Synthesis and characterization of 3-aminoquinoline derivatives and studies of photophysicochemical behaviour and antimicrobial activities

Article abstract of DOI:10.1016/j.molstruc.2015.09.016

A series of 3-aminoquinoline derivatives were synthesized, where their chemical structures were confirmed by various analytical techniques, such as, Elemental Analysis, Nuclear Magnetic Resonance Spectroscopy (¹H and ¹³C NMR), Liquid Chromatography-Mass-Mass Spectroscopy (LC-MS-MS), Ultraviolet-Visible Spectroscopy (UV-Vis), Fourier Transform Infrared Spectroscopy (FTIR) and Photoluminescence (PL). The quinoline ring core, typical of aminoquinolines, and a naphthalene group was combined to devise (4-alkyl-1-naphthyl)-quinolin-3-ylamide derivatives. These derivatives were designed and synthesized in light of the chemical and biological profiles of these important subunits. All the compounds were evaluated for their in vitro antibacterial and antifungal activities by the paper disc diffusion method with Gram-positive Bacillus subtilis, Bacillus megaterium and Staphylococcus aureus, Gram-negative Enterobacter aerogenes, Eschericha coli, Klebsiella pneumoniae and Pseudomonas aeruginosa and yeasts Candida albicans, Saccharomyces cerevisiae and Yarrovia lipolytica. These compounds showed antimicrobial activities against Gram-positive and Gram-negative bacteria and several yeasts, and thus their activity was not restricted to any particular type of microorganism.

Full text of DOI:10.1016/j.molstruc.2015.09.016

Journal of Molecular Structure 1103 (2016) 45e55
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
Synthesis and characterization of 3-aminoquinoline derivatives
and studies of photophysicochemical behaviour and antimicrobial
activities
a
,
*
a
a
a
Gulay Zengin , Ali Muayad Nafea Al Kawaz , Huseyin Zengin , Adem Mert ,
Bedia Kucuk
a
b
Department of Chemistry, Faculty of Science and Literature, Gaziantep University, Gaziantep, 27310, Turkey
Department of Biology, Faculty of Science and Literature, Kahramanmaras Sutcu Imam University, Kahramanmaras, 46100, Turkey
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 July 2015
Received in revised form
A series of 3-aminoquinoline derivatives were synthesized, where their chemical structures were
confirmed by various analytical techniques, such as, Elemental Analysis, Nuclear Magnetic Resonance
1
13
Spectroscopy ( H and C NMR), Liquid Chromatography-Mass-Mass Spectroscopy (LC-MS-MS), Ultra-
violeteVisible Spectroscopy (UVeVis), Fourier Transform Infrared Spectroscopy (FTIR) and Photo-
luminescence (PL). The quinoline ring core, typical of aminoquinolines, and a naphthalene group was
combined to devise (4-alkyl-1-naphthyl)-quinolin-3-ylamide derivatives. These derivatives were
designed and synthesized in light of the chemical and biological profiles of these important subunits. All
the compounds were evaluated for their in vitro antibacterial and antifungal activities by the paper disc
diffusion method with Gram-positive Bacillus subtilis, Bacillus megaterium and Staphylococcus aureus,
Gram-negative Enterobacter aerogenes, Eschericha coli, Klebsiella pneumoniae and Pseudomonas aeruginosa
and yeasts Candida albicans, Saccharomyces cerevisiae and Yarrovia lipolytica. These compounds showed
antimicrobial activities against Gram-positive and Gram-negative bacteria and several yeasts, and thus
their activity was not restricted to any particular type of microorganism.
