoporous Silica Particles.

Brain endothelial cells mediate the function and integrity of the blood brain barrier (BBB) by restricting its permeability and exposure to potential toxins. However, these cells are highly susceptible to cellular damage caused by oxidative stress and inflammation. Consequent disruption to the integrity of the BBB can lead to the pathogenesis of neurodegenerative diseases. Drug compounds with antioxidant and/or anti-inflammatory properties therefore have the potential to preserve the structure and function of the BBB. In this work, we demonstrate the enhanced antioxidative effects of the compound probucol when loaded within mesoporous silica particles (MSP) in vitro and in vivo zebrafish models. The dissolution kinetics were significantly enhanced when released from MSPs. An increased reduction in lipopolysaccharide (LPS)-induced reactive oxygen species (ROS), cyclooxygenase (COX) enzyme activity and prostaglandin E2 production was measured in human brain endothelial cells treated with probucol-loaded MSPs. Furthermore, the LPS-induced permeability across an endothelial cell monolayer by paracellular and transcytotic mechanisms was also reduced at lower concentrations compared to the antioxidant ascorbic acid. Zebrafish pre-treated with probucol-loaded MSPs reduced hydrogen peroxide-induced ROS to control levels after 24-h incubation, at significantly lower concentrations than ascorbic acid. We provide compelling evidence that the encapsulation of antioxidant and anti-inflammatory compounds within MSPs can enhance their release, enhance their antioxidant effects properties, and open new avenues for the accelerated suppression of neuroinflammation.

Bicontinuous cubic mesoporous materials with biphasic structures.

The replication of amphiphilic systems within an inorganic silica matrix allows the study of the fundamental properties of mesostructural changes, that is, kinetic and structural parameters. Herein we report a detailed study of the transition between cubic bicontinuous mesostructure with space groups Ia ̅3d and Pn ̅3m symmetry, which are associated with the minimal G and D surfaces, respectively. The transition may be induced through micellar swelling of the anionic amphiphilic surfactant N-lauroyl alanine by trimethylbenzene. Rich kinetic behaviour is observed and has been exploited to prepare particles with biphasic structures. Transmission electron microscopy evidence indicates that there is epitaxial growth from one mesostructure to the other involving the [111] and [110] orientations of the Ia ̅3d and Pn ̅3m symmetry structures, respectively. From kinetic studies, we show that the formation of the Ia ̅3d mesophase is preceded by a hexagonal phase (plane group p6mm) and an epitaxial relationship has been observed involving the sixfold or ̅3 axis orientations of both structures. Our data suggests that the Pn ̅3m mesostructure is kinetically stable at low temperatures whereas the Ia ̅3d mesostructure is the more stable structure after prolonged periods of hydrothermal treatment. We present evidence from transmission electron microscopy and small-angle X-ray diffractograms and also electron crystallography modelling of the unit cells at particular points in the structural change.

Mechanisms and kinetics for sorption of CO2 on bicontinuous mesoporous silica modified with n-propylamine.

We studied equilibrium adsorption and uptake kinetics and identified molecular species that formed during sorption of carbon dioxide on amine-modified silica. Bicontinuous silicas (AMS-6 and MCM-48) were postsynthetically modified with (3-aminopropyl)triethoxysilane or (3-aminopropyl)methyldiethoxysilane, and amine-modified AMS-6 adsorbed more CO(2) than did amine-modified MCM-48. By in situ FTIR spectroscopy, we showed that the amine groups reacted with CO(2) and formed ammonium carbamate ion pairs as well as carbamic acids under both dry and moist conditions. The carbamic acid was stabilized by hydrogen bonds, and ammonium carbamate ion pairs formed preferably on sorbents with high densities of amine groups. Under dry conditions, silylpropylcarbamate formed, slowly, by condensing carbamic acid and silanol groups. The ratio of ammonium carbamate ion pairs to silylpropylcarbamate was higher for samples with high amine contents than samples with low amine contents. Bicarbonates or carbonates did not form under dry or moist conditions. The uptake of CO(2) was enhanced in the presence of water, which was rationalized by the observed release of additional amine groups under these conditions and related formation of ammonium carbamate ion pairs. Distinct evidence for a fourth and irreversibly formed moiety was observed under sorption of CO(2) under dry conditions. Significant amounts of physisorbed, linear CO(2) were detected at relatively high partial pressures of CO(2), such that they could adsorb only after the reactive amine groups were consumed.

The synthesis of chiral periodic organosilica materials with ultrasmall mesopores.

Helical organosilica materials were synthesized for the first time using a novel binaphthyl-based chiral co-monomer in less than 1 hour. The incorporation of a chiral co-monomer in the wall was shown to influence the curvature of the helical materials. As the amount of the chiral co-monomer was increased, the degree of curvature increased, illustrating the importance of this monomer to the overall morphology.

Effects of Absorption Kinetics on the Catabolism of Melatonin Released from CAP-Coated Mesoporous Silica Drug Delivery Vehicles.

