Computational and Theoretical Chemistry 969 (2011) 1–12

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Computational and Theoretical Chemistry

journal homepage: www.elsevier.com/locate/comptc

DFT/B3LYP study of the substituent effect on the reaction enthalpies

of the individual steps of single electron transfer–proton transfer and sequential
proton loss electron transfer mechanisms of chroman derivatives antioxidant action
Meysam Najafi a, Kaveh Haghighi Mood a, Mansour Zahedi a,⇑, Erik Klein b,⇑
a
Department of Chemistry, Faculty of Sciences, Shahid Beheshti University, G.C., Evin, 19839-6313 Tehran, Iran
b
Department of Physical Chemistry, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic

a r t i c l e i n f o a b s t r a c t

Article history: In this paper, the study of various ortho and meta-substituted chroman-6-ol derivatives is presented. The
Received 27 March 2011 reaction enthalpies related to the individual steps of two stepwise mechanisms of phenolic antioxidants
Received in revised form 27 April 2011 action, single electron transfer–proton transfer (SET–PT) and sequential proton loss electron transfer
Accepted 4 May 2011
(SPLET), for studied compounds have been calculated using DFT/B3LYP method in gas-phase and water.
Available online 10 May 2011
Results reveal that electron-donating substituents induce rise in the proton dissociation enthalpy (PDE)
and proton affinity (PA) whereas Electron withdrawing groups cause increase in the ionization potentials
Keywords:
(IP) electron transfer enthalpy (ETE). Result indicated substituents in ortho have in comparison with the
Antioxidant
a-Tocopherol substituents in meta position significantly greater influence on PA and ETE, on the contrary, substituents
DFT in meta position cause considerable effect on IP and PDE rather than substituents in ortho positions.
SPLET mechanism Results reveal that water attenuates the substituent effect on IP, PA and PDE values. Computed results
SET–PT mechanism indicate that all dependences of reaction enthalpies on Hammett constants of the substituents are linear.
Substituent effect From the thermodynamic point of view, SPLET mechanism represents the most promising process in
water. Furthermore, results show that calculated enthalpies can be correlated with the length of phenolic
C–O and O–H+ (bond length of O–H after electron abstraction) bonds and partial charge on the phenoxy
radical oxygen atom q(O) of the studied molecules successfully.
Ó 2011 Elsevier B.V. All rights reserved.

1. Introduction Considerable experimental and theoretical work has been devoted

In recent years, the border between chemistry and biochemistry
has become even more diffuse. The role of natural antioxidants has
lately received much attention because they can avoid or at least
significantly reduce the peroxidation of lipids by free radicals,
which are related to a variety of disorders and diseases [1]. Among
the antioxidants, vitamin E components represent the most
important lipid-soluble peroxyl radical trapping antioxidants,
retarding the oxidative degradation of lipids [1,2] being located
in the lipophilic domains of membranes and lipoproteins [3].
Abbreviations: DFT, density functional theory; ZPE, zero point energy; IP, ioni-
zation potential; PDE, proton dissociation enthalpy; PA, proton affinity; ETE, elec-
tron transfer enthalpy; SET–PT,single electron transfer followed by proton transfer;
SPLET, sequential proton loss electron transfer; HAT, hydrogen atom transfer; PCM,
polarized continuum model; EDG-substituent, electron donating group; EWG-
substituent, electron withdrawing group; ROS, reactive oxygen species.
⇑ Corresponding authors. Tel./fax: +98 2122431661 (M. Zahedi), tel.: +421
259325535; fax: +421 252493198 (E. Klein).
E-mail addresses: m-zahedi@ccsbu.ac.ir (M. Zahedi), erik.klein@stuba.sk (E.
Klein).
to the study of the activity of chain-breaking antioxidants in
biological systems [4,5]. The most biologically active component
of vitamin E, namely a-tocopherol (a-TOH, Fig. 1A) acts as an effec-
tive inhibitor of lipid peroxidation in membrane systems [6]. Vita-
min E is a scavenger active against reactive oxygen species (ROS)
such as superoxide anion radical [7], singlet molecular oxygen
[8], and hydroxyl radical [9]. The antioxidant properties of vitamin
E are based on the ability of the chromanoxyl ring to interact with
free radicals [10]. The phenolic antioxidants (ArOH) inhibit
oxidation by transferring their phenolic H atom to a chain-carrying
peroxyl radical (ROO) at a rate much faster than that of chain
propagation [11]. This yields a nonradical product (ROOH) that
cannot propagate the chain reaction
ROO þ ArOH ! ROOH þ ArO ð1Þ
It is proposed [11–13] that chain-breaking antioxidants can
play their protective role via two major mechanisms. In the first
one, H-atom transfer (HAT) mechanism, the phenolic H atom is
transferred in one step, as shown in Eq. (1). In the HAT mechanism,
the bond dissociation enthalpy (BDE) of the phenolic O–H bond is

