Isotope pattern match

T. Griiner, A. Kerber, R. Laue, M. Liepelt, M. Meringer, K. Varmuza, and W. Werther. Determination of sum formulas from mass spectra by recognition of superposed isotope patterns. MATCH Common. Math. Comput. Chem., 37 163-177,1998. 

T. Pluskal, T. Uehara, and M. Yanagida. Highly accurate chemical formula prediction tool utilizing high-resolution mass spectra, MS/MS fragmentation, heuristic rules, and isotope pattern matching. Anal. Chem., 84 4396-4403, 2012. 

LeBlanc, A., Shiao, T.C., Roy, R., Sleno, L. (2010) Improved Detection of Reactive Metabolites with a Bromine-containing Glutathione Analog Using Mass Defect and Isotope Pattern Matching. Rapid Commun. Mass Spectrom. 24 1241-1250. 

CHCl3 acetone (2 1). (b) ESI mass spectrum ofthe same solution after addition of 1 eq. of a tetramethyl ammonium (TMA) salt, (c) Distribution of clusters with tetrabutyl ammonium (TBA) as the guest cation, (d) ESI mass spectrum ofthe hexamer encapsulating Ru(bpy)3 +. The experimental and calculated isotope patterns nicely match. 

In conventional mass spectra the isotope patterns deriving from the presence of polyisotopic elements are striking and quite noticeable. An excellent example is the ESP spectrum shown in Figure 17 for a compound with a C14H12NOFCI2 empirical formula. The zw/z 300 [M -I- H]" " and the m/z 269 neutral loss fragment (resulting from neutral loss of methylamine) clearly show CI2 isotope patterns which match well with simulations. The zzz/z 234... 

The close match of simulation (Fig. 18, upper panel) and observation (Fig. 18, lower panel) of the [M + H]+ of another chlorine-containing compound, along with some chemical considerations of the history of the sample, permitted assigning the structure of the unknown compound based solely upon the isotope pattern. 

At first sight, MS provides information on masses and abundances in the ion mixture obtained from the analyte. Isotope compositions and theoretical isotope distributions link these primary pieces of information. This connection is discussed in Subsection 8.3.3. Ideas from [98,168, 291] will be developed further to calculate match values for molecular formula candidates using mass, intensities and isotope patterns. Such quantities are used for ranking and selection of molecular formula candidates (Subsection 8.4.1). 

CE-ESTTOE-MS was successfully applied to analyze mixtures of unknown tropane alkaloids. Seven alkaloids (tropine, belladonnine, norhyoscyamine, apoatropine, hyoscyamine, 6(3-hydroxyhyoscyamine, and scopolamine) were simultaneously identified in a pharmaceutical preparation of Atropa belladonna leaf extract by TOE-MS by matching their mass accuracy and true isotopic pattern. CE-ESTIT-MS was used to discriminate the putative presence of littorine. Optimal separation conditions were achieved with 60 mM ammonium acetate buffer at pH 8.5 containing 5 % isopropanol [116]. 

The major composition of the Gd catalyst prepared from Gd(0-iPr)3 and ligand (7a) in a ratio of 1 2 was determined to be Gd/ligand = 2/3 by ESI-MS (electronspray ionization mass spectrometry) analysis [84a]. The mass value and the isotope distribution pattern matched well with the calculated values. NMR studies supported the formation of lanthanide cyanide. Free ligand (7a) was disilylated when treated with TMSCN. The relationship between the enantiomeric excess of the product and the ratio of Gd/ligand (Figure 13.6) was also consistent with these observations. The postulated mechanism is shown in Scheme 13.29. One of the Gd in the Gd/ligand (7a) =2 3 complex is speculated to work as Lewis acid to activate the ketone, and the other Gd center would work as a nucleophile. The two Gd centers work cooperatively to promote the reaction smoothly. 

An interesting feature in order to generate molecular formulas and to facihtate an extra confident identification is the use of different isotopic filters. These filters work based on the isotopic pattern deviation between the empirically measured and the theoretical spectrum. The presence of an abundant isotopic pattern in the analyte molecule helps to confirm the presence of that compound in the sample. Thus, the presence of atoms such as carbon, chlorine, bromine, or sulfur in the molecule gives a characteristic isotopic pattern that allows reducing the number of possible elemental compositions fora certain mass-accuracy window. The match between empirical and theoretical data is given by the isotope fit (i-FTT) or sigmaFlT values. These values are calculated, taking into account not only the isotopic distribution but also the accurate masses. The lower the value, the more plausible the elemental composition (Ojanpera et al., 2006 Ibanez et al., 2008). 

Figure 3.30 Diagram showing local normalization and the principle of match and reverse match calculation. Reverse match value high All masses in the library spectrum are present in the unknown spectrum and the isotope pattern also fits after local ...

If ICP-MS is used to measure Pb levels,care must be taken to sum the masses of 206, 207, and 208 m/z to account for the natural isotopic variation of Pb in the environment. Failure to sum masses can skew results above or below the actual concentration, as the isotopic abundance of a particular mass in the calibrator might not match the sample. However, this isotopic variation can be exploited to determine the source of Pb exposure. By determining the relative abundances of Pb in blood and also of potential sources of exposure (e.g., paint chips and soil), a matching pattern can be identified. The exposure source with the same ratio of major Pb isotopes as the blood should then be avoided or removed from the patient s environment. 

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