DFT and experimental (FT-IR and FT-Raman) investigation of vibrational spectroscopy and molecular docking studies of 2-(4-oxo-3-phenethyl-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl) acetamide

Article abstract of DOI:10.1016/j.molstruc.2016.02.038

A comprehensive structural and vibrational study of 2-(4-oxo-3-phenethyl-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl) acetamide is reported. FT-IR and FT-Raman wavenumbers were compared with the theoretical values obtained from DFT calculations. Theoretical values agree well with the experimental values. Molecular electrostatic potential, frontier molecular orbital analysis and nonlinear optical properties were investigated using theoretical calculations. Natural bond orbital analysis shows that charge in electron density in σ?and π?antibonding orbitals and E(2) energies confirms the occurrence of intermolecular charge transfer within the molecule. Nonlinear optical property has also observed by predicting the first and second order hyperpolarizability parameters. As can be seen from the molecular electrostatic potential map of the title molecule, negative region is mainly localized over the carbonyl groups and the mono substituted phenyl ring and the maximum positive region is localized on the NH and hydrogen atoms. Molecular docking results show that the docked ligand title compound forms a stable complex with BRCA2 complex and gives a binding affinity value of -7.6 kcal/mol and results suggest that the compound might exhibit inhibitory activity against BRCA2 complex.

Full text of DOI:10.1016/j.molstruc.2016.02.038

Journal of Molecular Structure 1113 (2016) 133e145
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
DFT and experimental (FT-IR and FT-Raman) investigation of
vibrational spectroscopy and molecular docking studies of 2-(4-oxo-3-
phenethyl-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-
trimethoxyphenyl) acetamide
,
,
, c
Adel S. El-Azab a b, Y. Sheena Mary e, C. Yohannan Panicker e *, Alaa A.-M. Abdel-Aziz a
,
Magda A. El-Sherbeny c d, C. Van Alsenoy f
,
a Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
b Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt
c Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt
d Department of Pharmaceutical Chemistry, College of Pharmacy, Delta University for Science and Technology, Gamasa City, Egypt
e Department of Physics, Fatima Mata National College, Kollam, Kerala, India
f Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium
a r t i c l e i n f o
a b s t r a c t
Article history:
A comprehensive structural and vibrational study of 2-(4-oxo-3-phenethyl-3,4-dihydroquinazolin-2-
ylthio)-N-(3,4,5-trimethoxyphenyl) acetamide is reported. FT-IR and FT-Raman wavenumbers were
compared with the theoretical values obtained from DFT calculations. Theoretical values agree well with
the experimental values. Molecular electrostatic potential, frontier molecular orbital analysis and
nonlinear optical properties were investigated using theoretical calculations. Natural bond orbital
Received 22 August 2015
Received in revised form
9 February 2016
Accepted 9 February 2016
Available online 11 February 2016
analysis shows that charge in electron density in
s* and p* antibonding orbitals and E(2) energies
confirms the occurrence of intermolecular charge transfer within the molecule. Nonlinear optical
property has also observed by predicting the first and second order hyperpolarizability parameters. As
can be seen from the molecular electrostatic potential map of the title molecule, negative region is
mainly localized over the carbonyl groups and the mono substituted phenyl ring and the maximum
positive region is localized on the NH and hydrogen atoms. Molecular docking results show that the
docked ligand title compound forms a stable complex with BRCA2 complex and gives a binding affinity
value of ꢀ7.6 kcal/mol and results suggest that the compound might exhibit inhibitory activity against
BRCA2 complex.
Keywords:
DFT
FT-IR
FT-Raman
Quinazoline
Molecular docking
© 2016 Elsevier B.V. All rights reserved.
1. Introduction
antihelmenthic, antihistaminic, antifungal and antibacterial [3].
Quinazoline derivatives have been reported for their anti-bacterial,
Quinazolines are widely used for the extraction and analytical
determination of metal ions and nitraquinazone, a quinazoline
derivative has been found to possess potent phosphodiesterase
inhibitory activity [1] which is potentially useful in the treatment of
asthma [2]. Phenyl acetamide derivatives are important and bio-
logically active compounds and have been reported as possible
metabolites of antimicrobial active benzoxazoles [3]. These de-
rivatives show various types of biological properties such as
anti-fungal, anti-HIV [4,5], anthelmintic [6], anti-tubercular [7],
hypotensive [8], anti-convulsant [9], anti-fibrillatory [10], diuretic
[11] and antiviral [12e14] activities. Among a wide variety of ni-
trogen heterocycles that have been explored for developing phar-
maceutically important molecules, the quinazolines have played an
important role in medicinal chemistry and subsequently emerged
as a phamacophore [15]. In the present study, FT-IR and FT-Raman
spectra, NBO, MEP and NLO properties of the title compound were
reported. Due to the different potential biological activities of the
title compound molecular docking of the title compound is also
reported.
* Corresponding author.
E-mail address: cyphyp@rediffmail.com (C. Yohannan Panicker).
http://dx.doi.org/10.1016/j.molstruc.2016.02.038
0022-2860/© 2016 Elsevier B.V. All rights reserved.

134
A.S. El-Azab et al. / Journal of Molecular Structure 1113 (2016) 133e145
2. Experimental details
A
mixture of 2-mercapto-3-phenethylquinazolin-4(3H)-one
(2 mmol, 564 mg) and 2-chloro-N-(3,4,5-trimethoxyphenyl)acet-
amide (2.1 mmol, 544 mg) in 15 ml acetone containing anhydrous
potassium carbonate (3 mmol, 415 mg) was stirred at room tem-
perature for 12 h. The reaction mixture was filtered, the solvent was
removed under reduced pressure and the solid obtained was dried
and recrystallized from ethanol. Mp: 218e219 ꢁC, yield 94%, 1H
NMR (DMSO-d6):
d
10.39 (s, 1H), 8.52 (d, 1H, J ¼ 3.0 Hz), 8.07 (d, 1H,
J ¼ 7.5 Hz), 7.80e7.73 (m, 2H), 7.52 (d, 1H, J ¼ 8.0 Hz), 7.44 (t, 1H,
J ¼ 7.5 Hz), 7.34 (d, 1H, J ¼ 7.5 Hz), 7.27 (t, 1H, J ¼ 5.0, 6.0 Hz), 7.01 (s,
2H), 4.45 (t, 2H, J ¼ 7.5, 8.0 Hz), 4.21 (s, 2H), 3.73 (s, 6H), 3.66 (s, 3H),
3.20 (t, 2H, J ¼ 7.5, 8.0 Hz). 13C NMR (DMSO-d6)
d: 35.2, 36.9, 43.9,
55.6, 60.0, 79.1, 96.9, 118.7, 121.9, 123.2, 125.7, 126.4, 133.5, 134.6,
135.1, 136.7, 146.6, 149.1, 152.7, 156.0, 157.5, 160.4, 165.5. MS:
Mþ ¼ 505. The FT-IR spectrum (Fig. 1) was recorded using KBr
pellets on a DR/Jasco FT-IR 6300 spectrometer. The FT-Raman
spectrum (Fig. 2) was obtained on a Bruker RFS 100/s, Germany.
For excitation of the spectrum the emission of Nd:YAG laser was
used, excitation wavelength was 1064 nm, maximal power was
150 mW and measurement was carried out on solid sample (Fig. 3).
Fig. 2. FT-Raman spectrum of 2-(4-oxo-3-phenethyl-3,4-dihydroquinazolin-2-ylthio)-
N-(3,4,5-trimethoxyphenyl) acetamide.
3. Computational details
4. Results and discussion
Calculations of the title compound were carried out using
Gaussian 09 software [16] by utilizing Becke's three parameter
hybrid model with the Lee-Yang-Parr correlation functional (B3LYP)
method. The 6-311þþG(d,p) (5D, 7F) basis set was employed to
predict the molecular structure and vibrational wave numbers
[17,18]. The DFT method tends to overestimate the fundamental
modes; therefore scaling factor (0.9613) has to be used for
obtaining a considerably better agreement with experimental data
[19] and the optimized geometrical parameters are given in Table 1.
The assignments of the calculated wave numbers are aided by the
animation option of GAUSSVIEW program [20] and the potential
energy distribution (PED) is calculated with the help of GAR2PED
software package [21].
4.1. IR and Raman spectra
The calculated (scaled) wave numbers, observed IR, Raman
bands and assignments are given in Table 2. The C]O stretching
mode [22e24] is expected in the region 1750e1650 cmꢀ1 and in the
present case these modes appears at 1670 cmꢀ1 in the IR spectrum,
and at 1675, 1664 cmꢀ1 in the Raman spectrum. The DFT calcula-
tions give these modes at 1670 and 1663 cmꢀ1. The in-plane and
out-of-plane C]O bending modes are expected in the regions
625 70 and 540 80 cmꢀ1, respectively [22]. For the title com-
pound, the C]O deformation bands are observed at 700, 618 cmꢀ1
in the IR spectrum, 618 cmꢀ1 in the Raman spectrum and at 693,
636, 618, 611 cmꢀ1 theoretically. The CeOeC stretching vibrations
are expected in the range 1200e850 cmꢀ1 [22,25]. The skeletal CeO
deformation can be found in the region 320 50 cmꢀ1 [22]. As
expected, the asymmetric and symmetric CeOeC vibrations are
assigned at 1198, 1009, 978, 948, 911, 848 cmꢀ1 theoretically for the
title compound, which is in agreement with the literature [24].
Experimentally bands are observed at 915 cmꢀ1 in the IR spectrum
and at 1201, 980, 915 cmꢀ1 in the Raman spectrum.
The NeH stretching vibrations give rise to bands at
3500e3300 cmꢀ1 [26]. According to Roeges the NeH stretching
vibration appears strongly and broadly in the region
3390 60 cmꢀ1 [22]. For the title compound NeH stretching mode
is assigned at 3439 cmꢀ1 theoretically and a strong band is
observed in the IR spectrum at 3243 cmꢀ1 and at 3235 cmꢀ1 in the
Raman spectrum. Mary et al. [27] reported a band at 3343 cmꢀ1 in
the IR spectrum, 3340 cmꢀ1 in Raman spectrum and 3433 cmꢀ1
theoretically as NeH stretching mode. For the title compound the
band at 1409 cmꢀ1 (DFT) is assigned as NeH in-plane bending
mode and experimentally at 1411 cmꢀ1 in both the spectra. The out-
of-plane bending of NH is expected around 650 50 cmꢀ1 [22]. In
the present case the band at 665 (IR), 667 (Raman) and 669 cmꢀ1
(DFT) is assigned as out-of-plane bending of NeH.
Louran et al. [28] reported a value at 1220 cmꢀ1 for
yC-N for poly
aniline. In the case of aromatic amines a strong CeN stretching
Fig. 1. FT-IR spectrum of 2-(4-oxo-3-phenethyl-3,4-dihydroquinazolin-2-ylthio)-N-
(3,4,5-trimethoxyphenyl) acetamide.
absorption is observed in the region in 1342e1266 cmꢀ1 [23,24].

