Photocatalysis of a [2+2] Cycloaddition in Aqueous Solution Using DNA Three‐Way Junctions as Chiral PhotoDNAzymes

Abstract

TwoD NA three-way junctions bearing 4-methylbenzophenone and 4-methoxybenzophenone as C-nucleosides at the hydrophobic binding pocket were synthesized.T hey were applieda s aptamersa nd photoDNAzymes to gain enantioselectivity for the photosensitized intramolecular [2+ +2] cycloaddition of aquinolinones ubstrate in aqueous solution. Irradiation by two l = 369 nm LEDs for 10 hy ielded5 8% of the regioisomeric product mixture with an enantiomeric excesso f2 8%.T he enantiomeric excess in the presenceo ft he three-wayj unction with 4methylbenzophenone yields higher enantiomeric excesst han that with 4-methoxybenzophenone which can be explained by differences in binding of the substrate accordingt om elting temperature analysis. This is the first time that the chirality of double-stranded DNA can be transferred to an asymmetric photosensitized reaction and opens the way for in vivo applications of chiral photosensitizing in biology.Benzophenone is am ajor tool in photochemistry [1] since 1) it is chemically and photochemicallys table, 2) the intersystem crossingt ot he triplet T 1 state occurs with quantitative yield, 3) the T 1 state has al ifetime in the ms time range, and 4) the distinct np*t ransition allows the use of UV-A light-emitting diodes (LEDs)f or photochemical and photocatalytical experiments.H ighly enantioselective photocatalysis with benzophenones [1b, d-g] was achieved by template-assisted triplet-triplet energy transfer,b ut only in organic media. [2] To bring this type of photocatalysis to aqueous media and to achievee nantioselectivity by the chirality of DNA, thereby enhancing the sustainability (as demonstrated previously for av ariety of thermal reactions), [3] we recently synthesized the C-nucleoside with benzophenone as an artificial DNA base. [4] However,p hotocatalysis of the intramolecular [2+ +2] cycloaddition of quinolinone substrate 1 to the regioisomeric products 2 and 3 by this artificial C-nucleoside in double-stranded DNA failed completely (see Scheme 1f or compound structures). The careful study of benzophenone dinucleotides by time-resolved transienta bsorptions pectroscopy and theoretical methodsi ncluding mo-lecular dynamics showed that photoinduced charget ransfero f base-stacked benzophenone (especially with guanosine) competes with the triplet-triplet energy transfer that is required for this [2+ +2] cycloaddition. [5] For alternative benzophenone nucleosides,the electron density had to be increased in order to inhibitc harge transfer in DNA while keeping the triplet energy as high as possible. With respect to quinolone 1 at riplet energy (E T )o fa tl east E T = 2.86 eV [6] is required and the extinctionc oefficienti nt he UV-A range (separate from the substrate absorption) must be sufficiently high to allow selective excitation.C onventional benzophenone has at riplet energy of E T = 2.98 eV that clearly fulfills this requirement, [7] butt he T 1 energies of 4-methylbenzophenone (E T = 3.00 eV) [8] and4 -methoxybenzophenone (BpOMe; E T = 3.01 eV) [8] are also about 15 ...

Enantioselective Photochemical Reactions Enabled by Triplet Energy Transfer

“…The resulting photo-DNAzyme 38 showed photocatalytic activity in aqueous solution and promoted the enantioselective formation of product 34a in up to 28% ee. 96 The regioisomer 35a was also formed (r.r. = 74:26), but its ee was not determined (Scheme 21).…”

“…The highest conversion in the reaction 33a → rac - 34a (λ = 369 nm) was found for the respective 4-methylbenzophenone which was then incorporated by solid-phase nucleotide synthesis as an artificial DNA base into a DNA three-way junction. The resulting photoDNAzyme 38 showed photocatalytic activity in aqueous solution and promoted the enantioselective formation of product 34a in up to 28% ee . The regioisomer 35a was also formed ( r.r .…”

A decade of DNA-hybrid catalysis: from innovation to comprehension

“…In a very recent study, Wagenknecht and co--workers enforced the applicability of DNA--based asymmetric catalysis by reporting a photocatalysed [2+2] cycloaddition using benzophenone-substituted DNA sequences. 98 Although the selectivity obtained with these chiral photoDNAzymes still remains moderate, this unprecedented methodology opens new perspectives in the field of DNA--based asymmetric catalysis.…”

Lactam Hydrogen Bonds as Control Elements in Enantioselective Transition-Metal-Catalyzed and Photochemical Reactions

“…In preliminary [2 + 2] photocycloaddition experiments with benzophenone 56a as the catalytic triplet sensitizer, the enantioselectivity remained relatively low (39% ee) . An explanation for this disappointing outcome rested on an insufficient association due to the nonplanarity of benzophenones.…”