DNA G-QuadruplexesActivate Heme for RobustCatalysis of Carbene Transfer Reactions

摘要

Guanine-rich single-stranded DNAs and RNAs that fold into G-quadruplexes (GQs) are known to complex tightly with Fe^II-heme and Fe^III-heme (hemin), ubiquitous cellular cofactors. Heme–GQ (DNA) complexes, known as heme·DNAzymes, are able to utilize hydrogen peroxide as an oxidant to vigorously catalyze a variety of one-electron (peroxidase) and two-electron (peroxygenase) oxidation reactions. Herein, we show that complexes of Fe^II-heme with GQs also robustly catalyze a mechanistically distinct reaction, carbene transfer to an alkene substrate. Significant enhancements were seen in both reaction kinetics and product turnover (∼180) relative to disaggregated Fe^II-heme in the absence of DNA or in the presence of other DNA folds, such as single-stranded or double-stranded DNA. Heme binds to GQs by end-stacking. Simple, intramolecularly folded GQs are unable to provide a complexly structured “distal side” environment to the bound heme; therefore, such DNAzymes do not display significant product stereoselectivity. However, intermolecular GQs with multiple pendant nucleotides show increasing stereoselectivityin addition to their enhanced catalytic rates. These results recapitulatethe unique functional synergy and highlight the surprising catalyticversatility of complexes formed between heme and DNA/RNA GQs. Ourfindings suggest that heme·DNAzymes and heme·ribozymes mayprove to be useful reagents for carbon–carbon bond forming“green” reactions carried out in vitro and likely withinliving cells.