Kinetic and Thermodynamic Adducts Formed by Quinone Methides

2 Kinetic and Thermodynamic Adducts Formed by Quinone Methides 

The reversibility of dA alkylation by QM3 creates both problems and opportunities. For example, an accurate profile of products formed by initial exposure of DNA to QMs may not be easily determined since labile products such as the N1 adduct of dA would not persist through the typical procedures of enzyme digestion and analysis of the subsequent deoxynucleoside products by reverse phase HPLC. Thus, the full extent of DNA alkylation by QMs may be severely underestimated. 

FIGURE 9.2 Time-dependent evolution of quinone methide adducts formed by an equimolar mixture of dA, dC, dG, and dT was monitored by reverse-phase chromatography. Source Reproduced with permission from Chem. Res. Toxicol. 2005, 18, 1364-1370.48 Copyright 2005, American Chemical Society. 

SCHEME 9.14 Partitioning of the dG N7 adduct between release of QM3 and release of deoxyribose (deglycosylation). 

SCHEME 9.15 Product profiles formed by QM3 depend on the fast and reversible addition of nucj in competition with the slow and irreversible addition of nuc2. 

---