Tuning singlet oxygen generation with caged organic photosensitizers.

Controlling the succession of chemical processes with high specificity in complex systems is advantageous for widespread applications, from biomedical research to drug manufacturing. Despite synthetic advances in bioorthogonal and photochemical methodologies, there is a need for generic chemical approaches that can universally modulate photodynamic reactivity in organic photosensitizers. Herein we present a strategy to fine-tune the production of singlet oxygen in multiple photosensitive scaffolds under the activation of bioresponsive and bioorthogonal stimuli. We demonstrate that the photocatalytic activity of nitrobenzoselenadiazoles can be fully blocked by site-selective incorporation of electron-withdrawing carbamate moieties and restored on demand upon uncaging with a wide range of molecular triggers, including abiotic transition-metal catalysts. We also prove that this strategy can be expanded to most photosensitizers, including diverse structures and spectral properties. Finally, we show that such advanced control of singlet oxygen generation can be broadly applied to the photodynamic ablation of human cells as well as to regulate the release of singlet oxygen in the semi-synthesis of natural product drugs.

Enzyme-Activatable Near-Infrared Hemicyanines as Modular Scaffolds for in vivo Photodynamic Therapy.

Photodynamic therapy is an anti-cancer treatment that requires illumination of photosensitizers to induce local cell death. Current near-infrared organic photosensitizers are built from large and non-modular structures that cannot be tuned to improve safety and minimize off-target toxicity. This work describes a novel chemical platform to generate enzyme-activatable near-infrared photosensitizers. We optimized the Se-bridged hemicyanine scaffold to include caging groups and biocompatible moieties, and generated cathepsin-triggered photosensitizers for effective ablation of human glioblastoma cells. Furthermore, we demonstrated that enzyme-activatable Se-bridged hemicyanines are effective photosensitizers for the safe ablation of microtumors in vivo, creating new avenues in the chemical design of targeted anti-cancer photodynamic therapy agents.

Corannulene: a molecular bowl of carbon with multifaceted properties and diverse applications.

Unlike typical polycyclic aromatic hydrocarbons, such as coronene, which are flat and planar, corannulene is a molecular bowl of carbon. It can be imagined as the cap region of fullerene C60 or an end of a single-walled carbon nanotube. This structural distinction manifests itself in unique properties. For example, corannulene exhibits bowl-flipping dynamics, electron accepting capability, and formation of a ball-in-socket type of interaction with C60. These varied properties allow for application of corannulene in a myriad of disciplines ranging from organic electronics and sensing to energy storage and self-assembly. In this feature article, our goal is to discuss the major synthetic developments in corannulene chemistry which allow the scientific community access to this beautiful molecule in a practical fashion, the unique properties of the corannulene nucleus that sets it apart from the planar polynuclear aromatic hydrocarbons, and lastly its applications in the arena of materials chemistry.