A.S. El-Azab et al. / Journal of Molecular Structure 1113 (2016) 133e145
135
Fig. 3. Optimized geometry of 2-(4-oxo-3-phenethyl-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl) acetamide.
Table 1
Optimized geometrical parameters of 2-(4-oxo-3-phenethyl-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl) acetamide.
Bond lengths (Å)
S1eC33
N3eC5
N4eC16
C5eC14
1.7853
1.3825
1.4765
1.4088
1.0846
1.3833
1.4628
1.5408
1.5124
1.0856
1.3941
1.0844
1.0879
1.2192
1.0125
1.0816
1.3919
1.4045
1.4391
1.0895
1.0917
1.0912
S1eC34
1.8304
1.2924
1.3859
1.0833
1.4056
1.0831
1.0902
1.0932
1.3996
1.3936
1.0842
1.3938
1.0906
1.3759
1.3947
1.3951
1.4031
1.3715
1.0937
1.4372
1.0892
1.0951
O2eC15
N4eC15
C5eC6
1.2205
N3eC33
N4eC33
C6eH7
1.4157
1.4082
1.3832
1.0836
1.4034
1.0887
1.0926
1.3995
1.0845
1.3939
1.0856
1.5216
1.4215
1.3973
1.0834
1.3701
1.374
C6eC8
C8eH9
C8eC10
C10eH11
C12eC14
C16eH18
C19eH21
C22eC31
C25eH26
C27eC29
C31eH32
C34eC37
N39eC40
C40eC42
C42eH44
C45eO59
C47eO49
C50eH52
C55eH56
O59eC60
C60eH63
C10eC12
C14eC15
C16eC19
C19eC22
C23eH24
C25eC27
C29eH30
C34eH35
C37eO38
N39eH48
C41eH43
C42eC46
C46eC47
O49eC50
C50eH53
C55eH57
C60eH61
Bond lengths (Å)
S1eC33
C12eH13
C16eH17
C19eH20
C22eC23
C23eC25
C27eH28
C29eC31
C34eH36
C37eN39
C40eC41
C41eC45
C45eC47
C46eO54
C50eH51
O54eC55
C55eH58
C60eH62
1.0932
1.0949
1.4367
1.0893
1.7853
1.3825
1.4765
1.4088
1.0846
1.3833
1.4628
1.5408
1.5124
1.0856
1.3941
1.0844
1.0879
1.2192
1.0125
1.0816
1.3919
1.4045
1.4391
1.0895
1.0917
S1eC34
1.8304
1.2924
1.3859
1.0833
1.4056
1.0831
1.0902
1.0932
1.3996
1.3936
1.0842
1.3938
1.0906
1.3759
1.3947
1.3951
1.4031
1.3715
1.0937
1.4372
1.0892
O2eC15
N4eC15
C5eC6
1.2205
1.4157
1.4082
1.3832
1.0836
1.4034
1.0887
1.0926
1.3995
1.0845
1.3939
1.0856
1.5216
1.4215
1.3973
1.0834
1.3701
1.374
N3eC5
N4eC16
C5eC14
C8eH9
N3eC33
N4eC33
C6eH7
C6eC8
C8eC10
C10eH11
C12eC14
C16eH18
C19eH21
C22eC31
C25eH26
C27eC29
C31eH32
C34eC37
N39eC40
C40eC42
C42eH44
C45eO59
C47eO49
C50eH52
C55eH56
O59eC60
C10eC12
C14eC15
C16eC19
C19eC22
C23eH24
C25eC27
C29eH30
C34eH35
C37eO38
N39eH48
C41eH43
C42eC46
C46eC47
O49eC50
C50eH53
C55eH57
C12eH13
C16eH17
C19eH20
C22eC23
C23eC25
C27eH28
C29eC31
C34eH36
C37eN39
C40eC41
C41eC45
C45eC47
C46eO54
C50eH51
O54eC55
C55eH58
1.0932
1.0949
1.4367
(continued on next page)

