Synthesis of hydroxyethyl tetrathiatriarylmethyl radicals OX063 and OX071

Abstract

Synthesis of OX063 and OX063-d24 spin probes and DNP agents.

Ox‐SLIM: Synthesis of and Site‐Specific Labelling with a Highly Hydrophilic Trityl Spin Label

“…While other lithium alkyls leave the corresponding alkyl halide behind, no electrophiles remain in the solution using t BuLi, so that the aryl lithium can only react with the ketone. In this way, 21 was obtained in an isolated yield of 83 %, while the use of s BuLi [33] resulted in our hands in a yield of only 31 %. Moreover, metal–halogen exchange performed superior compared to direct lithiation of 16 with conditions proposed by Hintz et al., [40] where the yield dropped to 11 %.…”

“…Accordingly, the Ox063 radical 7 . was reported early in patent literature but efficient synthetic access was disclosed only recently [33] . Based on this core, the hydrophilic spin label 8 .…”

“…[32] Accordingly,t he Ox063 radical 7C was reported early in patentl iterature but efficient synthetic access was disclosed only recently. [33] Based on this core, the hydrophilic spin label 8C has been introduced, [34] and utilized for distance measurementsonouter membranes of E. coli just recently. [35] Despite its high water-solubility,t he methanethiosulfonate bioconjugation site is not suitable for in-cell applications [36] and such long linking groups lead to unnecessarily broad distance distributions.…”

Biological Applications of Electron Paramagnetic Resonance Viscometry Using a 13C-Labeled Trityl Spin Probe

“…Note that in vivo applications of Finland trityl-based probes such as 13 C-dFT are limited to intratissue delivery only due to its lipophilic core being responsible for the hydrophobic interactions of the probes with plasma biomacromolecules (e.g., binding to albumin [24]) and associated toxicity. Recently, we published an efficient synthesis of hydrophilic trityl radicals OX063 and its deuterated analogue OX071 suitable for systemic delivery [54]. Both OX063 and OX071 do not bind to blood albumin.…”

A 13C‐Labeled Triarylmethyl Radical as an EPR Spin Probe Highly Sensitive to Molecular Tumbling

“…Communications compartment (e.g., intra-, extracellular space, blood pool) will allow studying the microviscosity of each compartment. A 13 C 1 -labeled Ox071, [25] which does not bind albumin, will allow intravenous delivery. Also, a 13 C 1 -labeled TAM could be used to study molecular dynamics and interactions upon conjugation to a molecule of interest.…”