Repetitive Capture and Release of a Quinone Methide Extends Its Effective Lifetime

2 Repetitive Capture and Release of a Quinone Methide Extends Its Effective Lifetime 

Standard alkylating and cross-linking agents such as dimethylsulfate or TV-mustards, respectively, have only one opportunity to partition between various nucleophiles since their reactions are irreversible. In contrast, QMs have the potential to partition between nucleophiles multiple times as long as the resulting adducts are formed reversibly. Continual capture and release of QMs consequently can extend their effective lifetime almost indefinitely and is ultimately limited by only the competitiveness of possible irreversible reactions. For DNA, the strongest nucleophiles act reversibly so terminal quenching remains an infrequent event. 

SCHEME 9.18 Quinone methides are quenched by water and prevented from cross-linking DNA. 

FIGURE 9.6 The loss of cross-linking activity of an aqueous solution of QMP11 (100 pM) in the presence (black) and absence (gray) of dA (20 mM). Cross-linking activity was measured at the indicated times by addition of duplex DNA (3 pM) and subsequent analysis by denaturing gel electrophoresis. Source Adapted from Angew. Chem. Int. Ed. 2008, 47, 1291-1293.69 

SCHEME 9.19 Reversible capture and release of quinone methides by dA extends their effective lifetime. 

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