Isomeric differentiation

John Siddall had intense scientific interest in two areas covered in this book. The chemical structures of the new bioactive substances discussed in the first section reveal configurations in which biological activity and specificity are highly dependent on isomeric differentiation, an area of synthesis that he understood and avidly pursued. He also advocated more extensive use of... 

Molecular complexation is a precondition for receptor functions such as substrate selection, substrate transportation, isomeric differentiation, and stereoselective catalysis. Although the investigation of such functions with synthetically derived compounds is a relatively new development in chemistry, they are well known and extensively studied functions in the biological domain. Evolution, gene expression, cell division, DNA replication, protein synthesis, immunological response, hormonal control, ion transportation, and enzymic catalysis are only some of the many examples where molecular complexation is a prerequisite for observing a biological process. 

Other means of manipulating ions trapped in the FTMS cell include photodissociation (70-74), surface induced dissociation (75) and electron impact excitation ("EIEIO")(76) reactions. These processes can also be used to obtain structural information, such as isomeric differentiation. In some cases, the information obtained from these processes gives insight into structure beyond that obtained from collision induced dissociation reactions (74). These and other processes can be used in conjunction with FTMS to study gas phase properties of ions, such as gas phase acidities and basicities, electron affinities, bond energies, reactivities, and spectroscopic parameters. Recent reviews (4, 77) have covered many examples of the application of FTMS and ICR, in general, to these types of processes. These processes can also be used to obtain structural information, such as isomeric differentiation. 

Isomeric Differentiation Using Tandem Mass Spectrometry... 

Table I). The next member is 2V,N,N, 2V",2V"-pentamethyldiethylenetri-amine, or PMDT (Compound 2). Abbreviations for the higher homologs are derived accordingly, and isomeric differentiation is made where applicable.

Niemeyer, E.D. Brodbelt, J.S. Isomeric differentiation of green tea catechins using gas-phase hydrogen/deuterium exchange reactions. J. Am. Soc. Mass Spectrom. 2007, 18,... 

Sharifi, M. and J. Einhorn, Isomeric Differentiation of Conjugated Diene Epoxides by Polar... 

Isomeric differentiation, as defined by chromatographic resolution, was insignificant on reversed-phase supports when compared with that on graphite support. 

In an efficient diastereo-differentiative assembly of three components of norbornene, tv. v-alkenyl iodide, and KCN, the isomerization of the cis to the trans double bond takes place to give the coupled product 224. The isomerization is explained by the formation of the cyclopropane 222. its rearrangement to give a irans double bond in 223, and trapping with CN anion to give 224[168],... 

Applications. The capabiHties of a gc/k/ms in separating and identifying components in complex mixtures is very high for a broad spectmm of analytical problems. One area where k information particularly complements ms data is in the differentiation of isomeric compounds. An example is in the analysis of tricresyl phosphates (TCPs) used as additives in a variety of products because of thek lubricating and antiwear characteristics (see Lubrication and lubricants). One important use of TCPs is in hydrauHc fluid where they tenaciously coat metal surfaces thereby reducing friction and wear. Tricresyl phosphate [1330-78-5] (7.2 21 exists in a variety of isomeric forms and the commercial product is a complex mixture of these isomers. 

Fig. 13.12. Energy diagram illustrating differential in energy deficit for photosensitized isomerization of cis and trans isomers.

Reduction with lithium aluminum hydride allows a differentiation from the isomeric nitrones. Whereas 2-tert-butyl-3-phenyloxazirane (9) gives benzylidene-tert-butylamine [Eq. (10)], reduction of the isomeric nitrone leads to iV-benzyl-xV-fert-butylbydroxylaminc [Eq. 

Most oxaziranes withstand temperatures of 100 C for a short time, e.g., on distillation. At higher temperatures isomerization and decomposition occur. Oxaziranes derived from aromatic aldehydes are here again differentiated from the alkyl-substituted oxaziranes. 

Certain problems, for example, the differentiation between the (is)-diazohydroxide (7.3) and the nitrosoamine (7.4), were quite insoluble in Hantzsch s day because of the lack of appropriate methods. The observation that the sodium salt of the anti-diazoate reacts with methyl iodide to yield the TV-derivative (A-methylnitrosoamine), whereas the silver salt gives the O-ether (diazo ether) was often taken to support the presence of constitutional isomerism, but Hantzsch, quite rightly, disagreed. 

Next we studied high temperature bromination of benzobarrelene at 150 C. NMR analysis indicated that the reaction mixture was very complex and consisted of at least ten products. After repeated column chromatography combined with fractional crystallization we have been able to separate 18 compounds (Scheme 6). Four of them were bromoalcohol compounds 18, 12, 22 and 2fl. After high temperature bromination we expected three isomeric non-rearranged products with benzobarrelene skeleton and isolated 22, 22, and 24 in yields of 34, 9.3, and 6.2 %, respectively. Because of the very close structural similarity we were not able to make a clear-cut differentiation between the stereochemistry of 22 and 24-Therefore, we carried out an X-ray analysis (ref. 9) of the isomer 22-... 

It is useful to differentiate between substrate specificity, which is the inclination of the given enzyme to react more efficiently with (or, in some cases, bind more tightly to) some potential substrates than others, and product specificity, which is the inclination of the enzyme to transform the substrate into only one (usually) of many possible isomeric products. As a consequence of the principle of microscopic reversibility, for a reversible reaction, product specificity for the reaction in one direction becomes equivalent to substrate specificity in the other direction. 

Bioassay of alternate molecular forms supports the view that the ORs are capable of resolving isomeric distinctions in neutral (non-biological) odourants. Stereochemical pairs of odours were tested for differential sensitivities in the blind subterranean mole rat (Spalax ehrenbergi). The subjects responded to one enantiomer, but not to its stereoisomer. Both sexes were attracted to the odour of R-(-)-carvone but unresponsive to S-(+)-carvone in contrast, males and females were repelled by the odour of (+)-citronellol, but not by (-)-citronellol (Heth et al., 1992). The lack of responsiveness by mole rats could be central due to lack of salience, or peripheral due to hyposmia/anosmia for one isomer. Both carvones have distinct odours for the human nose. 

Tandem MS (DFS equipped with EI/F1/FD source) in conjunction with off-line direct inlet HPLC-UV was used for separation and quantification of isomeric antioxidants, C22H30O2S (MW 358 Scheme 6.3), as antioxidants in THF extracts of surgeons gloves [232]. Collision activation MS enabled differentiation between the three isomeric structures (Fig. 6.20). Quantification was achieved by chromatographic analysis of the isomeric species, which are not distinguishable by MS. On-line LC-MS facilitates this kind of analysis. 

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