ISSN 0036-0244, Russian Journal of Physical Chemistry A, 2020, Vol. 94, No. 8, pp. 1678–1693. © Pleiades Publishing, Ltd.

, 2020.

PHYSICAL CHEMISTRY OF NANOCLUSTERS

AND NANOMATERIALS

A CAM-B3LYP DFT Investigation of Atenolol Adsorption

on the Surface of Boron Nitride and Carbon Nanotubes
and Effect of Surface Carboxylic Groups
Maryam Hesabia,* and Ghasem Ghasemib
a Young Researchers and Elite Club, Rasht Branch, Islamic Azad University, Rasht, Iran
b
Department of Chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran
*e-mail: hesabi@iaurasht.ac.ir, m.hesaby@gmail.com
Received August 22, 2019; revised August 22, 2019; accepted January 21, 2020

Abstract—The adsorption behavior of atenolol molecule over the pristine carbon nanotube and boron nitride
nanotube as well as functionalized carbon nanotube was performed employing the B3LYP and CAM-B3LYP
methods with 6-311G(d, p) basis set in two phases (gas and water solution). We used natural bond orbital,
non-covalent interactions and the quantum theory of atoms in molecules to investigate the hydrogen bonds,
interaction energies and charge transfers between the atenolol drug and nanosystems. In all cases, the process
of intermolecular interaction between atenolol and nanosystems is exothermic showing that the optimized
complexes are stable. The hydrogen-bonding interactions between drug and CNT–(COOH)3 play an import-
ant role for the different kinds of adsorption. In addition, data showed that there is a large charge donation
and back-donation for atenolol adsorption on the surface of CNT–(COOH)3. Results indicated that
although in the case of pristine carbon nanotube, the adsorption is weak, functionalization of carbon nano-
tube with –COOH groups can effectively modify the surface of nanotubes towards atenolol molecules
adsorption and improve their solubility in water solution.

Keywords: non-covalent interaction, density functional theory, drug delivery, natural bond orbital
DOI: 10.1134/S0036024420080117

1. INTRODUCTION nanocarriers in any system, it is necessary to achieve

Atenolol (AT), one of the most widely used β-
blockers, is employed for the treatment of hyperten-
sion, tachycardia and other cardiovascular diseases. It
is a vital drug for survival after heart attacks and coro-
nary artery patients [1]. The ability of drugs to apply a
biochemical modification in cellular activity, depend
mainly on its ability to interact with cellular receptors.
Despite its desired effects, some serious side effects
including hypotension, heart arrhythmias, pulmonary
embolism chest pain, and bronchospasm may be
caused by atenolol drug [2]. Side effects can happen
when drugs interact with off-target tissues. To reduce
toxicity and unwanted symptoms of drugs, there are
effectual methods to deliver drugs, one of which is
drug delivery methods that improve safety and adsorp-
tion efficacy. In order to reach efficient targeted deliv-
ery, the intended systems must be functional in the
target organs to avoid the host’s defense mechanisms
[3, 4].
Among the different types of nanotubes, boron
nitride nanotubes (BNNTs) and carbon nanotubes
(CNTs) are expected to improve the delivery of mole-
cules due to their unique properties [5, 6]. To use these
good dispersion or dissolution. In spite of the boron
nitride nanotubes that are well spread in the solvent
and usually do not show toxicity in biological systems,
there are major problems, such as low solubility, dis-
persion, and reactivity of carbon nanotubes, making
them inapplicable [7]. Therefore, the modification of
CNT to build a desired complex is of great signifi-
cance. Surface modification can be achieved through
chemical functionalization of CNT. Functionaliza-
tion provides chemical manipulation, useful in con-
trolling surface properties and designing self-assembly
procedures. It also increases their dispersibility in
water and provides suitable sites for the adsorption of
molecules. Among the many different ways that the
carbon nanotube surface can be modified, oxidation
of the surface with strong acids can be mentioned
which not only increases the solubility of the nano-
tubes, but also purifies them [8, 9]. In this study, den-
sity functional theory (DFT) is used to investigate
interactions between nanotubes and atenolol mole-
cule in two phases. For better evaluation, the different
methods including natural bond orbital (NBO 6),
quantum theory of atoms in molecules (QTAIM),
non-covalent interaction (NCI), and quantum

