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

Abstract

Natural biomolecules have been used extensively as chiral scaffolds that bind/surround metal complexes to achieve stereoselectivity in catalytic reactions. ATP is ubiquitously found in nature as an energy-storing molecule and can complex diverse metal cations. However, in biotic reactions ATP-metal complexes are thought to function mostly as co-substrates undergoing phosphoanhydride bond cleavage reactions rather than participating in catalytic mechanisms. Here, we report that a specific Cu(II)-ATP complex (Cu2+·ATP) efficiently catalyses Diels-Alder reactions with high reactivity and enantioselectivity. We investigate the substrates and stereoselectivity of the reaction, characterise the catalyst by a range of physicochemical experiments and propose the reaction mechanism based on density functional theory (DFT) calculations. It is found that three key residues (N7, β-phosphate and γ-phosphate) in ATP are important for the efficient catalytic activity and stereocontrol via complexation of the Cu(II) ion. In addition to the potential technological uses, these findings could have general implications for the chemical selection of complex mixtures in prebiotic scenarios.

A Localized Enantioselective Catalytic Site on Short DNA Sequences and their Amphiphiles

“…In a recent study of the same reaction catalyzed by Cu 2+ -adenosine triphosphate, density functional theory gas phase calculations suggested that Si-face attack was favored due to hydrogen bonding of (2) with phosphate oxygen atoms leading to a reduced energy barrier for the cycloaddition. 44 One possible explanation for our system is that DNA-(2) interactions in the pocket created between the Si-face of 1(a) and dsDNA lead to a free energy transition state reduction causing the observed rate increase and high ee observed experimentally for "21-10, 11". An alternative explanation for the observed ee, is that the relevant configuration for catalysis is with (1a) oriented as shown in Figure S26, i.e., with (1a) rotated by 180 o compared to its configuration in Figures 2g, 2h.…”

“…31,32 The ability for enantioselectivity by the DNA-ArM catalyst is determined by the enantiomeric excess (ee%) of the Si-endo versus Re-endo. 3 4,4'-dimethyl-2,2'bipyridine (dmbipy) was selected as the achiral ligand to bridge the Cu(II) catalytic center and the dsDNA scaffold. 33 We include for comparison the performance of the natural salmon testes DNA (st-DNA) and a G•C-rich dsDNA sequence composed of the 21 nucleotide G-rich human telomeric sequence HT21.…”

“…Artificial metalloenzymes (ArMs) can combine the chiral environment of biomolecular scaffolds with the catalytic properties of a transition metal. [1][2][3][4][5][6] Since the introduction of DNA-based ArMs in 2005, 7 enantioselective catalysis by metal ions or metal ion complexes assembled on a DNA scaffold has been demonstrated for Diels-Alder, [7][8][9][10][11][12][13] Friedel-Crafts alkylation, [14][15][16][17][18] Michael addition, [19][20][21][22] and other reactions. [23][24][25][26][27][28][29][30] Despite progress in correlating the catalytic performance of DNA-ArMs with their DNA sequence, 8-12, 15-18, 21, 24-28, 30 pinpointing which of the many possible chiral microenvironments created by the interaction between the DNA and the bound metal, or metal complex, is responsible for enantioselective catalysis, remains elusive.…”

A Localized Enantioselective Catalytic Site on Short DNA Sequences and their Amphiphiles

“…31,32 The ability for enantioselectivity by the DNA-ArM catalyst is determined by the enantiomeric excess (ee%) of the Si-endo versus Re-endo. 3 4,4'-dimethyl-2,2'bipyridine (dmbipy) was selected as the achiral ligand to bridge the Cu(II) catalytic center and the dsDNA scaffold. 33 We include for comparison the performance of the natural salmon testes DNA (st-DNA) and a G•C-rich dsDNA sequence composed of the 21 nucleotide G-rich human telomeric sequence HT21.…”

“…Artificial metalloenzymes (ArMs) can combine the chiral environment of biomolecular scaffolds with the catalytic properties of a transition metal. [1][2][3][4][5][6] Since the introduction of DNA-based ArMs in 2005, 7 enantioselective catalysis by metal ions or metal ion complexes assembled on a DNA scaffold has been demonstrated for Diels-Alder, [7][8][9][10][11][12][13] Friedel-Crafts alkylation, [14][15][16][17][18] Michael addition, [19][20][21][22] and other reactions. [23][24][25][26][27][28][29][30] Despite progress in correlating the catalytic performance of DNA-ArMs with their DNA sequence, 8-12, 15-18, 21, 24-28, 30 pinpointing which of the many possible chiral microenvironments created by the interaction between the DNA and the bound metal, or metal complex, is responsible for enantioselective catalysis, remains elusive.…”