Novel colloidal materials for high-throughput screening applications in drug discovery and genomics

Tracking the reaction history is the means of choice to identify bioactive compounds in large combinatorial libraries. The authors describe two approaches to synthesis on silica beads: a) addition of a reporter dye tag during each synthesis step (see Figure), which attaches itself to the bead by colloidal forces, and b) encapsulating arrays of fluorescent dyes into the beads to encode them uniquely, for recognition with a flow cytometer after each reaction step.

X-ray scattering studies of mixed langmuir monolayers and Langmuir-Blodgett films of a noncentrosymmetric porphyrin with cadmium arachidate

The structures of mixed Langmuir (floating) monolayers and Langmuir-Blodgett (LB) films of a phenanthroline-porphyrin with cadmium arachidate (PhenPor + CdAr) have been investigated by synchrotron X-ray grazing incidence diffraction (GIXD) and specular X-ray reflectivity (SXR). GIXD measurements of the floating monolayers showed only one peak, arising from the CdAr domains in the films, at a scattering angle of 21.5 degrees. This is consistent with a hexagonal structure (alpha = 4.77 Angstrom). The correlation length in these domains is 250 Angstrom. GMD measurements of the LB films, however, show two sets of diffraction features: one arises from CdAr domains with a rectangular in-plane structure (alpha = 7.44 Angstrom and b = 4.90 Angstrom) and a correlation length of 85 Angstrom; the other is from porphyrin domains with an oblique in-plane structure (alpha (p) 15.2 Angstrom, b(p) = 8.86 Angstrom, and gamma (p) = 80 degrees) and a correlation length of 105 Angstrom. These dimensions are consistent with the surface pressure-area isotherm measurements and indicate that the two components are immiscible. The thickness of the bilayer is 57 Angstrom, and there is no correlation between the bilayers. Introduction of a trigger compound does not alter the structure of the films but slightly increases the bilayer thickness. The SXR measurements of the floating monolayers also support the suggested immiscibility of the two components in the films.

Recent advances in processing and characterization of periodic mesoporous MCM-41 silicate molecular sieves

The discovery of periodic mesoporous MCM-41 and related molecular sieves has attracted significant attention from a fundamental as well as applied perspective. They possess well-defined cylindrical/hexagonal mesopores with a simple geometry, tailored pore size, and reproducible surface properties. Hence, there is an ever-growing scientific interest in the challenges posed by their processing and characterization and by the refinement of various sorption models. Further, MCM-41-based materials are currently under intense investigation with respect to their utility as adsorbents, catalysts, supports, ion-exchangers, and molecular hosts. In this article, we provide a critical review of the developments in these areas with particular emphasis on adsorption characteristics, progress in controlling the pore sizes, and a comparison of pore size distributions using traditional and newer models. The model proposed by the authors for adsorption isotherms and criticalities in capillary condensation and hysteresis is found to explain unusual adsorption behavior in these materials while providing a convenient characterization tool.

The Dubinin-Radushkevich equation and the underlying microscopic adsorption description

The Dubinin-Radushkevich (DR) equation is widely used for description of adsorption in microporous materials, especially those of a carbonaceous origin. The equation has a semi-empirical origin and is based on the assumptions of a change in the potential energy between the gas and adsorbed phases and a characteristic energy of a given solid. This equation yields a macroscopic behaviour of adsorption loading for a given pressure. In this paper, we apply a theory developed in our group to investigate the underlying mechanism of adsorption as an alternative to the macroscopic description using the DR equation. Using this approach, we are able to establish a detailed picture of the adsorption in the whole range of the micropore system. This is different from the DR equation, which provides an overall description of the process. (C) 2001 Elsevier Science Ltd. All rights reserved.

On the surface diffusion of hydrocarbons in microporous activated carbon

This paper addresses the current status of the various diffusion theories for surface diffusion in the literature. The inadequacy of these models to explain the surface diffusion of many hydrocarbons in microporous activated carbon is shown in this paper. They all can explain the increase of the surface diffusivity (D-mu) with loading, but cannot explain the increase of the surface permeability (D(mu)partial derivativeC(mu)/partial derivativeP) with loading as observed in our data of diffusion of hydrocarbons in activated carbon, even when the surface heterogeneity is accounted for in those models. The explanation for their failure was presented, and we have put forward a theory to explain the increase of surface diffusion permeability with loading. This new theory assumes the variation of the activation energy for surface diffusion with surface loading, and it is validated with diffusion data of propane, n-butane, n-hexane, benzene and ethanol in activated carbon. (C) 2001 Elsevier Science Ltd. All rights reserved.