1678
 A CAM-B3LYP DFT INVESTIGATION OF ATENOLOL ADSORPTION
Fig. 1. (Color online) Optimized geometries of atenolol drug and corresponding MEP maps (left).
descriptors were employed. In addition to investigat-
ing the nature of interactions, stabilization energies
and charge transfer, the effects of functional groups
(i.e., carboxyl groups) in the absorption process were
studied and compared to pristine nanotubes.
2. COMPUTATIONAL METHODS
The adsorption behavior of atenolol on (6, 0) sin-
gle-walled nanotube (boron nitride and carbon nano-
tube) and acid-functionalized carbon nanotube in gas
phase and water as a solution phase were studied. To
analyze the structural and electronic properties of
pristine and functionalized nanotube, the density
functional theory calculations were done at both
B3LYP and CAM-B3LYP [10, 11] levels of theory and
6-311G(d, p) basis set and UltraFineGrid keyword
[12] in GAUSSIAN 09 package [13]. The long-range
corrected coulomb-attenuating level (CAM-B3LYP)
which is effective in the DFT methods greatly
enhanced accuracy at reasonable additional cost. Sev-
eral other studies indicated that approximation meth-
ods such as ONIOM [14] is not a reliable method for
studying functionalized nanotubes due to disruption
of the π-network [15, 16], so we did not use this
method to optimize the structures. The adsorption
energies of the structures are defined as:
Eads = Ecomplex
ZPE ZPE
– (ENT + E AT
ZPE
) + BSSE,
where Ecomplex is total energy of atenolol-nanotubes
complexes; ENT and EAT are the energies of nanotubes
and atenolol molecule, respectively. Solvation calcu-
lations were performed to estimate the effect of the
solvent by integral equation formulation of the polar-
izable continuum model (IEFPCM) for water (e =
78.9) as a solvent to appreciate the interaction of aten-
olol–nanotubes complexes in human body [17]. All of
the total energies using two basic parameters, zero
point energy (ZPE) and basis set superposition error
(BSSE) were corrected. These parameters were com-
puted by frequency calculations and counterpoise
method [18], respectively. Calculation of quantum
theory of atoms in molecules (QTAIMs) to investigate
covalent and non-covalent interactions and bond
RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A
1679
characteristics was performed by AIM2000 program
[19]. Furthermore, for the visualization of non-cova-
lent interaction areas, the non-covalent interaction
index (NCI) and reduced density gradient (RDG)
analysis were performed using VMD 9.1 [20] and
MULTIWFN [21] softwares. Donor-acceptor natural
bond orbital interactions, stabilization energies and
orbital occupancies are investigated using NBO6 anal-
ysis [22] and graphical shapes of NBO created by the
JmolNBO program [23]. To evaluate the electronic
changes and to describe chemical reactivity and stabil-
ity, quantum molecular descriptors using the highest
occupied molecular orbital (HOMO) and the lowest
unoccupied molecular orbital (LUMO) have also been
calculated [24, 25]. Studied descriptors including
HOMO–LUMO energy gap (EHL), electrophilicity
index (ω), chemical potential (μ), and global hardness
(η) and as follows:
EHL = ELUMO − EHOMO, (2)
μ = (ELUMO + EHOMO )/2, (3)
η = EHL /2, (4)
ω = μ2 /η. (5)
3. RESULTS AND DISCUSSION
3.1. Optimized Structure
(1) We studied the behavior of Atenolol (AT, as a drug)
on the surface of nanotubes using the density func-
tional theory (DFT). Zigzag single-walled carbon
nanotube and Boron nitride nanotube with the length
of about 13 Å were used. The optimized structural
geometries of atenolol (AT) and its molecular electro-
static potential surface (MEP) are presented in Fig. 1.
To determine the preferred binding site, atenolol
was placed in several different sites and two sites, site1
(–CO–NH2 group) and site 2 (–OH group) of drug,
were chosen. The molecular electrostatic potential
(MEP) surfaces predict the reactive sites of molecule
and are signified by various colors. The negative and
positive potential areas displayed with red and blue
colors are associated with the strongest attraction and
repulsion, respectively [26]. It can be observed from
Vol. 94 No. 8 2020
1680 MARYAM HESABI, GHASEM GHASEMI
B1
2.606 2.071
3.149 1.674
Fig. 2. (Color online) Optimized structure of pristine BNNT and complexes B1 and B2.
Fig. 1 that the positive MEP surfaces are located
around the hydrogen atoms (blue color) while the neg-
ative surfaces (red color) are over the oxygen atoms
especially carbonyl group. It shows that site 1 of the
drug may be more suitable for the adsorption process.
Optimized boron nitride nanotube (BNNT) and com-
plexes between boron nitride nanotube and two sites of
the drug (B1 and B2) and complexes between the drug
and carbon nanotube (CNT) namely C1 and C2 are
displayed in Figs. 2, 3, respectively.
For the most stable complexes, the adsorption
energies are calculated using Eq. (1) and summarized
in Table 1.
Clearly, most of the complexes are stable with the
negative adsorption energies. Although most results of
B3LYP method are negative, the CAM-B3LYP does
not confirm all of them. According to this method,
energies of the C2 and B2 complexes are positive and
theses complexes are unstable. Therefore, to increase
accuracy in calculations, we must consider the long
range corrections.
RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A
B2
3.242 2.590
The results show that CNT is more suitable than
BNNT for adsorption process and also most negative
energies are related to complexes between nanotubes
and site1 of the drug (C1 and B1 complexes). Due to
the large π–π interactions and more aromaticity of
CNTs, the adsorption of AT on CNTs is more favor-
able than that of BNNTs. But to increase solubility of
the complex of carbon nanotube and to achieve better
dispersion of nanotube in solvent, carbon nanotube
with carboxyl groups was functionalized. Three sites of
carbon nanotube were functionalized by carboxyl
groups as follows: (1) the side-wall of CNT; (2) the tip
of CNT; (3) the end of side-wall of CNT (Fig. 4). The
complexes between the site 1 of the drug (the best site)
and carboxylated carbon nanotube were investigated
(P1–P3). The dipole moment is calculated by differ-
ence of energy values between the gas and liquid
phases. The solvation energies are negative in all com-
plexes so, in terms of energy acceptable. Both dipole
moment and solubility parameter increase after the
adsorption of atenolol on nanotubes which can be
considered as an important factor in drug delivery.
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 A CAM-B3LYP DFT INVESTIGATION OF ATENOLOL ADSORPTION 1681

C1 C2

2.812 2.699 3.055 2.958 3.180

Fig. 3. (Color online) Optimized structure of pristine CNT and complexes C1 and C2.

