Toward the Development of New Photolabile Protecting Groups That Can Rapidly Release Bioactive Compounds upon Photolysis with Visible Light

Abstract

The synthesis and characterization of a new photolabile protecting group (caging group) for carboxylic acids, the 2-(dimethylamino)-5-nitrophenyl (DANP) group, is described. This compound has a major absorption band in the visible wavelength region with a maximum near 400 nm (epsilon400 = 9077 M(-1) cm(-1) at pH 7.4 and 21 degrees C). The caging group is attached through an ester linkage to the carboxyl functionality of beta-alanine, which activates the inhibitory glycine receptor in the mammalian central nervous system. Such caged compounds play an important role in transient kinetic investigations of fast cellular processes. Upon photolysis of DANP-caged beta-alanine, the caging group is released within 5 micros. Quantum yields of 0.03 and 0.002 were obtained in the UV region (308 and 360 nm) and the visible region (450 nm), respectively. Laser-pulse photolysis experiments, using 337 or 360 nm light, were performed with the caged compound equilibrated with HEK 293 cells transiently transfected with cDNA encoding the alpha1 homomeric, wild-type glycine receptor. The experiments demonstrated that neither DANP-caged beta-alanine nor its byproducts inhibit or activate the glycine receptors on the cell surface. Under physiological conditions, the DANP-caged beta-alanine is water-soluble and stable and can be used for transient kinetic measurements.

o‐Nitrobenzyl Photolabile Protecting Groups with Red‐Shifted Absorption: Syntheses and Uncaging Cross‐Sections for One‐ and Two‐Photon Excitation

“…As illustrated in Figure 3c, the evolution of the absorbance and the fluorescence emission as a function of time were also accounted for satisfactorily by Equations (8,9) in the series of caged coumarin nc. The rate constants that were obtained from the analysis of the absorbance and of the fluorescence emission were in good agreement.…”

N‐Acetylmethionine and Biotin as Photocleavable Protective Groups for Ruthenium Polypyridyl Complexes

“…Thus, the thioether ligand corresponds to the classical picture of a photocleavable protective group in organic chemistry. [54][55][56][57] In conclusion, the coordination bond between the ruthenium polypyridyl fragment [RuA C H T U N G T R E N N U N G (terpy)A C H T U N G T R E N N U N G (bpy)] 2 + and monodentate thioether ligands such as N-acetylmethionine or biotin is thermally more stable in the dark than the rutheniumchloride bond. [58] Once coordinated, the thioether ligand can be efficiently cleaved from the metal center by visible light irradiation into the MLCT band of the Ru-thioether complex.…”

Caged Amino Acids for Visible‐Light Photodelivery

“…Banerjee et al presented two photolabile protecting groups for carboxylic acids that can be used with visible light. The DANP-caged alanine [4] presents a quantum yield of photodissociation Φ PD = 0.03 at 360 nm that decreases to 0.002 lease at 450 nm is Φ PD = 0.035, which is about 17 times higher than that of the most active organic caged compound at this wavelength. at 450 nm.…”