Complex halogenated inhibitors

Scheme 35.4. From carboxin (63) to halogenated inhibitors of succinate dehydrogenase complex II (64-67, see Table 35.9).

Table 35.9 Halogenated inhibitors of succinate dehydrogenase (SD) -complex II (64-67) (see Scheme 35.4 for the basic structure).

My last comment concerns the reaction of palladium olefin complexes with carbon monoxide discovered by Tsuji. I agree that this is most likely to proceed by an insertion rather than an ionic mechanism. Chloride attack on coordinated olefin is rare however. Chloride ion is an inhibitor, for example in the palladous chloride catalyzed hydration of ethylene (0). I, therefore, wondered whether carbon monoxide was affecting the ease with which chloride attacks olefin. One can postulate that carbon monoxide participates in this insertion either as a gas phase reactant or by first forming a carbonyl olefin complex. Such complexes of the noble metals were unknown, but examining the reaction between carbon monoxide and the halogen bridged olefin complexes of platinum revealed that they are formed very readily... 

Of more interest to coordination chemists is the Du Pont halogen tin process which is based on halo complexes of tin(II). The presence of fluoride is considered to form [SnF3], but much chloride is present to enhance the conductivity. Inhibitors are required to control the oxidation of tin(II) to tin(IV) and the consequent separation of the sparingly soluble Na2[SnF6] as a sludge. The process was originally introduced in 1942 for the continuous electrotinning of steel strip. 

Figure 7.1 Investigation on halogen—it interactions by X-ray structural analysis, database searching, and ab initio calculations reveals a significant contribution to binding affinity [48]. (a) Chlorine-Jt interaction present in the X-ray structure of a 3-oxybenzamide-based inhibitor in complex with human factor Xa (fC = 18nM, resolution = 2.7 A). The characteristic Cl Tyr228 interaction geometry was then used for ab initio calculations and database searches in the Cambridge...

Irreversible inhibition can also occur in the presence of halogenated methyl ketones which alkylate the active histidine residue (cf. 2.4.1.1), or as a result of the action of proteinase inhibitors, which are also proteins, by interaction with the enzyme to form inactive complexes. These natural inhibitors are found in the organs of animals and plants (pancreas, colostrum, egg white, potato tuber and seeds of many legumes cf. 16.2.3). The specificity of serine... 

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