Large-scale synthesis of a persistent trityl radical for use in biomedical EPR applications and imaging

Abstract

Tetrathiatriarylmethyl radicals are ideal spin probes for biological electron paramagnetic resonance (EPR) spectroscopy and imaging. The wide application of trityl radicals as biosensors of oxygen or other biological radicals was hampered by the lack of affordable large-scale syntheses. We report the large-scale synthesis of the Finland trityl radical using an improved addition protocol of the aryl lithium monomer to methylchloroformate. A new reaction for the formal one-electron reduction of trityl alcohols to trityl radicals using neat trifluoroacetic acid is reported as well. Initial applications show that the compound is very sensitive to molecular oxygen. It has already provided high-resolution EPR images on large aqueous samples and should be suitable for a broad range of in vivo applications.

Triarylmethyl and Related Radicals

“…27a The radical 86 was formed in one step in quantitative yield by treatment of the tri(tert-butyl ester) 85 in neat trifluoroacetic acid at room temperature (Equation 1.26). 28 Other trityl alcohols formed radicals in a similar fashion. 28 The presence of ionizable carboxyl groups on the TAM radicals leading to pH sensitivity of the EPR parameters has been examined, as has the presence of limited numbers of aryl ring protons leading to doublet or triplet EPR signals.…”

“…An earlier preparation of these compounds 29c has been improved by a convenient large scale synthesis of the sodium salt of 86 (known as Finland trityl). 28 The oxygen substituted analogue 87 and the methyl deuterated derivative have also been studied, and together with 86 are soluble in water with single sharp lines in the EPR spectra. 27a The radical 86 was formed in one step in quantitative yield by treatment of the tri(tert-butyl ester) 85 in neat trifluoroacetic acid at room temperature (Equation 1.26).…”

Frequency bandwidth extension by use of multiple Zeeman field offsets for electron spin-echo EPR oxygen imaging of large objects

“…Therefore, a reduction in the T 2e uncertainty by a factor of 2 is equivalent to a similar enhancement in the oxygen tension resolution. Based on calibration data published for the Finland trityl oxygen-versus-line width broadening, 18,30 single-B and multi-B images have pO 2 resolutions of about 6.3 and 2.8 Torr, respectively.…”

An efficient parallel algorithm for the calculation of unrestricted canonical MP2 energies

“…The least parallel-efficient step is the bin sort (the step that involves the most I/O). Table 4 reports parallel UMP2 energy timings for the Finland trityl radical [16] (Fig. 3) ran on 48-, 72-and 96-CPUs of the Star of Arkansas, a University-wide resource with 157 dual-processor nodes, each containing two 2.65 GHz Xeon E5430 quadcore processors, 16 GB RAM and at least 250 GB scratch storage.…”