2210-271X/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.comptc.2011.05.006
2 M. Najafi et al. / Computational and Theoretical Chemistry 969 (2011) 1–12
Fig. 1. (A) Structure of tocopherols: a-tocopherol (R1 = CH3, R2 = CH3, R3 = CH3), b-
tocopherol (R1 = CH3, R2 = H, R3 = CH3), c-tocopherol (R1 = H, R2 = CH3, R3 = CH3), d-
tocopherol (R1 = CH3, R2 = H, R3 = CH3). (B) The a-tocopherol molecule. (C) The basic
structure of vitamin E. (D) Studied molecules: X = Br, Ethyl, CH@CH2, CCH, CF3, Me,
Cl, CN, COMe, COH, COOH, F, NMe2, NHMe, NH2, NO2, OMe, OH, Ph, t-Bu.
one of the important parameters in evaluating the antioxidant ac-
tion; the lower the BDE, the easier the dissociation of the phenolic
O–H bond. The second mechanism, single electron transfer
followed by proton transfer (SET–PT), takes place in two steps
ROO þ ArOH ! ROO þ ArOHþ ð2:1Þ
ArOHþ ! ArO þ Hþ ð2:2Þ
In the first step, cation radical is formed (Eq. (2.1)). In the sec-
ond one, deprotonation of ArOH+ occurs (Eq. (2.2)), followed by
the protonation of ROO
ROO þ Hþ ! ROOH ð2:3Þ
Ionization potential (IP) and proton dissociation enthalpy (PDE)
[14,15] represent enthalpies of the SET–PT process. In the SET–PT
mechanism, the ionization potential (IP) is the most significant
parameter; the lower the IP value, the easier the electron abstrac-
tion. However, low IP values are favorable to raise the electron-
transfer reactivity, they enhance the chance of generating a
superoxide anion radical through the transfer of the electron
directly to surrounding O2 [11,16,17]. Recently, another mecha-
nism has been discovered [18–21]. This was named sequential
proton loss electron transfer (SPLET), taking place in two steps
(Eqs. (3.1) and (3.2))
ArOH ! ArO þ Hþ ð3:1Þ
ArO þ ROO ! ArO þ ROO ð3:2Þ
ROO þ Hþ ! ROOH ð3:3Þ
The reaction enthalpy of the first step (Eq. (3.1)) corresponds to
the proton affinity, PA, of the phenoxide anion (ArO) [22–24]. In
the second step (Eq. (3.2)), electron transfer from phenoxide anion
to ROO occurs and the phenoxy radical is formed. The reaction
enthalpy of this step is denoted as electron transfer enthalpy,
ETE. From the antioxidant action viewpoint, the net result of SPLET
is the same as in the two previously mentioned mechanisms, the
transfer of hydrogen atom to the free radicals. Although, reaction
enthalpies (BDE, IP, PA) related to three mechanisms are of impor-
tance in evaluating the antioxidant action, other criteria, including
solubility, bioavailability, and nontoxicity must also be considered
when designing an effective and safe antioxidant [25]. The biolog-
ical implications and the great potential of vitamin E as antioxidant
aroused our interest in elucidating its antioxidant activity by
means of DFT/B3LYP calculations, which have been successfully
used for a variety of antioxidants [26,27]. In many experimental
and theoretical studies [11,28–34], the tail of tocopherols is re-
placed by hydrogen, methyl or ethyl group because the phytyl
chain has little effect on the BDE, IP, PA of a-tocopherol. The
reactive part, i.e. the chromanol unit, was kept unchanged in all
of previous theoretical studies. Klein et al. [33] computed gas-
phase BDE of a-tocopherol with the full tail, which was then
replaced by ethyl group in the rest of calculations. The difference
between a-tocopherol and its ‘‘ethyl-analog’’ BDEs reached
2 kJ mol1. Mohajeri et al. [34] replaced phytyl chain in a-tocoph-
erol with hydrogen atom and calculated BDE and IP of this struc-
ture. Therefore, in this study, we have also used a model
structure, 3,4-dihydro-5,7,8-trimethyl-2H-chroman-6-ol molecule
(Fig. 1B). Because in chemistry one often needs to compare a group
of reactions differing only in the substitution, it is also important to
study the effect of substituents on the reaction enthalpy. Substitu-
ent effects are among the most important concepts of structural
effects influencing the chemical, physicochemical, and biochemical
properties of chemical species [35,36]. In recent years many previ-
ous experimental [22–24,37–42] and theoretical [12,22,33,43–50]
investigations have been carried out on phenol and mono-substi-
tuted phenols in gas and solvent environment. Theoretical study
of substituent effect can be utilized in the synthesis of substances
with enhanced antioxidant properties. Although previous experi-
mental [29,38,51–56] and theoretical [27,28,31,33,34,57–64]
investigations have been carried out on vitamin E and its antioxi-
dant action description, only few attempts to study the substituent
effects on antioxidant parameters have been performed so far
[65–68]. In a recent paper [69], we have investigated the effect of
various substituents such as electron-withdrawing groups (EWG)
and electron-donating groups (EDG) on O–H BDE of chroman-6-
ol (basic structure of vitamin E) in gas-phase and solvent environ-
ment. Results obtained indicate that BDEs can be successfully
correlated with Hammett constants, C–O and O–H bond lengths
and partial charge on phenoxy radical oxygen q(O) for the meta-
substituted chromans. Reported results are in accordance with
studies on substituted phenols [11,43,47,49,63,70]. In the present
paper, we investigate the effect of various substituents on reaction
enthalpies related to SPLET and SPT–ET mechanisms. In order to
achieve this goal, three methyl groups on aromatic ring of a-TOH
were replaced with hydrogen atom, and the resulting molecules
represents a basic structure of vitamin E (Fig. 1C). Various substit-
uents were located in three available positions on the aromatic
ring (Fig. 1D). Reaction enthalpies related to two above mentioned
mechanisms for all of mono substituted chromans were calculated.
 M. Najafi et al. / Computational and Theoretical Chemistry 969 (2011) 1–12
Correlations of calculated enthalpies with Hammett constants of
substituents were investigated. According to our knowledge, no
attempt to find a relationship between structural parameters and
reaction enthalpies related to SPLET and SET–PT mechanisms in
the case of chromans has been made previously. This work also
shows linear dependence between calculated enthalpies and struc-
tural parameters such as C–O bond length and O–H bond length in
radical cation, denoted as R(O–H) +, or partial charge on phenoxy
radical oxygen q(O). Because SET–PT and SPLET mechanisms are
of importance in solvated media [18–21,33,41,70], it is interesting
to explore how the solvent alters the reaction enthalpies of individ-
ual steps of the two mechanisms. To shed light on the solvent
effect, PCM (polarized continuum model) calculations have been
performed for studied molecules in water.
2. Computational details
The geometries of the molecules and respective radicals, radical
cations and anions were optimized using DFT method with B3LYP
functional [71–73] and the 6-31G (d, p) basis set [71,72] in the
gas-phase and solution phase. Single point calculations were
performed using 6-311++G (2d, 2p) basis set [74,75]. The
ground-state geometries of molecules were optimized at restricted
B3LYP level and the geometry of the radicals, radical cations,
anions were optimized at the restricted B3LYP open shell (half
electron) level. The optimized structures were confirmed to be real
minima by frequency calculation. For the species having more
conformers, all conformers were investigated. The conformer with
the lowest electronic energy was used in this work. All reported
enthalpies were zero-point (ZPE) corrected with un-scaled
frequencies. On the basis of the DFT optimized geometries, the par-
tial charges were obtained using 6-31(d, p) basis set [71,72].
Solvent contribution to the total enthalpies was computed employ-
ing PCM method [76,77]. All calculations were performed using
Gaussian 98 program package [78]. All enthalpies were calculated
for 298.15 K and 1.0 atmosphere pressure.
3. Results and discussion
Total enthalpies of the studied species X, H(X), at the tempera-
ture T are usually estimated from the expression (4) [14,42].
HðXÞ ¼ E0 þ ZPE þ DHtrans þ DHrot þ DHvib þ RT
where E0 is the calculated total electronic energy, ZPE stands for
zero-point energy, DHtrans, DHrot, and DHvib are the translational,
rotational, and vibrational contributions to the enthalpy, respec-
tively. Finally, RT represents PV-work term and is added to convert
the energy to enthalpy. From the calculated total enthalpies we
have determined following quantities:
IP ¼ HðArOHþ Þ þ Hðe Þ  HðArOHÞ
PDE ¼ HðArO Þ þ HðHþ Þ  HðArOHþ Þ
PA ¼ HðArO Þ þ HðHþ Þ  HðArOHÞ
ETE ¼ HðArO Þ þ Hðe Þ  HðArO Þ
+
The calculated gas-phase enthalpy of proton, H (H ), and elec-
tron, H (e), is 6.197 and 3.145 kJ mol1 [79], respectively.
Obtained results reveal that water causes considerable changes
of the total enthalpies of molecule, radical, anion and the radical
cation of studied compounds. Enthalpy of H+ hydration is
1090 kJ mol1 [80]. It severely affects PAs and PDEs. Since the
3
enthalpy of electron hydration, DhydrH(e), could not be found in
the literature, B3LYP/6-311++G computed electron hydration
enthalpy, DhydrH(e) = 105 kJ mol1, was employed [81].
3.1. IPs and their dependence on Hammett constants in the gas phase
and water
For structures with ortho substituents, it is necessary to
distinguish between the away and toward conformations of the
substituent. In this study, all of the away and the toward conform-
ers related to ortho-substituted structures and corresponding
cation radicals (ArOH+) have been optimized. The most stable
conformer has been used. The energy barrier of rotation between
these two conformers in non-substituted basic structure is 0.23
and 0.78 kJ mol1 for ArOH and ArOH+, respectively. For the vast
majority of examined substituted structures, the conformer with
the hydrogen pointing toward the substituent was found to be
energetically favorable. However, the most stable conformer for
the alkyls (Me, Ethyl, t-Bu) and NH2 substituent, is the away one.
In previous study, Bakalbassis et al. [12] investigated all possible
conformers for the ortho substituted phenols and respective
radical cations and reported energy differences between the to-
ward and the away conformers for ortho substituted phenols.
Results of our calculations show that energy differences between
the toward and the away conformers for same substituent in ortho
substituted chromans are in good agreement with those found for
ortho substituted phenols. The energy differences between the
toward and the away conformations for studied substituents were
in the range 4–83 kJ mol1. In the case of NO2 substitution, the OH
group forms a strong hydrogen bond to one of the nitro group oxy-
gens, increasing the energy difference to 42.2 and 45.0 kJ mol1 for
ArOH and ArOH+, respectively. For OMe substituent, the toward
conformer is the most stable because of hydrogen bond formation.
In away conformer, OMe group has to be twisted out of plane and
the non-planar conformer cannot form hydrogen bond. For the
respective anion, two planar conformers were identified while
hydrogen bond formation is not possible in the OMe substituted
anion. The lowest energy conformation has the OMe group point-
ing toward the radical O atom. The less stable one adopts the away
conformation with its energy differences from the former being
10.8 kJ mol1. In the toward isomer of NH2 substituted basic struc-
ture, the amino group has to rotate to an unfavorable out-of-plane
conformation in order to avoid H–H repulsion and to form a hydro-
ð4Þ gen bond to OH. The effects of the rotation of the amino group and
the formation of a hydrogen bond are almost canceled. Hence, the
energy difference between the away and toward isomers is only
about 1 kJ mol1 in favor of the away structures for both ArOH
and ArOH+. For the respective anion, two planar conformers were
identified. Also hydrogen bond is possible to be formed between
the phenolic oxygen atom and hydrogen atom of NH2 substituent.
The energy difference between the two conformers were negligi-
ble. In the case of NMe2 substituent, the toward isomer is favored
ð5Þ
by 17.3 and 16.0 kJ mol1 for ArOH and ArOH+, respectively. In
both isomers, the substituent rotates out of the plane due to repul-
ð6Þ sion between one of methyl groups and the phenolic oxygen.
Hydrogen bond in the toward structure can be formed between
ð7Þ the nonbonding electron pair of N atom and OH group, while for
away isomer this is impossible. Also, the toward isomer is more
stable than the away isomer in NHMe substituent case by about
ð8Þ
14.8 and 10 kJ mol1 for ArOH and ArOH+, respectively. For the
respective anion, Hydrogen bond in the toward structure can be
formed between the phenolic oxygen atom and hydrogen atom
of NHMe substituent, while for away isomer this is impossible.
The energy difference between the away and toward isomers is
about 26.5 kJ mol1 in favor of the toward structures. In the toward
isomer of halogen and CF3 substituted basic structures, the
4 M. Najafi et al. / Computational and Theoretical Chemistry 969 (2011) 1–12