Melatonin (MLT) is a pineal hormone involved in the regulation of the sleep/wake cycle. The efficacy of exogenous MLT for the treatment of circadian and sleep disorders is variable due to a strong liver metabolism effect. In this work, MLT is encapsulated in mesoporous silica (AMS-6) with a loading capacity of 28.8 wt%, and the mesopores are blocked using a coating of cellulose acetate phthalate (CAP) at 1:1 and 1:2 AMS-6/MLT:CAP ratios. The release kinetics of MLT from the formulations is studied in simulated gastrointestinal fluids. The permeability of the MLT released from the formulations and its 6-hydroxylation are studied in an in vitro model of the intestinal tract (Caco-2 cells monolayer). The release of MLT from AMS-6/MLT:CAP 1:2 is significantly delayed in acidic environments up to 40 min, while remaining unaffected in neutral environments. The presence of CAP decreases the absorption of melatonin and increases its catabolism into 6-hydroxylation by the cytochrome P450 enzyme CYP1A2. The simple confinement of melatonin into AMS-6 pores slightly affects the permeability and significantly decreases melatonin 6-hydroxylation. Measurable amounts of silicon in the basolateral side of the Caco-2 cell monolayer might suggest the dissolution of AMS-6 during the experiment.

Temperature-induced uptake of CO2 and formation of carbamates in mesocaged silica modified with n-propylamines.

Adsorption-mediated CO(2) separation can reduce the cost of carbon capture and storage. The reduction in cost requires adsorbents with high capacities for CO(2) sorption and high CO(2)-over-N(2) selectivity. Amine-modified sorbents are promising candidates for carbon capture. To investigate the details of CO(2) adsorption in such materials, we studied mesocaged (cubic, Pm3n symmetry) silica adsorbents with tethered propylamines using Fourier transform infrared (FTIR) spectroscopy and volumetric uptake experiments. The degree of heterogeneity in these coatings was varied by either cosynthesizing or postsynthetically introducing the propylamine modification. In situ FTIR spectroscopy revealed the presence of both physisorbed and chemisorbed CO(2) in the materials. We present direct molecular evidence for physisorption using FTIR spectroscopy in mesoporous silica sorbents modified with propylamines. Physisorption reduced the CO(2)-over-N(2) selectivity in amine-rich sorbents. Samples with homogeneous coatings showed typical CO(2) adsorption trends and large quantities of IR-observable physisorbed CO(2). The uptake of CO(2) in mesocaged materials with heterogeneous propylamine coatings was higher at high temperatures than at low temperatures. At higher temperatures and low pressures, the postsynthetically modified materials adsorbed more CO(2) than did the extracted ones, even though the surface area after modification was clearly reduced and the coverage of primary amine groups was lower. The principal mode of CO(2) uptake in postsynthetically modified mesoporous silica was chemisorption. The chemisorbed moieties were present mainly as carbamate-ammonium ion pairs, resulting from the quantitative transformation of primary amine groups during CO(2) adsorption as established by NIR spectroscopy. The heterogeneity in the coatings promoted the formation of these ion pairs. The average propylamine-propylamine distance must be small to allow the formation of carbamate-propylammonium ion pairs.

Release of folic acid in mesoporous NFM-1 silica.

Mesoporous NFM-1 silica with folic acid as template was prepared taking advantage of the supramolecular self-assembly of pterin groups and their abilities to form hexagonal liquid crystal phases. NFM-1 materials with the varied morphologies such as fiber, chiral twisting long-rod, gyroid, and amorphous particles were prepared by varying the amount of the co-structure directing agent, stirring speed and changing pH value of the synthesis. The release kinetics of NFM-1 samples with different morphologies were studied in phosphate buffer with pH = 7.4 in 37 degrees C under stirring. All the release kinetic curves are fitted by the power law and Higuchi equations. The fitting of the power law equation was separately done as for the released amount up to 60% or 100%. The materials show slow, long-term and sustained release of folic acid from mesoporous NFM-1 silica, which establishes a new foundation for the potential application in drug delivery and bioimaging.

A lysozyme corona complex for the controlled pharmacokinetic release of probucol from mesoporous silica particles.

Mesoporous silica particles (MSPs) enhance the release kinetics of poorly soluble compound probucol (PB) under the influence of a pore-blocking protein corona, prepared with lysozyme protein adsorption. In vivo oral administration experiments show a prolongation in the time to reach maximum systemic concentration and half-life of PB released from the lysozyme-MSP complex in comparison to the MSP alone. Specific hard protein corona complexes can act as functional diffusion barriers for the controlled release of drugs from MSP based formulations.

Nonsurfactant supramolecular synthesis of ordered mesoporous silica.