The carboxylated carbon nanotubes are the most tube and have some negative charge, making carbon
stable for two reasons: (1) the carboxylic acid groups nanotube slightly positive. (2) Each carboxyl group
are electron-withdrawing groups, so expected that provides specific sites for the formation of two hydro-
COOH groups may pull some density from the nano- gen bonds which makes the complexes stable. As

Table 1. Calculated corrected adsorption energies, solvation energies, enthalpies and dipole moment for the studied com-
plexes
ΔEZPE + BSSE, kcal/mol ΔEsolv, kcal/mol ΔH, kcal/mol ΔD, Debay
Complex
CAM– CAM– CAM– CAM–
B3LYP B3LYP B3LYP B3LYP
B3LYP B3LYP B3LYP B3LYP

B1 –1.8351 –4.7584 –25.5607 –26.3397 –7.2132 –10.7944 1.3017 1.2858

B2 –0.5624 0.8047 –25.5622 –26.4206 –2.4272 –3.8184 1.3887 1.3889
C1 –2.6162 –10.7897 –20.5929 –18.1599 –3.7243 –11.6428 0.6005 1.2243
C2 –1.1705 4.3547 –22.3075 –19.1593 –2.3287 –1.6215 0.2772 1.2917
P1 –14.5915 –15.2279 –24.1431 –24.2897 –17.4787 –19.0117 0.7105 0.8227
P2 –14.7806 –15.7306 –23.6262 –24.1232 –17.6035 –18.8999 0.6446 0.7447
P3 –14.8662 –15.8234 –23.9337 –24.6185 –17.7491 –18.9056 0.0329 0.2089

RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A Vol. 94 No. 8 2020

1682 MARYAM HESABI, GHASEM GHASEMI

shown in Table 1, formation of double hydrogen bonds

leads to stabilizing the interaction energies approxi-
1
mately 12 and 5 kcal mol–1 in B3LYP and
CAM-B3LYP methods, respectively.
Optimized complexes of P series are presented in
Fig. 5. The shorter the bond distance is, the greater the 2
strength hydrogen bond will be. It can be seen that
P3 complex has the shortest hydrogen bond compared
to other complexes, so it is expected to be more stable
than the others.

3.2. Electronic Properties

To compare the electronic changes of BNNT,
CNT, and CNT–(COOH)3, the electronic structure
descriptors should be computed. Important descrip-
tors such as the global indices of reactivity, HOMO–
LUMO energy gap (EHL), and dipole moment (d) are
obtained and showed in Table 2. Electrons were trans-
ferred from the higher electronic chemical potential
(μ) to the lower one, when AT was adsorbed on nano-
tubes. The μ value of drug (–3.336) is more than CNT
(–3.545), BNNT (–4.475), and CNT‒(COOH)3
(‒4.233), so electrons flow from AT to nanotubes,
showing that AT drug acts as an electron donor. The
capability of molecules to accept the electrons is
assessed by the values of electrophilicity parameter
(ω). After adsorption of AT on the carboxylated nano-
tubes, μ value increases and ω value of complexes
decreases, demonstrating charge transfer from AT
molecule to nanosystems. Dipole moment of com-
plexes increased too, illustrating the desired quality
3
Fig. 4. (Color online) Optimized geometries of carboxyl-
ated carbon nanotube (CNT–(COOH)3).
for drug delivery. Band gap and hardness descriptors
change partially which implies that adsorption
occurs as physisorption via weak van der Waals inter-
actions.
3.3. Natural Bond Orbital
and Charge Population Analysis
NBO analysis contains occupancies, orbital
hybridization and the stabilization energy (E(2))
between drug and nanosystems have been listed in
Table 3. Data reveals that the largest value of stabiliza-
tion energy (the strongest interaction) in most com-
plexes are between valence lone pair of oxygen (n2(O))
and valence unoccupied orbital (LV) of nanosystems

Table 2. The reactivity descriptors of all investigated complexes (all in eV) and dipole moment (Debye)
Complex HOMO LUMO EHL μ η ω D

