Catalysis of Michael Additions by Covalently Modified G‐Quadruplex DNA

Abstract

Enantioselective catalysis utilizing G-quadruplex DNA-based artificial metalloenzymes has emerged as a new approach in the field of aqueous-phase homogeneous catalysis. Recently, a catalytic asymmetric Michael addition employing a covalently modified G-quadruplex in combination with Cu ions has been reported. Here we assess, by systematic chemical variation and using various spectrometric techniques, a variety of parameters that govern rate acceleration and stereoselectivity of the reaction, such as the position of modification, the topology of the quadruplex, the nature of the ligand, the length of the linker between ligand and DNA, the chemical identity of monovalent ions and transition metal complexes. The DNA quadruplex modified at position 10 (dU10) with hexynyl-linked bpy ligand showed twice the initial reaction rate as compared with the DNA strand derivatized at position 12 (dU12). The strikingly different dependence of the stereoselectivity on the linker length, and their different spectroscopic properties indicate large differences in the architecture of the catalytic centers between the dU10-derivatized and the dU12-modified quadruplexes. Upon addition of Cu , both types of bpy-derivatized DNA strands form defined 1:1 Cu-DNA complexes stable enough for mass spectrometric analysis, while the underivatized strands exhibit weak and unspecific binding, correlated with much lower catalytic rate acceleration. Both dU10- and dU12-derivatized quadruplexes could be reused ten times without reduction of stereoselectivity.

A Cu(II)–ATP complex efficiently catalyses enantioselective Diels–Alder reactions

“…These artificial designs enable the fine-tuning of the microenvironment and provide a deeper understanding of the origin of chiral induction. Through their tuneable structures, Gquadruplexes containing 21-to 69-mer nucleotides have been employed to construct G-quadruplex DNA metalloenzymes, which have been successfully applied to several enantioselective transformations and demonstrated to depend largely on the conformation of the non-canonical G-quadruplex structure [29][30][31][32][33][34][35][36] . In addition, a short single-stranded 11 nt DNA within a G-triplex structure was shown to bind to copper(II) ions and modestly promote an enantioselective Diels-Alder (D-A) reaction 37 .…”

α,β‐Unsaturated 2‐Acyl‐Imidazoles in Asymmetric Biohybrid Catalysis

“…Interestingly, a stunning inversion of the selectivity was observed when using ODN17 , which carries the modification at position 12 compared to ODN18 which bears the exact same ligand at position 10 (Figure ). Also worth pointing out is the catalyst recyclability, which was later demonstrated by reusing the catalyst over 10 times without any erosion of the selectivity …”

“…Also worth pointing out is the catalyst recyclability, which was later demonstrated by reusing the catalyst over 10 times without any erosion of the selectivity. [77]…”

Histidine-conjugated DNA as a biomolecular depot for metal ions

“…[14][15][16] Among them, site-specic functionalization of DNA with metal ions has received attention because of the wide range of its applications, including molecular magnets, [17][18][19] electron transport chains, [20][21][22] and metalloenzymes. [23][24][25][26] Several metal-mediated natural or articial nucleobase pairs have been explored and various metal-binding ligands, such as bipyridine (bpy) and terpyridine, have been used in the development of metal-modied DNA. [27][28][29] In our previous study, we established the covalent anchoring strategy for direct incorporation of intrastrand metal-binding ligands such as bpy into the DNA phosphate backbone.…”