Optical barcoding of colloidal suspensions: applications in genomics, proteomics and drug discovery

The enormous amount of information generated through sequencing of the human genome has increased demands for more economical and flexible alternatives in genomics, proteomics and drug discovery. Many companies and institutions have recognised the potential of increasing the size and complexity of chemical libraries by producing large chemical libraries on colloidal support beads. Since colloid-based compounds in a suspension are randomly located, an encoding system such as optical barcoding is required to permit rapid elucidation of the compound structures. We describe in this article innovative methods for optical barcoding of colloids for use as support beads in both combinatorial and non-combinatorial libraries. We focus in particular on the difficult problem of barcoding extremely large libraries, which if solved, will transform the manner in which genomics, proteomics and drug discovery research is currently performed.

Modeling of phase equilibrium and vapor adsorption on carbon black based on a combination of a lattice theory and equation of state

A thermodynamic approach is developed in this paper to describe the behavior of a subcritical fluid in the neighborhood of vapor-liquid interface and close to a graphite surface. The fluid is modeled as a system of parallel molecular layers. The Helmholtz free energy of the fluid is expressed as the sum of the intrinsic Helmholtz free energies of separate layers and the potential energy of their mutual interactions calculated by the 10-4 potential. This Helmholtz free energy is described by an equation of state (such as the Bender or Peng-Robinson equation), which allows us a convenient means to obtain the intrinsic Helmholtz free energy of each molecular layer as a function of its two-dimensional density. All molecular layers of the bulk fluid are in mechanical equilibrium corresponding to the minimum of the total potential energy. In the case of adsorption the external potential exerted by the graphite layers is added to the free energy. The state of the interface zone between the liquid and the vapor phases or the state of the adsorbed phase is determined by the minimum of the grand potential. In the case of phase equilibrium the approach leads to the distribution of density and pressure over the transition zone. The interrelation between the collision diameter and the potential well depth was determined by the surface tension. It was shown that the distance between neighboring molecular layers substantially changes in the vapor-liquid transition zone and in the adsorbed phase with loading. The approach is considered in this paper for the case of adsorption of argon and nitrogen on carbon black. In both cases an excellent agreement with the experimental data was achieved without additional assumptions and fitting parameters, except for the fluid-solid potential well depth. The approach has far-reaching consequences and can be readily extended to the model of adsorption in slit pores of carbonaceous materials and to the analysis of multicomponent adsorption systems. (C) 2002 Elsevier Science (USA).

Study on diffusion and flow of benzene, n-hexane and CCl4 in activated carbon by a differential permeation method

In this paper the diffusion and flow of carbon tetrachloride, benzene and n-hexane through a commercial activated carbon is studied by a differential permeation method. The range of pressure is covered from very low pressure to a pressure range where significant capillary condensation occurs. Helium as a non-adsorbing gas is used to determine the characteristics of the porous medium. For adsorbing gases and vapors, the motion of adsorbed molecules in small pores gives rise to a sharp increase in permeability at very low pressures. The interplay between a decreasing behavior in permeability due to the saturation of small pores with adsorbed molecules and an increasing behavior due to viscous flow in larger pores with pressure could lead to a minimum in the plot of total permeability versus pressure. This phenomenon is observed for n-hexane at 30degreesC. At relative pressure of 0.1-0.8 where the gaseous viscous flow dominates, the permeability is a linear function of pressure. Since activated carbon has a wide pore size distribution, the mobility mechanism of these adsorbed molecules is different from pore to pore. In very small pores where adsorbate molecules fill the pore the permeability decreases with an increase in pressure, while in intermediate pores the permeability of such transport increases with pressure due to the increasing build-up of layers of adsorbed molecules. For even larger pores, the transport is mostly due to diffusion and flow of free molecules, which gives rise to linear permeability with respect to pressure. (C) 2002 Elsevier Science Ltd. All rights reserved.

Adsorption in slit-like pores of activated carbons: Improvement of the Horvath and Kawazoe method

Anew thermodynamic approach has been developed in this paper to analyze adsorption in slitlike pores. The equilibrium is described by two thermodynamic conditions: the Helmholtz free energy must be minimal, and the grand potential functional at that minimum must be negative. This approach has led to local isotherms that describe adsorption in the form of a single layer or two layers near the pore walls. In narrow pores local isotherms have one step that could be either very sharp but continuous or discontinuous benchlike for a definite range of pore width. The latter reflects a so-called 0 --> 1 monolayer transition. In relatively wide pores, local isotherms have two steps, of which the first step corresponds to the appearance of two layers near the pore walls, while the second step corresponds to the filling of the space between these layers. All features of local isotherms are in agreement with the results obtained from the density functional theory and Monte Carlo simulations. The approach is used for determining pore size distributions of carbon materials. We illustrate this with the benzene adsorption data on activated carbon at 20, 50, and 80 degreesC, argon adsorption on activated carbon Norit ROX at 87.3 K, and nitrogen adsorption on activated carbon Norit R1 at 77.3 K.