Atenolol (AT) –6.1498 –0.5216 5.6282 –3.3357 2.8141 1.9769 1.7189

CNT(6,0) –3.875 –3.215 0.660 –3.545 0.330 19.041 0.000
BNNT(6,0) –6.739 –2.212 4.527 –4.475 2.263 4.425 2.756
CNT–(COOH)3 –4.7075 –3.7584 0.9491 –4.2330 0.4745 18.8812 0.6522
C1 –3.8104 –3.1628 0.6476 –3.4866 0.3238 18.7714 1.3155
C2 –3.9497 –3.2774 0.6723 –3.6135 0.3361 19.4248 1.8667
B1 –6.3105 –1.8259 4.4846 –4.0682 2.2423 3.6905 3.9850
B2 –6.1649 –2.0882 4.0767 –4.1266 2.0383 4.1772 4.4612
P1 –4.5894 –3.6514 0.9380 –4.1204 0.4690 18.0999 2.3623
P2 –4.5657 –3.5695 0.9962 –4.0676 0.4981 16.6085 2.6306
P3 –4.5848 –3.6389 0.9459 –4.1118 0.4729 17.8762 1.8888

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 A CAM-B3LYP DFT INVESTIGATION OF ATENOLOL ADSORPTION 1683

P1
1.9045
1.6090

P2

1.6005
1.9055

P3

1.8969

1.6144

Fig. 5. (Color online) Optimized structure of complex AT/CNT–(COOH)3.

because n(O) has better spatial orientation than the is a favorable position for the interaction of drug. The
others. The NBO results confirmed that site 1 of the summation of E(2) values for BNNT complexes, B1
drug has the strongest interaction in CNT and BNNT (288.79 kcal mol–1) and B2 (19.32 kcal mol–1), in
complexes and site 3 of carboxylated carbon nanotube CNT complexes, C1 (11.04 kcal mol–1) and C2

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1684 MARYAM HESABI, GHASEM GHASEMI

Table 3. The most important donor-acceptor interaction for Atenolol adsorbed on nanosystems
Complex Donor Hybrid Occupancy Acceptor Hybrid Occupancy E(2), kcal mol–1

