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org/JPCA Article

Benchmarking Antioxidant-Related Properties for Gallic Acid

through the Use of DFT, MP2, CCSD, and CCSD(T) Approaches
Gabriel L. C. de Souza* and Kirk A. Peterson*
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ABSTRACT: We present a benchmark investigation on the O−H

bond dissociation enthalpies (BDEs) and ionization potential (IP)
for gallic acid (GA), a widely known polyphenolic antioxidant.
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These properties were determined in the gas-phase and in water

through the use of density functional theory (DFT), second-order
Møller−Plesset perturbation theory (MP2), coupled-cluster with
single and double excitations (CCSD), and coupled-cluster with
single and double excitations as well as perturbative inclusion of
triples (CCSD(T)). The 6-311++G(df,p), cc-pVDZ, aug-cc-pVDZ,
cc-pVTZ, and aug-cc-pVTZ basis sets were used. Regarding DFT
functionals, the M06-2X provided the best agreement for the BDEs when compared to the corresponding CCSD(T)/aug-cc-pVTZ
results; M06-2X was also found to be the most suitable for probing the IP for the protonated forms of GA while LC-ωPBE was the most
reliable in the case of deprotonated GA. Given that these properties represent important descriptors for examining mechanisms related
to the antioxidant potential of a given polyphenol, we hope that the present work can serve as a guide for computational chemists
venturing in the field.

■ INTRODUCTION
Polyphenols (i.e., organic molecules presenting multiple phenol
bond dissociation enthalpies (BDEs) are important descriptors
that represent the energy necessary for the O−H bonds to be
units in their chemical structures) are widely known for having cleaved.
considerable antioxidant activity.1 These compounds are often Another crucial mechanism related to antioxidant activity is
found in most parts (including leaf tissue, bark layers, flowers, single electron transfer (SET). In SET, one electron is transferred
and fruits) of a multitude of natural products, being classified as directly from the antioxidant molecule to the free radical, such as
flavonols, chalcones, flavones, lignans, etc. according to dif-
ferences in their chemical structures. Due to the fact that these ArOH + R• → ArOH+ + R− → ArO• + RH (2)
entities are highly desired for providing several health-related
features (such as anti-inflammatory, antiviral, and antitumor
actions2−5), there is an ongoing focus in chemical, food, and
pharmaceutical industries on finding sources of antioxidants.
From a general perspective, most of the benefits provided
by polyphenols arise from their capabilities to neutralize free
radicals.6 Moreover, since the seminal paper by Wright et al.7
(in combination with the study presented by Leopoldini et al.8)
it is well established that the antioxidant potential of a given
polyphenol can be successfully predicted through the examina-
tion of some specific mechanisms, by using results gathered from
electronic structure computations. One important path is the Figure 1. Illustration of the chemical structure for gallic acid (GA)
hydrogen atom transfer (HAT) mechanism, in which a O−H along with atom numbering.
bond is homoliticaly broken and a H atom is transferred to a
radical. The HAT mechanism can be written as
Received: October 7, 2020
ArOH + R• → ArO• + RH (1) Revised: December 14, 2020
where ArOH is the neutral molecule of the antioxidant, R• is Published: January 5, 2021
the free radical, ArO• is the molecule of the antioxidant after
suffering the abstraction of one of its H atoms, and RH is the
stabilized (former) free radical. In terms of HAT, the O−H

© 2021 American Chemical Society https://dx.doi.org/10.1021/acs.jpca.0c09116

198 J. Phys. Chem. A 2021, 125, 198−208
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Figure 2. Example of mechanisms relevant to the present work for protonated (GAOH) and deprotonated (GAOH−) GA. On the left, HAT for the
cleavage of the O−H bond at the 5-ArOH position for the protonated GA and its corresponding SET. On the right side, HAT for the cleavage of the
O−H bond at the 5-ArOH position for the deprotonated GA and its corresponding SET. Species on the left side were investigated through
computations in the gas-phase and considering water as solvent (IEF-PCM) environment; species on the right were investigated solely through the
consideration of (water) solvation.