136
A.S. El-Azab et al. / Journal of Molecular Structure 1113 (2016) 133e145
Table 1 (continued )
C60eH61
1.0912
C60eH62
1.0951
178.0
C60eH63
1.0893
Torsion angles (ꢁ)
C34eS1eC33eN3
C33eS1eC34eH36
C33eN3eC5eC14
C16eN4eC15eO2
C33eN4eC15eC14
C15eN4eC16eC19
C33eN4eC16eC19
C16eN4eC33eS1
N3eC5eC6eC8
ꢀ2.7
C34eS1eC33eN4
C33eS1eC34eC37
C5eN3eC33eS1
C16eN4eC15eC14
C15eN4eC16eH17
C33eN4eC16eH17
C15eN4eC33eS1
C16eN4eC33eN3
C14eC5eC6eH7
C33eS1eC34eH35
C33eN3eC5eC6
C5eN3eC33eN4
C33eN4eC15eO2
C15eN4eC16eH18
C33eN4eC16eH18
C15eN4eC33eN3
N3eC5eC6eH7
ꢀ57.4
60.1
0.1
179.7
ꢀ179.1
179.6
149.3
ꢀ32.4
178.4
ꢀ179.2
179.5
0.4
179.8
0.2
ꢀ0.4
ꢀ178.7
1.3
33.2
ꢀ87.3
91.1
0.1
180.0
180.0
ꢀ179.4
0.2
ꢀ148.5
ꢀ0.9
ꢀ0.3
C14eC5eC6eC8
C6eC5eC14eC12
C5eC6eC8eC10
ꢀ0.2
N3eC5eC14eC12
C6eC5eC14eC15
H7eC6eC8eH9
N3eC5eC14eC15
C5eC6eC8eH9
H7eC6eC8eC10
0.2
179.9
ꢀ179.7
0.1
0.0
C6eC8eC10eH11
H9eC8eC10eC12
H11eC10eC12eH13
C10eC12eC14eC15
C5eC14eC15eO2
C12eC14eC15eN4
N4eC16eC19eC22
H17eC16eC19eC22
H18eC16eC19eC22
H20eC19eC22eC23
H21eC19eC22eC31
C31eC22eC23eH24
C19eC22eC31eH32
C22eC23eC25eH26
H24eC23eC25eC27
H26eC25eC27eH28
C25eC27eC29eC31
C27eC29eC31eC22
H30eC29eC31eH32
H35eC34eC37eO38
H36eC34eC37eN39
O38eC37eN39eC40
C37eN39eC40eC42
N39eC40eC41eH43
C42eC40eC41eC45
C41eC40eC42eH44
C40eC41eC45eO59
C40eC42eC46eC47
H44eC42eC46eO54
O59eC45eC47eC46
C47eC45eO59eC60
O54eC46eC47eC45
C47eC46eO54eC55
C47eO49eC50eH51
C46eO54eC55eH56
C45eO59eC60eH61
180.0
ꢀ179.7
ꢀ0.1
C6eC8eC10eC12
0.2
H9eC8eC10eH11
C8eC10eC12eC14
C10eC12eC14eC5
H13eC12eC14eC15
C12eC14eC15eO2
N4eC16eC19eH21
H17eC16eC19eH21
H18eC16eC19eH21
C16eC19eC22eC31
H21eC19eC22eC23
C19eC22eC23eC25
C19eC22eC31eC29
C23eC22eC31eH32
H24eC23eC25CeH26
C23eC25eC27eC29
C25eC27eC29eH30
H28eC27eC29eC31
H30eC29eC31eC22
S1eC34eC37eN39
H36eC34eC37eO38
C34eC37eN39eH48
C37eN39eC40eC41
H48eN39eC40eC42
C42eC40eC41eH43
N39eC40eC42eC46
C40eC41eC45eC47
H43eC41eC45eO59
H44eC42eC46eC47
C41eC45eC47eO49
C41eC45eO59eC60
C42eC46eC47eO49
C42eC46eO54eC55
C46eC47eO49eC50
C47eO49eC50eH53
C46eO54eC55eH58
C45eO59eC60eH63
C8eC10eC12eH13
H11eC10eC12eC14
H13eC12eC14eC5
C5eC14eC15eN4
N4eC16eC19eH20
H17eC16eC19eH20
H18eC16eC19eH20
C16eC19eC22eC23
H20eC19eC22eC31
C19eC22eC23eH24
C31eC22eC23eC25
C23eC22eC31eC29
C22eC23eC25eC27
C23eC25eC27eH28
H26eC25eC27eC29
H28eC27eC29eH30
C27eC29eC31eH32
S1eC34eC37eO38
H35eC34eC37eN39
C34eC37eN39eC40
O38eC37eN39eH48
H48eN39eC40eC41
N39eC40eC41eC45
N39eC40eC42eH44
C41eC40eC42eC46
H43eC41eC45eC47
C40eC42eC46eO54
C41eC45eC47eC46
O59eC45eC47eO49
C42eC46eC47eC45
O54eC46eC47eO49
C45eC47eO49eC50
C47eO49eC50eH52
C46eO54eC55eH57
C45eO59eC60eH62
179.7
180.0
ꢀ179.9
ꢀ1.0
ꢀ58.0
64.1
ꢀ176.5
ꢀ88.0
ꢀ30.9
ꢀ1.9
0.1
ꢀ0.1
ꢀ0.1
179.8
ꢀ179.7
ꢀ0.0
179.6
ꢀ23.4
35.3
ꢀ0.2
0.0
179.6
178.9
179.4
ꢀ179.6
ꢀ57.5
61.9
ꢀ0.4
ꢀ0.6
59.2
ꢀ178.7
ꢀ59.4
90.3
150.8
ꢀ149.5
179.7
2.0
179.7
ꢀ179.8
0.0
32.2
178.4
ꢀ178.4
ꢀ179.6
0.0
0.1
179.7
ꢀ179.8
ꢀ179.7
156.5
95.0
ꢀ0.1
0.0
ꢀ0.1
ꢀ144.6
ꢀ85.1
176.0
ꢀ130.2
0.8
ꢀ3.9
ꢀ174.6
5.3
51.9
ꢀ137.8
178.4
2.9
40.2
ꢀ177.1
ꢀ177.3
ꢀ1.9
0.5
ꢀ179.2
ꢀ176.6
ꢀ0.3
0.6
175.7
176.5
2.2
ꢀ3.5
ꢀ1.1
2.4
96.6
60.5
60.2
60.5
1.0
179.5
ꢀ178.0
ꢀ117.2
179.2
113.0
ꢀ83.6
179.5
179.6
178.8
ꢀ3.7
176.8
68.1
ꢀ177.9
ꢀ70.2
ꢀ61.7
ꢀ62.1
ꢀ61.7
Varghese et al. [29] reported
y
C-N mode at 1203 cmꢀ1 in the IR
1354e1306 (wagging), 1292e1152 (twisting), 976e740 (rocking)
cmꢀ1 theoretically as expected [22e24].
spectrum and at 1208 cmꢀ1 theoretically. For the title compound,
the CeN stretching modes are assigned at 1335, 1323, 1272,
953 cmꢀ1 in IR, 1333, 1319, 1272, 1158, 1107 cmꢀ1 in Raman and in
the range 1326e952 cmꢀ1 theoretically which are in agreement
with literature [22e24]. The C]N stretching mode is observed at
1515 cmꢀ1 in IR, 1520 cmꢀ1 in Raman and 1517 cmꢀ1 theoretically
as expected [22]. For the title compound CeS stretching modes are
observed at 770 cmꢀ1 in the IR spectrum, and at 770, 636 cmꢀ1
theoretically as expected [22].
For the title compound, the CH3 stretching modes are assigned
at 3034, 3022, 2984, 2931 cmꢀ1 in the IR spectrum, 3023, 2982,
2929 cmꢀ1 in the Raman spectrum and in the range
3033e2903 cmꢀ1 theoretically and these modes are expected in the
region 2900e3050 cmꢀ1 according to literature [22]. The defor-
mation modes of the methyl group of the title compound are
assigned as 1411 cmꢀ1 in the IR spectrum and 1440, 1411, 1148,
1121 cmꢀ1 in the Raman spectrum and in the ranges 1452e1400
(scissoring) and 1170e1110 cmꢀ1 (rocking) theoretically as ex-
pected [22].
In the following discussion, the poly, ortho, mono-substituted
phenyl rings are designated as PhI, PhII and PhIII respectively and
the quinazoline ring as PhIV. For phenyl rings, the CeH stretching
modes are expected above 3000 cmꢀ1 [22] and for the title com-
pound, the CH stretching modes are assigned in the range
3077e3070 for PhI, 3087e3045 for PhII and 3065e3014 cmꢀ1 for
PhIII rings theoretically. Experimentally bands are observed at
3056 cmꢀ1 in IR and 3070, 3058 cmꢀ1 in Raman spectrum. The
The stretching vibrations of the CH2 group (the asymmetric and
symmetric stretch) and deformation modes of CH2 group (scis-
soring, wagging, twisting and rocking modes) appears in the re-
gions 3000
20, 2900
25, 1450
30, 1330
35, 1245
45,
780 55 cmꢀ1 respectively [22e24]. The CH2 stretching modes are
observed at 3036, 3008, 2955 cmꢀ1 in the Raman spectrum, 3034,
3005 cmꢀ1 in the IR spectrum and in the range 3035e2902 cmꢀ1
theoretically. The deformation modes of CH2 are assigned at 1388,
1323, 1242 cmꢀ1 in the IR spectrum, 1388, 1351, 1319, 853, 743 cmꢀ1
in the Raman spectrum and in the ranges 1445e1391 (scissoring),

A.S. El-Azab et al. / Journal of Molecular Structure 1113 (2016) 133e145
137
Table 2
Calculated (scaled) wavenumbers, observed IR, Raman bands and assignments of 2-(4-oxo-3-phenethyl-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)
acetamide.
B3LYP/6-311þþG(d,p) (5D,7F)
(cmꢀ1 (cmꢀ1
IR
Raman
(cmꢀ1
Assignmentsa
y
)
y
)
c
IRI
44.66
1.17
9.82
9.14
0.78
19.96
9.47
25.02
6.88
4.09
0.81
RA
y
(cmꢀ1
)
y
)
e
b
3577
3211
3201
3193
3191
3188
3183
3177
3168
3167
3157
3155
3141
3136
3136
3135
3132
3097
3095
3092
3091
3083
3083
3047
3022
3020
3019
1737
1730
1646
1644
1637
1623
1612
1608
1579
1526
1517
1511
1509
1503
1503
1501
1500
1490
1488
1488
1487
1486
1483
1478
1466
1457
1447
1418
1409
1380
1377
1363
1358
1344
1342
1321
1316
1306
1299
1265
1255
1246
1235
1226
3439
3087
3077
3070
3067
3065
3060
3054
3045
3045
3035
3033
3020
3015
3015
3014
3010
2977
2975
2972
2972
2964
2963
2929
2905
2903
2902
1670
1663
1583
1580
1573
1560
1549
1546
1517
1467
1458
1452
1451
1445
1444
1443
1442
1432
1431
1430
1430
1428
1426
1421
1409
1400
1391
1363
1354
1326
1323
1310
1306
1292
1290
1270
1265
1255
1248
1216
1206
1198
1188
1179
173.54
66.17
244.22
120.43
72.78
363.03
149.48
48.66
93.68
73.39
93.52
16.86
45.34
12.53
118.53
95.39
132.89
57.49
45.32
34.24
37.79
38.57
131.15
108.32
195.26
197.04
71.27
45.95
45.44
71.69
66.61
131.29
10.35
9.63
3243
e
3235
e
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
y
d
y
d
d
d
d
d
y
d
y
d
y
d
y
y
y
NH(100)
CHII(95)
CHI(99)
e
e
e
3070
e
CHI(99)
e
CHII(99)
CHIII(92)
CHII(100)
CHIII(99)
CHII(98)
CHIII(94)
CH2(100)
CH3(100)
CH3(100)
CHIII(91)
CH3(99)
CHIII(99)
CH2(91)
CH3(96)
CH3(98)
CH3(96)
CH2(99)
CH2(98)
CH2(95)
CH3(100)
CH3(95)
CH3(95)
CH2(99)
C ¼ O(64),
C ¼ O(52)
e
e
e
3058
e
3056
e
e
e
e
3034
3034
3022
e
3036
e
6.79
0.32
5.60
8.86
3023
e
e
e
26.55
22.88
32.36
21.27
19.61
9.24
12.09
10.68
11.09
50.84
75.67
41.52
473.91
414.33
48.93
8.11
e
e
3005
2984
e
3008
2982
e
e
e
e
e
e
e
e
2955
2929
e
2931
e
e
e
e
e
1670
e
1675
1664
1582
e
dNH(17)
e
PhII(56),
PhIII(61),
PhI(42), d
PhIII(67), d
PhI(56), d
PhII(50),
d
d
CHII(14)
CHIII(18)
PhI(10)
CHIII(20)
PhI(12)
C ¼ O(15)
PhIII(22)
e
127.47
1.05
e
e
e
e
118.62
105.75
484.97
17.80
181.35
8.48
10.47
14.63
21.84
79.78
47.59
8.36
1552
e
e
16.88
279.5
2.02
1547
1520
1470
1460
e
y
1515
1468
1456
e
C ¼ N(46),
y
CHIII(14),
y
PhIII(64)
3.67
CH3(30),
CH3(91)
CH3(55)
CH2(88)
CH3(87)
CH2(84)
CH3(92)
CHII(17),
CH3(86)
CH3(89)
CHII(15),
CHIII(22),
yPhI(59)
17.20
17.25
23.99
7.15
29.21
15.54
14.32
14.25
9.43
e
e
e
e
e
e
e
e
e
1440
e
e
y
PhII(55)
7.74
e
e
20.24
21.00
26.86
0.72
2.72
5.15
31.53
32.53
52.30
21.99
173.26
101.50
5.50
37.36
207.97
0.82
e
e
5.85
e
e
y
PhII(57)
yPhIII(62)
NH(12)
77.03
5.86
16.32
24.92
3.72
e
e
e
e
CH3(63),
CH3(72)
CH3(44),
CH3(58),
CH2(75)
PhI(58),
CH2(78)
d
e
e
1411
e
1411
e
d
d
NH(40)
NH(12),
d
CH2(10)
CHI(10)
0.97
1388
1365
e
1388
1363
1351
1333
1319
e
40.84
37.14
72.71
40.28
11.07
135.84
28.86
2.14
20.31
17.87
47.81
1.58
d
CH3(24),
d
1335
1323
e
CN(41),
d
CH2(20),
CN(41)
CH2(13)
CO(24)
yCC(13)
CH2(44),
CHIII(47),
CH2(52),
CH2(81)
CHII(54),
y
d
e
e
y
e
e
e
1292
1272
e
y
CC(13)
CH2(20),
CN(10),
CHII(12)
CN(19)
5.98
1272
e
CN(44),
d
d
y
CHII(10)
PhII(20)
27.22
34.14
39.96
4.33
24.61
58.03
216.99
146.43
CH2(43),
PhII(40),
CH2(41),
PhIII(50),
y
d
y
e
1253
e
1242
e
88.60
2.49
e
dCHIII(10)
e
e
CHI(54),
CO(46),
CN(46),
y
CO(14), PhI(12)
CHI(25)
PhII(11), dCHII(11)
y
8.79
4.11
e
1201
e
d
y
e
13.90
1181
e
CC(37),
d
CHIII(51)
(continued on next page)