nonbonding electron pair of halogen group forms hydrogen bond Table 1

with OH group. Hence, the energy difference between the away Calculated IPs and DIPs in (kJ mol1) of ortho1, ortho2 and meta-substituted
molecules in gas-phase, and Hammett constants of substituents rm [36].
and toward isomers is 15.5 and 17.0 kJ mol1 for ArOH and ArOH+,
respectively, in favor of the toward structure. All of the possible Substituent Ortho1 Ortho2 Meta rm
conformations for ArOH and the respective radical related to ortho IP DIP IP DIP IP DIP
substituted structures with COOH and OH groups have been inves- NMe2 648.2 54.4 646.1 56.5 630.3 72.3 0.24
tigated elsewhere [69]. In this study, for COOH and OH groups, all NHMe 648.3 54.3 646.4 56.2 633.4 69.2 0.24
of the possible conformations for ArOH+ and ArO anion have been NH2 655.4 47.2 653.2 49.4 649.3 53.4 0.16
investigated (Fig. 1s). It has been found that the difference between t-Bu 674.7 27.9 681.5 21.1 679.8 22.8 0.10
Ethyl 686.4 16.2 685.8 16.8 685.3 17.3 0.07
the most stable and the least stable isomers for COOH in ArOH and
Me 689.5 13.1 687.3 15.3 686.8 15.8 0.07
ArOH+ species is 49.7 and 82.8 kJ mol1 respectively. For the Ph 679.0 23.6 676.9 25.7 678.7 24.0 0.06
respective anion, hydrogen bond in the toward structure can be CH@CH2 690.0 12.7 691.4 11.2 687.0 15.6 0.06
formed between the phenolic oxygen atom and hydrogen atom OH 687.4 15.1 685.3 17.3 686.7 15.9 0.12
OMe 691.2 11.4 687.1 15.5 670.7 32.0 0.12
of COOH substituent, while for away isomer this is not possible.
CCH 705.9 3.3 705.1 2.5 697.3 5.3 0.21
The energy difference between the most stable and the least stable F 720.7 18.1 720.7 18.1 720.0 17.4 0.34
isomers for COOH is about 92.9 kJ mol1. Our calculations also COH 758.8 56.2 759.3 56.7 730.5 27.9 0.35
show that difference between the most stable and the least stable COOH 715.3 12.7 717.5 14.9 720.3 17.7 0.37
isomers for OH substituent in ArOH and ArOH+ species is 17.1 and Cl 718.9 16.3 718.6 16.0 716.2 13.6 0.37
COMe 710.3 7.7 713.3 10.7 714.6 11.9 0.38
15.6 kJ mol1 respectively. For the respective anion, Hydrogen
Br 716.7 14.1 716.3 13.7 714.8 12.2 0.39
bond in the toward structure can be formed between the phenolic CF3 736.0 33.3 739.0 36.4 738.3 35.7 0.43
oxygen atom and hydrogen atom of OH substituent, while for away CN 753.6 51.0 754.5 51.9 752.5 49.9 0.56
isomer this is impossible. The energy difference between the away NO2 760.4 57.8 761.0 58.4 760.0 57.4 0.71
and toward isomers is about 69.9 kJ mol1 in favor of the toward
structures. For COH group, the nonbonding electron pair of oxygen
forms hydrogen bond with OH group, therefore toward isomers are
in IPs (negative DIPs) of EDG-substituted basic structures is the
more stable than away isomers by 50.2 and 40 kJ mol1 for ArOH
combined result of the cation radical stabilization and the parent
and ArOH+, respectively. For the respective anion, Hydrogen bond
molecules destabilization. However, the increased IPs (positive
in the toward structure can be formed between the phenolic oxy-
DIPs) of EWG-substituted basic structures may stem from the
gen atom and hydrogen atom of COH substituent, while for away
combination of both the parents and the cation radical destabiliza-
isomer this is not possible. The energy difference between the
tion. These results are in accordance with data published for
away and toward isomers is about 27.1 kJ mol1 in favor of the to-
substituent phenols [41,47,82–85].
ward structures. Our result show that these differences for COMe
Klein et al. [33] estimated lower limit of IP of 267 kJ mol1 for
group are 42.4 and 35.0 kJ mol1 for ArOH and ArOH+, more stable
a-tocopherol model with ethyl group in place of phytyl tail and
are away isomers. For CCH, CN, Ph and CH@CH2 substituents, the
272 kJ mol1 for a-tocopherol model structure without tail in
toward isomers were more stable than the away isomers. This pa-
water. The present calculated lower limit of IP for the basic struc-
per represents the first theoretical systematic study of substituted
ture reached 298.0 kJ mol1 in water. The computed IPs using
chromans IPs. In previous studies [41,47] the substituent effect on
above mentioned calculated DhydrH(e) value [81] in the water
IPs of para and meta substituted phenols have been investigated in
for molecules substituted in meta, ortho1 and ortho 2 position
gas-phase employing B3LYP approach. Chandra et al. [82] calcu-
are reported in Table 2. These are higher than corresponding lower
lated IP values for substituted pyridinethiols in gas-phase. Mohaj-
limits by 131 kJ mol1. Table 2 summarizes DIP values, too. Water
eri et al. [34] and Chen et al. [31] calculated IP of chroman-6-ol and
causes considerable changes in the enthalpies of molecule and
obtained 675 and 700 kJ mol1, respectively. Zhang et al. [83]
found IP value of 650 kJ mol1 for chroman-6-ol using combination
of DFT and semi empirical AM1 methods. Klein et al. [33] calcu-
Table 2
lated gas-phase IP value of 650 kJ mol1 for a-tocopherol model Calculated IPs and DIPs in (kJ mol1) of ortho1, ortho2 and meta-substituted
with ethyl group in place of phytyl tail and 663 kJ mol1 for model molecules in water.
structure without the tail. In this paper, the calculated IP for the
Substituent Ortho1 Ortho2 Meta
basic structure (Fig. 1C) in gas-phase reached 702.6 kJ mol1. This
IP DIP IP DIP IP DIP
value is higher than above mentioned ones, because our basic
structure does not contain three methyl groups which decrease NMe2 381.0 48.0 378.5 50.5 374.9 54.1
NHMe 384.3 44.7 377.3 51.7 373.7 55.3
IP [41,47]. The computed gas-phase IPs for substituents in ortho
NH2 389.0 40.0 385.3 43.7 384.0 45.0
and meta positions are reported in Table 1. Relative IP values, DI- tBu 416.5 12.5 418.1 10.9 417.2 11.8
P = IP(X–ArOH)  IP(ArOH), i.e. the difference between substituted Ethyl 420.1 8.9 419.6 9.4 419.2 9.8
and non-substituted molecule IPs, are also summarized in the Me 420.8 8.2 419.2 9.8 418.6 10.4
Table 1. In the two ortho and meta positions, highest IP values Ph 425.5 3.5 425.1 3.9 426.2 2.7
CH@CH2 422.7 6.3 423.5 5.5 425.5 3.5
were found for strong EWG substituents (NO2, CF3 and CN); lowest
OH 418.2 10.8 417.1 11.9 417.1 11.9
IPs was obtained for strong EDG substituents (NMe2, NH2, and OMe 423.1 5.9 419.4 9.6 409.5 19.4
NHMe). For halogens in ortho positions, the IP values are by CCH 440.3 11.3 440.9 11.9 440.0 11.0
12.0–17.5 kJ mol1 higher in comparison to the basic structure. F 443.7 14.7 443.0 14.0 442.3 13.3
The difference between the highest and lowest IP values for ortho1, COH 451.2 22.2 453.7 24.7 454.3 25.3
COOH 444.0 15.0 449.7 20.7 451.7 22.7
ortho2 and meta positions were 112.2, 114.9 and 129.7 kJ mol1, Cl 444.6 15.6 444.8 15.8 444.0 15.0
respectively in the gas phase. As a known fact in organic chemistry, COMe 441.7 12.7 444.1 15.1 443.7 14.7
the EWG substituents stabilize the parent molecule and destabilize Br 444.1 15.1 444.6 15.6 444.1 15.1
the radical and radical cation. It results in the increase in IP. How- CF3 456.2 27.2 460.1 31.1 455.5 26.5
CN 466.7 37.7 468.0 39.0 467.4 38.4
ever, EDG substituents have an opposite effect. Therefore, their
NO2 472.0 43.0 474.3 45.3 476.6 47.6
presence in the molecule leads to a decrease in IP. The decrease
 M. Najafi et al. / Computational and Theoretical Chemistry 969 (2011) 1–12 5

