Fragmentation techniques

There are a few hundred stable nuclei but several thousand nuclei that are radioactive and have experimentally useful lifetimes. Since 1990, one of the fastest growing areas of research in nuclear science has been the study of nuclear reactions induced by radioactive projectiles. Using either ISOL (/sotope Separator On-Line) or PF (Projectile Fragmentation) techniques, several hundred new radioactive nuclear beams have become available (see Chapter 14). 

The fragmentation technique consists of the dissection of the target molecule into its composite parts. The basic principle of this bond clipping process is to search among the separated fragments for those molecular bits that resemble the composite parts of the starting materials a carbon chain here, a func-... 

Other fragmentation techniques have been introduced [108]. Some of these, e.g., sustained off-resonance irradiation (SORl) and infrared multiphoton dissociation (IRMPD), provide similar fragmentation as in CID, i.e., preferential backbone cleavages at the peptide amide bond (b- and y-ions). Others like electron-capture dissociation (ECD) [109-110] induce different fragmentation reactions, i.e., the formation of c- and z -ions due to cleavage of N-C bonds. 

FT-ICR-MS enables the identification of unknown proteins with hmited enzymatic cleavage and eventually in-cell fragmentation via a variety of ion-fragmentation techniques and high-resolution m/z determination of the fragment ions. This is the top-down protein identification approach [163] (Ch. 18.3.5). The introduction of ECD was an important development in this respecf as it allows incell fragmentation of the complete protein [110]. 

Inverse gas chromatography at infinite dilution appears to be a powerful tool for studying the surface properties of carbon fibres and polymer matrices. The use of alkane probes and acid/base probes allows the characterization of the surfaces in terms of their London dispersive component of surface energy and their acid/base or acceptor/donor characteristics. A strong correlation was obtained between fibre-matrix adhesion, measured by a destructive fragmentation technique, and the level of acid base interactions calculated from the chromatographic analysis. 

On the basis of the complementarity of CID/IRMPD and ECD/ETD, Zubarev et alul have concluded that de novo sequencing of peptides using these two fragmentation techniques in conjunction with high mass accuracy113,114 can be achieved with >95% reliability. They have furthermore stated that it is... 

A variety of indirect methods have been developed to estimate Kow (Table 5). These include simple PPRs and SPRs (Fig. 5), as well as group additivity methods in which the lipophilic contributions of molecular fragments have been estimated (e.g., Rekker s fragment technique and UNIFAC). The existence of so many methods to estimate Kow suggests there are some fundamental difficulties in accurately determining this important parameter. As a minimum, we can expect that there will be differences in the values of a compound s Kow determined by the different techniques. This is the case, and a large literature has arisen on this subject (Andren et al., 1987 Sabljic, 1987 Eadsworth, 1986 De Voogt et al., 1988 Veith et al., 1979). 

Makino S, Kayahara T, Tashiro K et al (2001) Discovery of a novel serine protease inhibitor utilizing a structure-based and experimental selection of fragments technique. J Comput Aided Mol Des 15 553-559... 

The crystallographic structure refinement approach suggested is based on the viability of a fuzzy and additive density fragmentation technique. Ultimately, the fundamental quantum mechanical properties of density functionals justify the fuzzy fragmentation procedure, and the very same fundamental properties also suggest new approaches to local electron density shape analysis. These possibilities have relevance both to crystallographic structure refinement as well as to a density-based interpretation of the chemical properties of functional groups and other local... 

The restriction fragment patterns produced from these loci can be used to identify individuals as accurately as the traditional fingerprint. In fact, this restriction fragment technique has been called DNA fingerprinting and is gaining widespread use in forensic analysis. Family relationships can be determined by this method, and it can be used to help acquit or convict suspects in criminal cases. 

The advent of such low-fragmentation techniques as fast-atom bombardinent (FAB) and electrospray ionization (ESI) permitted the direct observation of crown ether complexes in the gas phase. Complexation of a species such as (18-crown-6 Na) is readily detectable as a species having mlz (264 -f- 23) = 287. The corresponding complex would have a mass of 303. Selectivities were inferred by comparing peak intensities. The mass spec-trometric method is of great value, but comparisons between gas, solution, and solid phases should be made with appropriate circumspection. 

Chapter 15 Fragmentation Techniques for Protein Ions Using Various lypes of Ion Trap... 

Multiple studies have shown that the use of fragmentation techniques based on slow vibrational excitation of gaseous peptide ions (such as CID) induce complete intramolecular migration of deuteriums during activation [12,26-33]. While a number of early studies reported little or no scrambling in fragment ions produced by CID [13,14,16,17], other reports using well-characterized model peptides and... 

Of the fragmentation techniques MALDI-ISD, ECD, and ETD, it is only the latter that is directly compatible with the requirements and timescale of an online HX-MS workflow. By combining the classic bottom-up HX-MS workflow with gas-phase fragmentation by ETD, detailed information on protein HX can be obtained [47,57]. In such a combined workflow, enzymatic solution-phase cleavage is followed by automated (data-dependent acquisition) or manual (targeted) selection of peptides for gas-phase cleavage by ETD [57] (Eigure 8.6). 

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