B1 a
n1 N20 sp12.17d0.01 1.7450 σ* N86–H105 s 0.0158 1.03

π B23–N25 sp99.99d0.02 1.8156 σ* N89–H107 s 0.0242 5.58

n1 O98 sp2.82 1.9295 bLV(1) B26 sp11.29 0.3834 22.30

σ* N13–B26 sp2.21 0.0495 3.25

n2 O98 sp2.10 1.7107 LV(1) B26 sp11.29 0.3834 211.94

σ* N13–B26 sp2.21 0.0495 4.95

σ* N25–B26 sp2.17 0.0561 4.74

n3 O98 sp74.46d0.05 1.6217 σ* N28–B26 sp2.43 0.0379 3.71

LV(1) B26 sp11.29 0.3834 3.96

σ C97–O98 sp1.48 1.9886 LV(1) B26 sp11.29 0.3834 24.05

σ C96–C97 sp2.82 1.9668 LV(1) B26 sp11.29 0.3834 2.92

B2 n1 O87 sp4.91 1.9588 π* B23–N25 sp99.99d2.46 0.2434 3.19

n2 O87 sp2.18 1.9306 σ* B23–N24 sp1.97 0.0371 1.08

π* B23–N25 sp99.99d2.46 0.2434 13.18

σ O87–H106 sp3.77d0.01 1.9891 π* B23–N25 sp99.99d2.46 0.2434 1.87

C1 n1 O14 sp0.72 1.9723 LV(1) C97 sp99.99d0.06 0.8258 2.12

n2 O14 sp99.99d0.13 1.8450 LV(1) C97 sp99.99d0.06 0.8258 7.88

π C43–C98 sp99.99d0.32 1.5357 σ* N5–H23 s 0.0114 1.04

C2 n2 O75 sp99.99d0.1 1.9476 LV(1) C27 sp92.36d0.04 0.8652 1.30

P1 n1 O77 sp0.75 1.9659 σ* N88–H106 s 0.0348 4.16

n1 O77 sp99.99d0.12 1.8448 σ* N88–H106 s 0.0348 7.78

n2 O97 sp 1.9560 LV(1) H79 s 0.4861 12.43

n2 O97 sp99.99d0.01 1.8451 LV(1) H79 s 0.4861 53.88

P2 n1 O73 sp0.70 1.9672 σ* N88–H106 s 0.0344 4.55

n1 O73 sp99.99d0.1 1.8652 σ* N88–H106 s 0.0344 7.57

n2 O97 sp0.87 1.9562 LV(1) H75 s 0.4853 12.31

n2 O97 sp15.08d0.01 1.8457 LV(1) H75 s 0.4853 53.56

P3 n1 O81 sp0.71 1.9679 σ* N88–H106 s 0.0339 4.26

n1 O81 sp99.99d0.12 1.8514 σ* N88–H106 s 0.0339 7.57

n(2) O97 sp0.89 1.9554 LV(1) H83 s 0.4860 12.73

n(2) O97 sp14.05d0.01 1.8439 LV(1) H83 s 0.4860 56.39

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 A CAM-B3LYP DFT INVESTIGATION OF ATENOLOL ADSORPTION 1685

Table 4. The charge of AIM, NBO, and Mulliken for stud- (1.30 kcal mol–1), and also CNT–COOH complexes,
ied complexes P1 (78.25 kcal mol–1), P2 (77.99 kcal mol–1), and P3
Complex Atom AIM NBO Mulliken (80.95 kcal mol–1) which are in good agreement with
the results of the interaction energies (Table 1), the
B1 N20 –1.7602 –1.1229 –0.4273 highest charge transfer (Tables 4, 5), and the shortest
bond distance (Table 6). For example, in complex P
N25 –2.1373 –1.2818 –0.5568 series; complex P1 with stabilization energy
B26 2.1653 1.2232 0.7050 78.25 kcal/mol, has adsorption energy, charge trans-
fer, bond distance –15.228 kcal/mol, 1.163 e,
N32 –1.7811 –1.1062 –0.3954 1.610 kcal/mol, respectively and for complex P3, these
values are –15.823 kcal/mol, 1.175 e, and
O98 –1.1897 –0.6104 –0.3691 1.600 kcal/mol. Graphical figures of NBO interac-
H105 0.3604 0.3720 0.2112 tions have shown in Fig. 6. It can be seen there are
good donation and back-donation between AT and
H107 0.4812 0.4391 0.2632 nanotubes. HOMO and LUMO are located on the
atenolol and nanotubes respectively. It means ateno-
H121 –0.0159 0.1885 0.0931 lol is a donor and nanotubes are acceptors of elec-
B2 N21 –2.1437 –1.2070 –0.3830 tron, making charge to transfer from AT to
nanotubes.
B23 2.1602 1.27407 0.5333
The charge transfer between drug and nanosys-
O87 –1.0905 –0.7305 –0.4216 tems in all the complexes using the AIM, NBO and
mulliken population analysis are computed and
H117 0.0377 0.1911 0.1277 summarized in Tables 4, 5. As these tables show that
C1 O14 –1.1399 –0.6449 –0.3881 total charges (Qt) in all cases are negative. Com-
plexes B1 and C1 are more negative than complexes B2
H23 0.4354 0.4055 0.2536 and C2, respectively. In complexes of P series, P3
has the highest value of Qt, and P1 has the lowest
C97 0.0322 –0.0075 –0.0081
value in agreement with the other results. Brief ly,
C98 –0.0170 –0.0470 –0.0977 the results of NBO and charge population analyses
confirmed the atenolol-nanosystems interactions
C2 C18 –0.0275 –0.0487 –0.0608 and indicated that in comparison with CNT, func-
C20 –0.0332 –0.0247 –0.0301 tionalization of ‒COOH groups on the surface of
carbon nanotube increase the charge transfer energy
C27 0.0010 –0.0415 –0.0362 significantly.
O75 –1.0924 –0.7470 –0.4042
3.4. Quantum Theory of Atoms
H98 0.0531 0.2252 0.1409
in Molecules Theory (QTAIM)
H94 0.5836 0.4658 0.2558 In addition to NBO analysis, QTAIM parame-
P1 O77 –1.1603 –0.6502 –0.3885 ters are studied for the adsorbed AT on the surface
of nanotubes. Electron density, a major parameter
H79 0.6603 0.5081 0.2966 in QTAIM, was initially evaluated by Bader. In this
theory, the bond critical point (BCP) between two
O97 –1.1537 –0.6913 –0.4474
interacting and bonded atom are determined
H106 0.4904 0.4316 0.2627 [27, 28].
P2 O73 –1.1513 –0.6844 –0.4253
QTAIM parameters contain electron density
(ρ(r)), potential energy (V(r)), laplacian electron den-
H75 0.6437 0.5088 0.2995 sity (∇2(r)), total energy density (H), kinetic energy
(G(r)), the eigenvalues of electron density Hessian
O97 –1.1608 –0.6948 –0.4502 matrix (λ), and the ratio of |V(r)|/G(r) of critical point
H106 0.4969 0.4316 0.2634 in all cases are given in Tables 6, 7. Through these
quantities, the nature of interactions of AT on the
P3 O81 –1.1673 –0.6831 –0.4152 nanotubes can be detected. The total energy (H(r)) is
the sum of kinetic and potential energies and can help
H83 0.6596 0.5081 0.2993
to identify the nature of the interactions. Based on this
O97 –1.1525 –0.6924 –0.4490 method, the positive and negative values of ∇2(r), are
related to non-covalent and covalent bond, respec-
H106 0.4852 0.4304 0.2620 tively. The larger ρ(r) values correspond to the stron-

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1686 MARYAM HESABI, GHASEM GHASEMI

Table 5. Positive, negative and total charge of AIM, NBO, and Mulliken for the studied complexes
AIM NBO Mulliken
Complex
Q+ Q– Qt Q+ Q– Qt Q+ Q– Qt

B1 3.007 –6.884 –3.877 2.223 –4.121 –1.898 1.273 –1.749 –0.476

B2 2.198 –3.234 –1.036 1.465 –1.938 –0.473 0.661 –0.805 –0.144
C1 0.468 –1.157 –0.689 0.405 –0.699 –0.294 0.254 –0.494 –0.240
C2 0.638 –1.153 –0.515 0.691 –0.862 –0.171 0.427 –0.501 –0.171
P1 1.151 –2.314 –1.163 0.934 –1.342 –0.402 0.559 –0.836 –0.277
P2 1.141 –2.312 –1.171 0.940 –1.379 –0.439 0.563 –0.876 –0.313
P3 1.145 –2.320 –1.175 0.939 –1.376 –0.437 0.561 –0.864 –0.303