Surface diffusion of strong adsorbing vapours on porous carbon

Surface diffusion of strongly adsorbing hydrocarbon vapours on activated carbon was measured by using a constant molar flow method (D.D. Do, Dynamics of a semi-batch adsorber with constant molar supply rate: a method for studying adsorption rate of pure gas, Chem. Eng. Sci. 50 (1995) 549), where pure adsorbate is introduced into a semi-batch adsorber at a constant molar flow rate. The surface diffusivity was determined from the analysis of pressure response versus time, using a linear mathematical model developed earlier. To apply the linear theory over the non-linear range of the adsorption isotherm, we implement a differential increment method on the system which is initially equilibrated with some pre-determined loading. By conducting the experiments at different initial loadings, the surface diffusivity can be extracted as a function of loading. Propane, n-butane, n-hexane, benzene, and ethanol were used as diffusing adsorbate on a commercial activated carbon. It is found that the surface diffusivity of these strongly adsorbing vapours increases rapidly with loading, and the surface diffusion flux contributes significantly to the total flux and cannot be ignored. The surface diffusivity increases with temperature according to the Arrhenius law, and for the paraffins tested it decreases with the molecular weight of the adsorbate. (C) 2002 Elsevier Science Ltd. All rights reserved.

A comparative study of carbon gasification with O-2 and CO2 by density functional theory calculations

A comparative study of carbon gasification with O-2 and CO2 was conducted by using density functional theory calculations. It was found that the activation energy and the number of active sites in carbon gasification reactions are significantly affected by both the capacity and manner of gas chemisorption. O-2 has a strong adsorption capacity and the dissociative chemisorption of O-2 is thermodynamically favorable on either bare carbon surface or even isolated edge sites. As a result, a large number of semiquinone and o-quinone oxygen can be formed indicating a significant increase in the number of active sites. Moreover, the weaker o-quinone C-C bonds can also drive the reaction forward at (ca. 30%) lower activation energy. Epoxy oxygen forms under relatively high O-2 pressure, and it can only increase the number of active sites, not further reduce the activation energy. CO2 has a lower adsorption capacity. Dissociative chemisorption of CO2 can only occur on two consecutive edge sites and o-quinone oxygen formed from CO2 chemisorption is negligible, let alone epoxy oxygen. Therefore, CO2-carbon reaction needs (ca 30%) higher activation energy. Furthermore, the effective active sites are also reduced by the manner Of CO2 chemisorption. A combination of the higher activation energy and the fewer active sites leads to the much lower reaction rate Of CO2-carbon.

Adsorption of aromatic compounds by activated carbon: Effects of functional groups and molecular size

The adsorption of three aromatic compounds on to an untreated carbon was investigated. The solution pH was lowered in all experiments so that all the solutes were in their molecular forms. It was shown that the difference in the maximum adsorption of the solutes was mainly a result of the difference in the sizes of the molecules and their functional groups. Further-more, it was illustrated that the packing arrangement was most likely edge-to-face (sorbate-sorbent) with various tilt angles. On the other hand, the affinity and heterogeneity of the adsorption systems were apparently related to the pK(a) values of the solutes.

Conformational changes in SP-B as a function of surface pressure

X-ray reflectivity of bovine and sheep surfactant-associated protein B (SP-B) monolayers is used in conjunction with pressure-area isotherms and protein models to suggest that the protein undergoes changes in its tertiary structure at the air/water interface under the influence of surface pressure, indicating the likely importance of such changes to the phenomena of protein squeeze out as well as lipid exchange between the air-water interface and subphase structures. We describe an algorithm based on the well-established box- or layer-models that greatly assists the fitting of such unknown scattering-length density profiles, and which takes the available instrumental resolution into account. Scattering-length density profiles from neutron reflectivity of bovine SP-B monolayers on aqueous subphases are shown to be consistent with the exchange of a large number of labile protons as well as the inclusion of a significant amount of water, which is partly squeezed out of the protein monolayer at elevated surface pressures.