138
A.S. El-Azab et al. / Journal of Molecular Structure 1113 (2016) 133e145
Table 2 (continued )
B3LYP/6-311þþG(d,p) (5D,7F)
IR
Raman
(cmꢀ1
Assignmentsa
y
(cmꢀ1
)
b y(cmꢀ1
)
IRI
1.26
21.40
4.08
RA
47.08
y
(cmꢀ1
)
y
)
e
c
1224
1217
1209
1204
1199
1196
1182
1169
1168
1167
1167
1165
1155
1154
1176
1170
1162
1157
1152
1150
1136
1124
1123
1122
1122
1120
1110
1109
e
1174
e
d
d
d
d
d
d
d
d
d
y
d
d
d
y
CHIII(56),
CH3(74)
CH3(65)
CHII(46),
yPhIII(21)
2.46
5.20
3.71
2.04
2.51
4.50
7.34
6.22
9.14
27.29
5.83
4.32
11.73
e
e
e
0.10
e
1158
e
yCN(42)
PhI(50)
26.22
29.20
0.65
51.90
6.26
10.53
29.40
2.39
e
CH2(42),
CH3(68)
CH2(23),
y
e
1148
1135
e
e
y
PhI(72)
1127
e
CHIII(44),
CHII(62),
y
PhIII(18)
e
yPhII(14)
e
1121
1121
e
CN(12),
CH3(96)
CH3(86)
CH3(95)
CN(42),
d
CH3(19),
dCHI(48)
e
e
4.55
180.92
e
e
e
1107
dCH2(11)
1127
1105
1097
1059
1050
1047
1035
1030
1017
1015
1004
1004
1000
990
986
985
947
929
920
905
887
886
882
869
859
858
832
823
804
801
781
779
770
763
721
712
705
696
673
661
659
643
638
636
628
609
601
561
549
538
533
513
510
486
473
453
446
414
407
1084
1062
1055
1018
1009
1007
995
990
978
976
965
965
962
952
948
947
911
893
885
870
853
852
848
835
826
825
800
791
773
770
751
749
740
734
693
685
678
669
647
636
633
618
614
611
604
585
578
540
528
517
512
493
490
467
455
436
428
398
391
3.28
12.14
173.78
82.45
7.28
8.27
37.46
3.93
2.36
0.84
7.27
19.22
18.51
37.47
1.46
48.32
48.89
14.44
2.83
0.20
1.73
2.81
0.01
0.11
3.73
4.80
6.88
5.56
0.11
1.39
0.27
1.88
2.48
2.15
23.00
67.05
0.63
0.73
0.96
4.77
3.00
1.31
7.05
1.91
5.05
11.67
0.52
1.38
5.31
8.88
0.72
4.07
2.09
3.09
1.48
8.51
4.71
0.61
15.35
2.31
13.54
6.67
1.69
2.12
1.77
0.23
1.49
1080
e
1080
e
y
y
d
d
y
PhII(54), CHII(21)
PhIII(38), CHIII(24),
CHII(83), tPhII(14)
d
d
dCH2(11)
e
1050
1021
e
1020
e
CHIII(78),
CO(66)
t
PhIII(20)
1005
e
1002
e
g
g
CHII(87)
CHIII(91)
988
e
e
d
y
d
y
y
PhIII(17),
CO(44),
CH2(46),
PhII(14),
PhII(22),
yPhIII(55)
0.04
980
e
y
y
y
g
PhI(42)
PhIII(14)
CC(36)
CHII(61)
PhIII(16)
97.62
10.74
0.44
0.69
33.15
0.05
0.82
6.09
1.22
7.27
11.98
1.49
26.66
12.90
1.98
5.70
5.31
5.30
2.10
e
e
967
e
e
e
e
gCHIII(60), y
953
e
e
y
y
CN(48),
CO(76),
y
d
PhII(22),
PhI(10)
dPhIV(14)
e
e
942
915
892
e
g
y
g
g
g
CHIII(70),
CO(50), CHI(13)
CHI(80),
yCC(13)
915
895
e
g
t
PhI(10)
CHI(58),
CHII(73),
tPhI(17)
872
e
874
853
853
e
tPhII(10)
d
g
CH2(70),
CHIII(92)
CO(72),
PhII(26),
CC(44),
g
C ¼ O(23)
850
e
y
d
y
t
t
y
d
d
y
PhI(10)
PhIV(11),
CN(10)
C ¼ O(10),
C ¼ O(22),
e
836
e
yCN(13)
826
826
798
e
823
e
PhIV(10),
PhIV(25),
CC(10),
CHII(81)
CS(45),
PhI(38),
g
g
d
t
PhII(10)
PhII(17)
792
773
e
y
CS(10), dC ¼ O(10)
11.96
0.87
56.26
0.20
e
g
770
e
y
t
t
d
y
t
t
d
t
PhI(19), CN(15)
d
e
gCO(40)
e
e
PhIII(20),
CH2(63)
CS(12), tPhI(10),dCH2(10)
PhII(37),
PhIII(55),
PhII(21),
gCHIII(55)
7.63
e
743
729
e
18.77
16.66
41.62
17.38
10.31
9.38
3.14
89.92
7.61
4.39
0.11
28.77
1.61
4.30
731
700
e
g
g
C ¼ O(36)
685
e
CHIII(28)
e
t
PhIII(16),
d
CN(10)
gCO(14)
665
e
667
e
g
g
NH(47),
CN(26),
g
t
C ¼ O(10),
PhI(20)
C ¼ O(33)
CO(36),
e
e
y
t
d
d
t
d
d
d
t
CS(41),
PhI(18),
g
e
631
618
e
g
g
NH(10),
d
CO(12)
CS(10)
618
e
PhII(24), dC ¼ O(35),
d
CN(10), d
PhIII(81)
e
e
PhI(24), dC ¼ O(34),
g
CN(11)
599
586
e
598
e
CO(45), dCN(12), tPhI(11), gCO(18)
PhII(45),
PhIII(30), PhII(10),
PhII(62), tPhIV(10)
dPhIV(18)
576
538
525
e
d
dCS(10)
0.84
14.64
7.97
e
529
e
g
CO(18),
d
CO(28),
PhII(10)
CC(25)
PhI(21),
PhI(16),
dPhI(15)
d
t
PhIV(44),
PhIII(37),
d
g
t
0.74
510
e
509
e
11.79
31.79
16.53
4.61
4.53
2.00
dC ¼ O(17),
C ¼ O(36),
PhI(28),
dCS(15)
e
492
464
e
g
d
dCH2(14)
466
e
d
t
t
d
t
d
g
d
C ¼ O(19),
tNH(10)
PhII(25), PhIV(25),
PhII(49), tPhIV(21)
CO(12),
PhIII(85)
CN(49), dC ¼ O(21)
dPhIII(10)
e
438
423
401
e
425
e
dCN(11), gCO(18)
0.28
3.31
e