IP (kJ mol-1)

Fig. 2. Dependence of IP on rm for meta-substituted molecules in gas-phase (open triangles, bottom x-axis, left y-axis) and water (open squares, top x-axis, right y-axis).

cation radical of studied structures. Calculated IP related to basic
structure in water is lower than that in gas-phase by 273 kJ mol1.
Mainly, due to the negative enthalpy of electron hydration in
water, IP is significantly lower than that in gas-phase. In water,
EDG substituents decrease IP values, whereas EWG ones increase
IP values as it was found for the gas-phase. The difference between
the highest and lowest IP values for ortho1, ortho2 and meta
positions were 91, 95.8 and 102.9 kJ mol1, respectively in the
water. In water, substituent induced changes are lower than those
observed in the gas-phase. Attenuation of substituent effect
(decrease in DIP) reached ca 15 kJ mol1.
The Hammett equation (and its extended forms) has been one
of the most widely used means for the study and interpretation
of organic reactions and their mechanisms. Hammett constants
rm (for substituent in meta position) and rp (for substituent in
para position) obtained from the ionization of organic acids in
solutions can frequently successfully predict equilibrium and rate
constants for a variety of families of reactions [36]. Recently, the
review article on Hammett constants and other used descriptors
of the substituent effects was published [35]. Klein et al. [41] con-
firmed that there are linear relations between IPs of substituted
phenols and Hammett constants rp and rm in gas-phase. Here,
the IP values computed for the meta substituted basic structures
in gas-phase and water are plotted against Hammett constants in
Fig. 2. The correlation coefficients in gas-phase and water reached
0.95 and 0.94, respectively. Equations obtained from the linear
3.2. PDEs and their dependence on Hammett constants in the gas
phase and water
PDE represents the reaction enthalpy of the second step in SET–
PT mechanism (Eq. (2.2)). For the whole SET–PT mechanism
energetics knowledge, it is also important to study PDE and the
effect of substituents on it. PDEs of substituted chromans have
not been systematically studied previously. In papers [12,15,41]
the substituent effect on PDEs of para and meta substituted phe-
nols have been investigated by DFT using B3LYP function in
gas-phase. Klein et al. [33] calculated a PDE value of 970 kJ mol1
for a-tocopherol model with ethyl group in place of phytyl tail
and of 959 kJ mol1 for a-tocopherol model without the tail in
gas-phase. In this study, the calculated PDE for the basic structure
(chroman-6-ol) in gas-phase reached 948.1 kJ mol1. The
computed PDE and DPDE values for the various substituents in
ortho and meta positions in gas-phase are reported in Table 3.
Highest PDE values for ortho and meta positions were found in
the case of strong EDG substituents (NMe2, NH2, NHMe), the lowest
PDEs were found for strong EWG substituents (NO2, CF3, CN). For
halogens in ortho and meta positions, PDE values are about 5–13
Table 3
Calculated PDEs and DPDEs in (kJ mol1) of ortho1, ortho2 and meta-substituted
molecules in gasphase.

regression are as follows: Substituent Ortho1 Ortho2 Meta

PDE DPDE PDE DPDE PDE DPDE
1
IP ðkJ mol Þ ¼ 125:5  rm þ 675:4 ðgasÞ ð9Þ NMe2 979.8 31.7 982.5 34.4 1016.3 68.2
1
NHMe 971.2 23.1 972.6 24.6 1014.3 66.2
IP ðkJ mol Þ ¼ 97:5  rm þ 410:6 ðwaterÞ ð10Þ NH2 971.0 22.9 970.1 22.0 1006.9 58.8
t-Bu 956.1 8.0 957.2 9.1 970.1 22.0
We can conclude that DFT method describes the expected linear Ethyl 955.6 7.5 956.4 8.3 965.0 16.9
IP vs. Hammett constant dependence satisfactorily. If we compare Me 952.6 4.5 954.9 6.8 962.8 14.7
BDEs [69] and IPs for meta substituted chromans in the gas-phase Ph 964.8 16.7 961.7 13.7 963.7 15.6
CH@CH2 949.9 1.8 950.5 2.4 965.3 17.2
and water, we can see that both dependences are analogous.
OH 956.7 8.7 958.9 10.8 962.4 14.3
Electron donors cause considerable drop in the two quantities. OMe 953.2 5.1 955.9 7.8 966.4 18.3
Electron-withdrawing groups raise BDEs and IP values. The IP/ CCH 954.1 6.0 956.4 8.3 953.5 5.4
BDE ratios for both meta and ortho positions are in 1.93–2.38 F 934.5 13.5 935.3 12.8 933.7 14.4
and 1.21–1.47 ranges in the gas-phase and water, respectively. COH 930.6 17.5 935.8 12.3 928.7 19.4
COOH 939.5 8.6 940.0 8.1 935.9 12.2
IP/BDE ratio is increasing with the raise in Hammett constant. Cl 939.5 8.6 940.7 7.4 938.0 10.1
The trend can be considered linear – the correlation coefficients COMe 941.4 6.7 940.4 7.7 940.4 7.7
of these dependence reached 0.93 (gas-phase) and 0.9 (water). Br 942.1 6.0 943.5 4.6 939.5 8.6
However, due to lower O–H BDEs, hydrogen atom transfer mecha- CF3 929.6 18.5 928.1 20.0 919.3 28.8
CN 910.0 38.1 910.9 37.1 908.7 39.4
nism is thermodynamically favorable in the two studied
NO2 909.0 39.1 908.6 39.5 903.0 45.1
environments.
6 M. Najafi et al. / Computational and Theoretical Chemistry 969 (2011) 1–12

