Structural information sources

Physical, chemical, and biological properties are related to the 3D structure of a molecule. In essence, the experimental sources of 3D structure information are X-ray crystallography, electron diffraction, or NMR spectroscopy. For compounds without experimental data on their 3D structure, automatic methods for the conversion of the connectivity information into a 3D model are required (see Section 2.9 of this Textbook and Part 2, Chapter 7.1 of the Handbook) [16]. 

In contrast to IR and NMR spectroscopy, the principle of mass spectrometry (MS) is based on decomposition and reactions of organic molecules on theii way from the ion source to the detector. Consequently, structure-MS correlation is basically a matter of relating reactions to the signals in a mass spectrum. The chemical structure information contained in mass spectra is difficult to extract because of the complicated relationships between MS data and chemical structures. The aim of spectra evaluation can be either the identification of a compound or the interpretation of spectral data in order to elucidate the chemical structure [78-80],... 

Ions formed in an electrospray or similar ion source are said to be thermolized, which is to say that their distribution of internal energies is close to that expected for their normal room-temperature ground state. Such ions have little or no excess of internal energy and exhibit no tendency to fragment. This characteristic is an enormous advantage for obtaining molecular mass information from the stable molecular ions, although there is a lack of structural information. 

A single instrument — a hybrid of a quadrupole and a TOF analyzer — can measure a full mass spectrum of ions produced in an ion source. If these are molecular ions, their relative molecular mass is obtained. Alternatively, precursor ions can be selected for MS/MS to give a fragment-ion spectrum characteristic of the precursor ions chosen, which gives structural information about the original molecule. 

Plasma torches and thermal ionization sources break down the substances into atoms and ionized atoms. Both are used for measurement of accurate isotope ratios. In the breakdown process, all structural information is lost, other than an identification of elements present (e.g., as in inductively coupled mass spectrometry, ICP/MS). 

Spectrometers are designed to measure the absorption of electromagnetic radiation by a sample. Basically, a spectrometer consists of a source of radiation, a compartment containing the sfflnple through which the radiation passes, and a detector. The frequency of radiation is continuously varied, and its intensity at the detector is compar ed with that at the source. When the frequency is reached at which the sample absorbs radiation, the detector senses a decrease in intensity. The relation between frequency and absorption is plotted as a spectrum, which consists of a series of peaks at characteristic frequencies. Its interpretation can furnish structural information. Each type of spectroscopy developed independently of the others, and so the data format is different for each one. An NMR spectrum looks different from an IR spectrum, and both look different from a UV-VIS spectrum. 

The ionization techniques most widely used for LC-MS, however, are termed soft ionization in that they produce primarily molecular species with little fragmentation. It is unlikely that the molecular weight alone will allow a structural assignment to be made and it is therefore desirable to be able to generate structural information from such techniques. There are two ways in which this may be done, one of which, the so-called cone-voltage or in-source fragmentation, is associated specifically with the ionization techniques of electiospray and APCl and is discussed later in Section 4.7.4. The other, termed mass spectrometry-mass spectrometry (MS-MS) or tandem mass spectrometry, is applicable to all forms of ionization, provided that appropriate hardware is available, and is described here. 

Electrospray is a soft-ionization method prodncing intact molecular species and structural information is not usually available. Electrospray sources are capable of producing structural information from cone-voltage fragmentation but these spectra are not always easily interpretable. Experimentally, the best solution is to use a mass spectrometer capable of MS-MS operation but this has not inconsequential financial implications. 

MS-MS is a term that covers a number of techniques in which two stages of mass spectrometry are used to investigate the relationship between ions found in a mass spectrum. In particular, the product-ion scan is used to derive structural information from a molecular ion generated by a soft ionization technique such as electrospray and, as such, is an alternative to CVF. The advantage of the product-ion scan over CVF is that it allows a specific ion to be selected and its fragmentation to be studied in isolation, while CVF bring about the fragmentation of all species in the ion source and this may hinder interpretation of the data obtained. 

The use of cone-voltage fragmentation (CVF) to obtain structural information was discussed earlier in Section 4.7.4 and the comment was made there that because this has the potential to bring about fragmentation of aU ions in the source of the mass spectrometer the spectra were often difficult to interpret. When the analyte under consideration is of a low molecular weight, its spectrum is likely to consist only of a few ions and CVF is of more practical value. 

Angular restraints are another important source of structural information. Several empirical relationships between scalar couplings and dihedral angles have been found during the last decades. The most important one is certainly the Karplus relation for -couplings. Another, relaxation-based angular restraint is the so-called CCR between two dipolar vectors or between a dipolar vector and a CSA tensor. 

Various forms of off- and on-line AES/AAS can achieve element specific detection in IC. The majority of atomic emission techniques for detection in IC are based on ICP. In the field of speciation analysis both IC-ICP-AES and IC-ICP-MS play an important role. Besides the availability of the ICP ion source for elemental MS analysis, structural information can be provided by interfaces and ion sources like particle beam or electrospray. 

Principles and Characteristics Analytical multistage mass spectrometry (MSn) relies on the ability to activate and dissociate ions generated in the ion source in order to identify or obtain structural information about an unknown compound and to analyse mixtures by exploiting two or more mass-separating steps. A basic instrument for the currently most used form, tandem mass spectrometry (MS/MS), consists of a combination of two mass analysers with a reaction region between them. While a variety of instrument set-ups can be used in MS/MS, there is a single basic concept involved the measurement of the m/z of ions before and after a reaction in the mass spectrometer the reaction involves a change in mass and can be represented as ... 

Product-ion Selecting mtz Scanning To obtain structural information by CID of ions produced in the source... 

Within the multichannel Bayesian formalism of structure determination, it is indeed possible to make use ofMaxEnt distributions to model systems whose missing structure can be reasonably depicted as made of random independent scatterers. This requires that the structural information absent in the diffraction data be obtained from some other experimental or theoretical source. The known substructure can be described making use of a parametrised model. 

A single unstable compound of known composition is placed in the main first volume and is located on the basis of its empirical molecular formula expressed in the Hill system used by Chemical Abstracts (C and H if present, then all other element symbols alphabetically). The use of this indexing basis permits a compound to be located if its structure can be drawn, irrespective of whether a valid name is known for it. A representation of the structure of each compound is given on the third bold title line while the name of the compound appears as the first bold title line. References to the information source are given, followed by a statement of the observed hazard, with any relevant explanation. Cross-reference to similar compounds, often in a group entry, completes the entry. See Trifluoroacetyl nitrite p. 244. 

In soft ionization methods the excess energy deposited onto the ionized molecule is very small and stable even-electron ions are formed. This leads to easy determination of the molecular weight of the analyte, but as fragmentation is absent or it occurs to a very low extent, structural information is missing in the mass spectrum. However, one can obtain structural information by causing ion fragmentation out of the source by means of tandem mass spectrometry experiments (see below). 

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