Photoswitchable Oxidopyrylium Ylide for Photoclick Reaction with High Spatiotemporal Precision: A Dynamic Switching Strategy to Compensate for Molecular Diffusion

We describe a novel type of photoclick reaction between 2,3-diaryl indenone epoxide (DIO) and ring-strained dipolarophiles, in which DIO serves as a P-type photoswitch to produce mesoionic oxidopyrylium ylide (PY) to initiate an ultra-fast [5+2] cycloaddition (k(2h nu)=1.9x10(5) M-1 s(-1)). The photoisomerization between DIO and PY can be tightly controlled by either 365 or 520 nm photo-stimulation, which allows reversion or regeneration of the reactive PY dipole on demand. Thus, this reversible photoactivation was exploited to increase the chemoselectivity of the [5+2] cycloaddition in complex environments via temporal dual-lambda stimulation sequences and to recycle the DIO reagent for batch-wise protein conjugation. A dynamic photoswitching strategy is also proposed to compensate for molecular diffusion of PY in aqueous solution, enhancing the spatial resolution of lithographic surface decoration and bioorthogonal labeling on living cells via a spatiotemporal dual-lambda photo-modulation.

Automated summary

We present a novel photoclick reaction between 2,3-diaryl indenone epoxide (DIO) and ring-strained dipolarophiles, in which DIO acts as a P-type photoswitch to generate mesoionic oxidopyrylium ylide (PY) and initiate an ultra-fast [5+2] cycloaddition. The photoisomerization between DIO and PY can be tightly controlled by 365 or 520 nm photo-stimulation, enabling reversion or regeneration of the reactive PY dipole on demand. This reversible photoactivation is exploited to enhance chemoselectivity of the [5+2] cycloaddition in complex environments and to recycle DIO reagent for batch-wise protein conjugation. Additionally, a dynamic photoswitching strategy is proposed to improve spatial resolution of lithographic surface decoration and bioorthogonal labeling on living cells through spatiotemporal dual-lambda photo-modulation.