Table 4 significantly lower in comparison to gas-phase. In the two studied

Calculated PDEs and DPDEs in (kJ mol1) of ortho1, ortho2 and meta-substituted environments, EWG substituents decrease PDEs, whereas EDG
molecules in water.
ones increase PDEs. The difference between the highest and lowest
Substituent Ortho1 Ortho2 Meta PDE values for ortho1, ortho2 and meta substituents were 53.2,
PDE DPDE PDE DPDE PDE DPDE 55.2 and 84.2 kJ mol1, respectively in the water. In water, DPDEs
NMe2 106.4 22.9 107.5 23.9 130.2 46.6
are lower in comparison to those for gas-phase. Attenuation of sub-
NHMe 100.7 17.2 103.1 19.6 133.4 49.8 stituent induced changes in PDE can reach ca 20 kJ mol1. Obtained
NH2 97.2 13.6 98.7 15.1 121.4 37.8 results are in accordance with the study on substituted phenols
t-Bu 87.0 3.4 87.2 3.6 92.5 9.1 [41].
Ethyl 86.4 2.9 87.3 3.8 85.8 9.6
In previous studies [12,15,41], computed results confirmed that
Me 85.4 1.9 87.3 3.7 86.2 12.6
Ph 88.4 4.8 86.5 2.9 83.7 6.1 there is a linear dependence between gas-phase PDEs of substi-
CH@CH2 80.7 2.8 82.6 1.0 84.4 6.9 tuted phenols and Hammett constants rp and rm. Here, PDEs
OH 93.7 10.1 94.4 11.1 88.2 9.6 computed for the meta substituted basic structures in gas-phase
OMe 89.6 6.0 91.0 7.4 92.7 14.4
and water are plotted against Hammett constants in Fig. 3. The
CCH 75.5 8.0 75.4 8.1 80.1 3.5
F 67.7 15.8 68.0 15.6 70.5 9.5
correlation coefficients in gas-phase and water reached 0.94 and
COH 90.7 7.1 88.3 4.8 70.3 13.3 0.92, respectively. Equations obtained from the linear regressions
COOH 71.1 12.5 71.6 12.0 69.7 13.9 are as follows
Cl 70.1 13.5 69.6 14.0 72.6 19.1
1
COMe 79.2 4.3 78.1 5.5 71.3 17.3 PDE ðkJ mol Þ ¼ 109:8  rm þ 975 ðgasÞ ð11Þ
Br 71.1 12.4 70.3 13.2 71.4 19.2 1
CF3 62.7 20.9 61.2 22.3 55.7 27.9 PDE ðkJ mol Þ ¼ 72:1  rm þ 99:6 ðwaterÞ ð12Þ
CN 53.3 30.3 52.3 31.3 52.1 35.6
NO2 60.6 22.9 58.5 25.0 53.1 37.5
In all three mechanisms (HAT, SET–PT, and SPLET) the overall
result is the same (ArOH ? ArO + H), therefore the sum of slopes
of IP = f(rm) and PDE = f(rm) dependences should correspond to
and 8–14 kJ mol1, respectively lower in comparison to the basic the line slopes found for BDE = f(rm) dependence, as it was found
structure. The difference between the highest and lowest PDE for para- and meta-substituted phenols [41]. Linear dependences
values for ortho1, ortho2 and meta substituents were 70.8, 73.9 of BDEs on Hammett constants for studied molecules are as follows
and 113.3 kJ mol1, respectively in the gas phase. Electron-donat- [69]
ing substituents increase PDEs, whereas electron-withdrawing 1
BDE ðkJ mol Þ ¼ 15:7  rm þ 329:8 ðgasÞ ð13Þ
groups decrease PDEs. It is known that a charged species are more 1
sensitive to the effect of substituents than their neutral counter- BDE ðkJ mol Þ ¼ 25:4  rm þ 312:7 ðwaterÞ ð14Þ
parts. Electron donating groups stabilize ArOH+ but destabilize
the parent phenol, while electron-withdrawing groups have an Sums of line slope from Eqs. (9) and (11) and from Eqs. (10) and
opposite effect [15,39,84,85]. These results agree with previous pa- (12) actually reached values of 15.7 and 25.4 (as in Eqs. (13) and
pers on substituted phenols [12,15,41]. (14)), respectively. Although the line slopes of IP = f(rm) and
Klein et al. [33] calculated PDE value of 26 kJ mol1 for a- PDE = f(rm) dependences are significantly steeper in gas-phase,
tocopherol model with ethyl group in place of phytyl tail and the overall effect is inverse, i.e., the line slope of BDE = f(rm) is
25 kJ mol1 for a-tocopherol model without tail in water. For the steeped in water. As it can be supposed from the linearity of found
basic structure, we have calculated PDE = 83.6 kJ mol1 in water. IP = f(rm) and PDE = f(rm) dependences, PDE = f(IP) dependence
The computed PDEs and DPDEs in the water for molecules substi- (Fig. 4) should be linear, too. In the two environments, the linearity
tuted in meta, ortho1 and ortho 2 position are reported in Table 4. of this dependence is even better than linearity of IP = f(rm) and
Water causes considerable changes in the enthalpies of radical and PDE = f(rm) dependences, correlation coefficient reached 0.98
cation radical of studied structures. PDE of the basic structure in (gas-phase) and 0.99 (water). Equations obtained from the linear
water is lower than gas-phase value by 864.5 kJ mol1. Mainly, regressions are as follows
due to the large enthalpy of proton hydration in water, PDEs are
PDE (kJ mol-1)

Fig. 3. Dependence of PDE on rm for meta-substituted molecules in gas-phase (open triangles, bottom x-axis, left y-axis) and water (open squares, top x-axis, right y-axis).
 M. Najafi et al. / Computational and Theoretical Chemistry 969 (2011) 1–12 7

PDE (kJ mol-1)

IP (kJ mol-1)
Fig. 4. Dependence of PDE on IP for meta-substituted molecules in gas-phase (open triangles, bottom x-axis, left y-axis) and water (open squares, top x-axis, right y-axis).

Table 5 Table 6
Calculated PAs and DPAs in (kJ mol1) of ortho1, ortho2 and meta-substituted Calculated PAs and DPAs in (kJ mol1) of ortho1, ortho2 and meta-substituted
molecules in gas-phase. molecules in water.

Substituent Ortho1 Ortho2 Meta Substituent Ortho1 Ortho2 Meta

PA DPA PA DPA PA DPA PA DPA PA DPA PA DPA
NMe2 1479.8 14.5 1480.2 14.9 1470.7 5.4 NMe2 233.3 10.5 233.4 10.6 227.0 4.3
NHMe 1480.6 15.3 1477.5 12.2 1469.8 4.5 NHMe 234.6 11.8 235.1 12.3 227.3 4.6
NH2 1476.1 10.8 1479.4 14.1 1470.1 4.8 NH2 232.5 9.7 231.4 8.6 227.8 5.1
t-Bu 1468.0 2.7 1471.1 5.8 1467.8 2.5 t-Bu 231.1 8.3 230.3 7.5 226.0 3.2
Ethyl 1468.7 3.5 1471.7 6.4 1467.4 2.1 Ethyl 228.8 6.0 229 6.3 225.8 3.0
Me 1467.2 1.9 1468.1 2.8 1466.3 1.0 Me 228.1 5.3 226.6 3.8 225.6 2.8
Ph 1467.9 2.6 1469.1 3.8 1456.7 8.6 Ph 228.3 5.5 225.7 2.9 224.8 2.1
CH@CH2 1468.5 3.2 1468.3 3.0 1457.6 7.7 CH@CH2 225.2 2.4 225.2 2.4 222.2 0.6
OH 1474.5 9.2 1473.9 8.6 1465.8 0.5 OH 229.2 6.4 229.3 6.5 221.2 1.5
OMe 1468.9 3.6 1469.8 4.5 1466.5 1.2 OMe 226.1 3.3 227.1 4.4 224.1 1.3
CCH 1470.0 4.7 1468.8 3.4 1450.7 14.6 CCH 225.3 2.5 225.6 2.8 223.7 1.1
F 1455.8 9.5 1453.8 11.6 1450.7 14.6 F 210.6 12.1 209.3 13.4 211.5 11.3
COH 1429.0 36.3 1427.6 37.7 1435.2 30.1 COH 212.5 10.2 210.5 12.2 209.0 13.8
COOH 1417.4 47.9 1417.7 47.7 1437.6 27.7 COOH 204.6 18.2 206.4 16.4 212.6 10.1
Cl 1446.8 18.5 1445.8 19.5 1443.4 21.9 Cl 208.3 14.5 207.0 15.8 210.1 12.6
COMe 1426.9 38.5 1429.3 36.0 1438.2 27.1 COMe 207.2 15.6 208.2 14.5 214.2 8.6
Br 1442.5 22.8 1441.5 23.8 1440.2 25.1 Br 207.5 15.3 206.2 16.5 211.5 11.2
CF3 1415.9 49.4 1417.7 47.7 1427.6 37.7 CF3 192.7 30.1 193.6 29.2 206.8 15.9
CN 1405.6 59.7 1407.2 58.1 1417.4 47.9 CN 179.2 43.6 180.9 41.8 203.6 19.1
NO2 1402.9 62.4 1405.2 65.1 1420.7 44.6 NO2 182.3 40.5 184.2 38.5 200.8 21.9

