Surfing the limits of cyanine photocages one step at a time.

Near-infrared light-activated photocages enable controlling molecules with tissue penetrating light. Understanding the structural aspects that govern the photouncaging process is essential to enhancing their efficacy, crucial for practical applications. Here we explore the impact of thermodynamic stabilization on contact ion pairs in cyanine photocages by quaternarization of the carbon reaction centers.

Concurrent Subcellular Delivery of Hydrogen Sulfide and a Payload with Near-Infrared Light.

Hydrogen sulfide (HS) is a gaseous signaling molecule, exerting crucial regulatory functions in organelles and cellular environments. HS exhibits high therapeutic potential and synergistic effects with other drugs, and its potency is notably enhanced through organelle-specific targeting. Yet, the navigation of light-activated HS donors to specific organelles remains absent.

Light in a Heartbeat: Bond Scission by a Single Photon above 800 nm.

Photocages enable scientists to take full control over the activity of molecules using light as a biocompatible stimulus. Their emerging applications in photoactivated therapies call for efficient uncaging in the near-infrared (NIR) window, which represents a fundamental challenge. Here, we report synthetically accessible cyanine photocages that liberate alcohol, phenol, amine, and thiol payloads upon irradiation with NIR light up to 820 nm in aqueous media.

pH-Responsive Aminobenzocoumarins as Fluorescent Probes for Biological Acidity.

Regulation of pH plays an essential role in orchestrating the delicate cellular machinery responsible for life as we know it. Its abnormal values are indicative of aberrant cellular behavior and associated with pathologies including cancer progression or solid tumors. Here, we report a series of bent and linear aminobenzocoumarins decorated with different substituents.

Deuteration of heptamethine cyanine dyes enhances their emission efficacy.

The design of bright short-wave infrared fluorophores remains a grand challenge. Here we investigate the impact of deuteration on the properties in a series of heptamethine dyes, the absorption of which spans near-infrared and SWIR regions. We demonstrate that it is a generally applicable strategy that leads to enhanced quantum yields of fluorescence, longer-lived singlet excited states and suppressed rates of non-radiative deactivation processes.

Cyanine Renaissance: Tailoring the Properties to Applications.

In this account, we provide an overview of the applications that arose from the recently developed synthetic methodology that delivers heptamethine cyanines (Cy7) substituted at the central chain. The ability to easily introduce and manipulate various substituents in different substitution patterns along the cyanine chain enabled rational tailoring of the photophysical and photochemical properties. Exercising this control over the structure-property relationship proved to have a substantial impact in the field of cyanine dyes and was swiftly harnessed in a number of emerging applications in distinct areas, including fluorescent probes, biosensors, dye-sensitized upconversion nanoparticles, phototruncation of cyanines and photocages.

Structure-Activity Studies of Nitroreductase-Responsive Near-Infrared Heptamethine Cyanine Fluorescent Probes.

Two new classes of near-infrared molecular probes were prepared and shown to exhibit "turn on" fluorescence when cleaved by the nitroreductase enzyme, a well-known biomarker of cell hypoxia. The fluorescent probes are heptamethine cyanine dyes with a central 4'-carboxylic ester group on the heptamethine chain that is converted by a self-immolative fragmentation mechanism to a 4'-caboxylate group that greatly enhances the fluorescence brightness. Each compound was prepared by ring opening of a Zincke salt.

Photouncaging of Carboxylic Acids from Cyanine Dyes with Near-Infrared Light.

Near-infrared light (NIR; 650-900 nm) offers unparalleled advantages as a biocompatible stimulus. The development of photocages that operate in this region represents a fundamental challenge due to the low energy of the excitation light. Herein, we repurpose cyanine dyes into photocages that are available on a multigram scale in three steps and efficiently release carboxylic acids in aqueous media upon irradiation with NIR light up to 820 nm.