Table 6. Obtained topological parameters from AIM analysis

Complex BD, Å ρ, e/a30 ∇2ρ, e/a 50 λ1 λ2 λ3 |λ1|/λ3

B1
B26–O98 1.6737 0.0876 0.2642 –0.0973 –0.0905 0.4521 0.2152
H107–N25 2.0713 0.0245 0.0748 –0.0282 –0.0270 0.1298 0.2172
H105–N20 2.606 0.0083 0.0215 –0.0073 –0.0069 0.0357 0.2045
H121–N32 3.1493 0.0029 0.0095 –0.0018 –0.0012 0.0125 0.1440
B2
B23–O87 2.5902 0.0145 0.0426 –0.0073 –0.0060 0.0558 0.1308
N21–H117 3.2420 0.0028 0.0084 –0.0018 –0.0017 0.0120 0.1500
C1
O14–C97 2.8122 0.0126 0.0404 –0.0095 –0.0079 0.0578 0.1643
C98–H23 2.6992 0.0065 0.0172 –0.0051 –0.0033 0.0257 0.1984
C2
C20–H98 3.0552 0.0038 0.0098 –0.0025 –0.0017 0.0140 0.1786
C18–H94 2.9580 0.0045 0.0146 –0.0025 –0.0002 0.0173 0.1445
O75–C27 3.1801 0.0065 0.0199 –0.0045 –0.0031 0.0276 0.1630
P1
O77–H106 1.9045 0.0275 0.0976 –0.0388 –0.0381 0.1745 0.2223
O97–H79 1.6100 0.0558 0.1456 –0.1050 –0.1033 0.3540 0.2966
P2
O73–H106 1.8970 0.0279 0.1004 –0.0396 –0.0387 0.1785 0.2218
O97–H75 1.6145 0.0550 0.1448 –0.1030 –0.1012 0.3490 0.2951
P3
O81–H106 1.9055 0.0274 0.0904 –0.0387 –0.0378 0.1745 0.2218
O97–H83 1.6005 0.0570 0.1464 –0.1083 –0.1066 0.3614 0.2996

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 A CAM-B3LYP DFT INVESTIGATION OF ATENOLOL ADSORPTION 1687

n2 O98[HOMO] → LV(1)B26: 211 kcal/mol

n2 O75[HOMO] → LV(1)C27: 1.30 kcal/mol

n2 O97[HOMO] → LV(1)H79: 53.88 kcal/mol

Fig. 6. (Color online) Selected orbital interaction for AT adsorbed on nanotubes.

gest interactions. In addition, the |V(r)|/G(r) ratio is a closed-shell interactions and medium interactions
reliable quantity to classify different interactions. In respectively [29, 30]. The ratio of |λ1|/λ3 < 0.25 con-
this way, |V|/G ≤ 1 and 1 < |V|/G < 2 are associated with firms the close shell interactions [31, 32] where λ1 and

RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A Vol. 94 No. 8 2020

1688 MARYAM HESABI, GHASEM GHASEMI

B1 B2

C1 C2

Fig. 7. (Color online) Topological graphs calculated by QTAIM theory for atenolol on the surface of CNT and BNNT.

λ3 are the lowest and the highest eigenvalues of Hes-
sian matrix of electron density, respectively.
According to Table 7, the total energy H, is positive
in all of the CPs of complexes C and B, but in com-
plexes P there are both positive and negative values.
Laplacian parameter is positive in all complexes
therefore; the small bond length, high values of ρ(r)
and positive values of H and ∇2(r) confirm the par-
tially covalent-partially electrostatic interactions in
B1 and C1 complexes. Among complexes of
P series, the highest electron density (ρ(r) = 0.057)
and (∇2(r) = 0.146), the shortest bond distance
(1.60), positive (0.002), and negative (–0.010) H
values and also |λ1|/λ3 > 0.25 confirm that these
interaction are partially covalent. The topological
graphs of drug adsorption on the nanosystems sur-
face and the positions of all bond critical points
(BCPs) have shown in Figs. 7, 8.
3.5. Reduce Density Gradient and Non-Covalent
Interactions (RDG-NCI)
RDG is an extension of QTAIM method offered in
2010 [33]. NCI is a 2D plot of the RDG and ρ(r),
where defined in following equation:
1 ∇ρ .
RDG = (6)
2(3π)13 ρ34
NCI index was employed to characterize the nature of
the weak interactions for the studied complexes via the
spikes of graphs at small densities. sgn(λ2)ρ was used
to distinguish attraction and repulsion interactions.
The λ2 values of bonds are negative, suggestive of non-
covalent interactions. The λ2 values of bonds are neg-
ative, suggestive of non-covalent interactions (see
Table 6). The strength of weak interaction depends on
the electron density and the spikes can be classified
into three types according to electron density values.

RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A Vol. 94 No. 8 2020

 A CAM-B3LYP DFT INVESTIGATION OF ATENOLOL ADSORPTION 1689

P1

P2

P3

Fig. 8. (Color online) Topological graphs calculated by QTAIM theory for atenolol on the surface of carboxylated carbon nanotube.