1
0 September 2015
Accepted 12 September 2015
Available online 14 September 2015
Keywords:
Naphthalene
Quinoline derivatives
Antimicrobial activity
Photoluminescence
©
2015 Elsevier B.V. All rights reserved.
1
. Introduction
resembles the structure of naphthalene. Thus, it is not surprising to
find work in the literature involving these two quinoline and
naphthalene moieties, where these structural cores have been
interchanged, or derivatizations have been made. Quinoline-
bearing compounds are naturally present in plants. Quinoline de-
rivatives are varied, and have a wide range of applications, in
particular, are used as antibiotics against a variety of bacteria that
have acquired resistance to regular antibiotics. Quinoline de-
rivatives, like other types of heterocyclic compounds, possess
anticancer and anti-HIV properties [2]. Further, a study showed
quinoline cannabinoid derivatives having analgesic activity via se-
The basis of drug design is to develop chemical compounds
having maximum medicinal applications and minimum toxico-
logical effects. Both naphthalene and quinoline are important
structural units, commonly used in antimicrobial therapeutics.
Popular drugs containing naphthalene include the b-blocker drug
propranolol used for heart disease, and antimicrobial agents, such
as, naftifine and nafcillin, which have antifungal and antibacterial
properties, respectively; nafcillin is a penicillin-type antibacterial
drug, that has been structurally modified via naphthalene
replacement with quinoline, in an effort to overcome drug resis-
2
lective agonist activity for cannabinoid CB receptors [3]. The
tance, specifically by action on the
lococci [1].
Quinoline consists of a benzene ring fused to a pyridine ring,
thus is a heterocyclic aromatic compound, and very much
b
-lactamase enzyme of Staphy-
literature reveals a study on quinoline and naphthalene derivatives
evaluated for antimycobacterial properties [4]. Here the structural
design for derivatization was influenced by the drugs mefloquine
and TMC207, where mefloquine is a quinoline analogue, and
TMC207 bears both the naphthalene and quinoline subunits [5].
While both naphthalene and quinoline derivatives have been
shown to have an important role in medicinal chemistry, providing
*
Corresponding author.
E-mail address: gzengin@gantep.edu.tr (G. Zengin).
http://dx.doi.org/10.1016/j.molstruc.2015.09.016
022-2860/© 2015 Elsevier B.V. All rights reserved.
0

46
G. Zengin et al. / Journal of Molecular Structure 1103 (2016) 45e55
a wide variety of bioactivities, such as, antibiotic and anticancer
properties [6e9], a common feature of these structures is that they
have been shown to have antiinflammatory and analgesic effects. In
this context, the study herein presents work on novel compounds
bearing both these two structural cores for possible antiin-
flammatory and analgesic effects, in the development of effective
therapeutic compounds of nonsteroidal nature.
2.4. General procedure for synthesis of (4-alkyl-1-
naphthoylamino)-benzenesulfonamide compounds (3aed)
(4-Alkyl-1-naphthoylamino)-benzenesulfonamides (6e9) were
synthesized following a slightly modified method of the literature
[10], where the modifications used are described below in the text.
We have already reported work on the synthesis of new naph-
thoyl sulfonamides [10], where biological evaluations and photo-
chemical properties were presented. In this study, new 3-
aminoquinoline derivatives were synthesized and screened for
antimicrobial activity to assist in the development of antibiotic
drugs with analgesic and anti-inflammatory properties. Fluores-
cence properties of the derivatives were also investigated, as they
may bear good fluorescence, and have potential in optical tech-
nology for microscopic diagnostics.
