(P)-Helicene Displays Chiral Selection in Binding to Z-DNA

Abstract

Enantiomeric helicenes of (P)-A and (M)-A were synthesized. The binding of the helicenes to B- and Z-DNA was studied quantitatively by CD, equilibrium dialysis, and fluorescence spectroscopy. Enantiomeric (P)-A not only bound selectively to Z-DNA but also effectively converted the B-DNA conformation to Z-DNA. The enantioselectivity of the helicenes offers a new route for the rational design of inhibitors of biological functions that may depend on Z-DNA.

Helicene-Based Chiral Auxiliaries and Chirogenesis

“…The supramolecular association of chiral C 2 -symmetrical 180 with DNA revealed that the (P)-enantiomer of 180 displays chiral selection for binding Z-DNA over B-DNA [98]. The corresponding binding constants were found to be (8.0 ± 0.5) × 10 4 M −1 and (1.4 ± 0.3) × 10 4 M −1 for Z-and B-DNA, as measured by fluorescence titration.…”

“…Tanaka et al synthesized bis(hydroxymethyl)thia [7]helicene 174 to study its further synthetic chemistry and corresponding applications in the chirality recognition of biological molecules [97][98][99][100]. Hence, the helicene 174 was synthesized in a total of nine steps with an overall 33% yield, where the photochemical cyclization of alkene 175 was a key step to give silyl group protected rac-176.…”

“…In contrast, although the (M)-180 also showed a 20% reduction, it was observed upon binding both B-and Z-DNA, thus indicating the lack of its discrimination ability. Further, enantiopure alcohol 174 was converted to its dichloride 179, which was converted to 180 [98] and cyclic thia ethers 181-183 [99] using suitable synthetic procedures (Scheme 32). These helicene molecules were explored in terms of possible chiral recognition of biologically relevant molecules such as DNA [98,100].…”

“…The opposite trend was observed with (M)-184, which displayed strong binding for Z-DNA over B-DNA, as studied by performing CD, UV melting temperature, surface plasmon resonance measurements, and isothermal titration calorimetry. From the examples of 180 [98] and 184 [101], it appears that the cationic functional groups assist in binding with DNA through electrostatic interactions; along with this, the chiral helicity-based steric fit allows selectivity. The (P)-180 prefers Z-DNA, whereas in the case of 184, the (M)-enantiomer binds strongly to Z-DNA.…”

Synthesis and Characterization of Novel Chiral Conjugated Materials

“…Notably, redox states of helicenes are practically unknown [33,34]. Assembly of helicenes on surfaces, their uses as liquid crystals, chiral sensors, ligands or additives for asymmetric synthesis and helicene-biomolecule interactions are in the exploratory stages [35][36][37][38][39][40][41][42][43].…”