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Biomedical subjects

Kristin E Price

Publications and source records attributed to Kristin E Price.

10 recordsLinked to original sources

Microencapsulated linear polymers: "soluble" heterogeneous catalysts.

A new strategy for supporting catalysts based on the microencapsulation of linear polymers is presented. In this paper, we present a DMAP capsule that is capable of catalyzing acylation reactions. The catalyst is compared to DMAP on cross-linked and linear polystyrene, as well as small molecule DMAP. Rapid optimization through modification of encapsulation conditions is demonstrated. The optimization provides a dynamic range of catalysis from 90 to 300% of the rate of DMAP on polystyrene.

Capsules↗

Rapid self-assembly of core-shell organosilicon microcapsules within a microfluidic device.

The preparation of hierarchically structured organosilicon microcapsules from commercially available starting materials is described. Using a microfluidic device, an emulsion of dichlorodiphenylsilane is formed in a continuous phase of aqueous glycerol. The silane droplets undergo hydrolysis, condensation, and crystallization within minutes to form self-assembled, core-shell microcapsules. The microparticles have been characterized with light and electron microscopy, nuclear magnetic resonance spectroscopy (NMR), diffusion-ordered NMR spectroscopy (DOSY), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (XRD). The characterization data show that the microcapsule walls consist of amorphous, oligomeric poly(diphenylsiloxane) surrounded by a spiny layer of crystalline diphenylsilanediol. Glycerol is occluded within the wall material but is not covalently bound to the silicon components. Glycerol is a crucial element for producing low-dispersity microcapsules with well-ordered surface spines, as the use of methyl cellulose as viscomodifier yields amorphous surfaces.

Journal Article↗

Tissue targeted metabonomics: metabolic profiling by microdialysis sampling and microcoil NMR.

The concentration of low molecular weight compounds in tissues can yield valuable information about the metabolic state of an organism. Studies of changes in the metabolic state or metabonomics can reflect disease pathways, drug action, or toxicity. This research aims to develop a new approach, tissue targeted metabonomics. Microdialysis sampling and microcoil NMR analysis are employed to compare basal and ischemic metabolic states of various tissues (blood, brain, and heart) of Sprague-Dawley rats. Microdialysis sampling is localized, making the metabolic profile tissue specific. Coupling to NMR analysis is highly advantageous, because a complete metabolic profile is obtained in a single spectrum. However, small sample volumes and low analyte concentrations make analysis of microdialysis samples challenging. Microcoil NMR uses low sample volumes and has improved mass sensitivity, relative to standard 5 mm probes. The coupling of these techniques is a potentially powerful tool for metabonomics analysis.

Animals↗

One-pot multi-step synthesis: a challenge spawning innovation.

Creating one-pot synthetic routes is a challenge that is already spawning new chemistry, enzymes, materials, and mechanistic insight. Through one-pot reactions, the chemical products that add value to our lives can be produced with less waste and greater economic benefits. Within this Emerging Area, we describe models for designing one-pot reactions as well as advanced catalysts created to facilitate their realization.

Catalysis↗

A new interpretation of the Baylis-Hillman mechanism.

[reaction: see text] On the basis of reaction rate data, we have proposed a new mechanism for the Baylis-Hillman reaction involving the formation of a hemiacetal intermediate. We have determined that the rate-determining step is second order in aldehyde and first order in DABCO and acrylate. We have shown that this mechanism is general to aryl aldehydes under polar, nonpolar, and protic conditions using both rate data and two isotope effect experiments.

Journal Article↗

Baylis-Hillman mechanism: a new interpretation in aprotic solvents.

Using reaction rate data collected in aprotic solvents, we have determined that the Baylis-Hillman rate-determining step is second order in aldehyde and first order in DABCO and acrylate. On the basis of these data, we have proposed a new mechanism involving a hemiacetal intermediate. The proposed mechanism was then supported using two different kinetic isotope experiments.

Acrylates↗

Epitope mapping and competitive binding of HSA drug site II ligands by NMR diffusion measurements.

It is important to characterize drug-albumin binding during drug discovery and lead optimization as strong binding may reduce bioavailability and/or increase the drug's in vivo half-life. Despite knowing about the location of human serum albumin (HSA) drug binding sites and the residues important for binding, less is understood about the binding dynamics between exogenous drugs and endogenous fatty acids. In contrast to highly specific antibody-antigen interactions, the conformational flexibility of albumin allows the protein to adopt multiple conformations of approximately equal energy in order to accommodate a variety of ligands. Nuclear magnetic resonance (NMR) diffusion measurements are a simple way to quantitatively describe ligand-protein interactions without prior knowledge of the number of binding sites or the binding stoichiometry. This method can also provide information about ligand orientation at the binding site due to buildup of exchange-transferred NOE (trNOE) on the diffusion time scale of the experiment. The results of NMR diffusion and NOE experiments reveal multiple binding interactions of HSA with dansylglycine, a drug site II probe, and caprylate, a medium-chain fatty acid that also has primary affinity for HSA's drug site II. Interligand NOE (ilNOE) detected in the diffusion analysis of a protein solution containing both ligands provides insight into the conformations adopted by these ligands while bound in common HSA binding pockets. The results demonstrate the ability of NMR diffusion experiments to identify ternary complex formation and show the potential of this method for characterizing other biologically important ternary structures, such as enzyme-cofactor-inhibitor complexes.

Binding, Competitive↗

Synthesis and characterization of cross-linked reverse micelles.

The design and synthesis of a new cross-linkable amphiphile is reported. Solutions of the amphiphile in a toluene/water mixture form reverse micelles as indicated by dynamic light scattering and NMR spectroscopy. As indicated by dynamic light scattering, TEM, and NMR spectroscopy data, these reverse micelles can be cross-linked without drastically changing the radius of the reverse micelles. Mixed reverse micelles are also characterized and cross-linked. The cross-linked reverse micelles are demonstrated to facilitate phase transfer and can be used to site isolate a catalyst.

Journal Article↗