2.5. (4-Methyl-1-naphthyl)-quinolin-3-ylamide (6)
An orange colored oil formed: yield: 50%. FTIR (ATR): 3475 (NH-
secondary amine), 1714, 1627, 1589, 1493 and 1259 (C]O, carbonyl
group; C]N, C]C, CeC, CeN, aromatic ring), 1057 (CeN, amide),
2924 (CeH, aromatic ring) 2873 (CeH, alkane), 1441 (CH
2
, alkane),
max: 280, 290, 302 nm;
3.12 (s, 3H, eCH ), 6.88 (s, 1H,
NeH), 7.31 (d, J ¼ 7.2 Mz, 1H, AreH), 7.40 (d, J ¼ 6.8 Mz, 1H, AreH),
.56e7.63 (m, 8H, AreH), 7.72 (d, J ¼ 9.6 Mz, 1H, AreH), 8.09 (d,
ꢁ
1
1381 cm (CH
3
, alkane); UVeVis (CH
2 2
Cl ) l
1
H NMR (400 MHz, DMSO-d ppm):
6
d
3
7
13
2
. Materials and method
J ¼ 7.2 Mz, 1H, AreH); C NMR (100 MHz, DMSO-d
6
) d 19.5, 123.9,
125.1, 125.7 (2C), 126.3 (2C), 126.8 (3C), 127.1 (5C), 129.5, 132.4 (2C),
þ
2.1. Materials and reagents
133.8, 135.4, 170.0 (C]O); MS (EI) m/z (relative intensity) 312 (M ,
00), 197 (10), 183 (82), 170(4), 80 (48); Anal. Calcd. for C21 O:
1
16 2
H N
Solvents and reagents were purchased from Sigma Aldrich and
C, 80.75, H, 5.16, N, 8.97, O, 5.12. Found: C, 80.83, H, 5.45, N, 9.02.
Merck Chemical companies, and used without further purification,
unless reactions called for dry conditions. The solvents used were
diethyl ether, ethanol, methanol, tetrahydrofuran (THF), N,N-
dimethylformamide (DMF), dichloromethane (DCM), 1,2-
dichloroethane, diethylene glycol, petroleum ether, ethyl acetate
and hexane. The reagents used were ethylmagnesium bromide
2.6. (4-Ethyl-1-naphthyl)-quinolin-3-ylamide (7)
An orange colored oil formed: yield: 55%. FTIR (ATR): 2964 (NH-
secondary amine), 1705, 1629, 1586, 1493 and 1259, (C]O, carbonyl
group; C]N, C]C, CeC, CeN, aromatic ring), 1058 (CeN, amide),
(
3.0 M), propylmagnesium chloride (2.0 M), 1-cyanonaphthalene,
diphenylcarbamoyl chloride, oxalyl chloride, 1-ethylnaphthalene,
-aminoquinoline, anhydrous aluminum chloride, semicarbazide
hydrochloride, 4-methyl morpholine (N-ethyl morpholine, NEM),
2929 (CeH, aromatic ring) 2872 (CeH, alkane), 1452 (CH
2
, alkane),
max: 282, 292, 302 nm;
1.31 (t, J ¼ 7.4 Mz, 3H, eCH ),
), 6.88 (s, 1H, NeH), 7.34 (d, J ¼ 7.2 Mz,
1H, AreH), 7.40 (d, J ¼ 7.2 Mz, 1H, AreH), 7.54e7.62 (m, 8H, AreH),
ꢁ
1
1397 cm (CH
3
, alkane); UVeVis (CH
H NMR (400 MHz, DMSO-d ppm):
3.10 (q, J ¼ 6.9 Mz, 2H, eCH
2 2
Cl ) l
1
3
6
d
3
2
9
,10-diphenylanthracene and hydrochloric acid.
1
3
7
.72 (d, J ¼ 7.6 Mz, 1H, AreH), 8.14 (d, J ¼ 8.4 Mz, 1H, AreH);
NMR (100 MHz, DMSO-d 15.4, 25.7, 123.9, 124.6, 124.7 (2C),
25.9 (2C),126.8 (3C),126.9 (5C),129.8,131.6 (2C),133.8,141.2,170.0
C
2
.2. Instrumentation and conditions
6
) d
1
þ
Melting points of compounds were obtained by a SRS Model
(C]O); MS (EI) m/z (relative intensity) 325 ([Mꢁ1] , 100), 183 (99),
1
l3
melting point apparatus. H and C NMR data were obtained using
a Bruker Avance 400 MHz spectrometer, with deuterated chloro-
119 (35), 80 (46); Anal. Calcd. for C22 O: C, 80.96, H, 5.56, N,
18 2
H N
8.58, O, 4.90. Found: C, 81.07, H, 5.84, N, 8.93.
form (CDCl
3
) and dimethyl sulfoxide (DMSO-d
6
) as the solvent.