The SET mechanism is governed by the ionization potential Table 1. Previous Experimental and Computational Results
(IP). In this sense, the lower the IP, the easier is the electron of O−H BDEs and IP (Both Given in kcal/mol) for GA
abstraction and, thus, more likely for a given polyphenol to experimental BDEs
present antioxidant activity. Other less studied mechanisms
ref 34a 81.0
(such as the sequential proton loss electron-transfer, SPLET,
ref 35b 83.1
mechanism9,10) have also been connected to the antioxidant computational results
activity of a variety of compounds, however, in terms of poly-
protonated GA
phenols, the HAT and SET mechanisms are suggested as being
BDEs IP
the dominant paths.11,12 In particular, the computationally 4-ArO• 5-ArO• 6-ArO•
determined BDEs have been shown to be strongly correlated to ref 36c 82.2 141.1
experimentally measured antioxidant activity.13−15 ref 37d 78 188
In the very recent past, theoretical investigations focusing on ref 37e 77 143
the determination of the BDEs and IPs for polyphenolic com- ref 38f 84.6 77.2 77.9 189.3
pounds have been heavily accomplished.16−22 As polyphenols ref 38g 81.5 76.0 78.6 118.8
are (in general) mid- to large-sized molecules and examining ref 38h 83.4 76.7 78.2 161.8
their electronic structure through the consideration of solvent ref 39i 87.2 82.7 87.00 127.20
(mainly water) environments is required, almost the totality of ref 39j 81.5 77.0 81.3 112.6
these computational studies have employed density functional ref 40k 92.0 182.6
theory (DFT) with a wide variety of exchange-correlation func- ref 40l 90.9 138.4
tionals, the Becke, Lee, Yang, and Parr (B3LYP)23,24 deprotonated GA
BDEs IP
undoubtedly being the most prevalent. To the best of our
4-ArO• 5-ArO• 6-ArO•
knowledge, only a single benchmark investigation regarding the
ref 38f 76.2 66.4 68.8 62.38
evaluation of BDEs and IPs for a polyphenolic molecule was
ref 38g 78.2 71.9 74.8 88.0
carried out recently by Adamo and co-workers for quercetin.25 ref 38h 77.2 69.1 71.7 87.7
After benchmarking twenty-one DFT exchange-correlation
a
functionals against each other, the authors suggested the Determined in acetonitrile/chlorobenzene mixture. bDetermined in
LC-ωPBE,26 M05-2X,27 and M06-2X28 functionals as the most methyl linoleate. c(RO)B3LYP/6-311+G(2d,2p)//AM1/AM1 in
ethanol. dB3LYP/6-311++G(df,p) in the gas-phase. eB3LYP/6-311+
suitable for probing those antioxidant-related properties; no
+G(df,p) in water. fB3LYP/6-311++G(d,p) in the gas-phase. gB3LYP/
benchmarks involving the application of methods beyond DFT 6-311++G(d,p) in water. hB3LYP/6-311++G(d,p) in benzene. iM05-
(specially those based on high-level of theory) are available 2X/6-311++G(d,p) in water (SMD). jB3LYP-D2/6-311++G(d,p)
to date. Therefore, we decided to carry out the present work to in water (SMD). kB3LYP/6-31G(d,p) in the gas-phase. lB3LYP/
fill this gap. 6-31G(d,p) in water.

199 https://dx.doi.org/10.1021/acs.jpca.0c09116
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Table 2. BDEs (in kcal/mol) for Different OH Groups of Protonated GA As Determined in the Gas-Phasea
radical 6-311++G(df,p) cc-pVDZ aug-cc-pVDZ cc-pVTZ aug-cc-pVTZ
B3LYP
4-ArO• 84.9 82.4 (84.2) 84.4 (86.3) 84.8 85.2
5-ArO• 77.6 73.7 (75.2) 76.7 (78.2) 76.7 77.5
6-ArO• 78.3 75.14 (76.8) 77.7 (79.3) 78.0 78.6
LC-ωPBE
4-ArO• 85.6 83.2 84.8 85.5 85.8
5-ArO• 78.2 74.4 76.8 77.2 77.9
6-ArO• 78.9 76.1 77.8 78.6 79.0
M06-2X
4-ArO• 90.4 88.0 89.5 90.4 90.8
5-ArO• 83.3 79.8 81.9 82.7 83.2
6-ArO• 84.1 81.3 83.0 83.9 84.3
U-MP2
4-ArO• 109.0 113.1 116.9 118.0
5-ArO• 98.1 102.7 105.9 107.4
6-ArO• 101.3 105.1 108.8 109.9
RO-MP2
4-ArO• 81.3 83.9 86.9 87.6
5-ArO• 72.2 76.1 78.5 79.7
6-ArO• 73.9 77.0 79.8 80.5
U-CCSD
4-ArO• 82.8 85.7 88.5 89.2
5-ArO• 75.2 78.7 81.0 82.1
6-ArO• 76.6 79.5 82.2 82.8
RO-CCSD
4-ArO• 83.3 86.1 89.0 89.6
5-ArO• 75.8 79.3 81.6 82.6
6-ArO• 77.1 79.9 82.6 83.2
RO-CCSD(T)
4-ArO• 82.2 85.3 88.2 88.9
5-ArO• 74.4 78.2 80.5 81.6
6-ArO• 75.7 78.8 81.5 82.2
a
The values in parentheses were determined with the RO-B3LYP approach. Atom numbering is provided in Figure 1.

