Pearceconner0554

HPLC, being a solution based technique, revealed chemical decomposition of the API, but the technique was insensitive to physical transformations. Excipient properties such as hygroscopicity and microenvironmental acidity were identified to be critical determinants of both physical and chemical stability of LSP in a drug product. For drugs exhibiting both physical and chemical transformations, simultaneous solid-state and solution based analyses will enable comprehensive stability evaluation.By using Poisson's summation formula, we calculate periodic integrals over Gaussian basis functions by partitioning the lattice summations between the real and reciprocal space, where both sums converge exponentially fast with a large exponent. We demonstrate that the summation can be performed efficiently to calculate two-center Gaussian integrals over various kernels including overlap, kinetic, and Coulomb. The summation in real space is performed using an efficient flavor of the McMurchie-Davidson recurrence relation. The expressions for performing summation in the reciprocal space are also derived and implemented. The algorithm for reciprocal space summation allows us to reuse several terms and leads to a significant improvement in efficiency when highly contracted basis functions with large exponents are used. We find that the resulting algorithm is only between a factor of 5 and 15 slower than that for molecular integrals, indicating the very small number of terms needed in both the real and reciprocal space summations. An outline of the algorithm for calculating three-center Coulomb integrals is also provided.Self-association of cholesterol into aggregates and crystals is a hallmark of developing atherosclerosis. Intrinsically fluorescent sterols, such as dehydroergosterol (DHE), can be used to study sterol aggregation by fluorescence spectroscopy and microscopy, but a thorough understanding of DHE's photophysical and structural properties in the aggregated state is missing. Here, we show that DHE forms submicron fluorescent aggregates when evaporated from an ethanol solution. Nemtabrutinib clinical trial Using atomic force microscopy, we find that DHE, like cholesterol, forms compact oblate-shape aggregates of less then 100 nm in diameter. DHE's fluorescence is lowered in the aggregate compared to the monomeric form, and characteristic spectral changes accompany the aggregation process. Electronic structure calculations of DHE dimers in water indicate that Frenkel-type exciton coupling contributes to the lowered DHE fluorescence in the aggregates. Using molecular dynamics (MD) simulations, we show that DHE forms compact aggregates on the nanosecond scale and with strong intermolecular attraction, in which a broad range of orientations, and therefore electronic couplings, will take place. Tight packing of DHE in aggregates also lowers the apparent absorption cross section, further reducing the molecular brightness of the aggregates. Our results pave the way for systematic solubility studies of intrinsically fluorescent analogues of biologically relevant sterols.Erythrina alkaloids and their central nervous system effects have been studied for over a century, mainly due to their potent antagonistic actions at β2-containing nicotinic acetylcholine receptors (nAChRs). In the present work, we report a synthetic approach giving access to a diverse set of Erythrina natural product analogues and present the enantioselective total synthesis of (+)-Cocculine and (+)-Cocculidine, both found to be potent antagonists of the β2-containing nAChRs.Stress testing is one of the most important parts of the drug development process, helping to foresee stability problems and to identify degradation products. One of the processes involving stress testing is represented by forced degradation studies, which can predict the impact of certain conditions of pH, moisture, heat, or other negative effects due to transportation or packaging issues on drug potency and purity, ensuring patient safety. Regulatory agencies have been working on a standardization of laboratory procedures since the past two decades. One of the results of those years of intensive research is the International Conference on Harmonization (ICH) guidelines, which clearly define which forced degradation studies should be performed on new drugs, which become a routine work in pharmaceutical laboratories. Since used techniques based on high-performance liquid chromatography coupled with high-resolution mass spectrometry have been developed years ago and are now mastered by pharmaceutical scientists, automation of data analysis, and thus data processing, is becoming a hot topic nowadays. In this work, we present MassChemSite and WebChembase as a tandem to automatize the routine analysis studies without missing information quality, using as a case study the degradation of lansoprazole under acidic, oxidative, basic, and neutral stress conditions.Understanding the size- and shape-dependent properties of platinum nanoparticles is critical for enabling the design of nanoparticle-based applications with optimal and potentially tunable functionality. Toward this goal, we evaluated nine different empirical potentials with the purpose of accurately modeling faceted platinum nanoparticles using molecular dynamics simulation. First, the potentials were evaluated by computing bulk and surface properties-surface energy, lattice constant, stiffness constants, and the equation of state-and comparing these to prior experimental measurements and quantum mechanics calculations. Then, the potentials were assessed in terms of the stability of cubic and icosahedral nanoparticles with faces in the 100 and 111 planes, respectively. Although none of the force fields predicts all the evaluated properties with perfect accuracy, one potential-the embedded atom method formalism with a specific parameter set-was identified as best able to model platinum in both bulk and nanoparticle forms.Elevated reactive nitrogen (Nr) deposition is a concern for alpine ecosystems, and dry NH3 deposition is a key contributor. Understanding how emission hotspots impact downwind ecosystems through dry NH3 deposition provides opportunities for effective mitigation. However, direct NH3 flux measurements with sufficient temporal resolution to quantify such events are rare. Here, we measured NH3 fluxes at Rocky Mountain National Park (RMNP) during two summers and analyzed transport events from upwind agricultural and urban sources in northeastern Colorado. We deployed open-path NH3 sensors on a mobile laboratory and an eddy covariance tower to measure NH3 concentrations and fluxes. Our spatial sampling illustrated an upslope event that transported NH3 emissions from the hotspot to RMNP. Observed NH3 deposition was significantly higher when backtrajectories passed through only the agricultural region (7.9 ng m-2 s-1) versus only the urban area (1.0 ng m-2 s-1) and both urban and agricultural areas (2.7 ng m-2 s-1). Cumulative NH3 fluxes were calculated using observed, bidirectional modeled, and gap-filled fluxes.