Chemical shifts (
d) were given as parts per million (ppm) and
2.7. (4-Propyl-1-naphthyl)-quinolin-3-ylamide (8)
coupling constants in units of Hertz (Hz). Elemental analyses for C,
H and N were carried out on a Thermo Scientific FLASH 2000 CHNS
Organic Elemental Analyzer. FTIR spectra were obtained using a
Perkin Elmer 100 FTIR Spectrometer with a Gladia ATR Sampling
Accessory component. UVeVis spectra were recorded in the range
of 190e1100 nm using a PG model Instruments Ltd., T80 þ UV/VIS
Spectrophotometer. The single-photon fluorescence spectra were
recorded on a Perkin Elmer LS55 spectrofluorophotometer. Spec-
trophotometric grade DCM was used, and samples were examined
using a quartz sample cell of 1 cm optical path. Concentration of
An orange colored oil formed: yield: 56%. FTIR (ATR): 2956 (NH-
secondary amine), 1707, 1630, 1586, 1494 and 1258 (C]O, carbonyl
group; C]N, C]C, CeC, CeN, aromatic ring), 1057 (CeN, amide),
2928 (CeH, aromatic ring) 2869 (CeH, alkane), 1452 (CH
2
, alkane),
max: 282, 292, 302 nm;
0.98 (t, J ¼ 7.2 Mz, 3H, eCH ),
]), 6.85 (s, 1H, NeH), 7.33 (d, J ¼ 7.2 Mz, 1H,
AreH) 7.38 (d, J ¼ 7.2 Mz, 1H, AreH), 7.54e7.62 (m, 8H, AreH), 7.71
ꢁ1
1381 cm (CH
3
, alkane); UVeVis (CH
H NMR (400 MHz, DMSO-d ppm):
1.68e1.74 (m, 4H, 2[-CH
2 2
Cl ) l
1
6
d
3
2
13
(d, J ¼ 7.6 Mz, 1H, AreH), 8.14 (d, J ¼ 7.2 Mz, 1H, AreH); C NMR
(100 MHz, DMSO-d 14.4, 24.0, 34.6, 123.8, 124.8, 125.8 (2C),
ꢁ5
ꢁ1
samples in DCM was 1.0 ꢀ 10 molL , and a 266 nm excitation
wavelength was applied. The respective photoluminescence
quantum yields (QYs) were measured using the standard 9,10-
diphenylantracene [11e13].
6
) d
125.9 (2C), 126.7 (3C), 126.9 (5C), 129.8, 131.8 (2C), 133.8, 139.6,
þ
170.0 (C]O); MS (EI) m/z (relative intensity) 340 (M , 100), 197
20 2
(10), 183(82), 119 (34), 80 (55); Anal. Calcd. for C23H N O: C, 81.15,
H, 5.92, N, 8.23, O, 4.70. Found: C, 81.45, H, 6.37, N, 8.49.
2.3. Calculation of QSAR molecular descriptors
2.8. (4-Butyl-1-naphthyl)-quinolin-3-ylamide (9)
Quantitative Structure-Activity Relationships (QSAR) were
gathered to correlate biological activities with physiochemical
properties, and were obtained using HyperChem [14]; Molecular
Mechanics Force Field (MMþ) was used to pre-optimize structures
which were refined using the semi-empirical PM3 method. HOMO
and LUMO values were computed from the geometry optimized
structures.
