Supporting Informatio for:
Solvent Effects on the Activation Parameters of the
Reaction between an -Tocopherol Analogue and
dpph•: the Role of H-Bonded Complexes
Mario C. Foti
pKa values of phenols in various organic solvents
There exists a large body of experimental pKa values for phenols determined in
various organic solvents. These values can be related to the pKa’s determined in water
(the most commonly accessible data). The linear correlation between the pKas in DMF
and DMSO is taken from Maran, F.; Celadon, D.; Severin, M. G.; Vianello, E. J Am
Chem Soc 1991, 113, 9320 – 9329; the one between methanol and water from Rived,
F.; Rosés, M.; Bosch, E. Anal Chim Acta 1998, 374, 309 – 324 whereas the other
linear correlations among the pKas in HBA solvents were obtained from data reported
in Jover, J.; Bosque, R.; Sales J. QSAR Comb Sci 2007, 26, 385 – 397:
(a) pK aMeOH  1.08pK aH2O  3.66 , R = 0.991, (86 phenols), the largest deviation being ±
1.3;
(b) pK aDMSO  1.93pK aH2O  2.49 , R = 0.982, pK aH2O values in the range 0.43 - 10.3 (26
phenols), the largest deviation being ± 2.0;
(c) pK aDMF  0.96pK aDMSO  1.56 , R = 0.991, pK aDMSO 3 to 18, the largest deviation is
±1.8;
(d) pK aCH3CN  1.67pK aH2O  9.78 , R = 0.978, pK aH2O 0.43 – 10.3 (23 phenols), error ±
1.9.
S1
Given that the pK aH2O of ChrOH can be assumed to be similar to that of Trolox ≈11.8
(see Steenken, S.; Neta, P. J Phys Chem 1982, 86, 3661 – 3667; Drummond, C. J.;
Grieser, F. Biochim Biophys Acta 1985, 836, 275 – 278 and Davies, M. J.; Forni, L.G.;
Willson, R.L. Biochem J 1988, 255, 513 – 522) the above relationships yield: 16.4 ±
1.3 in methanol; 20.3 ± 2.0 in DMSO; 21.0 ± 2.0 in DMF; and 29.5 ± 1.9 in
acetonitrile. These estimates are in good agreement with data reported by Bordwell
and Zhang J Phys Org Chem 1995, 8, 529-535 or obtainable from Chantooni and
Kolthoff J Phys Chem 1976, 80, 1306 – 1310.
Kinetic analysis of the data reported in ref. 13
The overall rate constant koverall for reactions 5 - 9 is given by:
koverall =
k ET ,TrO  K a
[H  ]  K a

k ET ,TrOH [H  ]
[H  ]  K a


k ET ,TrO  K a
[H  ]
 k ET ,TrOH for pH << pKa
The data reported in ref. 13 show that the koverall varies linearly with 1/[H+] in the pH
range 6.4 – 8.4: koverall/M-1s-1 = 6×10-5/[H+] + 1.75×104 (R2 = 0.97). Given that the
pKa of Trolox is ca. 11.8 in water and >11.8 in water/ethanol, the rate constant kET,TrO->
6×10-5/10-11.8 ≈ 4×107 M-1s-1 whereas the value of k ET ,TrOH is 1.75×104 M-1s-1.
1/[H+]
k/M-1s-1
251188643.2
100000000
50118723.36
25118864.32
10000000
2511886.432
31200
25000
20270
18200
18000
17200
S2
Rate constant of ChrOH + dpph in water
Given that in methanol/water, ethanol/water and neat methanol the A3-factors are
essentially equal it can be assumed that even in neat water A3≈5×109 M-1s-1. By
contrast, in methanol/water the activation energy decreased by ca. 1.1 kcal/mol with
respect to the one in pure methanol. Assuming that the activation energy varies
linearly with x H 2O it can be estimated that Ea,3 ~ 7 kcal/mol in water. Therefore, the
rate constant k3 in water is calculated at 298 K to be approx. 3×104 M-1s-1.
Activation parameters in HBA solvents
The rate constant for HAT in a polar solvent S is given by,
k 3S 
k 30
k 30

1  K HB [S] K HB [S ]
(KHB[S]>>1)
where k 30 is the rate constant in an apolar solvent (the value measured in chx
k 3chx represents a good approximation); KHB the equilibrium constant for the formation
of the H-bond between ChrOH and S; [S] the concentration of the solvent.
S3
Substituting K HB  e
0
 GHB
/ RT
 e S HB / R e H HB / RT in the above eq. and using the Arrhenius
0
0
equation for k30  k 3chx  A3chx exp( Eachx
,3 / RT ) the following eq. is obtained:
k3S  ( A3chx /[ S ])e  S HB / R  e
0
0
 ( Eachx
, 3  H HB ) / RT
which has the formal aspect of the Arrhenius equation for k 3S with the pre-exponential
term
given
by
A3S  ( A3chx /[ S ])e  S HB / R and
0
the
activation
energy
equal
to
0
EaS,3  ( Eachx
,3  H HB ) .
CIPs in acetonitrile solution
Scheme S1. Thermodynamic cycle for the formation of CIPs between ChrOH (2H = 0.39) and
pyridine, Py, (2H = 0.62) in acetonitrile at 298 K. The equilibrium constant of the H-bonded
complex ChrOH•••Py, KHB, is calculated with the eq. Log KHB = 7.3542H2H - 1.094 (see
Abraham, M. H.; Grellier, P. L.; Prior, D. V.; Taft, R. W.; Morris, J. J.; Taylor, P. J.; Laurence,
C.; Berthelot, M.; Doherty, R. M.; Kamlet, M. J.; Abboud, J.-Luis M.; Sraidi, K.; Guiheneuf, G.
J Am Chem Soc 1988, 110, 8534 – 8536). The pKa's of ChrOH and pyridinium ion, PyH+, in
acetonitrile are about 29 (see above) and 12 (see Rhile, I. J.; Markle, T. F.; Nagao, H.;
DiPasquale, A. G.; Lam, O. P.; Lockwood, M. A.; Rotter, K. R.; Mayer, J. M. J Am Chem Soc
2006, 128, 6075 – 6088), respectively. The free energy of the ionic H-bonding, GIHB, in ChrO•••HPy+ is evaluated to be ≤ -10 kcal/mol (see Desiraju, G. R. Acc Chem Res 2002, 35, 565573 and Mautner, M. Chem Rev 2005, 105, 213-284).
S4