The β-phosphorus hyperfine coupling constant in nitroxides: 6. Solvent effects in non-cyclic nitroxides

Abstract

In two recent articles (Org. Biomol. Chem., 2015 and 2016), we showed that changes in the phosphorus hyperfine coupling constant aP at position β in β-phosphorylated nitroxides can be dramatic. Such changes were applied to the titration of water in organic solvents and conversely of organic solvents in water. One of the molecules tested was a non-cyclic nitroxide meaning that a thorough investigation of the solvent effect on the EPR hyperfine coupling constant is timely due. In this article, we show that the aP of persistent non-cyclic β-phosphorylated nitroxides decrease with the normalized polarity Reichardt's constant E(N)T. The Koppel-Palm and Kalmet-Abboud-Taft relationships were applied to gain deeper insight into the effects influencing aN and aP: polarity/polarizability, hydrogen bond donor properties, and the structuredness of the cybotactic region.

New Amino‐Acid‐Based β‐Phosphorylated Nitroxides for Probing Acidic pH in Biological Systems by EPR Spectroscopy

“…function ( 10 b in Figure B). Accordingly, unlike DEPN, 20 , 21 , and congeners, which yield EPR sextets in organic solvents, all the nitroxides of our series should adopt a preferred conformation in aqueous medium with θ H not close to 90°, that is, the N‐O and C α ‐H β (for 5 a and 5 c ) or C α′ ‐H β (for 10 b and 11 b ) bonds are not totally eclipsing. This geometry was observed in the X‐ray structure of 10 b because packing constrains the H β ‐C α′ ‐N‐O and P‐C α′ ‐N‐O torsion angles to about 171° and −76°, respectively (Table ), which correspond to dihedral angles θ H ≈99° and θ P ≈13° (Figure A).…”

“…Regardless of the nucleus considered, limiting hfs and p K a values of 5 a , 5 c , and 10 b in synthetic buffer were not substantially different from those for the CytM prepared from rat organs (<0.1 G and <0.2 pH units, respectively). In particular, the a N values were almost constant, although spin density at nitrogen in β‐phosphorylated nitroxides is known to increase with solvent polarity . For all nitroxides in a given milieu, acidic p K a values extracted from titration curves of a X (X=N, H, P) against pH ( n= 2–4) showed little variation (≤0.06 pH units), except when a H was used to probe pH for 11 b , probably because of the very small EPR sensitivity found in this case.…”

“…With this in mind, our target EPR probes for acidic pH were α‐carboxy, α′‐diethoxyphosphoryl nitroxides, where ionization occurs at the CO 2 H function, and the scaffold (Figure C) is close to that of the linear α‐aminophosphonates we developed as 31 P NMR pH probes . Many fully alkylated members of this family, such as N‐tert ‐butyl‐ N ‐[1‐diethylphosphono(2,2‐dimethylpropyl)] nitroxide (DEPN; Figure C), are popular for nitroxide‐mediated living polymerization, and more recently a small set of α‐substituted acyl derivatives has been used to model solvent‐related EPR hfs . Although they bear one α‐hydrogen, all these nitroxides are very persistent in water and other solvents, because their disproportionation into diamagnetic species can be prevented (or slowed) by steric crowding at the remaining α,α′ positions, a substitution pattern we adopted in our target nitroxides by using (Y,Y′)=Ph, i Pr, or t Bu groups (Figure C).…”

Cybotactic Effect on Nitrogen and Phosphorus Hyperfine Coupling Constants in β-Phosphorylated Nitroxides.

“…Nitroxide 3d• was prepared as already reported [] and the corresponding nitrogen and phosphorous hyperfine coupling constant (hcc) an and a P , respectively, were measured as previously described. [6][7][8][9][10][11] Due to the presence of both Nand P-atoms at the positions a and b to the odd electron with nuclear spin I N = 1 and I P = ½, respectively, EPR signal of 2•, 3a-d• displays 6 lines (doublet of triplet) with a large doublet due to a P and a small triplet due to a N ( Table 1). Hcc at position a is directly related to the spin population localized on the nucleus, [] and to the shape of the SO-MO (Fermi contact term Q N , eq.…”

“…[,,,,-] However, in the series of nitroxyl radical 3 only minor steric changes were investigated with 3a and 3b,c. [8,9] Indeed, one methyl group in 3a is replaced either by the CH 2 OAc (3b) or by the CH 2 OPiv (3c). Hereafter, we report on the effect on a N and a P of more significant changes in the steric strain as Me group in 3a is replaced by COOMe group in 3d (Figure 1).…”