Molecular elucidation from unknown mass

Computer Methods of Molecular Structure Elucidation from Unknown Mass Spectra... 

There are two limitations of electron impact ionization, which in other ways is nearly an ideal ion source for identification of organic compounds. The sample must be stable as neutral molecules in the gas phase prior to ionization. There are many compounds, however, that are simply not stable at the temperatures required for vaporization. Radical molecular ions are formed with excess energy that may be sufficient for complete elimination of molecular mass information from the mass spectrum, even at low electron energies (e.g. 15-20 eV). Molecular mass information is almost always required for structure elucidation of unknown compounds. A softer ionization technique, such as chemical ionization, may be used in these circumstances to establish the compound molecular mass. 

MS-MS in the product-ion scan mode is generally quite successful in structure elucidation of unknowns. There are ample examples available in the literature. However, the interpretation of the production mass spectrum is not always straightforward. When a protonated molecule is selected as precursor ion, the fragmentation rules significantly differ from the well-known fragmentation rules valid for molecular ions generated by electron ionization. Upon fragmentation, protonated molecules have a... 

Figure 14 Application of spectra classification results in systematic structure elucidation. Given data for an unknown molecular structure are the molecular formula and the low resolution mass spectrum. MOLGEN is an isomer generator program, MSclass is a program for the automatic recognition of some substructures. The total number of isomers is 596. From the mass spectrum a substructure that has to be present (goodlist) and a substructure that has to be absent (badlist) was recognized. The final result consists of seven molecular candidate structures. [Reproduced from Ref. 103 with kind permission of Gesellschaft Deutscher Chemiker]...

Figure 9 Systematic structure elucidation using the molecular formula of the unknown, structural restrictions from automatic mass spectra classification and exhaustive isomer generation. Ethyl 2-(2-hydroxyphenyl)acetate is the unknown .

Nevertheless, the given momentum flux formula (2.368) is not useful before the unknown average velocity after the collisions v( has been determined. For elastic molecular collisions this velocity can be calculated, in an averaged sense, from the classical momentum conservation law and the definition of the center of mass velocity as elucidated in the following. 

Although significant data are available from the dereplication process, the mass accuracy of spectra produced by TOF instruments ( 5 ppm) is often insufficient to allow for the proposal of a single molecular formula for an unknown. This case is especially true for the higher molecular-weight molecules that are often encountered in nature. In these instances, the increased mass accuracy of the MS, MS/MS, and MS data provided by FTMS systems can prove critical to structure elucidation. 

Mass spectrometry (MS) is faster than NMR and has much better sensitivity the result (e.g. a molecular weight) can also be easier to interpret automatically -so MS may be the method of choice for structure confirmation, particularly in surveying large numbers of samples such as those that result from combinatorial or array chemistry. However, MS rarely gives sufficient information to elucidate fully the stmctures of unknowns and NMR is required, especially to settle questions of regiochemistry. 

One of the most important pieces of information required to elucidate the molecular structure of an unknown organic compound is its molecular mass, which provides a window within which the elemental composition and the final structure of the compound must fit. Therefore, the first essential step to identifying a compound is to measure its molecular mass by determining the m/z value of the molecular ion. Molecular mass measurements can be performed at either low or high resolution. A low-resolution measmement provides information about the nominal mass of the analyte, and its elemental composition can be also determined for low-molecular-weight compounds from the isotopic pattern. From a high-resolution mass spectrum, the accurate molecular mass can be determined, from which it is also feasible to deduce the elemental composition. Chemists who work with synthetic compounds and natural products rely heavily on the exact mass measurement data for structmal assignment. This value is acceptable in lieu of the combustion or other elemental analysis data. An acceptable value of the measured mass should be within 5 ppm of the accmate mass [1]. As shown below, the mass measurement error is reported either in parts per million (ppm) or in millimass units (mmu). 

The universality of El (aU organic molecules are ionizable by the process) justifies the success of this technique, which is by far the most used in GC-MS coupling. It nevertheless happens that this techniqne is unsuitable for certain analyses. In structural elucidation, the fact that the molecular ion is not always present poses a crucial problem. Indeed, the interpretation of a mass spectrum implies establishing the observed fragmentations from a molecular ion. Confronted with the electron ionization spectrum of an unknown product, it is difficult if not impossible to start the interpretation since one cannot know whether the highest m/z ratio present in the spectrum corresponds to the molecular ion or not. Chemical ionization (see next section) is very valuable in... 

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