Synthesis of a BDPA-TEMPO Biradical

Abstract

The synthesis and characterization of a biradical containing a 1,3-bisdiphenylene-2-phenylallyl (BDPA) free radical covalently attached to a 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) free radical are described. The synthesis of the biradical is a step towards improved polarizing agents for dynamic nuclear polarization (DNP).Biradicals are of considerable interest as polarizing agents for microwave driven dynamic nuclear polarization (DNP) NMR experiments. 1,2 Irradiation of the biradical's electron paramagnetic resonance (EPR) drives electron-nuclear transitions that transfer the large polarization of the electrons to the nuclear spins and thereby enhances the signal-to-noise ratio in NMR experiments. The enhancement factors can reach a theoretical maximum of ~660 for electron-1 H polarization transfer and ~2600 when 13 C is the nuclear spin of interest. 3 Thus, optimized biradical polarizing agents can dramatically decrease acquisition times. These signal enhancements are important for a variety of applications involving solid-state NMR, particularly for systems that are not amenable to crystallographic studies, such as amyloid 4 and membrane 5 proteins.In previous work, we demonstrated that bis-nitroxide biradicals, which contain two tethered TEMPO moieties, provide 1 H/ 13 C-signal enhancements ~200 fold in solid-state magic-anglespinning (MAS) NMR spectra. 2 We are interested in molecules that can produce DNP by a cross effect (CE) mechanism 3 that involves three spins, two dipolar coupled electrons and a nuclear spin (usually 1 H), denoted by S 1 and S 2 and I, with electron and nuclear Larmor frequencies, ω 0S 1 , ω 0S 2 , and ω 0 I , respectively. In a DNP experiment, microwave irradiation of the biradical's EPR spectrum induces the two electrons to undergo a spin flip-flop process, during which a nuclear spin is polarized if the electron Larmor frequencies are separated by the nuclear Larmor frequency and therefore satisfy the matching condition, ω 0S 1 -ω 0S 2 = ω 0 I . The high 1 H polarizaton is then transferred via cross-polarization to 13 C or 15 N, resulting in an enhanced MAS NMR spectrum. 6 The efficiency of the CE mechanism depends on how many pairs of electrons satisfy the matching condition. Thus, the ideal CE polarizing agent would be a biradical with an EPR spectrum consisting of two sharp lines separated by ω 0I . However, at the high magnetic fields (>5T) where contemporary NMR experiments are performed, only a few known radicals NIH Public Access exhibit narrow spectra. Among them are two stable species -trityl radical derivatives 7 and the BDPA radical 8 (Scheme 1), which have similar isotropic g-values (g iso (trityl)= 2.00307, 1 g iso (BDPA)= 2.00264). If trityl or BDPA serves as one of the lines in the EPR spectrum of a polarizing agent, then to satisfy the CE matching condition it is necessary to introduce another radical with a line separated from the first by ω 0I . There are no known stable radicals that provide a narrow line and meet this condition, however TEMPO ...

A Slowly Relaxing Rigid Biradical for Efficient Dynamic Nuclear Polarization Surface-Enhanced NMR Spectroscopy: Expeditious Characterization of Functional Group Manipulation in Hybrid Materials

“…With nitroxidebased biradicals, the EPR frequency difference is provided by ganisotropy, and the difference in EPR frequencies can match the 1 H Larmor frequency when the g xx (or g yy ) component of the g tensor of one of the unpaired electrons is parallel to the g yy (g zz ) component of the other. 25,26 Recently, triradical, 23 heterogeneous biradical species or mixtures of radical species, 27,28 and metal ions 29 have been proposed as alternatives to dinitroxide polarizing agents.…”

Trityl-nitroxide biradicals as unique molecular probes for the simultaneous measurement of redox status and oxygenation

“…1 They also found applications in the fields of dynamic nuclear polarization (DNP) 2 and living free radical polymerization. 3 To date, most stable biradicals consist of two identical radical moieties, but mixed biradicals have also exhibited unique physico-chemical properties and found applications for sensing NO, 4 pH 5 and redox status 6 in biological systems.…”

Synthesis of a Water-Soluble 1,3-Bis(diphenylene)-2-phenylallyl Radical

“…Building on our previously reported synthesis of a BDPA-TEMPO biradical9 (Scheme 1), the conjugate addition of a fluorene anion to compound 1 became the crucial transformation in our route to WS-BDPA. Compound 1 contains a carboxylic acid at the para -position of its phenyl ring that can aid in aqueous solubility.…”