Regions which have the positive and negative values of
density are associated with repulsion and attractive
interaction, respectively. Furthermore, the sgn(λ2)ρ
values approach zero (λ ∼ 0, ρ ∼ 0) are related to Van
der Waals forces. The scatter graphs of RDG versus
sign (λ2)ρ and NCI surface gradient are displayed,
which are placed on the reaction sites between AT-
nanotubes complexes have shown in Figs. 9, 10. Green
color discs display weak H-bonds. There are several
kinds of spike in the scatter plots. Spikes are the points
near the bottom. Some peaks appear in the region of
0.02 to 0.05, which is related to the repulsive interac-
tions (steric effects) within the ring. Also, the region of
–0.02 to –0.05 corresponds to attractive interactions
especially hydrogen bonds [34]. It is noted from the
plots that about ρ = 0, there are Van der Waals forces
in pristine nanotube complexes.
In unfunctionalized complexes except C1 complex,
distinct deep spikes of density are seen around zero
confirming the effect of Van der Waals interaction in
these complexes. In functionalized complexes
(p series), there is no spike near zero λ and hydrogen
bonds can be observed clearly in all complexes. These
results are in agreement with the obtained results of
QTAIM and NBO analyses.

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1690 MARYAM HESABI, GHASEM GHASEMI

B1
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0
0.04 0.02 0 0.02 0.04
B2
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0
0.04 0.02 0 0.02 0.04
C1
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0
0.04 0.02 0 0.02 0.04
C2
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0
0.04 0.02 0 0.02 0.04

Fig. 9. (Color online) Plots of the reduced density gradient (RDG) vs. sgn(λ2)*ρ values (left) and NCI surface gradient (right).

RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A Vol. 94 No. 8 2020

 A CAM-B3LYP DFT INVESTIGATION OF ATENOLOL ADSORPTION 1691

2.0
1.8 P1
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0
0.04 0.02 0 0.02 0.04

2.0 P2
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0
0.04 0.02 0 0.02 0.04

2.0 P3
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0
0.04 0.02 0 0.02 0.04

Fig. 10. (Color online) Plots of the reduced density gradient (RDG) vs. sgn(λ2)*ρ values (left), and NCI surface gradient (right).

4. CONCLUSIONS hydrogen bonds. The interaction strength of site

We employed two hybrids functional of DFT
method (CAM-B3LYP and B3LYP) and QTAIM,
NBO, and NCI-RDG analyses to assess the interac-
tion energies between atenolol and nanotubes.
Although CAM-B3LYP level is large, it must be
employed to consider the long-range interaction
effects. Interaction energies reveal that the carbon
nanotube is more suitable than the boron nitride
nanotube, but to improve the performance of the car-
bon nanotube, its surface must be modified. The sur-
face substitution with –COOH groups increase the
distance between aromatic rings of nanotubes and
atenolol then lead to the stabilizing formation of
1 (‒CO–NH2) of atenolol on the surface of pristine
nanotube is higher than site 2 (–OH). The QTAIM
parameters, electron density values and its laplacian
indicate the closed-shell nature interaction in pristine
complexes and partially covalent interaction in car-
boxylated complexes. Charge transfer and stabiliza-
tion energies from NBO analysis are in agreement with
QTAIM classification, and confirm interactions
between atenolol and nanotubes. Finally, functional-
ization of carbon nanotube with carboxyl groups
enhances the solubility in water solution and can
improve the surface reactivity of nanotube toward the
drug adsorption.

RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A Vol. 94 No. 8 2020

1692 MARYAM HESABI, GHASEM GHASEMI

Table 7. Potential energy, kinetic energy, total energy, and REFERENCES

ratio of potential to kinetic energy of critical points in all of
complexes 1. A. Kuster, A. C. Alder, B. I. Escher, K. Duis, K. Fen-
ner, J. Garric, T. H. Hutchinson, D. R. Lapen, A. Pery,
Complex V(r) G(r) H(r) |V(r)|/G(r) and J. Rombke, Integr. Environ. Assess. Manage. 6, 514
(2010).
B1
2. B. Egan, J. Flack, M. Patel, and S. Lombera, J. Clin.
B26–O98 –0.0169 0.1174 0.1005 0.1440 Hypertens. 20, 1464 (2018).

H107–N25 –0.0158 0.0172 0.0014 0.9186 3. N. Bertrand and J.-C. Leroux, J. Control. Release 161,
152 (2012).
H105–N20 –0.0041 0.0048 0.0007 0.8542 4. C. Chen, H. Zhang, L. Hou, J. Shi, L. Wang, C. Zhang,
H121–N32 –0.0015 0.0019 0.0004 0.7895 M. Zhang, H. Zhang, X. Shi, and H. Li, J. Pharm.
Pharm. Sci. 16, 40 (2013).
B2 5. M. Hesabi and R. Behjatmanesh-Ardakani, Comput.
B23–O87 –0.0099 0.0103 0.0004 0.9612 Theor. Chem. 1117, 61 (2017).

