Determination of limonene oxidation products using SPME and GC-MS

Limonene is a common component found in consumer goods ranging from beverages to cleaning compounds. Limonene oxidation products, however, have a less desirable flavor and fragrance. Early detection of limonene oxide formation would aid quality control. A method is developed to determine the concentration of limonene oxide in essential oils and beverages using solid-phase microextraction (SPME). A headspace sampling technique is used to reduce or eliminate the presence of less volatile components. Several different SPME fibers are tested, varying in polymer thickness, polymer cross-linking and bonding, and polarity of the polymer. For each fiber tested, the sampling time is optimized for reproducible results. The 7-microm-thick bonded poly(dimethylsiloxane) fiber provides the best results. External standards are used for quantitation.     

Overcoming Selectivity and Sensitivity Issues of Direct Inject Electrospray Mass Spectrometry via DAPNe-NSI-MS

Direct inject electrospray mass spectrometry offers minimal sample preparation and a “shotgun” approach to analyzing samples. However, complex matrix effects often make direct inject an undesirable sample introduction technique, particularly for trace level analytes. Highlighted here is our solution to the pitfalls of direct inject mass spectrometry and other ambient ionization methods with a focus on trace explosives. Direct analyte-probed nanoextraction coupled to nanospray ionization mass spectrometry solves selectivity issues and reduces matrix effects while maintaining minimal sample preparation requirements. With appropriate solvent conditions, most explosive residues can be analyzed with this technique regardless of the nature of the substance (i.e., nitroaromatic, oxidizing salt, or peroxide).

Solutions of two-factor models with variable interest rates

The focus of this work is on numerical solutions to two-factor option pricing partial differential equations with variable interest rates. Two interest rate models, the Vasicek model and the Cox–Ingersoll–Ross model (CIR), are considered. Emphasis is placed on the definition and implementation of boundary conditions for different portfolio models, and on appropriate truncation of the computational domain. An exact solution to the Vasicek model and an exact solution for the price of bonds convertible to stock at expiration under a stochastic interest rate are derived. The exact solutions are used to evaluate the accuracy of the numerical simulation schemes. For the numerical simulations the pricing solution is analyzed as the market completeness decreases from the ideal complete level to one with higher volatility of the interest rate and a slower mean-reverting environment. Simulations indicate that the CIR model yields more reasonable results than the Vasicek model in a less complete market.     

Effects of purification on the crystallization of lysozyme

We have additionally purified a commercial lysozyme preparation by cation exchange chromatography, followed by recrystallization. This material is 99.96% pure with respect to macromolecular impurities. At basic pH, the purified lysozyme gave only tetragonal crystals at 20°C. Protein used directly from the bottle, prepared by dialysis against distilled water, or which did not bind to the cation exchange column had considerably altered crystallization behavior. Lysozyme which did not bind to the cation exchange column was subsequently purified by size exclusion chromatography. This material gave predominately bundles of rod-shaped crystals with some small tetragonal crystals at lower pHs. The origin of the bundled rod habit was postulated to be a thermally dependent tetragonal ↔ orthorhombic change in the protein structure. This was subsequently ruled out on the basis of crystallization behavior and growth rate experiments. This suggests that heterogeneous forms of lysozyme may be responsible. These results demonstrate three classes of impurities: (1) small molecules, which may be removed by dialysis; (2) macromolecules, which are removable by chromatographic techniques; and (3) heterogeneous forms of the protein, which can be removed in this case by cation exchange chromatography. Of these, heterogeneous forms of the lysozyme apparently have the greatest affect on its crystallization behavior.     

Utility-aware screening with clique-oriented prioritization

Most methods of deciding which hits from a screen to send for confirmatory testing assume that all confirmed actives are equally valuable and aim only to maximize the number of confirmed hits. In contrast, "utility-aware" methods are informed by models of screeners' preferences and can increase the rate at which the useful information is discovered. Clique-oriented prioritization (COP) extends a recently proposed economic framework and aims--by changing which hits are sent for confirmatory testing--to maximize the number of scaffolds with at least two confirmed active examples. In both retrospective and prospective experiments, COP enables accurate predictions of the number of clique discoveries in a batch of confirmatory experiments and improves the rate of clique discovery by more than 3-fold. In contrast, other similarity-based methods like ontology-based pattern identification (OPI) and local hit-rate analysis (LHR) reduce the rate of scaffold discovery by about half. The utility-aware algorithm used to implement COP is general enough to implement several other important models of screener preferences.     

Expanding stereochemical and skeletal diversity using petasis reactions and 1,3-dipolar cycloadditions

A short and modular synthetic pathway using intramolecular 1,3-dipolar cycloaddition reactions and yielding functionalized isoxazoles, isoxazolines, and isoxazolidines is described. The change in shape of previous compounds and those in this study is quantified and compared using principal moment-of-inertia shape analysis.     

Relationship of stereochemical and skeletal diversity of small molecules to cellular measurement space

Systematic and quantitative measurements of the roles of stereochemistry and skeleton-dependent conformational restriction were made using multidimensional screening. We first used diversity-oriented synthesis to synthesize the same number (122) of [10.4.0] bicyclic products (B) and their corresponding monocyclic precursors (M). We measured the ability of these compounds to modulate a broad swath of biology using 40 parallel cell-based assays. We analyzed the results using statistical methods that revealed illuminating relationships between stereochemistry, ring number, and assay outcomes. Conformational restriction by ring-closing metathesis increased the specificity of responses among active compounds and was the dominant factor in global activity patterns. Hierarchical clustering also revealed that stereochemistry was a second dominant factor; whereas the stereochemistry of macrocyclic appendages was a determinant for bicyclic compounds, the stereochemistry of the carbohydrates was a determinant for the monocyclic compounds of global activity patterns. These studies illustrate a quantitative method for measuring stereochemical and skeletal diversity of small molecules and their cellular consequences.     

Inductively coupled plasma mass spectrometry with an enlarged sampling orifice and offset Ion Lens. I. Ion trajectories and detector performance

A new inductively coupled plasma mass spectrometer (ICP-MS) with four stages of differential pumping is described. The relatively large sampling orifice (1.31-mm dia.) improves signals for metal ions and resists plugging from deposited solids. A new ion lens is described that deflects ions off center and then back on center into the differential pumping orifice; there is no photon stop in the center of the beam. Calculations of ion trajectories using SIMIOn show that only those ions that leave the skimmer on center are transmitted, whereas most other lenses used in ICP-MS transmit only ions that leave the skimmer off axis. The performance of a Channeltron electron multiplier is compared to that of a Daly detector. Both detectors yield similar sensitivities of ≈ 10⁶ counts s^?1 per ppm and detection limits of ≈ 1 pptr. The background with a Channeltron electron multiplier is only 0.4 counts s^?1 and is only slightly higher than the dark current count rate. Presumably the offset ion lens used in the present work efficiently screens the detector from photons emitted by the plasma. The background with the Daly detector is 4 counts s^?1, which represents a substantial improvement over the background obtained in previous use of the Daly detector with JCP-MS.