A.S. El-Azab et al. / Journal of Molecular Structure 1113 (2016) 133e145
139
Table 2 (continued )
B3LYP/6-311þþG(d,p) (5D,7F)
IR
Raman
Assignmentsa
y
(cmꢀ1
)
y
(cmꢀ1
)
IRI
RA
y
(cmꢀ1
)
y
(cmꢀ1
)
e
b
c
385
379
355
348
342
370
364
342
334
328
2.04
6.42
8.54
2.10
0.51
4.65
1.31
3.58
5.19
0.46
e
e
e
e
e
372
e
d
d
g
CS(32),
PhI(31),
CN(24),
d
g
t
d
PhIV(17), dC ¼ O(10)
CO(10), CS(10)
PhIII(14), CH2(20), tPhII(11)
d
340
e
d
t
d
PhI(30),
CC(54),
CO(41),
dCN(10)
e
t
PhI(22)
340
309
304
296
291
281
252
246
206
194
180
164
161
159
154
138
127
101
98
90
85
82
81
69
62
56
36
327
297
292
285
280
270
243
236
198
186
173
158
154
152
148
133
123
97
94
87
82
79
78
66
59
54
2.18
1.77
5.69
1.94
0.33
2.70
9.74
4.91
4.58
4.50
5.61
0.01
0.54
0.18
0.36
3.46
1.84
1.61
5.78
5.53
0.03
1.35
0.31
1.45
1.15
1.02
0.31
1.13
0.19
1.51
1.15
0.40
0.09
0.18
1.53
2.94
0.81
2.34
0.98
0.94
1.82
4.10
2.10
1.43
3.45
0.63
0.85
1.00
1.04
0.87
1.04
0.89
2.38
1.20
4.30
0.55
2.11
2.91
2.99
0.58
0.63
1.93
2.95
1.98
0.85
0.88
3.89
0.96
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
325
295
d
d
d
t
t
d
t
t
CO(24),
CN(28),
CS(15),
PhII(42),
PhI(26),
CS(10),
PhIII(28), d
PhI(16),
CO(17),
CO(32),
d
t
t
CC(10)
PhI(16),
t
NH(10), dCO(17)
e
PhI(13), dC ¼ O(10)
PhIV(26)
CO(43), PhI(10)
PhI(10), PhII(10),
CH2(10)
PhIII(10),
CO(17), CS(14)
PhI(15), CO(25)
CS(20)
PhII(21)
e
e
t
d
t
d
d
272
dCN(10)
250
232
195
184
t
d
t
d
dCO(30)
g
d
g
d
d
t
t
e
CH2(39),
PhIV(52),
CH3(81)
162
e
t
e
e
e
e
gCN(19), tPhIV(29), dCH2(10)
t
t
CH3(86)
CH3(81)
g
t
t
CO(38),
PhIV(48),
CO(36),
CC(12),
CO(39),
CH2(20),
tCH3(23)
107
tPhII(13)
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
g
d
t
CC(10),
dCH2(10)
g
CH2(13),
NH(28)
CO(17),
CH2(16),
tCO(21)
t
t
t
t
t
t
t
t
t
t
t
t
t
t
t
t
t
PhI(10)
CS(13),
tCS(20)
CO(17),
t
t
C ¼ O(13)
C ¼ O(24),
t
NH(25),
CO(21), PhI(10),
CS(23), PhI(12)
CH2(20),
t
t
tC ¼ O(10)
CO(23),
CO(79)
d
t
35
31
29
28
21
15
9
9
32
30
29
22
16
9
9
PhIV(24), dCH2(21), tCC(12), gCN(10)
CH2(32),
CC(38), tCH2(24),
CH2(27),
CH2(53),
CN(51),
C ¼ O(40),
tCC(14),
t
t
CN(10)
CN(10)
d
t
CN(20),
CC(11)
gCN(13)
t
PhI(10),
t
CH2(10)
CS(10)
tCN(31), t
a
y-streching; d-in-plane deformation; g-out-of-plane deformation; t-torsion; PhI-poly substituted phenyl ring; PhII-ortho substituted phenyl ring; PhIII- mono-substituted
phenyl ring; PhIV-Quinazoline ring; potential energy distribution (%) is given in brackets in the assignment column; The first column with subscript b represents unscaled
wavenumbers and second column with subscript c represents scaled wavenumbers.
phenyl ring stretching modes are assigned at 1552, 1456, 1365 (IR),
1460, 1363, 1135 (Raman), in the range 1573e1136 (DFT) for PhI,
1582, 1547, 1253 (Raman), in the range 1583e1255 (DFT) for PhII
and 1468 (IR), 1470 (Raman), in the range 1580e1216 cmꢀ1 (DFT)
for PhIII. The sixth phenyl ring stretching mode, the ring breathing
vibration appears as a weak band near 1000 cmꢀ1 in mono-, 1-3-di-
and 1,3,5-tri substituted benzenes [22,30]. In the otherwise
substituted benzenes however, this vibration is substituent sensi-
tive and difficult to distinguish from the ring in-plane deformation
[22]. In ortho disubstitution the ring breathing mode has three
frequency intervals according to whether both substituents are
heavy, or one of them is heavy while the other is light, or both of
them are light. In the first case the interval is 1100e1130 cmꢀ1, in
the second case 1020e1070 cmꢀ1, while in the third case it is be-
tween 630 and 780 cmꢀ1 [30]. In the present case the PED analysis
gives ring breathing modes at 978 cmꢀ1 for PhI, 1084 cmꢀ1 for PhII
and 990 cmꢀ1 for PhIII, as expected [22]. Raj et al. [31] reported the
ring breathing mode of poly substituted benzene at 1025 cmꢀ1 in
IR, 1027 cmꢀ1 in Raman and 1032 cmꢀ1 theoretically. For ortho
substitutꢀe1d phenyl ring the ring breathing mode is reported at
1041 cm [32] and at 1086, 1011 cmꢀ1 (theoretically) [33] and at
1020 cmꢀ1 (theoretically) [34]. The CeH deformation modes of the
phenyl ring, in-plane and out-of-plane modes are expected above
and below 1000 cmꢀ1 respectively [22]. For the title compound, the
in-plane CH deformation modes are assigned at 1121 (Raman) for
PhI,1292,1158,1050 (Raman) for PhII and 1181,1127,1020 (IR),1174,
1021 cmꢀ1 (Raman) for PhIII. The DFT calculations give these modes
in the ranges 1206e1122 cmꢀ1 for PhI, 1290e1055 cmꢀ1 for PhII
and 1310e1018 cmꢀ1 for PhIII, as expected [22]. The out-of-plane
CeH modes are assigned at 895 (IR), 892 (Raman), 893, 885 (DFT)
for PhI, 1005, 872 (IR), 1002, 874, 773 (Raman), 1007, 965, 870, 773
(DFT) for PhII and 850 (IR), 942, 853 (Raman), 995, 947, 962, 852,
749 cmꢀ1 (DFT) for PhIII. The ring substituent deformation modes
are also identified and assigned (Table 2) and most of the modes are
not pure but contains significant contributions from other modes
also. Inorder to investigate the performance of vibrational wave-
numbers of the title compound, the root mean square value be-
tween the calculated and observed wavenumbers were calculated
and the RMS errors are 3.12 for IR and 3.29 for Raman modes
(without considering the NH stretching mode).
4.2. Natural bond orbital analysis
In NBO analysis, a large stabilization energy E(2) value shows an

140
A.S. El-Azab et al. / Journal of Molecular Structure 1113 (2016) 133e145
Table 3
Second-order perturbation theory analysis of Fock matrix in NBO basis corresponding to the intramolecular bonds of the title compound.
Donor(i)
Type
ED/e
Acceptor(j)
Type
ED/e
E(2)a
E(j)-E(i)b
F(i,j)c
S1eC33
s
e
1.97343
e
N3eC5
N4eC15
s
s
*
*
0.02753
0.09003
5.15
3.66
1.09
1.05
0.067
0.056
e
O2eC15
p
e
1.99367
e
O2eC15
C5eC14
p
p
*
*
0.32981
0.42100
1.05
4.51
0.37
0.40
0.019
0.042
e
N3eC33
s
e
1.98682
e
N3eC5
N4eC16
s
s
*
*
0.02753
0.03136
1.80
2.26
1.38
1.22
0.045
0.047
e
e
e
e
e
e
p
e
e
N4eC33
C5eC6
s
*
*
0.05934
0.02485
0.35171
0.03841
1.60
2.26
1.35
1.48
0.34
0.37
0.042
0.052
0.023
0.074
e
s
1.87937
N3eC33
C5eC14
p
*
1.70
e
s*
15.76
e
N4eC15
s
e
1.98078
e
S1eC33
N4eC16
s
s
*
*
0.06401
0.03136
3.19
1.26
0.96
1.13
0.050
0.034
e
e
e
e
e
e
N4eC33
s
*
*
0.05934
0.02198
2.48
1.80
1.25
1.39
0.050
0.045
C12eC14
s
e
N4eC33
s
e
1.98690
e
O2eC15
N3eC33
s
s
*
*
0.00906
0.01537
2.32
1.60
1.44
1.46
0.052
0.043
e
e
e
e
e
e
N4eC15
N4eC16
s
*
*
0.09003
0.03136
1.58
1.73
1.28
1.16
0.041
0.040
s
e
C5eC6
s
e
1.97510
e
N3eC5
N3eC33
s
s
*
*
0.02753
0.01537
1.65
2.40
1.17
1.31
0.039
0.050
e
e
e
e
e
e
e
e
e
C5eC14
C6eC8
s*
s*
s*
0.03841
0.01415
0.05967
4.08
2.57
2.92
1.28
1.30
1.18
0.065
0.052
0.053
C14eC15
e
C5eC14
s
e
1.97215
e
O2eC15
N3eC5
s
s
*
*
0.05967
0.05967
2.64
1.28
1.30
1.18
0.052
0.035
e
e
e
e
e
e
e
e
e
C5eC6
s*
s*
s*
0.02485
0.02198
0.05967
3.82
4.36
1.93
1.28
1.29
1.19
0.062
0.067
0.043
C12eC14
C14eC15
e
C14eC15
s
e
1.97396
e
O2eC15
N4eC16
s
s
*
*
0.00906
0.03136
1.36
3.31
1.27
0.99
0.037
0.051
e
e
e
e
e
e
e
e
e
e
e
e
C5eC6
s*
s*
s*
s*
s*
0.02485
0.03841
0.03841
0.02198
3.05
2.72
1.99
2.40
1.25
1.27
1.29
1.26
0.055
0.053
0.045
0.049
C5eC14
C10eC12
C12eC14
e
C16eC19
C37eO38
C37eN39
s
p
s
e
1.97268
1.99033
1.98668
e
C22eC31
C37eO38
S1eC34
0.02331
0.28224
0.01537
0.03238
2.47
1.12
1.54
1.73
0.65
0.38
0.97
1.24
0.039
0.020
0.034
0.042
p
*
s
s
*
*
N39eC40
e
C40eC41
s
e
1.97181
e
N39eC40
C40eC42
s
s
*
*
0.03238
0.02780
1.01
3.85
1.12
1.29
0.030
0.063
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
C41eC45
C45eO59
C40eC41
C42eC46
C46eO54
s*
s*
s*
s*
s*
0.02610
0.02670
0.02783
0.02598
0.02671
2.63
4.12
3.85
2.63
4.12
1.29
1.08
1.29
1.29
1.08
0.052
0.059
0.063
0.052
0.059
e
C41eC45
s
e
1.97256
e
N39eC40
C40eC41
s
s
*
*
0.03238
0.02783
4.31
2.93
1.12
1.29
0.062
0.055
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
C45eC47
C47eO49
O59eC60
C40eC42
C46eC47
s*
s*
s*
0.04625
0.02450
0.01010
0.02780
0.39624
3.46
3.80
1.28
1.08
0.98
0.29
0.29
0.060
0.057
0.033
0.072
0.069
1.41
p
p
*
21.79
19.84
*
e
C42eC46
s
e
1.97250
e
N39eC40
C40eC42
s
s
*
*
0.03238
0.02780
4.31
2.93
1.12
1.29
0.062
0.055
e
e
e
e
e
e
e
e
e
C46eC47
C47eO49
O54eC55
s*
s*
s*
0.04625
0.02450
0.01011
3.46
3.80
3.80
1.28
1.08
1.08
0.060
0.057
0.057
e
C45eC47
s
e
1.97627
e
C41eC45
C46eC47
s
s
*
*
0.02610
0.04625
3.44
3.38
1.31
1.29
0.060
0.059
e
e
e
C46eO54
s*
0.02671
3.63
1.09
0.056
e
C46eC47
s
e
1.97628
e
C42eC46
C45eC47
s
s
*
*
0.02598
0.02598
3.44
3.38
1.31
1.29
0.060
0.059
e
e
e
e
C45eO59
s*
0.02598
3.63
1.09
0.056