1 for a-tocopherol model without tail. Calculated gas-phase PA for

PDE ðkJ mol Þ ¼ 0:88 IP þ 1564 ðgasÞ
1
PDE ðkJ mol Þ ¼ 0:76 IP þ 407:8 ðwaterÞ
Obtained equations may be used to predict PDEs for meta
substituted basic structures from their IPs in the gas phase and
water.
3.3. PAs and their dependence on Hammett constants in the gas phase
and water
PA represents the reaction enthalpy of the first step in SPLET
mechanism (Eq. (3.1)). PAs of substituted chromans have not been
obtained by theoretical calculations previously. In previous studies
[22–24,41,42] the substituent effect on PAs of para and meta
substituted phenols have been investigated by DFT using B3LYP
functional in gas-phase. Chandra et al. [82] calculated PA values
for substituted pyridinethiols in gas-phase, too. Klein et al. [33]
calculated gas-phase PA value of 1456 kJ mol1 for a-tocopherol
model with ethyl group in place of phytyl tail and 1455 kJ mol1
ð15Þ
the basic structure (chroman-6-ol) reached 1465.3 kJ mol1. The
ð16Þ
computed PA and DPA values for the various substituents in ortho
and meta positions in gas-phase are reported in Table 5. The
highest values of PA for ortho and meta positions were found for
NMe2, NH2, and NHMe groups and The lowest PA values were
found in the case of NO2, CF3 and CN groups. The difference
between the highest and lowest PA values for ortho1, ortho2 and
meta substituents were 77.7, 80 and 53.3 kJ mol1, respectively
in the gas phase. In agreement with previous studies on
substituted phenols [22–24,42], it can be concluded that EDG
substituents increase PA, whereas EWG ones decrease PA. It is
known that a charged molecule is more sensitive to the effect of
substituent than its neutral counterpart. EWG substituents stabi-
lize ArO but destabilize the parent phenol. Electron donating
groups have an opposite effect [15,39,84,85].
Klein et al. [33] calculated PA value 171 kJ mol1 for a-tocoph-
erol model with ethyl group in place of phytyl tail and 164 kJ mol1
for a-tocopherol model without tail in water. The present calcu-
lated PA for the basic structure reached 53.3 kJ mol1 in water.
8 M. Najafi et al. / Computational and Theoretical Chemistry 969 (2011) 1–12

PA (kJ mol-1)

Fig. 5. Dependence of PA on rm for meta-substituted molecules in gas-phase (open triangles, bottom x-axis, left y-axis) and water (open squares, top x-axis, right y-axis).

For molecules substituted in meta, ortho1 and ortho2 positions,
computed PAs and DPAs in the water are reported in Table 6.
Water causes considerable changes in the enthalpies of anions.
Calculated PA for basic structure in water is lower than gas-phase
value by 1425.5 kJ mol1. Mainly, due to the large negative enthal-
py of H+ hydration, PAs in the water are significantly lower than
gas-phase values. Again, EWG substituents decrease PAs, whereas
EDG groups increase PAs in agreement with results for substituted
phenols in water [70]. The difference between the highest and
lowest PA values for ortho1, ortho2 and meta substituents were
27, 55.4 and 54.1 kJ mol1, respectively in the water. Water atten-
uates substituent induced changes. For strong EDG substituents
(NH2, NMe2 and NHMe) in all positions, DPAs are lower by ca
1–6 kJ mol1 in comparison to gas-phase. For strong EWG substit-
uents (NO2 and CN) drops in DPA values are in 20–26 kJ mol1
range.
Klein et al. [41,70] found a linear dependence between PAs of
substituted phenols and Hammett constants in gas-phase and
water. There is a linear relation between PAs substituted pyridin-
ethiols with Hammett constants [82], too. For the meta substituted
basic structures in gas-phase and water, computed PAs are plotted
against Hammett constants in Fig. 5. The correlation coefficients in
gas-phase and water reached 0.94 and 0.95, respectively. Equations
obtained from the linear regression are as follows
3.4. ETEs and their dependence on Hammett constants in the gas phase
and water
For substituted chromans, ETEs (reaction enthalpies of the
second step in SPLET, Eq. (3.2)) were not studied previously. Klein
et al. [33,41] investigated the substituent effect on gas-phase ETEs
of para substituted phenols, tocopherols and several chromans
using DFT/B3LYP method. They obtained ETE value of 163 kJ mol1
for a-tocopherol model with ethyl group in place of phytyl tail and
167 kJ mol1 for a-tocopherol model without the tail. In this paper,
calculated gas-phase ETE for the basic structure (chroman-6-ol)
reached 185.4 kJ mol1. The computed gas-phase ETEs and DETE
for the various substituents in ortho1, ortho2 and meta positions
are reported in Table 7. Highest ETEs were always found for strong
EWG substituents (NO2, CF3 and CN). Lowest ETEs were found in
the case of strong EDG substituents (NMe2, NH2, NHMe). The
differences between the highest and lowest ETE values for ortho1,
ortho2 and meta positions reached 85.8, 87.8 and 53.7 kJ mol1,
respectively. Found trends are in accordance with results for
substituted phenols [41]. It is known that a charged molecule is
Table 7
Calculated ETEs and DETEs in (kJ mol1) of ortho1, ortho2 and meta-substituted
molecules in gas-phase.

1 Substituent Ortho1 Ortho2 Meta

PA ðkJ mol Þ ¼ 63:3  rm þ 1459:2 ðgasÞ ð17Þ
1
ETE DETE ETE DETE ETE DETE
PA ðkJ mol Þ ¼ 32:2  rm þ 223:1 ðwaterÞ ð18Þ
NMe2 163.1 22.2 161.2 24.2 179.9 5.5
NHMe 159.5 25.9 158.9 26.5 178.8 6.6
These results show good linearity of found PA = f(rm) depen-
NH2 157.8 27.5 158.0 27.4 175.0 10.4
dences. From the comparison of BDEs [69] and PAs for meta t-Bu 182.5 2.8 181.6 3.7 183.4 2.0
substituted chromans it is clear that these quantities follow oppo- Ethyl 182.1 3.2 183.2 2.1 183.0 2.4
site trends. Although electron-donating groups lowered BDEs, they Me 178.7 6.7 179.7 5.7 183.3 2.1
cause slight increase in the proton affinities. Electron-withdrawing Ph 199.0 13.7 201.1 15.7 199.7 14.3
CH@CH2 201.7 16.4 201.6 16.2 198.6 13.2
substituents lower PAs and raise BDEs. The PA/BDE ratios for both
OH 170.1 15.3 168.9 16.5 188.3 3.0
meta and ortho positions are in 3.8–5.1 and 0.45–0.81 range in OMe 174.5 10.9 173.1 12.3 180.6 4.8
gas-phase and water, respectively. PA/BDE ratio decreases with CCH 213.4 28.0 213.6 28.3 209.1 23.8
the increase in Hammett constant. The trend can be considered F 199.5 14.1 202.2 16.8 208.0 22.6
linear because the correlation coefficients of PA = f(BDE) depen- COH 225.3 40.0 223.4 38.0 219.0 33.7
COOH 225.3 40.0 227.9 42.5 218.6 33.2
dences reached 0.93 and 0.96 in gas-phase and water, respectively. Cl 211.6 26.2 213.5 28.2 215.8 30.4
Therefore, we can expect that molecules with strong electron- COMe 221.0 35.7 217.9 32.5 216.7 31.4
withdrawing groups will have a higher tendency to enter the SPLET Br 216.2 30.9 218.2 32.9 219.0 33.7
mechanism. Computed results also indicate that SPLET mechanism CF3 239.7 54.3 239.4 54.1 229.9 44.5
CN 258.0 72.6 258.2 72.8 246.8 61.4
should be thermodynamically favored in water, because PA values
NO2 263.4 78.0 260.6 75.1 252.2 66.9
in water are lower than IPs and BDEs of studied molecules.
 M. Najafi et al. / Computational and Theoretical Chemistry 969 (2011) 1–12 9

