was sublimed under static vacuum onto a −78 °C cold finger. BHT and
DHA were recrystallized 3 times from absolute EtOH and dried in vacuo.
show that the CR/KSE model is a conceptual and predictive tool
that can be used to understand a wide range of organic HAT re-
actions in solution, including biologically important hydrogen
atom transfer reactions involving tocopherol, ascorbate, and
hydroperoxides.
Stopped-Flow Kinetic Experiments. In
a typical procedure, solutions of
tBu3PhO• (1.1 mM) and BHT (5.5–78 mM) were prepared in anhydrous MeCN
in an N2-filled glovebox and loaded into syringes. The two syringes were
removed from the glovebox and placed immediately into the stopped-flow
apparatus. The mixing chamber of the stopped-flow apparatus was flushed
with reagents before collecting kinetic data. A minimum of five kinetic runs
were collected at each concentration. The data were well fit over four
half-lives in using an A → B kinetic model with SPECFIT software. Plots of
the pseudo-first-order kobs as a function of [BHT] were linear with a zero
intercept, the slope giving the bimolecular rate constant.
Materials and Methods
Physical Techniques and Instrumentation. UV-vis stopped-flow measurements
used an OLIS RSM-1000. 1H NMR spectra were recorded on Bruker Avance
spectrometers at 300 or 500 MHz. All reactions were performed anaerobically
by using standard glovebox and high vacuum techniques.
Materials. Reagent grade solvents were purchased from Fischer Scientific,
unless otherwise noted. Anhydrous MeCN (Honeywell Burdick and Jackson)
was sparged with Ar. C6H6 and DMSO were dried by using a Seca solvent
system. CCl4 (99.9%; Aldrich) was used as received in a Sure/Seal bottle. Deut-
erated solvents were obtained from Cambridge Isotope Laboratories. CDCl3
was stored over CaH2 and freshly distilled before use. TEMPOH (27) and
tBu3PhO• (29) were prepared according to the literature. 4-oxo-TEMPO
ACKNOWLEDGMENTS. Professor Michael Abraham is acknowledged for help-
ful discussions concerning the H-bonding properties of tBuOOtBu. We grate-
fully acknowledge support from the National Institutes of Health (GM50422)
and the University of Washington, Department of Chemistry.
25. Mulder P, et al. (2005) Critical re-evaluation of the O—H bond dissociation enthalpy
in phenol. J Phys Chem A 109:2647–2655.
1. Fossey J, Lefort D, Sorba
New York).
J (1995) Free Radicals in Organic Chemistry (Wiley,
26. Borges dos Santos RM, Costa Cabral BJ, Martinho Simões JA (2007) Bond-dissociation
enthalpies in the gas phase and in organic solvents: Making ends meet. Pure Appl
Chem 79:1369–1382 . Martinho Simões and co-workers have criticized this model
when applied to solution bond dissociation enthalpies. Since Abraham’s model is
based upon free energies it is expected be more appropriate for solution BDFEs..
27. Mader EA, Davidson ER, Mayer JM (2007) Large ground-state entropy changes for
hydrogen atom transfer reactions of iron complexes. J Am Chem Soc 129:5153–5166.
28. Yoder JC, Roth JP, Gussenhoven EM, Larsen AS, Mayer JM (2003) Electron and
hydrogen-atom self-exchange reactions of iron and cobalt coordination complexes.
J Am Chem Soc 125:2629–2640.
2. Halliwell B, Gutteridge JMC (1999) Free Radicals in Biology and Medicine (Oxford
Univ Press, New York), 3rd Ed.
3. (2007) Hydrogen Transfer Reactions, ed Hynes JT (Wiley-VCH, Weinheim), Vol 1–4.
4. (1994) Radical Reaction Rates in LiquidsLandolt-Börnstein New Series, ed Fischer H
(Springer, Berlin), (Supplement to Vol 13), Vol 18, Subvols A–E2,.
5. Neta P, Grodkowski J (2005) Rate constants for reactions of phenoxyl radicals in
solution. J Phys Chem Ref Data 34:109–199.
6. Shaik SS, Schlegel HB, Wolfe S (1992) Theoretical Aspects of Physical Organic Chem-
istry: The SN2 Mechanism (Wiley, New York), pp 11–23.
7. Sutin N (1983) Theory of electron transfer reactions: Insights and hindsights. Prog
Inorg Chem 30:441–499.
8. Mayer JM (2004) Proton-coupled electron transfer. Annu Rev Phys Chem 55:363–390.
9. Waidmann CR, et al. (2009) Slow hydrogen transfer reactions of oxo- and
hydroxo-vanadium compounds: The importance of intrinsic barriers. J Am Chem
Soc 131:4729–4743.
10. Roth JP, Yoder JC, Won TJ, Mayer JM (2001) Application of the Marcus cross relation
to hydrogen atom transfer reactions. Science 294:2524–2526.
11. Mader EA, Larsen AS, Mayer JM (2004) Hydrogen atom transfer from iron(II)-Tris[2,2′-
bi(tetrahydropyrimidine)] to TEMPO: A negative enthalpy of activation predicted by
the Marcus equation. J Am Chem Soc 126:8066–8067.
12. Wu A, Mayer JM (2008) Hydrogen atom transfer reactions of a ruthenium imidazole
complex: Hydrogen tunneling and the applicability of the Marcus cross relation. J Am
Chem Soc 130:14745–14754.
13. HAT vs. proton-coupled electron transfer nomenclature is discussed in ref. 9.
14. Albery WJ (1980) The application of the Marcus cross relation to reactions in solution.
Annu Rev Phys Chem 31:227–263.
15. Lee I-SH, Jeoung EH, Kreevoy MM (1997) Marcus theory of a parallel effect on a α for
hydride transfer reaction between NADþ analogues. J Am Chem Soc 119:2722–2728.
