Leaving group strength

The reversibility of DNA cross-linking by the QMPs illustrated in Fig. 9.4 has not been examined directly but is presumably controlled as before by the leaving group strength of the DNA nucleophiles and the electronic characteristics of the QM intermediates. Unless both possible QMs form simultaneously, the cross-linking agents still remain bound to DNA at one site as the other is transiently released during... 

Identification According to Disturbance of "Leaving-Group Strength" Correeation... 

Identification Through Disturbance of the Leaving-Group Strength Correlation... 

As we have seen the nucleophile attacks the substrate m the rate determining step of the Sn2 mechanism it therefore follows that the rate of substitution may vary from nucleophile to nucleophile Just as some alkyl halides are more reactive than others some nucleophiles are more reactive than others Nucleophilic strength or nucleophilicity, is a measure of how fast a Lewis base displaces a leaving group from a suitable substrate By measuring the rate at which various Lewis bases react with methyl iodide m methanol a list of then nucleophihcities relative to methanol as the standard nucleophile has been compiled It is presented m Table 8 4... 

The role of the leaving group in determining the reaction rate is somewhat different from its role in 8 2 and 8 1 substitution at alkyl groups. In those cases, the bond strength is usually the dominant factor so that the order of reactivity of the halogens is... 

We have seen how the polarity of the solvent influences the rates of Sn 1 and Sn2 reactions. The ionic strength of the medium has similar effects. In general, the addition of an external salt affects the rates of SnI and Sn2 reactions in the same way as an increase in solvent polarity, though this is not quantitative different salts have different effects. However, there are exceptions though the rates of SnI reactions are usually increased by the addition of salts (this is called the salt effect), addition of the leaving-group ion often decreases the rate (the common-ion effect, p. 395). 

In a dissociative process the reaction rate is expected to decrease as the strength of the metal to leaving ligand bond increases. This trend is generally observed in Co(III) ammine complexes. As can be seen in Table 2, a partial leaving group order is... 

In contrast to the lability of certain dN adducts formed by the BHT metabolite above, amino acid and protein adducts formed by this metabolite were relatively stable.28,29 The thiol of cysteine reacted most rapidly in accord with its nucleophilic strength and was followed in reactivity by the a-amine common to all amino acids. This type of amine even reacted preferentially over the e-amine of lysine.28 In proteins, however, the e-amine of lysine and thiol of cysteine dominate reaction since the vast majority of a-amino groups are involved in peptide bonds. Other nucleophilic side chains such as the carboxylate of aspartate and glutamate and the imidazole of histidine may react as well, but their adducts are likely to be too labile to detect as suggested by the relative stability of QMs and the leaving group ability of the carboxylate and imidazole groups (see Section 9.2.3). 

The observed order of ability did not, however, correlate with the P Ka of YH, with the strength of the C—Y bond, or with the polar effect of Y Clearly, leaving group ability even in this simple reaction is a highly complex attribute. 

In summary, reactions of nitronates with acid anhydrides or acyl chlorides give the O-acylated products, and reactions with acyl imidazoles, phenyl esters, acyl nitriles, and enol-lactones gives the C-acylated products, (see Eq. 5.13).25 The C/O selectivity of nitronate acylation by RCOX is qualitatively correlated with strength (pKJ of the acid HX conjugated to the leaving group X .25... 

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