S,S‐Chiral Linker Induced U Shape with a Syn‐facial Sensitizer and Photocleavable Ethene Group

Abstract

There is a major need for light-activated materials for the release of sensitizers and drugs. Considering the success of chiral columns for the separation of enantiomer drugs, we synthesized an S,S-chiral linker system covalently attached to silica with a sensitizer ethene near the silica surface. First, the silica surface was modified to be aromatic rich, by replacing 70% of the surface groups with (3-phenoxypropyl)silane. We then synthesized a 3-component conjugate [chlorin sensitizer, S,S-chiral cyclohexane and ethene building blocks] in 5 steps with a 13% yield, and covalently bound the conjugate to the (3-phenoxypropyl)silane-coated silica surface. We hypothesized that the chiral linker would increase exposure of the ethene site for enhanced O -based sensitizer release. However, the chiral linker caused the sensitizer conjugate to adopt a U shape due to favored 1,2-diaxial substituent orientation; resulting in a reduced efficiency of surface loading. Further accentuating the U shape was π-π stacking between the (3-phenoxypropyl)silane and sensitizer. Semiempirical calculations and singlet oxygen luminescence data provided deeper insight into the sensitizer's orientation and release. This study has lead to insight on modifications of surfaces for drug photorelease and can help lead to the development of miniaturized photodynamic devices.

Visible-to-NIR-Light Activated Release: From Small Molecules to Nanomaterials

“…The drug can then be liberated in the presence of a sensitizer, oxygen, and light. 1414 − 1417 The triplet-excited photosensitizer may also participate in electron exchange, that is, in Type I photooxygenation, as discussed in section 6.2 .…”

“…Diverse chemical functionalities and entities can be cleaved by reaction with singlet oxygen (Type II photo­oxygenation) including olefins, vinyl ethers, vinyl disulfides, thioketals, and lipids. , Such singlet oxygen-sensitive groups can be inserted into tethers connecting drug molecules to structures such as membranes, nanomaterials, surfaces, or supramolecular carriers. The drug can then be liberated in the presence of a sensitizer, oxygen, and light. − The triplet-excited photosensitizer may also participate in electron exchange, that is, in Type I photo­oxygenation, as discussed in section .…”

“…This mechanism was demonstrated to be responsible for the release of chlorin, which was used as a sensitizer (sens) that was covalently attached to silica via a tether containing a 1,2-diphenoxyethene unit (Scheme ). Many other studies have exploited the reaction between 1 O 2 and ethene derivatives such as vinyl ethers, bis­(alkylthio)­alkenes, or aminoacrylates for substrate liberation. ,,− The uncaging photo­oxidation of lipids or liposomes in the presence of organic sensitizers may also proceed via mechanisms involving singlet oxygen. − …”

Spatiotemporal Control of Biology: Synthetic Photochemistry Toolbox with Far-Red and Near-Infrared Light

“…These functionalities undergo a [2 + 2] cycloaddition with 1 O 2 , followed by a retrocycloaddition to release two aldehyde products (Figure 4a). 74−76 Early studies with singlet oxygen cleavable linkers employed vinyl ether 77,78 and vinyl dithioether 79,80 functionality. More recently, You and co-workers designed aminoacrylate as an efficient, easy-to-prepare 1 O 2 -cleavable linker for the photosensitized release of a drug molecule protected on its hydroxyl group.…”

A Cyanine Photooxidation/β‐Elimination Sequence Enables Near‐infrared Uncaging of Aryl Amine Payloads

“…Given the modest photonic energies of these wavelengths, it is not surprising that these approaches employ a range of chemical mechanisms for bond cleavage . These include the direct cleavage of certain chromophore–payload bonds, the cleavage of carbon–metal bonds, the use of photoinduced electron transfer (PET)‐mediated processes and the local generation of singlet oxygen ( 1 O 2 ) . Despite progress, significant reaction discovery efforts are needed to uncover methods characterized by broad payload flexibility, activation with wavelengths over 700 nm and rapid release.…”