A.S. El-Azab et al. / Journal of Molecular Structure 1113 (2016) 133e145
141
Table 3 (continued )
Donor(i)
Type
ED/e
Acceptor(j)
Type
ED/e
E(2)a
E(j)-E(i)b
F(i,j)c
LPS1
s
p
1.98337
1.98337
N3eC33
N3eC33
s
p
*
*
0.01537
0.35171
2.78
21.59
1.25
0.25
0.053
0.069
e
LPO2
s
e
1.97668
e
N4eC15
C14eC15
s
s
*
*
0.09003
0.05967
1.58
2.64
1.10
1.15
0.038
0.050
e
e
p
1.97668
N4eC15
s
*
*
0.09003
0.05967
28.12
17.45
0.67
0.72
0.124
0.102
e
e
C14eC15
s
e
LPN3
s
e
1.97668
e
S1eC33
N4eC33
s
s
*
*
0.06401
0.05934
4.16
16.33
0.49
0.77
0.041
0.101
e
e
e
e
e
e
C5eC6
s
*
*
0.02485
0.03841
1.49
8.71
0.91
0.92
0.034
0.081
C5eC14
s
e
LPN4
s
e
1.58809
e
O2eC15
N3eC33
p
p
*
*
0.32981
0.35171
54.56
55.07
0.28
0.27
0.112
0.110
e
e
e
C16eC19
s*
0.02253
5.58
0.64
0.059
e
LPO38
s
e
1.97472
e
C34eC37
C37eN39
s
s
*
*
0.06367
0.07460
2.55
1.33
1.06
1.15
0.047
0.035
e
e
e
p
e
e
1.86415
S1eC33
s*
s*
s*
0.06401
0.06367
0.07460
1.73
20.29
25.09
0.40
0.63
0.72
0.024
0.103
0.122
e
e
C34eC37
C37eN39
e
LPN39
s
e
1.72310
e
C37eO38
C40eC41
p
*
0.28224
0.02783
67.39
6.62
0.27
0.84
0.122
0.071
s*
e
e
e
C40eC42
s*
0.02780
6.62
0.84
0.071
e
LPO49
s
p
1.93978
1.93519
C46eC47
C45eC47
p
*
0.39624
0.04625
6.32
7.53
0.58
0.87
0.060
0.073
s*
s*
s*
e
e
e
C46eC47
0.04625
7.42
0.87
0.072
e
LPO54
s
e
1.95095
e
C46eC47
C46eC47
0.04625
0.39624
7.22
2.15
1.03
0.49
0.077
0.032
p*
e
e
e
p
e
e
1.91374
C42eC46
C46eC47
C46eC47
s
*
*
0.02598
0.04625
0.39624
4.82
1.41
8.88
0.96
0.95
0.41
0.062
0.033
0.058
e
e
s
p*
e
LPO59
s
e
1.95096
e
C41eC45
C45eC47
s
s
*
*
0.02610
0.04625
2.05
7.20
0.49
1.03
0.031
0.077
e
e
e
e
a
p
e
e
1.91374
C41eC45
C41eC45
C45eC47
s*
0.02610
0.37415
0.04625
4.86
8.94
1.42
0.96
0.41
0.95
0.062
0.058
0.033
e
e
p*
s*
E(2) means energy of hyper-conjugative interactions (stabilization energy in kJ/mol).
Energy difference (a.u) between donor and acceptor i and j NBO orbitals.
F(i,j) is the Fock matrix elements (a.u) between i and j NBO orbitals.
b
c
intensive interaction between electron-donors and electron-
acceptors and the possible intensive interactions are given in
Table 3. The second-order perturbation theory analysis of Fock-
matrix in NBO basis shows strong intra-molecular hyper con-
jugative interactions are formed by orbital overlap between n(O),
1.86415, 1.93519, 1.91374, 1.91374. The lower energy orbitals are,
n1(S1), n1(O2), n1(O38), n1(O49), n1(O54), n1(O59) with lower en-
ergies, ꢀ0.63930, ꢀ0.67242, ꢀ0.67181, ꢀ0.56242, ꢀ0.46983,
ꢀ0.46997a.u. and p-characters, 28.92, 40.92, 51.02, 57.86, 72.01,
71.89% and high occupation numbers, 1.98337, 1.97668, 1.97472,
1.93978, 1.95095, 1.95096.
n(N), n(S) and s*(CeN), p*(CeN), s*(CeC), p*(CeC), p*(CeO) bond
orbitals which result in intra-molecular charge transfer causing
stabilization of the system.
Thus, a very close to pure p-type lone pair orbital participates in
the electron donation to the n2(S1)/
p
*(N3eC33), n2(O2)/
*(N4eC15), n1(N3)/ *(N3eC33), n2(O38)/
*(C37eN39), n1(N39)/ n2(O49)/ *(C46eC47),
*(C46eC47) and n2(O59)/p*(C41eC45) interactions in
The important hyper-conjugative interactions are: N3eC33 from
s
s
s
*(N4eC33), n1(N4)/
p
S1 of n2(S1)/
N4eC33 from N3 of n1(N3)/
n1(N4)/ *(N3eC33), C37eN39 from O38 of n2(O38)/
37eO38 from N39 of n1(N39)/ *(C37eO38), C46eC47 from O49 of
n2(O49)/ *(C46eC47), C46eC47 from O54 of n2(O54)/ *(C46eC47),
O59 of n2(O59)/ *(C41eC45) with electron densities, 0.35171,
p
*(N3eC33), N4eC15 from O2 of n2(O2)/
*(N4eC33), N3eC33 from N4 of
*(C37eN39),
s
*(N4eC15),
p*(C37eO38),
s
s
n2(O54)/
p
p
s
the compound. The results are tabulated in Table 4.
C
p
s
p
4.3. Molecular electrostatic potential (MEP)
p
0.09003, 0.05934, 0.35171, 0.07460, 0.28224, 0.04625, 0.39624e,
0.37415e and stabilization energies, 21.59, 28.12, 16.33, 55.07, 25.09,
67.39, 7.42, 8.88, 8.94 kJ/mol. The natural hybrid orbitals with
higher energy orbital and considerable p-characters and low oc-
cupations numbers are: n2(S1), n2(O2), n2(O38), n2(O49), n2(O54),
n2(O59) with energies, ꢀ0.24547, ꢀ0.24101, ꢀ0.24295, ꢀ0.30641,
ꢀ0.38355, ꢀ0.38346a.u. and p-characters, 99.99, 99.99, 99.85, 100,
86.50%, 86.59% and low occupation numbers, 1.84721, 1.86231,
Molecular electrostatic potential (MEP) generally present in the
space around the molecule by the charge distribution is very useful
in understanding the sites of electrophilic and nucleophilic reaction
for the study of biological recognition process and hydrogen
bonding interactions. The electrostatic potential is also well suited
for analyzing processes based on the recognition of one molecule
by another, as in drug-receptor, and enzyme-substrate interactions,
because it is through their potentials that the two species first see