In this work, we performed a benchmark investigation on the
BDEs and IP for gallic acid (GA), see Figure 1 for its chemical
structure. GA is a compound commonly used as a standard in
experimental tests of antioxidant activity29−31 and, thus, it has
been extensively studied both experimentally and computation-
ally.32−40 In the present work, the properties of interest were
determined in the gas-phase and in water through the use of
DFT, second-order Møller−Plesset perturbation theory (MP2),
coupled-cluster with single and double excitations (CCSD), and
coupled-cluster with single and double excitations as well as
perturbative inclusion of triples (CCSD(T)) with the 6-311+
+G(df,p), cc-pVDZ, aug-cc-pVDZ, cc-pVTZ, and aug-cc-pVTZ
basis sets.41−50 After comparing the BDEs and IP computed
using all the different approaches with each other, as well as with
previous experimental and theoretical results available in the
literature, a general conclusion regarding the usage of the methods
for probing antioxidant-related properties of polyphenols was
drawn.
(RO-B3LYP, RO-MP2, RO-CCSD, and RO-CCSD(T)) were
employed. LC-ωPBE26 and M06-2X28 functionals were chosen
based on the results by Adamo and co-workers,25 while
B3LYP23,24 was employed to facilitate future comparisons.
The spin contamination for the DFT methods was found to be
quite modest, e.g., an S2 value of 0.77 for the doublet 5-ArO•
radical derived from protonated GA at the B3LYP/aug-cc-pVTZ
level in the gas-phase, while the analogous value was very large
for UHF, S2 = 1.25 (which of course is the basis for the U-MP2
calculations). The 6-311++G(df,p),44−47 cc-pVDZ, aug-cc-pVDZ,
cc-pVTZ, and aug-cc-pVTZ48−50 basis sets were used throughout.
All the optimizations were accomplished using default convergence
criteria and without imposing any symmetry constraints. The initial
structure for geometry optimizations of GA was based on the most
stable conformation found by Rajan and Muraleedharan37 at the
B3LYP/6-311++G(df,p) level of theory in water. Vibrational
frequencies were computed for all the optimized structures to
confirm the conformations as minima, to evaluate the zero-point

■ COMPUTATIONAL METHODS
The electronic structure computations for GA were performed
using DFT (with the B3LYP,23,24 LC-ωPBE,26 and M06-2X28
exchange-correlation functionals), MP2, CCSD, and CCSD-
(T);41−43 for the open-shell species, the corresponding unrestricted
formalisms (i.e., U-B3LYP, U-LC-ωPBE, U-M06-2X, U-MP2,
U-CCSD, and U-CCSD(T)) as well as restricted open-shell
200
energy (ZPE) corrections, and to determine enthalpies (at 298 K).
The computations were performed in the gas-phase and in water.
Through the investigation of the antioxidant activity of propyl
gallate, Medina et al.51 concluded that the addition of explicit
solvent molecules presents no advantages over continuum solvation
models and, thus, we utilized the integral equation formalism
polarizable continuuum model (IEF-PCM)52−54 for taking solvation
into account. The Gaussian 09 software suite55 was used for
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Table 3. BDEs (in kcal/mol) for Different OH Groups of

Protonated GA As Determined in Water (IEF-PCM) at 298 Ka
6-311+ cc- aug-cc- cc- aug-cc-
Radical +G(df,p) pVDZ pVDZ pVTZ pVTZ
B3LYP
4-ArO• 81.9 80.3 81.4 82.1 82.2
5-ArO• 76.4 73.4 75.7 76.0 76.5
6-ArO• 79.1 76.4 78.4 78.9 79.3
LC-ωPBE
4-ArO• 82.7 81.2 81.9 82.9 83.0
5-ArO• 77.0 74.2 75.9 76.5 77.0
6-ArO• 79.9 77.6 78.9 79.7 80.0
M06-2X
4-ArO• 87.4 85.9 86.7 87.7 87.8
5-ArO• 82.2 79.4 81.0 81.9 82.3
6-ArO• 85.0 82.6 84.0 84.9 85.1
U-MP2
4-ArO•  106.9 109.5 113.6 114.3
5-ArO•  97.6 101.1 104.6 105.8
6-ArO•  102.8 105.9 109.7 110.5
RO-MP2
4-ArO•  79.4 81.8 85.1 85.4
5-ArO•  72.3 75.6 78.3 79.2
6-ArO•  75.7 78.6 81.5 82.1
U-CCSD
4-ArO•  81.3 83.3 86.4 86.7
5-ArO•  74.8 77.8 80.3 81.1
6-ArO•  78.2 80.7 83.5 84.0
U-CCSD(T)
4-ArO•  82.6 84.5 87.9 
5-ArO•  75.8 78.8 81.5 82.4
6-ArO•  79.2 81.7 84.7 
a
Atom numbering is provided in Figure 1.

