Detecting Reaction Intermediates in Solution and Guiding Cancer Surgery Using Mass Spectrometry
I wish to describe two recent developments in my laboratory using ambient ionization mass spectrometry, a mass spectrometric technique in which the sample of interest is in open air at room temperature. The first concerns detection and identification of solution-phase reaction intermediates, the second concerns mass spectrometric imaging.
Palladium complexes catalyze a variety of oxidation reactions, including the Wacker oxidation, the oxidation of alcohols, and oxidative C-C bond-forming reactions. Simple Pd(II) salts react sluggishly with oxygen, but in the presence of suitable ligands or solvents, Pd complexes are capable of aerobic oxidation reactions. A key step in these reactions is the oxidation of Pd(0) by O2 to regenerate a Pd(II) intermediate. We have employed a battery of mass spectroscopic techniques such as desorption electrospray ionization mass spectrometry (DESI-MS, millisecond reaction times), electrospray ionization mass spectrometry (ESI-MS, minutes reaction times), and nano-electrospray ionization mass spectrometry (nanospray-MS, minutes reaction times) to search for reaction intermediates formed during the aerobic oxidation of 1,2-diols. By monitoring active reactions with mass spectrometry operating at various timescales, we have directly detected and identified a number of novel intermediates generated in solution during the fast alcohol oxidation and slow aerobic re-oxidation of (neocuproine)Pd(0). These studies reveal the formation of a novel trinuclear palladium complex, [(neocuproinePd(II))3(m3-O)2]2+. The identification of this previously unreported species provides new insights on the mechanism of aerobic oxidation mediated by Pd complexes.
Surgical resection is the main curative option for gastrointestinal cancers. The extent of cancer resection is commonly assessed during surgery by pathologic evaluation of (frozen sections) of the tissue at the specimen margin(s). We compare this to an alternative procedure, desorption electrospray ionization mass spectrometric imaging (DESI-MSI), for 62 human cancerous and normal gastric tissue samples. In DESI-MSI, microdroplets strike the tissue sample, the resulting splash enters a mass spectrometer, and a statistical analysis, the Lasso method (multi-class logistic regression with L1 penalty), is applied to classify tissues based on the molecular information obtained directly from DESI-MSI. The results obtained suggest that DESI-MSI/Lasso may be valuable for routinely assessing margins in gastric cancer surgery.