Photolabile Amphiphiles with Fluorogenic Thioxanthone-Dithiane Functionality: Synthesis and Photoinduced Fragmentation in Micelles.

Novel photolabile amphiphiles containing thioxanthone-based fluorogenic caging groups are developed. Photoinduced fragmentation in dithiane-thioxanthone adducts was demonstrated to occur with 100% quantum efficiency at λ ~ 320 nm and more than 50% at λ ~ 360 nm. A plausible mechanism involves homolytic fission of a carbon-carbon single bond in the excited thioxanthone followed by disproportionation via hydrogen transfer. The critical feature of the system is that fluorescence of a substituted thioxanthone is recovered as a result of photofragmentation, making dithiane-thioxanthone adducts efficient fluorogenic caging groups. Photolabile amphiphiles containing these fluorogens are synthesized and their photoinduced disassembly is probed while following the fluorescence recovery. This methodology allows for destabilizing supramolecular assemblies of amphiphiles and at the same time offers a feedback mechanism for monitoring the process by fluorescence.

Photoinduced signal amplification through controlled externally sensitized fragmentation in masked sensitizers.

Addition of lithiated dithianes to diaryl ketones, potential electron-transfer sensitizers, disrupts conjugation between the two aromatic moieties, effectively masking the sensitizer. A novel photoamplification strategy is developed based on photosensitized cleavage in such adducts, where each fragmentation event releases more diaryl ketone, capable of sensitization. As a result, mass release of dithianes, triggered with a very small amount of the initiator, is observed. Such amplified release can be made contingent on a molecular recognition event, offering a promising methodology for high throughput bioanalytical applications. The concept is proved with the use of micro- and nanosized polymeric supports, including dendrimers.

Release and report: a new photolabile caging system with a two-photon fluorescence reporting function.

A new efficient photocaging system with a fluorescence reporting function has been developed. The photolabile latch is based on adducts of C-nucleophiles with aromatic ketones, such as thioxanthones and xanthones. The system is designed to quantify the release of biological effectors and to monitor their spatial distribution and localization by single- and two-photon fluorescence microscopy. In the armed state the ketone's conjugation is disrupted by nucleophilic addition, resulting in a blue shift of the absorption maxima and a dramatic decrease in fluorescence intensity. The mechanism of the photoinduced uncaging involves homolytic C-C bond fragmentation followed by radical disproportionation, regenerating the carbonyl moiety and restoring fluorescence. The uncaging can be initiated via either a one- or two-photon process, offering a new powerful tool for molecular life sciences. The synthesis and uncaging of dendrimer- and polymeric bead-based model systems are described.