Photocage Chameleon: Bond Scission by a Single Photon Above 800 nm

Photocages enable scientists to seize full control over the activity of molecules using light as a biocompatible stimulus. Their emerging applications in photoactivated therapies call for efficient uncaging in the near-infrared (NIR) window which represents a fundamental challenge. Here we report synthetically accessible cyanine photocages that liberate alcohol, phenol, amine, and thiol payloads upon irradiation with NIR light up to 820 nm in aqueous media. The photocages display unique chameleon-like behavior and operate via two distinct uncaging mechanisms – photooxidation and heterolytic bond cleavage. The latter process constitutes the first example of a direct bond scission by a single photon ever observed in cyanine dyes, or at wavelengths exceeding 800 nm. Modulation of the beating rates of human cardiomyocytes that we achieved by light-actuated release of adrenergic agonist etilefrine at nanomolar concentrations and low NIR light doses (~12 J cm-2) highlights the potential of these photocages in biology and medicine.