Molecular structure fragment

A proper representation of the molecular structure is crucial for the prediction of spectra. Fragment-based methods, topological descriptors, physicochemical descriptors, and 3D descriptors have been used for this endeavor. 

Several relationships aid in deducing the empirical formula of the parent ion (and also molecular fragments). From the empirical formula hypothetical molecular structures can be proposed, using the entries in the formula indices of Beilstein and Chemical Abstracts. 

Because there is little fragmentation on FD, it is necessary to activate the molecular or quasi-molecular ions if molecular structural information is needed. This can be done by any of the methods used in tandem MS as, for example, collisional activation (see Chapters 20 through 23 for more information on tandem MS and collisional activation). 

Some mild methods of ionization (e.g., chemical ionization. Cl fast-atom bombardment, FAB electrospray, ES) provide molecular or quasi-molecular ions with so little excess of energy that little or no fragmentation takes place. Thus, there are few, if any, normal fragment ions, and metastable ions are virtually nonexistent. Although these mild ionization techniques are ideal for yielding molecular mass information, they are almost useless for providing details of molecular structure, a decided disadvantage. 

Metastable ions yield valuable information on fragmentation in mass spectrometry, providing insight into molecular structure. In electron ionization, metastable ions appear naturally along with the much more abundant normal ions. Abundances of metastable ions can be enhanced by collisionally induced decomposition. 

The steps (reactions) by which normal ions fragment are important pieces of information that are lacking in a normal mass spectrum. These fragmentation reactions can be deduced by observations on metastable ions to obtain important data on molecular structure, the complexities of mixtures, and the presence of trace impurities. 

Metastable and collisionally induced fragment ions can be detected efficiently by a triple quadrupole instmment. By linking the scanning regions of the first and third quadrupoles, important information about molecular structure is easily obtained. 

Typical MS/MS configuration. Ions produced from a source (e.g., dynamic FAB) are analyzed by MS(1). Molecular ions (M or [M + H]+ or [M - H]", etc.) are selected in MS(1) and passed through a collision cell (CC), where they are activated by collision with a neutral gas. The activation causes some of the molecular ions to break up, and the resulting fragment ions provide evidence of the original molecular structure. The spectrum of fragment ions is mass analyzed in the second mass spectrometer, MS(2). 

Normal ions (M+, Fj+,. .., F +) in a spectrum can provide a molecular structure for substance M if the fragments can be theoretically reassembled. The problem is rather like deducing an original jigsaw puzzle by putting the pieces together correctly. For most molecules containing more than a few atoms, this reassembly exercise is difficult and often problematic. 

Metastable ions are useful for determining the paths by which molecular ions of an unknown substance have decomposed to give fragment ions. By retracing these fragmentation routes, it is often possible to deduce some or all of the molecular structure of the unknown. 

Molecular ion. An ion formed by the removal (positive ions) or addition (negative ions) of one or more electrons from a molecule without fragmentation of the molecular structure. The mass of this ion corresponds to the sum of the masses of the most abundant naturally occurring isotopes of the various atoms that make up the molecule (with a correction for the masses of the electrons lost or gained). For example, the mass of the molecular ion of the ethyl bromide CzHjBr will be 2 x 12 plus 5 x 1.0078246 plus 78.91839 minus the mass of the electron (m ). This is equal to 107.95751p -m, the unit of atomic mass based on the standard that the mass of the isotope = 12.000000 exactly. 

Wang, A.H.-J., et al. Molecular structure of a left-handed DNA fragment at atomic resolution. Nature 282 680-686, 1979. 

Now, it is seen that polar groups dominate the molecular structure, resulting from hydroxyl groups from the two serine and threonine fragments in addition to the peptide bonds themselves. Only weak dispersive interactions will be contributed by glycine fragments (CH2 groups). 

GC/MS was used to distinguish between the two structures. The mass spectrum showed a molecular ion at m/z 260. The fragment ions occurred at m/z 245, 241, 231, and 205. This is a good example of nitrogen atom-influenced fragmentation therefore, structure I was highly favored. 

The first step in the application of mass spectra is obviously to obtain a list of fragment ions formed by electron bombardment of the molecule under study and their relative amounts by appropriate techniques. The goal from this point will necessarily be to relate the positive ions to the molecular structure whether it be an unknown structure to be identified, or a known structure of which a knowledge of fragmentation is desired. The fragment ions observed indicate the pieces of which the molecule is composed... 

