Long-wavelength photoremovable protecting groups: On the way to in vivo application

Abstract

Photoremovable protective groups (PPGs) and related “caged” compounds have been recognized as a powerful tool in an arsenal of life science methods. The present review is focused on recent advances in design of “caged” compounds which function in red or near-infrared region. The naive comparison of photon energy with that of organic bond leads to the illusion that long-wavelength activation is possible only for weak chemical bonds like N-N. However, there are different means to overcome this threshold and shift the uncaging functionality into red or near-infrared regions for general organic bonds. We overview these strategies, including the novel photochemical and photophysical mechanisms used in newly developed PPGs, singlet-oxygen-mediated photolysis, and two-photon absorption. Recent advances in science places the infrared-sensitive PPGs to the same usability level as traditional ones, facilitating in vivo application of caged compounds.

Photoresponsive molecular tools for emerging applications of light in medicine

“…In the design of PPGs, toxicity plays an important part because the removed cage should not show general toxicity. 18,93 It is known that oNP-based PPGs can form harmful by-products upon photocleavage (Fig. 17, compounds 98 and 99).…”

A Red Light‐Triggered Drug Release System Based on One‐Photon Upconversion‐Like Photolysis

“…Some of the borondipyrromethene (BODIPY) or cyaninebased PPGs can achieve photolysis at the wavelength longer than 650 nm, but they usually contain complex conjugations in the molecular structures and exhibit relatively low photolysis quantum yields. [16][17][18] The multiphoton upconversion processes, including twophoton excitation and upconversion luminescence (UCL) systems, were employed to activate the photolysis of PPGs with longwavelength light excitation. [19][20][21][22][23] Due to the small two-photon absorption cross sections of current PPGs, high-power femtosecond pump lasers are required for two-photon excitation, [13] increasing the risk of local overheating.…”

Photochemistry of a 9‐Dithianyl‐Pyronin Derivative: A Cornucopia of Reaction Intermediates Lead to Common Photoproducts

“…Later, several meso ‐methyl‐BODIPY‐based PPGs (Scheme b) have been designed to release LGs, representing synthetically accessible and thermally stable scaffolds with structurally easily adjustable optical and photophysical properties. Many other transition‐metal‐free PPG systems have been reported to date …”