IP = H0(GAOH+) − H0(GAOH) (4)

Figure 3. Relative deviations (in kcal/mol) to the 5-ArO• BDE
for GA as determined at the CCSD(T)/aug-cc-pVTZ//M06-2X/
aug-cc-pVTZ level in the gas-phase.
performing all the DFT in the gas-phase and in water as well as the
MP2, CCSD, and CCSD(T) calculations when solvation was
considered. Molpro56,57 was employed for all the RO-MP2, RO-
CCSD, and RO-CCSD(T) computations in the gas-phase.
In Figure 2, an illustration of selected examples of the mech-
anisms investigated here is presented; it is important to mention
that the H abstraction associated with the O−H bond breaking
from positions 4-ArOH and from its chemically equivalent
6-ArOH (that are not being explicitly shown in Figure 2) were
also investigated in this work. In the case of the protonated GA,
the 298 K BDEs were determined as
BDE = H298(GAO•) + H298(H•) − H298(GAOH) (3)
where H298(GAO•) is the enthalpy for the radical generated via
H atom abstraction, H298(H•) the enthalpy for the H atom,
and H298(GAOH) the enthalpy for GA. The enthalpies here
are defined as the total electronic energies plus any zero-point
vibrational energy and a standard thermal correction from 0 to
298 K.58 The 0 K IP for GA was obtained by
201
+
where H0(GAOH ) and H0(GAOH) are the electronic energies
corrected with the zero-point vibrational energies computed for
the cationic GA and for its neutral form, respectively.
It is well-known that at physiological pH (7.4) considerable
amounts of hydroxybenzoic acid (HBA) molecules are found
deprotonated.59,60 As GA is a compound derived from HBA,
probing the BDEs and the IP also for its deprotonated (at its
carboxylic acid site) form seems to be quite logical. See also
Figure 2. With this in mind, the BDEs for the deprotonated
version of the GA were computed as
BDE = H298(GAO•−) + H298(H•) − H298(GAOH−)
(5)
where H298(GAO•−) is the 298 K enthalpy for the radical
generated via H atom abstraction from deprotonated GA and
H298(GAOH−) the analogous enthalpy for deprotonated GA.
The IP for deprotonated GA was obtained by
IP = H0(GAOH•) − H0(GAOH−) (6)
• −
where H0(GAOH ) and H0(GAOH ) are the electronic
energies (corrected with the zero-point vibrational contribu-
tions) computed for the deprotonated neutral (radical) GA and
for its anionic form, respectively.
■ RESULTS AND DISCUSSION
Structures. Figure S1 presents examples of the structure
of GA as fully optimized using the B3LYP/6-311++G(df,p),
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LC-ωPBE/6-311++G(df,p), M06-2X/6-311++G(df,p), MP2/

