Snm as a Photolabile Protecting Group for the Cysteinyl Radical − Direct Evidence from Time‐Resolved IR and UV/Vis Spectroscopies

Abstract

The cysteinyl radical and the methyl(phenyl)thiocarbamic acid radical have been generated by laser flash photolysis (266 nm) of BOC−Cys(Snm)−OH in acetonitrile and characterized both by time‐resolved (IR and UV/Vis) and standard spectroscopic methods (UV, IR, and NMR). The mode of action of the Snm unit [methyl(phenyl)thiocarbamic acid] is similar to the so‐called “caging” technique. Cleavage of the disulfide bridge by irradiation is possible in acceptable quantum yields. Time‐resolved IR (TR‐IR) spectroscopic experiments using the step‐scan FTIR technique allowed the detection of the methyl(phenyl)thiocarbamic acid radical (νC=O = 1607.7 and 1579.3 cm−1), which has a lifetime of about 3 µs. Because of the weak absorptions in the IR spectrum and the tendency for fast recombination to BOC‐protected cystine, the cysteinyl radical cannot be monitored by TR‐IR spectroscopy. Time‐resolved UV/Vis spectroscopy revealed the formation of both of these radicals and permitted the determination of the decay rates of the methyl(phenyl)thiocarbamic acid radical in the presence of several quenchers. NMR spectroscopic studies of the photolysis of BOC−Cys(Snm)−OH allowed us to identify N‐methylaniline, carbonyl sulfide, and BOC‐protected cystine as the major products. This study clearly demonstrates that the thiol protection group Snm is a suitable photolabile protecting group. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy

“…402 The S–S bond cleavage and the cysteinyl radicals’ recombination was studied by time-resolved IR spectroscopic techniques.…”

Synthetic Routes to, Transformations of, and Rather Surprising Stabilities of (N-Methyl-N-phenylcarbamoyl)sulfenyl Chloride, ((N-Methyl-N-phenylcarbamoyl)dithio)carbonyl Chloride, and Related Compounds

“…Primary references cited by Zumach and Kühle were exclusively to unpublished studies from industrial laboratories, and a comprehensive, current literature search revealed a paucity of additional information on these species. − In contrast, the present paper reports not only the capability to generate the title functional groups by several complementary routes – as supported by thorough spectroscopic characterization as well as studies on several further transformations – it also documents their extraordinary (and rather surprising) stabilities. This work may have applications in the preparation of thiolyzable and/or photolabile protecting groups for the sulfhydryl of cysteine − and for the development of protein modification reagents …”

Intramolecular Disulfide Bridges as a Phototrigger To Monitor the Dynamics of Small Cyclic Peptides

“…In this perspective a variety of model systems have been investigated by fs−ps infrared spectroscopy. − To study protein- or peptide folding, a triggering event that perturbs the protein/peptide from a “starting” conformation is required to initiate the process. The incorporation of a photoswitch in the peptide/protein sequence or the use of “caged compounds” (photolabile protecting groups) − is one possibility, and a variety of these concepts have been introduced successfully into biomolecules and applied to time-resolved spectroscopies. ,− …”