An orange colored oil formed: yield: 65%. FTIR (ATR): 2953 (NH-
secondary amine), 1707, 1632, 1587, 1494 and 1260 (C]O, carbonyl
group; C]N, C]C, CeC, CeN, aromatic ring), 1057 (CeN, amide),
2928 (CeH, aromatic ring) 2868 (CeH, alkane), 1458 (CH
2
, alkane),
max: 282, 292, 302 nm;
0.93 (t, J ¼ 7.4 Mz, 3H, eCH ),
ꢁ1
1381 cm (CH
3
, alkane); UVeVis (CH
2 2
Cl ) l
1
H NMR (400 MHz, DMSO-d ppm):
6
d
3

G. Zengin et al. / Journal of Molecular Structure 1103 (2016) 45e55
47
1
.36e1.45 (m, 4H, 2[-CH
NeH), 7.32 (d, J ¼ 7.2 Mz, 1H, AreH), 7.38 (d, J ¼ 7.2 Mz, 1H, AreH),
.56e7.63 (m, 8H, AreH), 7.72 (d, J ¼ 8.0 Mz, 1H, AreH), 8.13 (d,
2
]),1.66 (t, J ¼ 7.4 Mz, 2H, eCH
2
), 6.85 (s,1H,
3.3. Antimicrobial activity
7
An agar diffusion method with sterile filter paper disks was
utilized to detect antimicrobial activity [16]. The following mi-
crobes were used: three Gram-positive bacteria (Bacillus subtilis,
Bacillus megaterium and Staphylococcus aureus), four Gram-
negative bacteria (Enterobacter aerogenes, Escherichia coli DM,
Klebsiella pneumonia and Pseudomonas aeruginosa) and three yeasts
(Candida albicans, Saccharomyces cerevisiae and Yarrowia lipolytica).
All microorganisms were obtained from the Department of Biology,
Kahramanmaras Sutcu Imam University, Turkey.
1
3
J ¼ 6.8 Mz, 1H, AreH); C NMR (100 MHz, DMSO-d
3.0, 34.6, 123.8, 124.7, 125.7 (2C), 125.9 (2C), 126.7 (3C), 126.9 (5C),
29.8, 131.7 (2C), 133.8, 139.9, 170.0 (C]O); MS (EI) m/z (relative
intensity) 355 ([Mþ1], 8), 278 (100), 101 (7), 57 (9); Anal. Calcd. For
O: C, 81.33, H, 6.26, N, 7.90, O, 4.51. Found: C, 81.79, H, 6.59,
6
) d 14.3, 22.6,
3
1
24 22 2
C H N
N, 7.98.
3
. Results and discussion
The in vitro antimicrobial data collection was performed
following typical techniques [16]. The test solutions were prepared
in methanol. The inhibition zones on media were measured in
triplicate, expressed as average values, and given in mm. The
antimicrobial activities are given in Table 1.
The derivatives exhibited impressive antimicrobial activities. As
a representative example, the photographs of the antimicrobial
activity, reflected as inhibition zones of Gram-positive and Gram-
negative bacteria (Staphylococcus aureus and Klebsiella pneumo-
niae, respectively) for the derivatives (6e9) and 3-aminoquinoline
3
.1. General properties of 4-alkyl-1-naphthyl)-quinolin-3-ylamide
derivatives (6e9)
The synthesized derivatives were obtained as orange coloured
oils and were stable at room temperature. They were miscible with
DMF, THF, methanol, ethanol, chloroform and DCM, and immiscible
in water. The elemental analyses are given in the materials and
method section, and are in good agreement with the calculated
values.
(5) are given in Fig. 1.
3.2. Chemistry
The antimicrobial activity observed for all the synthesized de-
rivatives (6e9), in general, showed greater antimicrobial activity
than the precursor compound 3-aminoquinoline (5). Antimicrobial
data obtained showed that the 4-methyl- analogue (6) had some-
what the lowest degree of activity, while the 4-ethyl-, 4-propyl-
and 4-butyl- analogues had reasonably high and similar activities;
it was the highest for the 4-butyl- analogue (9). It was noted the
antibacterial activity of both the Gram-positive and Gram-negative
bacteria were indistinguisable, but the antifungal activity was less
profound for all the compounds. The derivatives (6e9) had inhi-
bition zones of the range 11e32 mm, whereas the precursor com-
pound (5) had a range of 11e13 mm. An examination of the
antibacterial and antifungal activities of these derivatives revealed
that antimicrobial activity was not restricted to any particular type
of microorganism, giving antimicrobial activities against Gram-
positive and Gram-negative bacteria and several yeasts.