6-311++G(df,p), CCSD/cc-pVDZ, CCSD(T)/cc-pVDZ,
B3LYP/aug-cc-pVTZ, and M06-2X/aug-cc-pVTZ approaches
in the gas-phase and can be found in the Supporting Information;
selected optimized bond lengths (for C−C, CC, C−H, C−O,
CO, and O−H bonds and the intramolecular O−H···O
hydrogen-bond interaction) are also represented in the struc-
tures for comparison purposes. From a general perspective, struc-
tures obtained through all approaches are in good agreement with
each other, presenting differences within 0.03 Å in terms of bond
lengths and 0.04 Å regarding the H···O interactions. Moreover, all
of the methods suggested GA as having a considerably planar
(nearly Cs) structure with any given dihedral being within 0.03°.
Therefore, it can be gleaned that any approach used (even those
considering a lower level of theory or a smaller basis set) can
provide a good structure for GA. Nearly identical outcomes
was observed for the case of the structures obtained in water
(IEF-PCM); Cartesian coordinates of all the structures can also
be found in the Supporting Information.
BDEs and IP. In Table 1, we show previous experimental and
computational results of BDEs and the IP for GA that were
available in the literature.34−40 In general, it is possible to notice
that all the computed results found 5-ArOH as having the lowest
BDE (suggesting that this hydroxyl is the main contributor to
the antioxidant activity in the case of a HAT mechanism)
followed by 6-ArOH and 4-ArOH for both protonated and
deprotonated GA. In addition, a systematic decrease in the BDE
values is observed for the deprotonated GA in comparison to the
results obtained (at a given approach) for the protonated form.
Considering the 5-ArOH as an example, Š korňa et al.38 obtained
a value of 66.4 kcal/mol at the B3LYP/6-311++G(d,p) level of
theory in the gas-phase versus 77.2 kcal/mol for the protonated
version computed using the same approach. In terms of
experiments, Alberti et al.34 through EPR experiments based
on a radical equilibration technique in acetonitrile/chloroben-
zene obtained 81.0 kcal/mol. Denisova et al.35 measured
83.1 kcal/mol utilizing the rate constants of the reaction between
GA and peroxy radicals in nonpolar environment (methyl
linoleate). The IP computed for the protonated form of GA was
reported (by all the studies) as being considerably higher than any
Figure 4. Relative deviations (in kcal/mol) to the 5-ArO• BDE of the BDEs. For instance, Rajan and Muraleedharan37 obtained an
for GA as determined at the CCSD(T)/aug-cc-pVTZ//M06-2X/ IP of 188 kcal/mol at the B3LYP/6-311++G(df,p) level of theory
aug-cc-pVTZ level in water. in the gas-phase and 143 kcal/mol at the B3LYP/6-311++G(df,p)
Table 4. BDEs (in kcal/mol) for Different OH Groups of Deprotonated GA As Determined in Water (IEF-PCM) at 298 Ka
radical 6-311++G(df,p) cc-pVDZ aug-cc-pVDZ cc-pVTZ aug-cc-pVTZ
B3LYP
4-ArO• 78.5 76.5 78.0 78.5 78.8
5-ArO• 72.3 68.6 70.9 70.9 71.8
6-ArO• 75.3 72.0 74.5 74.7 75.4
LC-ωPBE
4-ArO• 80.4 78.1 78.9 79.7 79.9
5-ArO• 74.3 70.1 71.7 72.1 72.2
6-ArO• 77.3 73.8 75.4 76.0 76.5
M06-2X
4-ArO• 85.1 82.6 83.6 84.5 84.7
5-ArO• 79.0 75.0 77.0 77.7 77.7
6-ArO• 81.7 78.7 80.4 81.1 81.5
U-MP2
4-ArO• 102.5 105.3 109.2 110.0
5-ArO• 91.2 95.6 98.6 100.0
6-ArO• 97.0 100.6 104.0 105.1

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Table 4. continued
radical 6-311++G(df,p) cc-pVDZ aug-cc-pVDZ cc-pVTZ aug-cc-pVTZ
RO-MP2
4-ArO• 76.6 79.1 82.3 82.7
5-ArO• 68.4 72.4 74.4 75.4
6-ArO• 72.0 75.2 77.9 78.6
U-CCSD
4-ArO• 78.3 80.5 83.3 83.7
5-ArO• 71.1 74.5 76.7 77.6
6-ArO• 74.4 77.2 80.0 80.4
U-CCSD(T)
4-ArO• 79.0 81.5 84.7 ---
5-ArO• 71.5 75.1 77.6 78.6
6-ArO• 74.8 78.0 80.7 ---
a
Atom numbering is provided in Figure 1.

