Daniel K. Schwartz

Controlled selectivity for palladium catalysts using self-assembled monolayers

The selective reaction of one part of a bifunctional molecule is a fundamental challenge in heterogeneous catalysis and for many processes including the conversion of biomass-derived intermediates. Selective hydrogenation of unsaturated epoxides to saturated epoxides is particularly difficult given the reactivity of the strained epoxide ring, and traditional platinum group catalysts show low selectivities. We describe the preparation of highly selective Pd catalysts involving the deposition of n-alkanethiol self-assembled monolayer (SAM) coatings. These coatings improve the selectivity of 1-epoxybutane formation from 1-epoxy-3-butene on palladium catalysts from 11 to 94% at equivalent reaction conditions and conversions. Although sulphur species are generally considered to be indiscriminate catalyst poisons, the reaction rate to the desired product on a catalyst coated with a thiol was 40% of the rate on an uncoated catalyst. Interestingly the activity decreased for less-ordered SAMs with shorter chains. The behaviour of SAM-coated catalysts was compared with catalysts where surface sites were modified by carbon monoxide, hydrocarbons or sulphur atoms. The results suggest that the SAMs restrict sulphur coverage to enhance selectivity without significantly poisoning the activity of the desired reaction.

Extensive phosphorylation with overlapping specificity by Mycobacterium tuberculosis serine/threonine protein kinases

The Mycobacterium tuberculosis genome encodes 11 serine/threonine protein kinases (STPKs) that are structurally related to eukaryotic kinases. To gain insight into the role of Ser/Thr phosphorylation in this major global pathogen, we used a phosphoproteomic approach to carry out an extensive analysis of protein phosphorylation in M. tuberculosis. We identified more than 500 phosphorylation events in 301 proteins that are involved in a broad range of functions. Bioinformatic analysis of quantitative in vitro kinase assays on peptides containing a subset of these phosphorylation sites revealed a dominant motif shared by six of the M. tuberculosis STPKs. Kinase assays on a second set of peptides incorporating targeted substitutions surrounding the phosphoacceptor validated this motif and identified additional residues preferred by individual kinases. Our data provide insight into processes regulated by STPKs in M. tuberculosis and create a resource for understanding how specific phosphorylation events modulate protein activity. The results further provide the potential to predict likely cognate STPKs for newly identified phosphoproteins.

Langmuir-Blodgett film structure

Abstract Langmuir-Blodgett (LB) films occupy a unique niche at the crossroads of materials science, complex fluids, and biophysics. They have many similarities to inorganic epitaxial films due to the layer by layer deposition process; however, the amphiphilic nature of the constituent molecules provides the connection to lyotropic liquid crystals and membranes. A great deal is known about LB film structure and thermodynamic behavior; both from classical studies as well as from recent experiments using sophisticated characterization techniques such as synchrotron X-ray scattering and scanning probe microscopy. This article summarizes the current understanding of these systems from a physical/structural point of view. Included are discussions of the deposition process, the layered nature of LB films, intralayer molecular packing, defects, stability, and phase transitions.

DNA hybridization-induced reorientation of liquid crystal anchoring at the nematic liquid crystal/aqueous interface.

Interactions between DNA and an adsorbed cationic surfactant at the nematic liquid crystal (LC)/aqueous interface were investigated using polarized and fluorescence microscopy. The adsorption of octadecyltrimethylammonium bromide (OTAB) surfactant to the LC/aqueous interface resulted in homeotropic (untilted) LC alignment. Subsequent adsorption of single-stranded DNA (ssDNA) to the surfactant-laden interface modified the interfacial structure, resulting in a reorientation of the LC from homeotropic alignment to an intermediate tilt angle. Exposure of the ssDNA/OTAB interfacial complex to its ssDNA complement induced a second change in the interfacial structure characterized by the nucleation, growth, and coalescence of lateral regions that induced homeotropic LC alignment. Fluorescence microscopy showed explicitly that the complement was colocalized in the same regions as the homeotropic domains. Exposure to noncomplementary ssDNA caused no such response, suggesting that the homeotropic regions were due to DNA hybridization. This hybridization occurred in the vicinity of the interface despite the fact that the conditions in bulk solution were such that hybridization did not occur (high stringency), suggesting that the presence of the cationic surfactant neutralized electrostatic repulsion and allowed for hydrogen bonding between DNA complements. This system has potential for label-less and portable DNA detection. Indeed, LC response to ssDNA target was detected with a lower limit of approximately 50 fmol of complement and was sufficiently selective to differentiate a one-base-pair mismatch in a 16-mer target.

Surface Order and Stability of Langmuir-Blodgett Films

Angstrom-resolution atomic force microscope images of Langmuir-Blodgett monolayers and multilayers of cadmium arachidate in air and under water show a dramatic change from a disordered arrangement to a crystalline lattice by the addition or removal of a single layer of molecules. The disordered surface is less stable than the ordered one to mechanical stresses such as atomic force microscopy tip forces or at the air-water contact line during contact angle measurements. The difference in the degree of order in the alkyl chains is attributed to the strong attractive interaction between headgroups in the presence of the divalent cation.