Neutral Loss Only a limited number of neutral fragments of low mass which are eliminated in decompositions of molecular ions. Examples are H, H2, CH3 and OH. Therefore, the presence of a major ion below the molecular ion at an improbable interval (eg, loss of 4 to 14, 21 to 25 amu) will indicate that the latter is not the molecular ion Postulation of Molecular Structures The. postulation of the structure of an unknown molecule is based on several major kinds of general structural information available in the mass spectmm. McLafferty (Ref 63) suggests the following systematic approach ... 

Fig. 2. The generic molecular structure of calamitic liquid crystals illustrating the semi-rigid core fragments, the positions of the end-groups (C and A), linking groups (B) and, possibly, laterally substituted groups (L)...

In 1990, Baumeister et al. [127] described the crystal and molecular structure of 4-ethoxy-3 -(4-ethoxyphenyliminomethyl)-4 -(4-methoxy-benzoy-loxy)azobenzene. The molecules have a bifurcated shape. The phenyliminom-ethyl branch is bent markedly from the nearly linear three ring fragment, but is almost coplanar with the azobenzene moiety. They found that the molecular conformation is affected by an intramolecular interaction of the carboxylic and azomethine groups. The crystal packing was described in terms of a sheet structure with interdigitating rows of molecules. 

Palytoxin (PTX) is one of the most potent marine toxins known and the lethal dose (LD q) of the toxin in mice is 0.5 Mg/kg when injected i.v. The molecular structure of the toxin has been determined fully (1,2). PTX causes contractions in smooth muscle (i) and has a positive inotropic action in cardiac muscle (4-6). PTX also induces membrane depolarization in intestinal smooth (i), skeletal (4), and heart muscles (5-7), myelinated fibers (8), spinal cord (9), and squid axons (10). PTX has been demonstrated to cause NE release from adrenergic neurons (11,12). Biochemical studies have indicated that PTX causes a release of K from erythrocytes, which is followed by hemolysis (13-15). The PTX-induced release of K from erythrocytes is depress by ouabain and that the binding of ouabain to the membrane fragments is inhibited by PTX (15). 

Schtiurmann, G., Ebert, R. U Ktihne, R. Prediction of physicochemical properties of organic compounds from 2D molecular structure - fragment methods vs. LEER models. Chimia 2006, 60, 691-698. 

For the confirmatory procedure, it is recommended that the sponsor develop spectral data based on at least three structurally specific ions that completely define the marker residue molecule. These ions may or may not include the molecular ion. The use of water loss and isotopic ions is usually unacceptable and CVM concurrence should be sought when water loss ions or isotopic ions are selected for the confirmatory analysis. The proposed fragment ion structures should be consistent with the fragmentation pattern, and justification for specificity of selected ions or scan range should be included. All confirmation criteria should be specified in the standard operating procedure. 

Molecular structures from mass-spectral fragmentation patterns... 

Desorption/ionisation techniques such as LSIMS are quite practical, as they give abundant molecular ion signals and fragmentation for structural information. In the conditions of Jackson et al. [96], all the molecular ion and/or protonated molecule ion species were observed in the LSIMS spectrum when only 1 pmol of each additive was placed on the probe tip. However, as mentioned above, in LSIMS/MS experiments the choice of the matrix (e.g. NBA, m-nitrobenzylalcohol) is very important. Matrix effects can lead to suppression of the generation of molecular ions for some additives. LSIMS is not ideal for the quantitative detection of polymer additives, as matrix effects are very important [96]. 

Ion trap MS is particularly suited for chemical structure elucidation, as it allows for simultaneous ion storage, ion activation and fragmentation, and product ion analysis. The fragmentation pathway of selected ions and the fragmentation products provide information on the molecular structure. Compared with triple-quadrupole and especially with sector instruments, the ion trap instrument provides more efficient conversion of precursor ion into product ions. However, the CID process via resonance excitation, although quite efficient in terms of conversion yield, generally results in only one (major) product ion in the product-ion mass spectrum. MS/MS with a quadrupole ion trap offers a number of advantages ... 

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