Unambiguous evaluation of the relative photolysis rates of nitro indolinyl protecting groups critical for brain network studies

Abstract

a b s t r a c tNitrated indolinyl photoprotecting groups are crucial tools extensively used in the study of neuronal signal transduction. Mononitrated photolabile protecting groups have been used effectively, however, recent advances in the introduction of a second nitro group have shown improvement in the photo efficiency of neurotransmitter (agonist) release, albeit, to varying extents, depending on the assessment methods employed. An unambiguous method is discussed based on Nuclear Magnetic Resonance (NMR), which is shown to be an effective technique in the relative overall rate comparison amongst varying nitrated protecting groups. Mononitrated and dinitrated photolabile protecting groups such as CDNIGlu and MNI-Glu are used as an example to assess the relative value of adding a second nitro group in photoactive cage designs. Using this technique, it was shown that the second nitro group in CDNI systems enhances the overall relative rate of photocleavage by a factor of 5.8. This reported method can also be used to unambiguously determine relative rate of agonist photorelease.

Competition Between Cyclization and Unusual Norrish Type I and Type II Nitro-Acyl Migration Pathways in the Photouncaging of 1-Acyl-7-nitroindoline Revealed by Computations

“…73 These results are summarized in Figure 5, where each contributing state is labelled on the λM = 0.15 curve. For this specific value of λM, we also obtain quantitative agreement with the available experimental data, 21,34,36 with an estimated value of 3.88 for the MDNI/MNI ratio, against experimental values of ~ 4 (see Section S12 of the Supporting Information). The same considerations and results apply to α-MDNI-Glu and α-MNI-Glu (Table S6), for which the calculated ratio is 4.14.…”

Competition Between Cyclization and Unusual Norrish Type I and Type II Nitro-Acyl Migration Pathways in the Photouncaging of 1-Acyl-7-nitroindoline Revealed by Computations

“…The numerical results are reported in Table 2. According to previous work, 21,34,36 the quantum yield of MDNI-Glu is about five times the quantum yield of MNI-Glu.…”

“…33,34 Although the second nitro at the C-5 is not directly participating in the mechanism, as we will show later, its presence results in an improved quantum yield by at least fivefold according to experimental data. [35][36][37] The mechanisms of uncaging for the 7-indolinyl system was studied by at least three groups using kinetic, fast pulse IR, and computation. 33,38,39 However, the most recently reported computational mechanisms of uncaging do not explain the difference in quantum yield, which is an important parameter, especially for consideration in future improved designs.…”

Unusual Norrish Type I and Type II Nitro-Acyl Migration Transition State in the Photo-Uncaging of 1-Acyl-7-Nitroindolines Revealed by Computations

“…The numerical results are reported in Table 1. According to previous work, 23,38,40 the quantum yield of MDNI-Glu is about five times the quantum yield of MNI-Glu. By comparing the two ISC rate constants we calculated, we can estimate the relative quantum yield of the reaction of MDNI-Ac to be 3.75 times that of MNI-Ac, in good agreement with the experimental data.…”

“…37,38 Although the second nitro at the C-5 is not directly participating in the mechanism, as we will show later, its presence results in an improved quantum yield by at least 5 fold according to experimental data. [39][40][41] The mechanisms of uncaging for the 7-indolinyl system was studied by at least three groups using kinetic, fast pulse IR, and computation. 37,42,43 However, the most recently reported computational mechanisms of uncaging do not explain the difference in quantum yield, which is an important parameter especially for consideration in future improved designs.…”