Table 8 for strong EDG substituents (NH2, NMe2 and NHMe) DETEs grow.
Calculated ETEs and DETEs in (kJ mol1) of ortho1, ortho2 and meta-substituted We can conclude that in comparison to gas-phase, the effect of
molecules in water.
EDG substituents in terms of DETE is increased, while the effect
Substituent Ortho1 Ortho2 Meta of EWG substituents is attenuated in water.
ETE DETE ETE DETE ETE DETE Klein et al. [41] showed a linear dependence between gas-phase
NMe2 261.6 28.2 258.6 31.2 278.1 11.7
ETEs of substituted phenols and Hammett constants. In Fig. 6, ETE
NHMe 259.0 30.8 257.9 31.9 279.7 10.1 values computed for the meta substituted basic structures are plot-
NH2 257.1 32.7 257.8 32.0 277.2 12.6 ted against Hammett constants. The correlation coefficients for
t-Bu 272.6 17.2 275.0 14.8 281.7 8.1 gas-phase and water reached 0.94 and 0.96, respectively. Equations
Ethyl 277.7 12.1 277.9 11.9 283.5 6.2
obtained from the linear regression are as follows:
Me 278.1 11.6 279.9 9.9 283.2 6.6
Ph 284.6 5.2 287.8 2.0 291.1 1.3 1
CH@CH2 291.0 1.2 292.7 2.9 293.7 3.9 ETE ðkJ mol Þ ¼ 78:9  rm þ 191:2 ðgasÞ ð19Þ
OH 266.3 23.5 268.3 20.5 289.0 0.8 1
OMe 274.5 15.3 272.3 17.5 283.5 6.3
ETE ðkJ mol Þ ¼ 57:7  rm þ 287:3 ðwaterÞ ð20Þ
CCH 307.5 17.8 308.3 18.5 305.4 15.6
Because in all three possible mechanisms (HAT, SET–PT, and
F 304.8 15.0 305.7 15.9 304.9 15.1
COH 319.3 29.5 321.5 31.7 315.6 25.9 SPLET) the overall result is the same (ArOH ? ArO + H), the sum
COOH 321.5 31.7 324.4 34.6 310.8 21.0 of line slopes of PA = f(rm) and ETE = f(rm) dependences should
Cl 306.4 16.6 307.4 17.6 308.4 18.7 correspond to the line slopes found for BDE = f(rm) dependence,
COMe 311.4 21.6 317.9 28.1 305.7 16.0
Eqs. (13) (gas-phase) and 14 (water) [69] as it was previously
Br 307.8 18.0 308.7 18.9 308.9 19.1
CF3 309.2 33.4 313.7 37.9 318.3 28.6
showed for phenols in gas-phase [41]. Sums of line slope for
CN 335.8 46.0 335.4 45.6 324.8 35.0 meta-substituted chromans, Eqs. (17) and (19) for gas-phase, and
NO2 342.9 53.1 345.6 55.8 330.9 41.1 Eqs. (18) and (20) for water, reached values of 15.6 and 25.5 in
accordance with the line slopes in Eqs. (13) and (14), respectively.
As it can be supposed from the linearity of PA = f(rm) and
more sensitive to the effect of substituent than its radical counter- ETE = f(rm) dependences, ETE = f(PA) dependence should be linear,
part. Electron withdrawing groups are favorable to stabilize ArO. too. The ETEs computed for the meta substituted basic structures
Electron donating groups have an opposite effect. Therefore, elec- are plotted against PAs in gas-phase and water in Fig. 7. The corre-
tron withdrawing groups increase ETE values, while electron lation coefficients reached 0.99 and 0.97, respectively. Eq. (21) for
donating groups decrease ETEs [15,39,84,85]. gas-phase and 22 for water are as follows:
Klein et al. [33] estimated lower limit of ETE value of 1
122 kJ mol1 for a-tocopherol model with ethyl group in place of ETE ðkJ mol Þ ¼ 1:25PA þ 2015:0 ðgasÞ ð21Þ
1
phytyl tail and 133 kJ mol1 for a-tocopherol model without the ETE ðkJ mol Þ ¼ 1:75PA þ 678:5 ðwaterÞ ð22Þ
tail in water. For the basic structure, lower limit of ETE reached
158.8 kJ mol1 in water. The computed ETEs and DETEs in the The linearity of ETE = f(PA) dependences is even better than that
water for molecules substituted in meta, ortho1 and ortho 2 posi- of PA = f(rm) and ETE = f(rm) dependences. Found equations may
tions are reported in Table 8. Calculated ETE for the basic structure be used to predict ETEs for meta substituted basic structures from
in water is lower than gas-phase value by 26.6 kJ mol1. In water, their PAs in gas-phase and water.
EDG substituents again decrease ETE values, whereas EWG ones in-
crease ETEs. The differences between the highest and lowest ETE 3.5. Reaction enthalpies of the individual steps of SET–PT and their
values for ortho1, ortho2 and meta positions reached 77.3, 105.5 dependence on structure parameters in gas-phase and water
and 102.5 kJ mol1, respectively in water. Water increases DETEs
by 2–4 kJ mol1 for strong EDG substituents (NH2, NMe2 and In the recent study [69] computed results revealed that BDE val-
NHMe). For strong EWG substituents (NO2 and CN) DETEs in water ues can be successfully correlated with C–O, DR(C–O) and O–H
are lower by 14–25 kJ mol1 in comparison to gas-phase. As in bond lengths for the meta substituted chromans in gas-phase
meta position, in ortho positions attenuation of substituent effect and water. For groups in ortho positions, no linear dependence of
occurs for strong EWG substituents (NO2 and CN groups), while BDEs on these geometry parameters was found. In this paper we
ETE (kJ mol-1)