142
A.S. El-Azab et al. / Journal of Molecular Structure 1113 (2016) 133e145
Table 4
each other. To visually consider the most probable sites of the title
compound for an interaction with electrophilic and nucleophilic
species, MEP was calculated at the DFT/B3LYP method with 6-
311þþG(d,p) (5D, 7F) set from the optimized geometry. While
electrophilic reactivities visualized by red color which indicate the
negative regions of the molecule, the nucleophilic reactivities
colored by blue, indicating the positive regions of the molecule as
shown in Fig. 4. Regions of negative potential are usually associated
with the lone pair of electronegative atoms. As can be seen from the
MEP map of the title molecule, negative region is mainly localized
over the C]O groups and the mono substituted phenyl ring which
are electrophilic. The maximum positive region is localized on the
NH and hydrogen atoms which are nucleophlic.
NBO results showing the formation of Lewis and non-Lewis orbitals.
Bond(A-B)
S1-C33
ED/ea
EDA% EDB% NBO
s%
p%
85.65
s
1.97343 44.97 55.03 0.6706(sp5.92)Sþ
14.35
28.53
ꢀ0.61816
e
e
0.7418(sp2.50)C
71.47
e
p
O2-C15
1.98232 69.94 30.06 0.8363(sp1.00)Oþ
0.00 100.0
0.00 100.0
ꢀ0.35803
e
e
0.5483(sp1.00)C
e
s
N3-C33
1.97269 59.30 40.70 0.7701(sp1.50)Nþ 39.87
60.13
62.58
ꢀ0.77565
e
e
0.6379(sp1.67)C
37.42
e
p
N3-C33
1.98682 61.69 38.31 0.7855(sp1.00)Nþ
0.00 100.0
0.00 100.0
ꢀ0.90925
e
e
0.6189(sp1.00)C
e
s
N4-C15
1.98078 64.20 35.80 0.8012(sp1.97)Nþ 33.70
66.30
70.44
ꢀ0.80959
e
e
0.5984(sp2.38)C
29.56
e
s
N4-C33
1.98690 37.20 62.80 0.6099(sp1.88)Nþ 34.69
65.31
65.96
ꢀ0.84791
e
e
0.7925(sp1.93)C
34.04
e
4.4. Nonlinear optical properties
s
C5-C6
1.97510 48.85 51.15 0.6989(sp1.78)Cþ 36.02
63.98
65.91
ꢀ0.69569
e
e
0.7152(sp1.93)C
34.09
e
s
C5-C14
1.97215 49.29 50.71 0.7021(sp1.80)Cþ 35.67
64.33
66.01
The calculated first hyperpolarizability of the title compound is
2.66 ꢂ 10ꢀ30 e.s.u which is 20.46 times that of standard NLO ma-
terial urea (0.13 ꢂ 10ꢀ30 e.s.u) [35]. For quinazoline derivatives the
reported values of first hyperpolarizability are 2.75 ꢂ 10ꢀ30 e.s.u
[36] and 5.05 ꢂ 10ꢀ30 e.s.u [37]. The molecular second hyper-
polarizability value can aid in gaining information about the
physical properties of materials to understand the origin of third
harmonic signals generated in chemical and biological structures.
Such knowledge is effective in the development of optical devices
including the application of optical communication, optical
switching, signal processing and optical computing [38]. The
average second hyperpolarizability has been calculated by using
the following expression.
ꢀ0.70636
e
e
0.7121(sp1.94)C
33.99
e
s
C14-C15
1.97396 51.70 48.30 0.7190(sp2.26)Cþ 30.64
69.36
61.94
ꢀ0.67720
e
e
0.6950(sp1.63)C
38.06
e
s
C16-C19
1.97268 50.45 49.55 0.7103(sp2.53)Cþ 28.33
71.67
74.61
ꢀ0.59509
e
e
0.7039(sp2.94)C
25.39
e
p
C37-O38
1.99033 30.20 69.80 0.5495(sp1.00)Cþ
0.00 100.0
0.00 100.0
ꢀ0.35969
e
e
0.8355(sp1.00)O
e
s
C37-N39
1.98668 37.38 62.62 0.6114(sp2.15)Cþ 31.75
68.25
62.83
ꢀ0.83783
e
e
0.7913(sp1.69)N
37.17
e
s
C40eC41
1.97181 50.44 49.56 0.7102(sp1.74)Cþ 36.45
63.55
64.77
ꢀ0.71495
e
e
0.7040(sp1.84)C
35.23
e
s
C40-C42
1.97181 50.44 49.56 0.7102(sp1.74)Cþ 36.45
63.55
64.77
ꢀ0.71494
e
e
0.7040(sp1.84)C
35.23
e
s
C41-C45
1.97256 50.05 49.95 0.7074(sp1.90)Cþ 34.52
65.48
62.01
h
ꢀ0.71671
e
e
0.7068(sp1.63)C
37.99
e
gav ¼ 1=5 gxxxx þ gyyyy þ gzzzz þ 2gxxyy þ 2gxxzz þ 2gyyzzꢃ
s
C42-C46
1.97250 50.04 49.96 0.7074(sp1.90)Cþ 34.52
65.48
62.01
ꢀ0.71668
e
e
0.7068(sp1.63)C
37.99
e
The amount of charge transfer for the molecule depends on the
s
C45-C47
1.97627 49.81 50.19 0.7057(sp1.72)Cþ 36.78
63.22
62.52
nature of the end group of the molecule. Increase of p-conjugated
ꢀ0.72734
e
e
0.7085(sp1.67)C
37.48
e
chain length in organic molecules, in general, enhances the
magnitude of hyperpolarizability. The calculated value of gav for the
title compound is ꢀ56.009 ꢂ 10ꢀ37 esu. Thus the present investi-
gation provides a new route to design high performance NLO
materials.
s
C46-C47
1.97628 49.80 50.20 0.7057(sp1.72)Cþ 36.77
63.23
62.53
ꢀ0.72736
1.98337
ꢀ0.63930
1.84721
ꢀ0.24547
1.97668
ꢀ0.67242
1.86231
ꢀ0.24101
1.89048
ꢀ0.33265
1.58809
ꢀ0.26520
1.97472
ꢀ0.67181
1.86415
ꢀ0.24295
1.72310
ꢀ0.25904
1.93978
ꢀ0.56242
1.93519
ꢀ0.30641
1.95095
ꢀ0.46983
1.91374
ꢀ0.38355
1.95096
ꢀ0.46997
1.91374
ꢀ0.38346
e
e
0.7085(sp1.67)C
37.49
e
n1S1
e
e
e
e
sp0.41
e
71.08
e
28.92
e
e
n2S1
e
e
e
e
sp1.00
e
0.01
e
99.99
e
e
n1O2
e
e
e
e
sp0.69
e
59.08
e
40.92
e
4.5. Frontier molecular orbital analysis
e
n2O2
e
e
e
e
sp99.99
e
0.01
e
99.99
e
HOMO-LUMO band gap plays a very crucial role in determining
the chemical reactivity, stability of the molecule, UVeVis spectra,
chemical reactions, electrical and optical properties. LUMO energy
means the ability to accept an electron while HOMO energy means
ability to donate an electron. The conjugated molecules are char-
acterized by a highest occupied molecular orbital-lowest unoccu-
pied molecular orbital gap (HOMO-LUMO), which is the result of a
significant degree of intermolecular charge transfer from the end
capping electron-donor groups to the efficient electron-acceptor
groups through a pi-conjugated path. The strong charge transfer
interaction through pi-conjugated bridge results in substantial
groundstate donor-acceptor mixing the appearance of a charge
transfer band in the electronic spectrum. Therefore, an electron
density transfers occurs from the more aromatic part of the pi-
conjugated system in the electron-donor side to its electron-
withdrawing part. The energy gap between the HOMO and LUMO
is a critical parameter in determining molecular electrical transport
properties and for predicting the most reactive position in pi-
electron systems and also explains several types of reaction in
conjugated system. The highest occupied molecular orbital
(HOMO) and the lowest unoccupied molecular orbital (LUMO) of
the title compound are shown in Fig. 5). HOMO is localized over the
mono-substituted phenyl ring, ortho-substituted phenyl ring, the
e
n1N3
e
e
e
e
sp2.79
e
26.34
e
73.66
e
e
n1N4
e
e
e
e
sp1.00
e
0.00 100.0
e
e
e
n1O38
e
e
e
e
sp0.69
e
58.98
e
51.02
e
e
n2O38
e
e
e
e
sp99.99
e
0.15
e
99.85
e
e
n1N39
e
e
e
e
sp1.00
e
0.00 100.0
e
e
e
n1O49
e
e
e
e
sp1.37
e
42.14
e
57.86
e
e
n2O49
e
e
e
e
sp1.00
e
0.00 100.0
e
e
e
n1O54
e
e
e
e
sp2.57
e
27.99
e
72.01
e
e
n2O54
e
e
e
e
sp6.40
e
13.50
e
86.50
e
e
n1O59
e
e
e
e
sp2.57
e
28.01
e
71.89
e
e
n2O59
e
e
e
e
sp6.41
e
13.49
e
86.51
e
e
a
ED/e is expressed in a.u.