level of theory in water, while Kalita et al.40 found 182.6 and

138.4 kcal/mol at the B3LYP/6-31G(d,p) level of theory in the
gas-phase and in water, respectively. On the other hand, Š korňa
et al.,38 who used B3LYP/6-311++G(d,p), suggested a steep
decrease in the IP value for the deprotonated GA.
In Table 2, we present the gas phase BDEs for GA as
computed using DFT, MP2, CCSD, and CCSD(T) methods
and the 6-311++G(df,p), cc-pVDZ, aug-cc-pVDZ, cc-pVTZ,
and aug-cc-pVTZ basis sets in the gas-phase. In general, all the
approaches suggested the same relative order for the BDEs
(5-ArOH < 6-ArOH < 4-ArOH) observed in the previous DFT-
based works performed by Š korňa et al.38 and by Dorović et al.39
The basis set dependence is quite small for all the DFT
exchange-correlation functionals used in this work, as expected,
although the changes from cc-pVDZ to aug-cc-pVDZ are non-
negligible. With the aug-cc-pVTZ basis set, the B3LYP results
are in excellent agreement with the corresponding results
determined using the more sophisticated LC-ωPBE functional,
which adds long-range corrections to the short-range variant of
the PBE exchange functional. For instance, the BDE for the
5-ArOH was computed as 77.5 and 77.9 kcal/mol at the B3LYP/
aug-cc-pVTZ and LC-ωPBE/aug-cc-pVTZ levels of theory,
respectively, in the gas-phase. The results using these two func-
tionals, however, are not in very good agreement with the value
of 83.2 kcal/mol obtained at the M06-2X/aug-cc-pVTZ level of
theory. M06-2X is a functional that takes into account the high
nonlocality nature of the physical processes under scope.
Given that the coupled cluster methods employed here
present considerably higher computational cost, the results at
the MP2, CCSD, and CCSD(T) levels of theory that are shown
in Table 2 were determined using the structures and thermal
corrections obtained at the M06-2X/aug-cc-pVTZ level of
theory. However, the CCSD BDE value (for 5-ArOH) was
obtained through full optimization with a thermal correction
evaluated at the CCSD/cc-pVDZ level of theory in the gas-
phase, and the result, 75.26 kcal/mol, is nearly identical to that
determined at the CCSD/cc-pVDZ//M06-2X/aug-cc-pVTZ
level of theory (75.17 kcal/mol). Thus, the validity of such
procedure is attested. BDE results computed using the U-MP2
approach were found to be considerably higher than those
calculated using any other methods, suggesting that this method Figure 5. Relative deviations (in kcal/mol) to the 5-ArO• BDE for
considerably over binds when compared to DFT, coupled deprotonated GA as determined at the CCSD(T)/aug-cc-pVTZ//
M06-2X/aug-cc-pVTZ level in water.
cluster, and the experimental results, as suggested previously
elsewhere.61 The poor accuracy observed in the case of U-MP2
is in agreement with the findings by Klein and Lukeš,62 which reference, do not provide reliable results after investigating the
concluded that MP2, MP3, and MP4 methods, based on a UHF BDEs for 37 substituted phenols. Interestingly, as shown here,
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Table 5. IPs (in kcal/mol) Determined for GA (Gas-Phase and Water) and Deprotonated GA (Water)
6-311++G(df,p) cc-pVDZ aug-cc-pVDZ cc-pVTZ aug-cc-pVTZ
protonated (gas)
B3LYP 188.6 179.7 187.2 184.9 187.4
LC-ωPBE 191.6 183.7 189.7 187.9 189.9
M06-2X 193.6 185.9 191.3 190.9 192.5
U-MP2 190.6 201.6 201.1 205.1
RO-MP2 181.4 191.9 190.9 194.6
RO−CCSD 179.4 188.5 187.4 190.7
RO−CCSD(T) 178.9 189.1 187.9 191.6
protonated (water)
B3LYP 144.1 129.1 142.8 140.6 142.8
LC-ωPBE 147.0 139.5 145.2 143.5 145.3
M06-2X 149.2 141.9 146.7 146.6 148.1
U-MP2 156.9 167.1 167.3 171.3
RO-MP2 142.9 152.1 151.9 155.5
U-CCSD 141.3 149.5 149.3 152.5
U-CCSD(T) 141.0 150.1 149.9 153.6
deprotonated (water)
B3LYP 130.0 119.1 128.5 125.1 128.5
LC-ωPBE 137.0 127.3 135.0 132.3 135.0
M06-2X 139.0 129.3 136.4 135.1 137.4
U-MP2 132.5 146.1 144.0 149.2
RO-MP2 124.9 137.5 135.2 140.0
U-CCSD 122.7 133.8 131.5 134.3
U-CCSD(T) 122.6 135.0 132.7 135.2

