Molecular engineering enabling reversible transformation between helical and planar conformations by cyclization of alkynes

Molecular engineering enabling reversible transformation between helical and planar conformations is described herein. Starting from easily available 2-(pyridin-2-yl)anilines and alkynes, a one-pot strategy is set up for the synthesis of aza[4]helicenes via two successive rhodium-catalyzed C-H activation/cyclizations. Helical pyrrolophenanthridiziniums can be transformed into planar conformations through the cleavage of acidic pyrrole N-H, leading to turn-off fluorescence. NMR spectra, single crystal X-ray diffraction and DFT calculations demonstrate that the formation of an intramolecular C-HMIDLINE HORIZONTAL ELLIPSISN hydrogen bond is beneficial to stabilize the pyrrole nitrogen anion of the planar molecule and provide increased planarity. The reversible conformation transformations can be finely adjusted by the electron-donating and -withdrawing groups on the pi(+)-fused pyrrole skeleton in the physiological pH range, thus affording an opportunity for pH-controlled intracellular selective fluorescence imaging. Pyrrolophenanthridiziniums show turn-on fluorescence in lysosomes owing to the acidic environment of lysosomes and turn-off fluorescence out of lysosomes, indicating the occurrence of the deprotonation reaction outside lysosomes and the corresponding transformation from helical to planar conformations.

Automated summary

This study demonstrates the reversible transformation between helical and planar conformations through molecular engineering, leading to the synthesis of aza[4]helicenes. By adjusting the stabilization of pyrrole nitrogen anion and planar molecules, conformation transformations can be finely tuned in the physiological pH range.