Control of Metal Catalyst Selectivity through Specific Noncovalent Molecular Interactions

The specificity of chemical reactions conducted over solid catalysts can potentially be improved by utilizing noncovalent interactions to direct reactant binding geometry. Here we apply thiolate self-assembled monolayers (SAMs) with an appropriate structure to Pt/Al2O3 catalysts to selectively orient the reactant molecule cinnamaldehyde in a configuration associated with hydrogenation to the desired product cinnamyl alcohol. While nonspecific effects on the surface active site were shown to generally enhance selectivity, specific aromatic stacking interactions between the phenyl ring of cinnamaldehyde and phenylated SAMs allowed tuning of reaction selectivity without compromising the rate of desired product formation. Infrared spectroscopy showed that increased selectivity was a result of favorable orientation of the reactant on the catalyst surface. In contrast, hydrogenation of an unsaturated aldehyde without a phenyl ring showed a nontunable improvement in selectivity, indicating that thiol SAMs can improve reaction selectivity through a combination of nonspecific surface effects and ligand-specific near-surface effects.

Textures and phase transitions in Langmuir monolayers of fatty acids. A comparative Brewster angle microscope and polarized fluorescence microscope study

Brewster angle microscopy (BAM) and polarized fluorescence microscopy (PFM) are used to observe the distinctive textures of and the transitions between condensed phases in Langmuir monolayers of n‐alkanoic acids. BAM is sensitive to film anisotropy even when the molecules are not tilted as long as the unit cell is anisotropic. Every transition is visible with one or both of the techniques, either as a dramatic change in the degree of contrast or as a sudden alteration of the mosaic domain texture. The two techniques are generally consistent, although the presence of the fluorescent probe impurity (for PFM) causes a subtle difference in the appearance of one transition and small shifts in transition surface pressures.

Directing reaction pathways by catalyst active-site selection using self-assembled monolayers

One key route for controlling reaction selectivity in heterogeneous catalysis is to prepare catalysts that exhibit only specific types of sites required for desired product formation. Here we show that alkanethiolate self-assembled monolayers with varying surface densities can be used to tune selectivity to desired hydrogenation and hydrodeoxygenation products during the reaction of furfural on supported palladium catalysts. Vibrational spectroscopic studies demonstrate that the selectivity improvement is achieved by controlling the availability of specific sites for the hydrogenation of furfural on supported palladium catalysts through the selection of an appropriate alkanethiolate. Increasing self-assembled monolayer density by controlling the steric bulk of the organic tail ligand restricts adsorption on terrace sites and dramatically increases selectivity to desired products furfuryl alcohol and methylfuran. This technique of active-site selection simultaneously serves both to enhance selectivity and provide insight into the reaction mechanism.

Re-entrant Appearance of Phases in a Relaxed Langmuir Monolayer of Tetracosanoic Acid as Determined by X-Ray Scattering

The structure of the fully relaxed phases of a Langmuir monolayer of tetracosanoic acid is determined by x‐ray diffraction and reflection along an isotherm at ∼20.5 °C. Isotherms taken by allowing the surface pressure to stabilize between incremental compressions are seen to be qualitatively different from the constant‐rate nonrelaxed isotherms typically seen in the literature. At low densities the monolayer consists of an inhomogeneous film of islands of a crystalline (or hexatic) phase with molecular tilt ordering that is analogous to that of the smectic I liquid crystal. Small amounts of impurities (∼0.5% of the monolayer) account for the change in surface pressure with area in this region. Upon compression to the point that the free space between islands becomes negligible the film appears homogeneous. On further compression the time required for full relaxation becomes long (i.e., ∼ hours), the tilt angle of the molecular axis decreases and the x‐ray unit cell is compressed. Including this homogeneou...

Production of particles of therapeutic proteins at the air–water interface during compression/dilation cycles

Particles in protein therapeutics are undesirable because they may have the potential for causing adverse immunogenicity in patients. Agitation-induced exposure to the air–water interface during manufacturing, shipping, and administration can cause particle formation in therapeutic protein products. We systematically studied how application of surface pressure during periodic interfacial compressions caused a model monoclonal antibody to form particles. Above a critical interfacial compression ratio of 5 we observed a dramatic increase in the rate of protein particle formation. During continuous interfacial compression/dilation cycles, particle numbers increased but the particle size distribution remained unchanged. When cyclic compressions were halted, particles did not nucleate additional particles or grow further in bulk solution suggesting that they are formed only at the air–water interface. In fact, we found that particles in the bulk slowly decreased in number upon standing. The rate of particle formation was only weakly dependent on both the bulk protein concentration and the period of cyclical interfacial compressions. These observations are consistent with the interfacial aggregation of proteins during periods of high surface pressure, followed by collapse of the adsorbed layer and detachment of protein particles from the interface into the bulk.