A.S. El-Azab et al. / Journal of Molecular Structure 1113 (2016) 133e145
143
Fig. 4. MEP plot of 2-(4-oxo-3-phenethyl-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl) acetamide.
Fig. 6. Schematic for the docked conformation of active site of title compound at
BRCA2 complex.
the following relations
h
¼ (I-A)/2 and
m
¼ ꢀ (I þ A)/2, where I and
A are the first ionization potential and electron affinity of the
chemical species [40]. For the title compound, EHOMO ¼ ꢀ8.539 eV,
ELUMO ¼ ꢀ2.327 eV, Energy gap ¼ HOMO-LUMO ¼ 6.212 eV, Ioni-
zation potential I ¼ 8.539 eV, Electron affinity A ¼ 2.327 eV, global
Fig. 5. HOMO-LUMO plots of 2-(4-oxo-3-phenethyl-3,4-dihydroquinazolin-2-ylthio)-
N-(3,4,5-trimethoxyphenyl) acetamide.
quinzoline ring and the sulfur atom while the LUMO is localized
over ortho-substituted phenyl ring and quinzoline ring. Therefore a
charge transfer occurs through the ring systems. For understanding
various aspects of pharmacological sciences including drug design
and the possible eco-toxicological characteristics of the drug mol-
ecules, several new chemical reactivity descriptors have been
proposed. Using HOMO and LUMO orbital energies, the ionization
hardness
electrophiliciy ¼
h
¼ 3.106 eV, chemical potential
m
¼ ꢀ5.433 eV, global
m
2/2
h
¼ 4.752 eV. It is seen that the chemical
potential of the title compound is negative and it means that the
compound is stable.
4.6. Molecular docking
energy and electron affinity can be expressed as: I ¼ ꢀEHOMO
,
Quinazoline are a large class of active chemical compounds
possess a wide variety of biological activities such as anti HIV,
A ¼ ꢀELUMO [39]. The hardness and chemical potential are given
h
m

144
A.S. El-Azab et al. / Journal of Molecular Structure 1113 (2016) 133e145
(
p
-anion) with phenyl ring. The docked ligand title compound
forms a stable complex with BRCA2 complex and gives a binding
affinity (
D
G in kcal/mol) value of ꢀ7.6 (Table 5). These preliminary
results suggest that the compound might exhibit inhibitory activity
against BRCA2 complex.
4.7. Geometrical parameters
In the title compound, the CeS bond lengths are 1.7853 and
1.8304
Å
while the reported values are in the range
1.7675e1.8641 Å [46] and 1.7710e1.8110 Å [31]. The shortening of
the bond length of C15eO2 (1.2205 Å) and C37eO38 (1.2192 Å) could
be assigned a double bond character. The CeO bond lengths of the
title compound are C46eO54 ¼ 1.3715 Å, C55eO54 ¼ 1.4372 Å,
C
C
47eO49 ¼ 1.3740 Å, C50eO49 ¼ 1.4391 Å, C45eO59 ¼ 1.3701 Å and
60eO59 ¼ 1.4367 Å and all the CeO bond lengths are greater than
the average distance of 1.362 Å found among phenols [47] and the
increase is due to the noticeable intra-molecular hydrogen bonding
experienced by the molecule [48]. The bond lengths of C40eN39
Fig. 7. The docked protocol reproduced the co-crystallized conformation with H-bond
(1.4215 Å),
C37eN39 (1.3759 Å), C15eN4 (1.4157 Å), C33eN4
(green),
p-alkyl (pink) and p-anion (brown).
(1.3859 Å), and C5eN39 (1.3825 Å) are shorter than the normal CeN
bond length of about 1.48 Å and this point into the effect of reso-
nance in this part of the molecule [49]. All the carbonecarbon bond
lengths in the benzene rings lie in the range 1.3919e1.4045 Å for
PhI, 1.3832e1.4088 Å for PhII and 1.3936e1.3996 Å for PhII and
bond lengths are somewhere in between the normal values for a
single (1.54 Å) and a double bond (1.33 Å) [50]. The acetamide
group is tilted from the phenyl ring PhI according to the torsion
angles, C45eC41eC40eN39 ¼ 178.4ꢁ, C41eC40eN39eC37 ¼ 51.9ꢁ,
Table 5
The binding affinity values of different poses of the title compound predicted by
AutodockVina.
Mode
Affinity (kcal/mol)
Distance from best mode (Å)
e
RMSD l.b.
RMSD u.b.
e
1
2
3
4
5
6
7
8
9
ꢀ7.6
ꢀ7.5
ꢀ7.4
ꢀ7.3
ꢀ7.3
ꢀ7.3
ꢀ7.3
ꢀ7.2
ꢀ7.2
0.000
2.639
3.828
2.319
2.881
2.330
2.804
3.640
1.962
0.000
5.713
7.711
4.846
5.062
4.964
4.694
6.122
5.952
C
46eC42eC40eN39 ¼ ꢀ177.3ꢁ and C42eC40eN39eC37 ¼ ꢀ130.2ꢁ. The
quinazoline moiety is planar with respect to the phenyl ring PhII, as
is evident from the torsion angles C12eC14eC15eN43 ¼ 179.4ꢁ,
C
12eC14eC5eN3
¼
180.0ꢁ, C6eC5eN3eC33
¼
179.8ꢁ and
C6eC5eC14eC15 ¼ ꢀ179.4ꢁ and the CH2 groups at C19 and C16 are
tilted from the phenyl ring PhIII, as is evident from the torsion
angles, C25eC23eC22eC19 ¼ 178.4ꢁ, C23eC22eC19eC16 ¼ ꢀ88.0ꢁ,
C
29eC31eC22eC19 ¼ ꢀ178.4ꢁ and C31eC22eC19eC16 ¼ 90.3ꢁ. At N4
position, the bond angles
C
33eN4eC15 is increased by 1.0ꢁ,
C
33eN4eC16 is increased by 2.6ꢁ and C15eN4eC16 is decreased by
anticancer [41,42], antifungal, antibacterial, anti-mutagenic, anti-
convulsant etc. [43]. High resolution crystal structure of BRCA2
complex was downloaded from the protein data bank website (PDB
ID: 3EU7). All molecular docking calculations were performed on
Auto Dock Vina software [44]. The protein was prepared for docking
by removing the co-crystallized ligands, waters and co-factors. The
Auto Dock Tools (ADT) graphical user interface was used to calcu-
late Kollman charges and polar hydrogen's. The ligand was pre-
pared for docking by minimizing its energy at B3LYP/6-
311þþG(d,p) (5D, 7F) level of theory. Partial charges were calcu-
lated by Geistenger method. The active site of the enzyme was
defined to include residues of the active site within the grid size of
40 Å ꢂ 40 Å ꢂ 40 Å. The most popular algorithm, Lamarckian
Genetic Algorithm (LGA) available in Autodock was employed for
docking. The docking protocol was tested by extracting co-
crystallized inhibitor from the protein and then docking the
same. The docking protocol predicted the same conformation as
was present in the crystal structure with RMSD value well within
the reliable range of 2 Å [45]. Amongst the docked conformations,
one which binded well the active site was analyzed for detailed
interactions in Discover Studio Visualizer 4.0 software. The ligand
binds at the active site of the substrate (Figs. 6 and 7) by weak non-
covalent interactions. Lys1062, Asp1125 and Val1123 amino acid
forms H-bond with pyrimidine ring, C]O and NeH group respec-
3.7ꢁ from 120ꢁ and this is due to the interaction between O2 and the
methylene at C16 position. At C22 position, the bond angles are
C
C
31eC22eC23
¼
118.6ꢁ,
C31eC22eC19
¼
120.8ꢁ
and
23eC22eC19 ¼ 120.7ꢁ and the reduction in the angle C31eC22eC23
is due to presence of adjacent methylene groups. At C15 position,
the bond angles, N4eC15eC14 is decreased by 5.6ꢁ and C14eC15eO2
is increased by 5.0ꢁ from 120ꢁ and this variation is due to the
interaction between O2 and the adjacent methylene groups. Simi-
larly at C5 position, the bond angles C6eC5eC14
¼
118.9ꢁ,
N3eC5eC6 ¼ 119.1ꢁ and C14eC5eN3 ¼ 122.0ꢁ and this asymmetry in
angles is due to the interaction between the quinazoline and PhII
rings. Also at C33 position, the bond angles N3eC33eN4 ¼ 124.8ꢁ and
N4eC33eS1 ¼ 115.3ꢁ and this asymmetry in angles is due to the
interaction between the quinazoline ring and adjacent moieties.
Similarly at N39 position, the bond angles C40eN39eC37 ¼ 130.9ꢁ,
C
40eN39eH48 ¼ 116.6ꢁ and C37eN39eH48 ¼ 119.9ꢁ and this asym-
metry in angles is due to the interaction between the NH group and
the oxygen atom O38 and at C37 position, the bond angle
N
39eC37eC34 is reduced by 2.6 and C34eC37eO38 is increased by 2.2
from 120, which shows the hydrogen bonding between O38 and
H48
.
5. Conclusion
tively. Leu970, Ala1017 and Lys1062 form
phenyl ring. Asp1122 amino acid forms electrostatic interaction
p-alkyl interaction with
The experimental and theoretical vibrational spectra of 2-(4-
oxo-3-phenethyl-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-

A.S. El-Azab et al. / Journal of Molecular Structure 1113 (2016) 133e145
145
J.B. Foresman, J.V. Ortiz, J. Cioslowski, D.J. Fox, Gaussian 09, Revision D.01,
Gaussian, Inc, Wallingford CT, 2013.
trimethoxyphenyl) acetamide were investigated. The complete
assignments were performed on the basis of potential energy dis-
tribution of the vibrational modes. The stimulated FT-IR and Raman
spectra of the title compound show good agreement with the
observed spectra. The calculated HOMO and LUMO energies show
that charge transfer occur within the molecule. The calculated first
hyperpolarizability of the title compound is 20.46 times that of
standard NLO material urea and hence the title compound and its
derivatives are good object for further studies in nonlinear optics.
Molecular docking study shows that the ligand binds at the active
site of the substrate by weak non-covalent interactions; Lys1062,
Asp1125 and Val1123 amino acid forms H-bond with pyrimidine
ring, C]O and NeH group respectively; Leu970, Ala1017 and
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