16. Marcus RA (1997) Theory of rate of SN2 reactions and relation to those of outer
sphere bond rupture electron transfers. J Phys Chem A 101:4072–4087.
17. Litwinienko G, Ingold KU (2007) Solvent effects on the rates and mechanisms of
reaction of phenols with free radicals. Acc Chem Res 40:222–230.
18. Abraham MH, et al. (1988) A general treatment of hydrogen bond complexation
constants in tetrachloromethane. J Am Chem Soc 110:8534–8536.
19. Abraham MH, et al. (1989) Hydrogen bonding part 7. A scale of solute hydrogen-
bond acidity based on log K values for complexation in tetrachloromethane. J Chem
Soc Perk T 2:699–711.
20. Abraham MH, Grellier PL, Prior DV, Morris JJ, Taylor PJ (1990) Hydrogen bonding part
10. A scale of solute hydrogen-bond basicity using log K values for complexation in
tetrachloromethane. J Chem Soc Perk T 2:521–529.
21. Mader EA, et al. (2009) Trends in ground-state entropies for transition metal based
hydrogen atom transfer reactions. J Am Chem Soc 131:4335–4345.
22. For example, in the case for phenol, S∘f ½PhO•ꢀ − Sf∘ ½PhOHꢀ ¼ −0.8 cal mol−1 K−1. See
23. Afeefy HY, Liebman JF, Stein SE () Neutral thermochemical data. NIST Chemistry Web-
Book, NIST Standard Reference Database Number 69, ed Linstrom PJ (National Insti-
tute of Standards and Technology, Gaithersburg, MD) Available at http://webbook.
24. Roduner E (2005) Hydrophobic solvation, quantum nature, and diffusion of atomic
hydrogen in liquid water. Radiat Phys Chem 72:201–206 shows that ΔG∘solvðH2Þ is a
good approximation to ΔG∘solvðH•Þ (see SI Text)..
29. Manner VW, Markle TF, Freudenthal JH, Roth JP, Mayer JM (2008) The first crystal
structure of
a monomeric phenoxyl radical: 2,4,6-tri-tert-butylphenoxyl radical.
Chem Commun 2008:256–258.
30. Lucarini M, Pedrielli P, Pedulli GF, Cabiddu S, Fattuoni C (1996) Bond dissociation en-
ergies of O-H bonds in substituted phenols from equilibration studies. J Org Chem
61:9259–9263.
31. Wu A, et al. (2009) Nitroxyl radical plus hydroxylamine pseudo self-exchange reac-
tions: Tunneling in hydrogen atom transfer. J Am Chem Soc 131:11985–11997.
32. Prokof’ev AI, Malysheva NA, Bubnov NN, Solodovnikov SP, Kabachnik MI (1976)
Investigation of fast reactions of sterically hindered aroxyl radicals. B Acad Sci USSR
Ch+ 25:494–497.
33. Abraham MH, Abraham RJ, Byrne J, Griffiths L (2006) NMR method for the determi-
nation of solute hydrogen bond acidity. J Org Chem 71:3389–3394.
34. Abraham’s 1H NMR method in dry CDCl3 or DMSO gives ΣαH2 , which, for a solute with
only one H-bonding R-OH group, is essentially equal to αH2 (33).
35. Litwinienko G, Ingold KU (2003) Abnormal solvent effects on hydrogen atom
abstractions 1. The reactions of phenols with 2,2-diphenyl-1-picrylhydrazyl (dpph•)
in alcohols. J Org Chem 68:3433–3438.
36. Astolfi P, Greci L, Paul T, Ingold KU (2001) Revision of the αH2 value for N; N-dialkylhy-
droxylamines based on kinetic and spectroscopic measurements. J Chem Soc Perk T
2:1631–1633.
37. Gregor W, Grabner G, Adelwöhrer C, Rosenau T, Gille L (2005) Antioxidant properties
of natural and synthetic chromanol derivatives: Study by fast kinetics and electron
spin resonance spectroscopy. J Org Chem 70:3472–3483.
38. Shin-ichi N, Kuranaka A, Tsuboi H, Nagashima U, Mukai K (1992) Mechanism of
antioxidant reaction of vitamin E. Charge transfer and tunneling effect in proton
transfer reaction. J Phys Chem 96:2754–2761.
39. Brigati G, Lucarini M, Mugnaini V, Pedulli GF (2002) Determination of the substituent
effect on the O-H bond dissociation enthalpies of phenolic antioxidants by the EPR
radical equilibration technique. J Org Chem 67:4828–4832.
40. f is taken to be 1 for this calculation of kXH∕X•ðTocOHÞ. By using the derived value of
kXH∕X•ðTocOHÞ, f ¼ 0.85, indicating that taking f ¼ 1 introduces only a small error.
41. Warren JJ, Mayer JM (2008) Surprisingly long-lived ascorbyl radicals in acetonitrile:
Hydrogen atom transfer reactions and thermochemistry.
J Am Chem Soc
130:2774–2776.
42. The deviation is defined as kobs∕kcalc or kcalc∕kobs, whichever is greater than 1.
43. Snelgrove DW, Lusztyk J, Banks JT, Mulder P, Ingold KU (2001) Kinetic solvent
effects of hydrogen-atom abstractions: Reliable, quantitative predictions via a single
empirical equation. J Am Chem Soc 123:469–477.
44. Lowry TH, Richardson KS (1987) Mechanism and Theory in Organic Chemistry (Harper &
Row, New York), 3rd Ed, pp 143–159.
45. Hammes-Schiffer S, Proton-Coupled Electron Transfer: Theoretical Formulation and
Applications, ref. 3, Vol. 2, pp. 479–502.
Warren and Mayer
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