(
4-Alkyl-1-naphthyl)-quinolin-3-ylamide derivatives (6e9)
were obtained from 3-aminoquinoline (5) and 4-alkylnaphthalene
carboxylic acids, following a slightly modified synthetic method of
the literature [10]. These modifications entailed the final step of
nucleophilic addition/elimination reaction, where the solvent me-
dia for the naphthoyl chloride preparation was DMF, rather than
DCM, due to solubility complications. Further, removal of the NEM
salt by filtration was left to the end, where precipitation of this
NEM. HCl salt was initiated by ethyl acetate addition. Drying
(
4
MgSO ), concentration by in vacuo evaporation, and finally puri-
fication by column chromatography yielded the derivatives.
The 4-alkylnaphthoic acids, except for 4-methylnaphthoic acid
which was readily available, were synthesized as described in the
literature [15]. This series of compounds was developed such that
the 4-alkyl carbon length varied in size from the small methyl to the
larger butyl group. The synthesis of (4-alkyl-1-naphthyl)-quinolin-
3.4. Physicochemical data in QSAR studies
3
-ylamide derivatives (6e9) was achieved using the methodology
given in Scheme 1.
QSAR studies of the synthesized derivatives were examined. The
COOH
O
N
1
2
. (COCl) / DMF
2
N
H
NH2
R
.
R
N
*
1 R = CH3
6 R = CH3
7 R = C H
2 5
*5
2
3
4
R = C H5
2
DMF/ NEM
R = C H7
8 R = C H
3
3
7
R = C H9
9 R = C H
4 9
4
*
Commercially available
Scheme 1. Synthesis of (4-alkyl-1-naphthyl)-quinolin-3-ylamide derivatives.

48
G. Zengin et al. / Journal of Molecular Structure 1103 (2016) 45e55
Table 1
Antimicrobial activity data for (4-alkyl-1-naphthyl)-quinolin-3-ylamide derivatives (6e9) and 3-aminoquinoline (5).
Compoundb Microorganisma
Gr (þ)
Gr (ꢁ)
Yeast
Bacillus
Subtilis
Bacillus
megaterium
Staphylococcus Enterobacter
Eschericha Klebsiella
Pseudomonas
aeruginosa
Candida
albicans
Saccharomyces
cerevisiae
Yarrovia
lipolytica
aureus
aerogenes
coli
pneumoniae
5
6
7
8
9
12
20
28
24
26
11
12
24
28
32
13
26
28
26
24
12
16
24
24
28
11
16
24
22
20
11
18
22
26
24
12
16
18
24
24
e
e
12
11
12
11
12
12
21
14
11
13
14
18
19
-
no activity observed.
a
%
growth inhibition.
b
Concentration 1,2 mg/per disk.
known as the octanol-water partition coefficient [17e19]. High
lipophilic parameters show good permeation of compounds
through cell membranes. It can be seen from Table 2 that there
were slight increases in lipophilicity from (4-methyl-1-naphthyl)-
quinolin-3-ylamide (6) through to (4-butyl-1-naphthyl)-quinolin-
3-ylamide (9), and likewise the antimicrobial activity showed a
similar trend, with slight increases in antimicrobial activity. The
same pattern was noted with respect to the molecular volume (MV)
and molecular refractivity (MR) values, where higher MV and MR
values gave greater antimicrobial activities. Chain length in-
crements led to molecular weight (MW) increases as expected. The
MW of the precursor compound 3-aminoquinoline (5) has a much
lower MW than its derivatives. MR increased from the 4-methyl- to
4-butyl- derivatives; compound 5 had the lowest MR value. It can
be seen that the log P values also increased from the 4-methyl to 4-
butyl derivatives; this is expected as log P is a measure of lip-
ohilicity, and chain length increments of eCH
2
- from 4-methyl- to
4-butyl- increase lipohilicity. There was a great change in the en-
ergy difference (
compared to its derivatives (6e9). However,
in general increased slightly with eCH
D
E) between the HOMO and LUMO of compound 5
E for the derivatives
- increments from the 4-
D
2
methyl- to 4-butyl- derivatives. The naphthoyl and quinoline sub-
units are the unchanged components of the derivatives, thus this
may be the main reason for the slight energy differences (DE) be-
tween HOMO and LUMO of the derivatives. Thus, the 4-alkyl chain
lengths, and naphthoyl and quinoline subunits all affected lip-
ophilicity and antimicrobial activity in slightly differing degrees.