Hoogsteen-bonded tetrads and pentamers are formed by a large variety of organic molecules through H-donor and acceptor groups capable of inducing self-organization to form columnar and hexagonal mesophases. The biological importance of such macromolecular structures is exemplified by the assembly of guanosine-rich groups of telomere units and their implication in chromosomal replication. Folic acid is composed of a pterin group, chemically and structurally similar to guanine, conjugated to an l-glutamate moiety via a p-amino benzoic acid. Our aim has been to develop a delivery vehicle for folic acid and at the same time provide a novel synthetic route for ordered mesoporous materials without the use of amphiphilic surfactants. We present a new nonsurfactant route for the synthesis of highly ordered mesoporous materials, based on the supramolecular templating of stacked arrays of the tetramer-forming pterin groups of folic acid under a variety of synthetic conditions. This method leads to hexagonally ordered mesoporous structures with gyroid, spherical, and chiral morphologies with pores on the order of 25-30 A in diameter and surface areas above 1000 m(2)/g. More importantly circular dichroism studies reveal that the folate template possesses a chiral signature within the pores in the as-synthesized solid and that chirality is transferred from the folate template to the pore surface via the aminopropyl triethoxysilane costructure directing agent used in the supramolecular assembly. This novel templating approach for ordered mesoporous materials breaks the hegemony of surfactant micellar systems for the preparation of these exciting high surface area solids and opens new opportunities for structural control, design of pore geometry, and novel applications.

Efficient internalization of mesoporous silica particles of different sizes by primary human macrophages without impairment of macrophage clearance of apoptotic or antibody-opsonized target cells.

Macrophage recognition and ingestion of apoptotic cell corpses, a process referred to as programmed cell clearance, is of considerable importance for the maintenance of tissue homeostasis and in the resolution of inflammation. Moreover, macrophages are the first line of defense against microorganisms and other foreign materials including particles. However, there is sparse information on the mode of uptake of engineered nanomaterials by primary macrophages. In this study, mesoporous silica particles with cubic pore geometries and covalently fluorescein-grafted particles were synthesized through a novel route, and their interactions with primary human monocyte-derived macrophages were assessed. Efficient and active internalization of mesoporous silica particles of different sizes was observed by transmission electron microscopic and flow cytometric analysis and studies using pharmacological inhibitors suggested that uptake occurred through a process of endocytosis. Moreover, uptake of silica particles was independent of serum factors. The silica particles with very high surface areas due to their porous structure did not impair cell viability or function of macrophages, including the ingestion of different classes of apoptotic or opsonized target cells. The current findings are relevant to the development of mesoporous materials for drug delivery and other biomedical applications.

Antioxidant properties of probucol released from mesoporous silica.

Antioxidants play a vital role in scavenging reactive oxygen species (ROS) produced by the reduction of molecular oxygen from various cellular mechanisms. Under oxidative stress, an increase in the levels of ROS overwhelms the antioxidant response, causing oxidative damage to biological molecules, and leading to the development of various diseases. Drug compounds with potent antioxidant properties are typically poorly water soluble and highly hydrophobic. An extreme case is Probucol (PB), a potent antioxidant with reported water solubility of 5 ng/ml, and oral bioavailiability of <10%. In this study, PB was loaded in mesoporous silica at various drug loadings to understand the changes to the physical properties of the loaded drug, and it's in vitro drug release. Further in vitro studies were conducted in endothelial and microglia cell models to compare the free radical scavening efficiency of ascorbic acid, PB, and PB release from mesoporous silica particles. Out of the three different mesostructured particles studied, the maximum loading of PB was achieved for large pore mesoporous particles (SBA-15) at 50 wt% drug loading, before complete pore filling was observed. For all materials, loadings above complete pore filling resulted in the recrystallization of PB on the external surface. In vitro drug release measurements showed a rapid dissolution rate at low drug loadings compared to a bimodal release profile of amorphous and crystalline drug at higher drug loadings. PB loaded in mesoporous particle was shown to enhance the antioxidant response to extracellular ROS in the endothelial cell line model, and to intracellular ROS in the microglia cell model. Our results indicate that the antioxidant properties of PB can be significantly improved by using mesoporous silica as a delivery vehicle.

Sustained release from mesoporous nanoparticles: evaluation of structural properties associated with release rate.

We present here a detailed study of the controlled release of amino acid derived amphiphilic molecules from the internal pore structure of mesoporous nanoparticle drug delivery systems with different structural properties; namely cubic and hexagonal structures of various degrees of complexity. The internal pore surface of the nanomaterials presented has been functionalised with amine moieties through a one pot method. Release profiles obtained by Alternating Ionic Current measurements are interpreted in terms of specific structural and textural parameters of the porous nanoparticles such as pore geometry and connectivity. Results indicate that diffusion coefficients are lower by as much as four orders of magnitude in 2-dimensional structures in comparison to 3-dimensional mesoporous solids. A fast release in turn is observed from mesocaged materials AMS-9 and AMS-8 where the presence of structural defects is thought to lead to a slightly lower diffusion coefficient in the latter. Amount of pore wall functionalisation and number of binding sites on the model drug are found to have little effect on the drug release rate.