Sanger’s Reagent Sensitized Photocleavage of Amide Bond for Constructing Photocages and Regulation of Biological Functions

Abstract

Photolabile groups offer promising tools to study biological processes with high spatial and temporal control. In the investigation, we designed and prepared several new glycine amide derivatives of Sanger's reagent and demonstrated that they serve as a new class of photocages for Zn 2+ and an acetylcholinesterase (AChE) inhibitor. We showed that the mechanism for photocleavage of these substances involves initial light-driven cyclization between the 2,4dinitrophenyl and glycine methylene groups to form acyl benzimidazole N-oxides, which undergo secondary photoinduced decarboxylation in association with rupture of an amide bond. The cleavage reactions proceed with modest to high quantum yields. We demonstrated that these derivatives can be used in targeted intracellular delivery of Zn 2+ , fluorescent imaging by light-triggered Zn 2+ release, and regulation of biological processes including the enzymatic activity of carbonic anhydrase (CA), negative regulation of N-methyl-D-aspartate receptors (NMDARs), and pulse rate of cardiomyocytes. The successful proof-of-concept examples described above open a new avenue for using Sanger's reagentbased glycine amides as photocages for the exploration of complex cellular functions and signaling pathways.

Azo-Enhanced Raman Scattering for Enhancing the Sensitivity and Tuning the Frequency of Molecular Vibrations

“… 45 − 47 The intramolecular cis/trans structure change has been widely applied to study photoconversion processes. 48 − 50 Inspired by the findings, we demonstrate here a new concept of azo-enhanced Raman scattering (AERS, Figure 1 ). Conjugated azobenzene structures are the enhancing unit to boost Raman signals of various vibrational modes.…”

2‐Fluoro‐5‐nitrophenyldiazonium: A Novel Sanger‐Type Reagent for the Versatile Functionalization of Alcohols

“…Sanger‐type reagents have a long history in organic chemistry, [1] and it is now 75 years ago that Frederick Sanger introduced 1‐fluoro‐2,4‐dinitrobenzene ( 1 ) for the labeling of terminal amino groups in peptides (Scheme 1 A). [1a] Since then, the dinitro‐benzenes 1 and 2 —representing key derivatives—have been widely used, [2] with recent applications in such diverse fields as water analysis, [2a] photosensitization, [2b] and medicinal chemistry [2c] . Given this vast potential, it was interesting to note that among the Sanger reagents, the free diazonium derivative 3 has not yet been studied (Scheme 1 D).…”

Theoretical Design, Synthesis, and In Vitro Neurobiological Applications of a Highly Efficient Two-Photon Caged GABA Validated on an Epileptic Case

“…Caged compounds are excellent tools to simulate and modulate neuronal activity patterns from the subcellular to network level. 1 Although highly efficient excitatory caged molecules have already been synthesized, 2 − 4 the development of inhibitory caged molecules for two-photon (2P) microscopy has proven to be a more difficult task. 5 , 6 The previously reported photo-activable caged-GABA compounds are just at the limit of their usability, and they have exhibited several drawbacks in their stability, solubility, 2P uncaging efficiency, or antagonistic effect on GABA A receptors.…”