Fig. 6. Dependence of ETE on rm for meta-substituted molecules in gas-phase (open triangles, bottom x-axis, left y-axis) and water (open squares, top x-axis, right y-axis).
10 M. Najafi et al. / Computational and Theoretical Chemistry 969 (2011) 1–12
ETE (kJ mol-1)
Fig. 7. Dependence of ETE on PA for meta-substituted molecules in gas-phase (open triangles, bottom x-axis, left y-axis) and water (open squares, top x-axis, right y-axis).
tried to correlate calculated IPs and PDEs with C–O, DR(C–O), O–H
bond lengths. Moreover, the correlation with O–H bond length in
radical cation, further denoted as R(O–H)+ , were investigated.
No linear dependence of IPs and PDEs on C–O and DR(C–O) bond
lengths for studied chromans was found. The linearity of
IP = R(O–H) and PDE = R(O–H) dependences is poor; the correlation
coefficients are in 0.7–0.75 range in gas-phase and water. However,
we have found that IPs of meta substituted species can be corre-
lated with O–H bond lengths in radical cations. The values of
R(O–H)+ bond lengths for studied meta-substituted molecules in
gas-phase and water are summarized in Table 1s. In Fig. 2s in Sup-
plementary data, IP = f(R(O–H) +) dependences for meta substi-
tuted chromans are plotted. Equations from the linear
regressions are as follows
IP ðkJmol  1Þ ¼ 33762RðO—H; ÅÞþ  32085 ðgasÞ
IP ðkJmol  1Þ ¼ 26095RðO—H; ÅÞþ  24933 ðwaterÞ
The correlation coefficients reached 0.94 (gas-phase) and 0.96
(water). Fig. 2s shows that higher IPs correspond to longer R(O–
H)+. Analogous linear dependences for PDEs are depicted in
Fig. 3s in Supplementary data. Following equations were found
1 þ
PDE ðkJ mol Þ ¼ 19938RðO—H; ÅÞ þ 19464 ðgasÞ
1
PDE ðkJ mol Þ ¼ 29870RðO—H; ÅÞþ þ 29959 ðwaterÞ
The correlation coefficients reached 0.97 (gas-phase) and 0.95
(water). Obtained results show that the increase in IPs and
decrease in PDEs for meta substituted chromans can be correlated
with the O–H bond length in radical cation, R(O–H)+. BDEs of meta
substituted chromans in gas-phase and water can be successfully
correlated also with phenoxy radical oxygen charge q(O) [69].
Therefore, we tried to correlate IPs and PDEs with q(O). The
computed q(O) values for meta-substituted molecules are reported
in Table 1s. Linear IP = f(q(O)) dependences for the meta substi-
tuted molecules for the two environments are shown in Fig. 4s in
Supplementary data. The correlation coefficients reached 0.94
and 0.97 for gas-phase and water, respectively. Obtained Eq. (27)
(gas-phase) and Eq. (28) (water) are as follows:
1
IP ðkJ mol Þ ¼ 3392:3qðOÞ þ 2420 ðgasÞ
1
IP ðkJ mol Þ ¼ 1879:7qðOÞ þ 1512 ðwaterÞ
Analogous PDE = f(q(O)) dependences are plotted in Fig. 5s in
Supplementary data, the correlation coefficients reached 0.93 and
0.95 in gas-phase and water, respectively. Eqs. (29) and (30)
obtained from the linear regressions are as follows
PA (kJ mol-1)
1
PDE ðkJ mol Þ ¼ 2940:1qðOÞ  537:9 ðgasÞ ð29Þ
1
PDE ðkJ mol Þ ¼ 1385:7qðOÞ  712:6 ðwaterÞ ð30Þ
The computed results show that IP values of substituted
chromans increase with the increasing q(O) in gas-phase and
water. On the contrary, PDE values of substituted chromans
decrease with the increasing q(O). Therefore, there is a good
agreement between calculated IPs and PDEs with q(O) for meta
substituted basic structures in gas-phase and water. The calculated
q(O) values for ortho1 and ortho2 substituted basic structures are
summarized in Tables 2s and 3s in Supplementary data. For groups
in ortho positions, no linear dependence of IPs and PDEs with R(O–
H)+ lengths and q(O) is apparent. The calculated R(O–H)+ lengths
and q(O) values for ortho1 and ortho2 substituted chromans in
gas-phase and water are summarized in Tables 2s and 3s in Sup-
ð23Þ
plementary data.
ð24Þ
3.6. Reaction enthalpies of the individual steps of SPLET and their
dependence on structure parameters in gas-phase and water
In this paper, we tried to correlated PAs and ETEs with R(C–O)
and R(O–H) bond lengths. Linearity of PA = R(O–H) and
ð25Þ
ETE = R(O–H) dependences for substituted chromans is poor; the
ð26Þ correlation coefficients reached only 0.7–0.75 in gas-phase and
water. Klein et al. [44] shown, there is a linear relation between
PAs of substituted phenols and phenolic C–O bond lengths in
gas-phase. Phenolic C–O bond lengths for investigated meta-
substituted chromans in gas-phase and water are summarized in
Table 1s. Obtained PA = f(R(C–O)) dependences
1
PA ðkJ mol Þ ¼ 9806:7RðC—O; ÅÞ  11997 ðgasÞ ð31Þ
1
PA ðkJ mol Þ ¼ 3424:7RðC—O; ÅÞ  4477 ðwaterÞ ð32Þ
are plotted in Fig. 6s in Supplementary data. The correlation coeffi-
cients reached 0.95 (gas-phase) and 0.98 (water). From the Fig. 6s, it
can be seen that higher PA values correspond to longer C–O bonds.
Klein et al. [44] also found that there is a linear dependence
between ETEs of substituted phenols and C–O bond lengths in
gas-phase. In Fig. 7s in Supplementary data, linear ETE = R(C–O)
ð27Þ
dependences for the meta substituted chromans are presented.
ð28Þ The correlation coefficients reached 0.95 and 0.98 in gas-phase
and water, respectively. Obtained equations are as follows
1
ETE ðkJ mol Þ ¼ 12230RðC—O; ÅÞ þ 16973 ðgasÞ ð33Þ
1
ETE ðkJ mol Þ ¼ 6050:8RðC—O; ÅÞ þ 8591:8 ðwaterÞ ð34Þ
 M. Najafi et al. / Computational and Theoretical Chemistry 969 (2011) 1–12
Results in this study show that the increase in PA and decrease
in ETE of meta substituted chromans is related to elongation of the
C–O bond length. Klein et al. [44] also found linear dependences
between PAs or ETEs substituted phenols and q(O) in gas-phase.
Computed PAs and ETEs for the meta substituted chromans in
gas-phase and water are plotted against q(O) in Fig. 8s in Supple-
mentary data. We can conclude that PA values of meta substituted
species show good correlation with q(O) in gas-phase and water.
The correlation coefficients reached 0.95 and 0.92, respectively.
Equations obtained from the linear regressions are as follows
1
PA ðkJ mol Þ ¼ 1749:4qðOÞ þ 559:6 ðgasÞ
1
PA ðkJ mol Þ ¼ 577:2qðOÞ  115:7 ðwaterÞ
ETEs of the meta substituted chromans are plotted against q(O)
in Fig. 9s in Supplementary data. The correlation coefficients
reached 0.96 (gas-phase) and 0.95 (water). Linear regressions pro-
vided these equations
1
ETE ðkJ mol Þ ¼ 2201qðOÞ þ 1323 ðgasÞ
1
ETE ðkJ mol Þ ¼ 1071qðOÞ þ 915:7 ðwaterÞ
The computed results show that PA values of substituted chro-
mans decrease with the increase in q(O). On the contrary, ETE
values grow with the increase in q(O). Calculated C–O bonds
lengths, R(C–O) and q(O) values for ortho1 and ortho2 substituted
basic structures are summarized in Tables 2s and 3s in Supplemen-
tary data. However, there is no linear dependence between
calculated PAs and ETEs for ortho substituted molecules and q(O)
values.
3.7. Thermodynamically preferred mechanism
In present study the found ranges of substituent induced in gas-
phase changes are in this order: IP (131 kJ mol1) > PDE
(112 kJ mol1) > ETE (105 kJ mol1) > PA (80 kJ mol1). These are
significantly larger than 70 kJ mol1 range found for BDEs [69].
Because calculated gas-phase ionization potentials and proton
affinities are significantly higher than phenolic O–H group BDEs,
we can conclude that homolytic O–H bond splitting-off represents
the most probable process in the gas-phase from the thermody-
namic point of view. Abstraction of the proton from the O–H group
of a substituted phenol represents the process with the highest
energy requirement. However, in water, proton affinities are signif-
icantly lower than phenolic O-H group BDEs. PAs are also lower
than IPs in water. Therefore SPLET mechanism represents for
studied substituted chromans thermodynamically preferred mech-
anism in water.
4. Conclusions
In this article, the reaction enthalpies of the individual steps of
two antioxidant action mechanisms, SET-PT and SPLET, for various
meta and ortho substituted chromans (basic structure of vitamin E)
were calculated using DFT/B3LYP method in gas-phase and water.
The calculations provided the full information related to the energy
requirements of the two mechanisms. Results indicate that elec-
tron donating substituents induce rise in PDEs and PAs, whereas
electron-withdrawing groups cause increase in the reaction
enthalpies of the processes where the electron is abstracted (IPs
and ETEs). It has been found that substituents in ortho positions
exert significantly stronger influence upon PA and ETE than
substituents in meta position. In comparison to PA and ETE, sub-
stituents in meta position exert stronger influence upon IP and
PDE when compared with same substituents in ortho positions.
In comparison to the gas-phase, the effect of studied substituents
11
on the IPs, PDEs and PAs was decreased in water. In the case of
ETE values, effect of electron withdrawing groups in water is
decreased, while the effect of electron donating groups on ETE in
water is higher in comparison to gas-phase. Solvation attenuates
the substituent effect especially in the case of PDEs and PAs. From
the thermodynamic point of view, SPLET mechanism represents
the most probable process in water. Computed results indicate that
all dependences of reaction enthalpies on Hammett constants of
the substituents are linear. It has been revealed that calculated
enthalpies can be correlated with the length of phenolic R(C–O)
and R(O–H)+ bond lengths and partial charge on the phenoxy
ð35Þ radical oxygen q(O) of the studied molecules successfully.
ð36Þ
Acknowledgment
The financial support of Research Council of Shahid Beheshti
University is gratefully acknowledged. This work has also been
supported by the Slovak Grant Agency VEGA (Project No. 1/0137/
09).
ð37Þ
ð38Þ Appendix A. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.comptc.2011.05.006.
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