Journal of Mass SpectrometryVolume 43, Issue 11 p. 1565-1568 JMS Letter Atmospheric solids analysis probe: a rapid ionization technique for small molecule drugs Chris Petucci, Corresponding Author Chris Petucci [email protected] Discovery Analytical Chemistry, Wyeth Research, Collegeville, PA 19426, USADiscovery Analytical Chemistry, Wyeth Research, S2402, Collegeville, PA, 19426, USA.===Search for more papers by this authorJason Diffendal, Jason Diffendal Medicinal Chemistry, Wyeth Research, Collegeville, PA 19426, USASearch for more papers by this author Chris Petucci, Corresponding Author Chris Petucci [email protected] Discovery Analytical Chemistry, Wyeth Research, Collegeville, PA 19426, USADiscovery Analytical Chemistry, Wyeth Research, S2402, Collegeville, PA, 19426, USA.===Search for more papers by this authorJason Diffendal, Jason Diffendal Medicinal Chemistry, Wyeth Research, Collegeville, PA 19426, USASearch for more papers by this author First published: 12 May 2008 https://doi.org/10.1002/jms.1424Citations: 53Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1Takáts Z, Wiseman JM, Gologan B, Cooks RG. Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 2004; 306: 471. 2Kauppila TJ, Wiseman JM, Ketola RA, Kotiaho T, Cooks RG, Kostiainen R. Desorption electrospray ionization mass spectrometry for the analysis of pharmaceuticals and metabolite. Rapid Communications in Mass Spectrometry 2006; 20: 387. 3Chen H, Pan Z, Talaty NN, Cooks RG, Raftery D. Combining desorption electrospray ionization mass spectrometry and nuclear magnetic resonance for differential metabolomics without sample preparation. Rapid Communications in Mass Spectrometry 2006; 20: 1577. 4Myung S, Wiseman JM, Valentine SJ, Takáts Z, Cooks RG, Clemmer DE. Coupling desorption electrospray ionization with ion mobility/mass spectrometry for analysis of protein structure: evidence for desorption of folded and denatured states. 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Direct analysis in real time (DART) is a novel ionization technique that provides for the rapid ionization of small molecules under ambient conditions. In this study, several commercially available drugs as well as actual compounds from drug discovery research were examined by LC/UV/ESI-MS and DART interfaced to a quadrupole mass spectrometer. For most compounds, the molecular ions observed by ESI-MS were observed by DART/MS. DART/MS was also studied as a means to quickly monitor synthetic organic reactions and to obtain nearly instantaneous molecular weight confirmations of final products in drug discovery. For simple, synthetic organic transformations, the trends in the intensities of the mass spectral signals for the reactant and product obtained by DART/MS scaled closely with those of the diode array or the total ion chromatogram obtained by LC/UV/ESI-MS. In summary, DART is a new tool that complements electrospray ionization for the rapid ionization and subsequent mass spectral analysis of compounds in drug discovery.

A surfactant-free method based on power ultrasound was used to emulsify biphasic mixtures of liquid, near-critical carbon dioxide and water (T = 30 degreesC, P = 80 bar). When ultrasound above a threshold power density (roughly 0.15 W/cm(3) at 20 kHz) was applied to a biphasic system of carbon dioxide and water, emulsions were formed which remained turbid for approximately 30 min (after 2 min of continuous ultrasound). Pulsed ultrasound (20% duty of a 2.5 s cycle at 20 kHz) could be used to maintain the emulsions indefinitely. Benzoyl chloride hydrolysis was selected as a model chemical reaction because of its rapid rate in pure water and the relative insolubility of the aroyl halide in the aqueous phase as compared to the carbon dioxide phase. The kinetic rate was measured under a range of ultrasonic pulsed power densities and zero ultrasound (i.e., silently) as a control. The measured, apparent, first-order rate constant was accelerated 100-fold in the presence of ultrasound at 0.50 W/cm(3) relative to silent conditions. The accelerative effect of ultrasound saturates with increasing power beginning at 0.50 W/cm3. These results demonstrate the use of power ultrasound to create liquid carbon dioxide-water emulsions that, without surfactants or other additives, accelerate hydrolysis of substrates with low water solubility.

A number of aromatic cyclopropylidenes have been converted to diols using the Sharpless asymmetric dihydroxylation (AD) procedure. The enantiomeric ratios were determined by chiral phase HPLC by comparison with their racemates.