N21–H117 –0.0014 0.0017 0.0003 0.8235 6. H. Xu, Q. Wang, G. Fan, and X. Chu, Theor. Chem.
Acc. 7, 104 (2018).
C1 7. O. A. Oyetade, V. O. Nyamori, B. S. Martincigh, and
O14–C97 –0.0078 0.0090 0.0012 0.8735 S. B. Jonnalagadda, RSC Adv. 6, 2731 (2016).
8. K. Z. Milowska, J. Phys. Chem. C 119, 26734 (2015).
C98–H23 –0.0028 0.0035 0.0007 0.7825
9. M. Mananghaya, M. A. Promentilla, K. Aviso, and
C2 R. Tan, J. Mol. Liq. 215, 780 (2016).
C20–H98 –0.0017 0.0021 0.0004 0.8095 10. R. Kobayashi and R. D. Amos, Chem. Phys. Lett. 420,
106 (2006).
C18–H98 –0.0024 0.0030 0.0006 0.8000
11. T. Yanai, D. P. Tew, and N. C. Handy, Chem. Phys.
O75–C27 –0.0036 0.0043 0.0007 0.8372 Lett. 393, 51 (2004).
P1 12. L. Simon and J. M. Goodman, Org. Biomol. Chem. 9,
689 (2011).
O77–H106 –0.0206 0.0225 0.0019 0.9156
13. M. Frisch, G. Trucks, H. Schlegel, G. Scuseria, M. Robb,
O97–H79 –0.0554 0.0459 –0.0095 1.2070 J. Cheeseman, G. Scalmani, V. Barone, B. Mennucci,
and G. Petersson, Gaussian 09, Revision B.01 (Gaussian,
P2 Inc., Wallingford, CT, 2009).
O73–H106 –0.0213 0.0232 0.0019 0.9181 14. S. Dapprich, I. Komaromi, K. S. Byun, K. Morokuma,
and M. J. Frisch, J. Mol. Struct. 461, 1 (1999).
O97–H75 –0.0544 0.0543 –0.0001 1.0018
15. W. L. Yim and Z. F. Liu, Chem. Phys. Lett. 398, 297
P3 (2004).
O81–H106 –0.0207 0.0226 0.0019 0.9151 16. Z. Chen, S. Nagase, A. Hirsch, R. C. Haddon,
W. Thiel, and P. V. Schleyer, Angew. Chem., Int. Ed.
O97–H83 –0.0570 0.0468 –0.0102 1.2181 43, 1552 (2004).
17. J. Tomasi, B. Mennucci, and R. Cammi, Chem. Rev.
105, 2999 (2005).
ACKNOWLEDGMENTS
18. S. Boys and F. Bernardi, Mol. Phys. 100, 65 (2002).
This work was supported by a grant from the Young
Researchers club of Islamic Azad University and we thank 19. F. A. I. M. Biegler-Konig, AIM 2000 1.0 (Univ. Appl.
Sci., Bielefeld, 2000).
for this valuable cooperation.
20. W. Humphrey, A. Dalke, and K. Schulten J. Mol.
Graph. 14, 33 (1996).
CONFLICT OF INTEREST 21. T. Lu and F. Chen, J. Comput. Chem. 33, 580 (2012).
The authors declare that they have no conflict of interest. 22. E. D. Glendening, C. R. Landis, and F. Weinhold,
J. Comput. Chem. 34, 1429 (2013).
23. Jmol-NBO Visualization Helper. http://chemgplus.blog-
AUTHOR CONTRIBUTIONS spot.com/2013/08/jmolnbo-visualization-helper.html.
Both authors participated in writing the manuscript. 24. R. G. Parr, R. A. Donnelly, M. Levy, and W. E. Palke,
Both authors read and approved the final manuscript. J. Chem. Phys. 68, 3801 (1978).

RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A Vol. 94 No. 8 2020

 A CAM-B3LYP DFT INVESTIGATION OF ATENOLOL ADSORPTION 1693

25. R. G. Parr and W. Yang, J. Am. Chem. Soc. 106, 4049
(1984).
26. P. Politzer, P. Lane, J. S. Murray, and M. C. Concha,
J. Mol. Model. 11, 1 (2005).
27. S. J. Grabowski, J. Phys. Chem. A 116, 1838 (2012).
28. I. Rozas, I. Alkorta, and J. Elguero, J. Am. Chem. Soc.
122, 11154 (2000).
29. M. Ziolkowski, S. J. Grabowski, and J. Leszczynski,
J. Phys. Chem. A 110, 6514 (2006).
30. C. F. Matta, J. Hernandez-Trujillo, T. H. Tang, and
R. F. Bader, Chem.-Eur. J. 9, 1940 (2003).
31. A. Shahi and E. Arunan, Phys. Chem. Chem. Phys. 16,
22935 (2014).
32. A. Varadwaj, P. R. Varadwaj, and B. Y. Jin, RSC Adv.
6, 19098 (2016).
33. E. R. Johnson, S. Keinan, P. Mori-Sanchez, J. Contre-
ras-Garcia, A. J. Cohen, and W. Yang, J. Am. Chem.
Soc. 132, 6498 (2010).
34. H. Xiao, J. Tahir-Kheli, and W. A. Goddard III,
J. Phys. Chem. Lett. 2, 212 (2011).

RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY A Vol. 94 No. 8 2020