Intramolecular End-to-End Reactions of Photoactive Terminal Groups Linked by Poly(oxyethylene) Chains

Abstract

The triplet-sensitized photochemical reaction using a series of poly(oxyethylene) chains with a pair of photoactive terminal groups, dibenz[b,f]azepine (DBA) chromophores (DBA–COCH2CH2(OCH2CH2)nOCH2CH2CO–DBA, n=0–10) was examined. The photoirradiation of bichromophoric compounds caused either intra- or intermolecular reactions. These reactions were kinetically analyzed by two different methods: the measurement of deactivation processes of the reaction intermediates (excited triplet state of DBA) by nanosecond laser photolysis and the quantitative analysis of the reaction products by GPC. The intramolecular deactivation rate constant, kintra, showed a remarkable chain-length dependence; the maximum kintra value appeared at n=5 and it was found to be 5.9×104 s−1. On the other hand, the intramolecular cyclization rate also depends on the chain length; the maximum quantum yield, φdintra, was given at n=7 (φdintra=0.51). The chain length for the maximum cyclization yield shifted slightly to the longer region than that for the maximum kintra value due to the restriction of the terminal structure (anti-configuration). The results obtained for this reaction system are compared with those obtained for the previously reported polymethylene system and the effect of chain flexibility on the intramolecular ring-closure reaction is discussed.

Synthesis and Self-Alkylation of Isotope-Coded Affinity Tag Reagents

“…Synthesis of ICAT compounds began with the reaction of ethylene glycol or di(ethylene glycol) 1a, 1b, 1c, and 1d with acrylonitrile 2a and 2b to form ether dinitrile 3a, 3b, 3c, and 3d by Michael addition in benzene (16). After removal of solvent, the desired compounds were obtained in yield of 96% or higher and with good purity as shown on TLC (only one spot with R f values around 0.65).…”

Efficient Synthesis of Isotopically Pure Isotope-Coded Affinity Tagging Reagents

“…Although many reports have highlighted the utility of the ICAT methodology for proteomic profiling (9)(10)(11)(12)(13)(14)(15)(16), few have discussed the synthetic methodologies for generating 'heavy' ICAT reagents with respect to the isotopic purity and the cost of the synthesis. As initially reported for the synthesis of the 'heavy' ICAT reagent (9,17), the d 8 -diamine linker was synthesized in two steps: first by Michael addition of diethylene glycol-d 2 (i.e. O(CH 2 CH 2 -OD) 2 ) on the expensive d 3 -acrylonitrile, in the presence of catalytic NaOD solution in D 2 O, and then subsequent nitrile reduction using Raney nickel, providing an octadeuterodiamine linker.…”

“…The problems associated with the reported synthesis of "heavy" ICAT reagent (9,17) are as follows. (a) The Michael addition reaction results in significant (about 10%) loss of deuterium due to exchange with protium at the carbon R to the nitrile group.…”

Analysis of Rates of Multiple Enzymes in Cell Lysates by Electrospray Ionization Mass Spectrometry

“…The N -biotinylsarcosine block is linked to a polyether diamine, the length of which can be varied to avoid mass/charge overlaps of products and internal standards. The linker also allows facile introduction of multiple deuterium atoms (i.e., 8 deuteriums in 5 and 4 in 6 , Scheme ) to permit the synthesis of internal standards. In addition, the linker is hydrophilic to ensure good water solubility of the substrate conjugate, and it has basic groups which are efficiently protonated by ESI and thus ensure sensitive detection by mass spectrometry.…”