Towards Photoredox-Cleavable Prodrugs
type: CreativeWork
description: Photouncaging is a field of study in which light is used to release or activate molecules from inactive precursors, e.g. prodrugs. Photouncaging is most often achieved through a direct release approach employing a chromophore as the photocaging group, which absorbs light and followingly undergoes cleavage. While this approach operationally simple, it requires complex photocaging groups, which have the inherent drawback of being unstable towards light. Photouncaging can also be achieved by a less-explored sensitised approach in which the photocaging group itself is inert to light and uncaging is mediated by a photosensitiser, which engages the photocaging group in energy transfer or redox reactions. The sensitised photouncaging approach overcomes the challenges encountered in direct photouncaging by employing simple light-stable photocaging groups. With the increasing popularity of visible-light photoredox chemistry in organic synthesis, there is an increasing number of photosensitiser-mediated reactions being reported, which can also be applied to photouncaging. For this project it was envisaged that a photooxidative approach would be useful for release of prodrugs carrying electron-rich benzyl groups as a photocage, which would be oxidised by a photocatalyst with molecular oxygen as a terminal oxidant. It was found that only sufficiently electron-rich benzyl groups underwent efficient photooxidative cleavage, and in particular the 2,4-dimethoxybenzyl group was identified as a suitable photocaging group. With the identified 2,4-dimethoxybenzyl photocaging group it was found that 2,4-dimethoxybenzylcarbamates, ethers and sulfonamides all underwent photooxidative cleavage, and release could be achieved by use of transitionmetal and organic photocatalysts, including riboflavin. The rate of release was found to be dependent on concentration, and the cleavage proceeded in minutes under high dilution. Attempts at extending the photooxidative cleavage to a proof-of-concept…
abstract: Photouncaging is a field of study in which light is used to release or activate molecules from inactive precursors, e.g. prodrugs. Photouncaging is most often achieved through a direct release approach employing a chromophore as the photocaging group, which absorbs light and followingly undergoes cleavage. While this approach operationally simple, it requires complex photocaging groups, which have the inherent drawback of being unstable towards light. Photouncaging can also be achieved by a less-explored sensitised approach in which the photocaging group itself is inert to light and uncaging is mediated by a photosensitiser, which engages the photocaging group in energy transfer or redox reactions. The sensitised photouncaging approach overcomes the challenges encountered in direct photouncaging by employing simple light-stable photocaging groups. With the increasing popularity of visible-light photoredox chemistry in organic synthesis, there is an increasing number of photosensitiser-mediated reactions being reported, which can also be applied to photouncaging. For this project it was envisaged that a photooxidative approach would be useful for release of prodrugs carrying electron-rich benzyl groups as a photocage, which would be oxidised by a photocatalyst with molecular oxygen as a terminal oxidant. It was found that only sufficiently electron-rich benzyl groups underwent efficient photooxidative cleavage, and in particular the 2,4-dimethoxybenzyl group was identified as a suitable photocaging group. With the identified 2,4-dimethoxybenzyl photocaging group it was found that 2,4-dimethoxybenzylcarbamates, ethers and sulfonamides all underwent photooxidative cleavage, and release could be achieved by use of transitionmetal and organic photocatalysts, including riboflavin. The rate of release was found to be dependent on concentration, and the cleavage proceeded in minutes under high dilution. Attempts at extending the photooxidative cleavage to a proof-of-concept…
author: Mandrup Kandemir, Jiyan
language: eng
keywords: Organic synthesis, Photoredox, Prodrug
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/e1e65794-414e-4522-9510-43dbfbf82429/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2023-07-05
date modified: 2026-07-22T22:24:06Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.109055