RO-MP2 provided results that are in good agreement with those
computed using coupled-cluster theory, presenting no signal of
over binding. Hence, RO-MP2 appears to be a good choice of
wave function method in this case regarding the balance between
computational cost and accuracy for determining BDEs. Results
calculated using U-CCSD and RO-CCSD are in excellent
agreement and the inclusion of perturbative triples contributes
just under 1 kcal/mol. As expected, there is a not insignificant
basis set dependence observed for these wave function-based
methods, e.g., the CCSD(T) BDE (4-ArOH) increased by
4.6 kcal/mol between aug-cc-pVDZ and aug-cc-pVTZ whereas
the analogous change for M06-2X was just 1.3 kcal/mol. Overall,
the M06-2X functional provided the best agreement for the
BDEs when compared to the corresponding CCSD(T)/aug-cc-
pVTZ//M06-2X/aug-cc-pVTZ results.
In Figure 3, the relative deviations for the 5-ArOH BDEs are
presented. It is possible to notice that even the values obtained
using the M06-2X functional with the small cc-pVDZ basis set
(79.8 kcal/mol for the 5-ArOH, 81.3 kcal/mol for the 6-ArOH,
and 88.0 kcal/mol for the 4-ArOH) are in better agreement
in regards to the results determined at the CCSD(T)/aug-cc-
pVTZ//M06-2X/aug-cc-pVTZ (81.6 kcal/mol for the 5-ArOH,
82.2 kcal/mol for the 6-ArOH, and 88.9 kcal/mol for the
4-ArOH) than those computed using the B3LYP and the
LC-ωPBE functionals with the larger aug-cc-pVTZ basis set,
for example. These results were found to be 77.5, 78.6, and
85.2 kcal/mol for the 5-ArOH, 6-ArOH, and 4-ArOH, respec-
tively, at the B3LYP/aug-cc-pVTZ in the gas-phase, as well as
77.9, 79.0, and 85.8 kcal/mol for the 5-ArOH, 6-ArOH, and
4-ArOH, respectively, at the LC-ωPBE/aug-cc-pVTZ in the
gas-phase. In addition, in the case of the Minnesota functional,
all of the Dunning basis sets provided results that are closer
to the corresponding values obtained at the CCSD(T)/aug-cc-
pVTZ//M06-2X/aug-cc-pVTZ level than those determined
with the 6-311++G(df,p) basis set.
204
Although the BDEs in the gas-phase can provide useful
insights, determining such properties in water is substantially
more relevant for biological antioxidant activity.63 Therefore,
such results are available in Table 3. It is possible to see that the
relative order of the BDEs in water remains the same as those
seen in the results computed in the gas-phase: 5-ArOH < 6-ArOH <
4-ArOH. On the other hand, as observed in the previous works for
GA,37,38,40 the BDEs experience a slight decrease when the polar
solvent environment is taken into account. Once again, B3LYP and
LC-ωPBE functionals yielded results that are quite close to each
other (using a given basis set) while the M06-2X functional provided
results that are in quite good agreement to those determined at the
CCSD(T)/aug-cc-pVTZ//M06-2X/aug-cc-pVTZ level of theory,
suggesting that the Minnesota exchange-correlation functional as
being considerably accurate for probing the BDEs in the case of a
neutral polyphenol. The relative deviations for the 5-ArOH BDEs
determined in water for the protonated GA can be seen in Figure 4.
In Table 4, we show the BDEs computed for different OH
groups of the deprotonated GA. Similarly to what was observed
previously by Š korňa et al.38 using the B3LYP/6-311++G(d,p)
approach in the gas-phase, water, and benzene, the present
results suggest the BDEs for deprotonated GA as being lower
than their corresponding counterparts obtained for the protonated
version of the GA at all levels of theory. For example, the BDE of the
5-ArOH was determined as 78.6 kcal/mol at the CCSD(T)/aug-
cc-pVTZ//M06-2X/aug-cc-pVTZ level of theory in water against
the 82.4 kcal/mol for protonated GA (see Table 3) at the same
approach. Again, the M06-2X functional provided the best results in
comparison to those calculated at the CCSD(T)/aug-cc-pVTZ
level of theory. However, due to the anionic nature of the
deprotonated GA, diffuse functions are necessary for accurately
describing the system and, thus, the use of the aug-cc-pVXZ
basis set (instead of the cc-pVXZ, with X = D and T) is advised.
The relative deviations for the 5-ArOH BDEs determined in
water for the deprotonated GA can be seen in Figure 5.
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The Journal of Physical Chemistry A
Figure 6. Relative deviations (in kcal/mol) to the IP for GA as
determined at the CCSD(T)/aug-cc-pVTZ//M06-2X/aug-cc-pVTZ
level in the gas-phase.
The IPs obtained in the gas-phase and in water for protonated
GA, as well as the IP for deprotonated GA in water are given in
Table 5. Similarly to what was previously observed for the BDEs,
all the methods provided IP results that are lower in water than
205
pubs.acs.org/JPCA Article
Figure 7. Relative deviations (in kcal/mol) to the IP for protonated GA
as determined at the CCSD(T)/aug-cc-pVTZ//M06-2X/aug-cc-
pVTZ level in water.
their corresponding counterpart computed in the gas-phase.
Furthermore, such decrease is considerably more marked in the
case of the IP rather than in the BDEs. This behavior is well-
known and generally assigned to the charge-separation caused
by polar solvents.64 The IP for the deprotonated GA was found
to be lowest in comparison to the IP obtained for the protonated
GA, independently from the approach employed, although only
by about 14−19 kcal/mol. However, and most important, even
the lowest obtained IP is considerably higher than any of the
BDEs determined in the present work, which suggest the HAT
mechanism as being preferred over the SET mechanism in the
case of GA. Interestingly, Š korňa et al.38 observed a much more
marked decrease in the IP values for the deprotonated form
of the GA compared to protonated GA, by nearly 30 kcal/mol
in water. This is particularly puzzling since the method they
used, B3LYP/6-311++G(d,p) with IEF-PCM for solvation, is
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J. Phys. Chem. A 2021, 125, 198−208
The Journal of Physical Chemistry A
Figure 8. Relative deviations (in kcal/mol) to the IP for deprotonated
GA as determined at the CCSD(T)/aug-cc-pVTZ//M06-2X/aug-cc-
pVTZ level in water.
nearly identical to some of the current calculations. However,
unlike their protonated results (their Scheme 1), the values
they give for the BDEs and proton dissociation enthalpies of
the deprotonated GA do not yield consistent values for the IP
using their Scheme 2 thermodynamic cycle. Hence it is proposed
that their deprotonated GA IP values are perhaps slightly
in error.
Figures 6−8 present the relative deviations for the IP
determined for GA considering the gas-phase, protonated in
water, and deprotonated in water, respectively. As seen previously
for the BDEs, it is possible to notice that the IP results obtained
206
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with the M06-2X functional show considerably good agreement
when compared to the results computed at the CCSD(T)/aug-
cc-pVTZ level of theory for the protonated GA (either in the
gas-phase as well as in water); LC-ωPBE results are closer to the
CCSD(T)/aug-cc-pVTZ in the case of the deprotonated GA.
■ CONCLUSIONS
In summary, a benchmark investigation was carried out on
the O−H bond dissociation enthalpies (BDEs) and ionization
potential (IP) for the antioxidant polyphenol gallic acid. These
properties were probed in both the gas-phase and water using
DFT, MP2, and coupled cluster approaches. Five basis sets
ranging from cc-pVDZ to aug-cc-pVTZ were employed. In terms
of the DFT functionals that were evaluated, M06-2X provided the
best agreement for the BDEs (for all the chemical species and
solvent environment) and the IP for protonated GA as compared
to the corresponding results obtained using the CCSD(T)
method with the aug-cc-pVTZ basis set with differences less than
2 kcal/mol for all the gas phase values and within 6 kcal/mol for
the IP in water. For all of these latter cases the MP2 method, when
based on ROHF orbitals, was only slightly less accurate than
M06-2X for the gas phase values, more accurate for the IP in
water, and in all cases better than the other two functionals
employed. The UHF-MP2 method yielded much poorer results
throughout. The LC-ωPBE functional yielded nearly identical
results for the IP of deprotonated GA in water compared to
CCSD(T)/aug-cc-pVTZ, which were about 2 kcal/mol larger
than the value obtained with M06-2X. The commonly used
B3LYP functional yielded the worst agreement with CCSD(T)
in all cases among the three functionals investigated. Given that
the O−H BDEs and the IP represent important descriptors for
probing two essential mechanisms related to the antioxidant
potential of mid- and large-sized polyphenols (the hydrogen
atom transfer, HAT, mechanism and the single-electron transfer,
SET, mechanism) it is hoped that these results will be of clear
interest for computational chemists working in this area.
■ ASSOCIATED CONTENT
* Supporting Information
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.jpca.0c09116.
Cartesian coordinates as discussed in the text (PDF)
■ AUTHOR INFORMATION
Corresponding Authors
Gabriel L. C. de Souza − Departamento de Química,
Universidade Federal de Mato Grosso, Cuiabá, Mato Grosso
78060-900, Brazil; Department of Chemistry, Washington
State University, Pullman, Washington 99164, United States;
orcid.org/0000-0002-2192-7345; Phone: +55-65-3615-
8000; Email: gabriellcs@pq.cnpq.br; Fax: +55-65-3628-
1219
Kirk A. Peterson − Department of Chemistry, Washington State
University, Pullman, Washington 99164, United States;
orcid.org/0000-0003-4901-3235; Phone: +1-509-335-
7867; Email: kipeters@wsu.chem.edu
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.jpca.0c09116
Notes
The authors declare no competing financial interest.
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J. Phys. Chem. A 2021, 125, 198−208
The Journal of Physical Chemistry A
■
ACKNOWLEDGMENTS
The Brazilian agency CNPq funded this work (Grants: 306433/
2019-2 and 204748/2018-6).
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