3
.5. UltravioleteVisible spectrophotometer (UVeVis)
Fig. 1. Inhibition zones of Gram-positive and Gram-negative bacteria (Staphylococcus
aureus and Klebsiella pneumoniae, respectively) for (4-alkyl-1-naphthyl)-quinolin-3-
ylamide derivatives (6e9) and 3-aminoquinoline (5).
measurements
The UVeVis spectra of the synthesized compounds (6e9) and
the precusor compound 3-aminoquinoline (5) were examined in
spectrophotometric grade DCM solvent, and are shown in Fig. 2.
Spectrophotometric grade DCM solvent was used for the analysis.
DCM solvent has a polarity index of 3.1, and two absorptions can be
distinguished at 274 and 344 nm for the precursor compound (5),
and this is in agreement with data given in the literature [20,21].
values of selected descriptors for the new 3-aminoquinoline de-
rivatives are given in Table 2.
The field of QSAR allows us relate the biological activity of a
series of compounds to their physicochemical parameters [17e19]
Lipophilicity is the physicochemical property widely used in me-
dicinal chemistry, and is designated as the logP value; this is also
The absorption at 274 nm is ascribed to the
p-p* transition in the
Table 2
Selected QSAR descriptors for the derivatives synthesized, HOMO and LUMO calculated by the PM3 method.
Compound
logP
MW
MV (Ǻ3)
MR (Ǻ3)
HOMO (eV)
LUMO (eV)
DE (eV)
5
6
7
8
9
ꢁ1.30
1.19
1.58
1.98
2.38
144.18
312.37
326.40
340.42
354.45
452.87
871.69
903.09
970.96
1023.25
50.48
105.64
110.24
114.84
119.44
ꢁ8.174
ꢁ8.984
ꢁ8.988
ꢁ8.984
ꢁ8.983
ꢁ0.4112
ꢁ0.8317
ꢁ0.8317
ꢁ0.8324
ꢁ0.8317
7.763
8.152
8.156
8.152
8.151

G. Zengin et al. / Journal of Molecular Structure 1103 (2016) 45e55
49
Table 3
UVeVis data for (4-alkyl-1-naphthyl)-quinolin-3-ylamide derivatives (6e9) and 3-
aminoquinoline (5).
2
,5
1
9
8
7
6
5
ꢁ1
ꢁ1
)
Compound
ε (L mol cm
lmax Abs (nm)
In Abs
1
4
5
6
7
8
9
6.68 ꢀ 10
274
290
292
292
292
1.336
1.684
1.796
1.950
2.085
4
8.42 ꢀ 10
4
8.98 ꢀ 10
4
9.75 ꢀ 10
4
10.43 ꢀ 10
l
max Abs: maximum absorption wavelength, In Abs: maximum absorption intensity,
ꢁ
5
ε: molar absorptivity coefficient, sample concentrations: 2.0 ꢀ 10 mol/L.
0
,5
0
precursor compound 3-aminoquinoline. However, this increase in
molar absorptivity coefficient values was very small for the 3-
aminoquinoline derivatives. These differences in molar absorptiv-
ity coefficient values may originate from the slight size differences
of the alkyl substituents, while the remaining larger main molec-
ular structures are unchanged. The introduction of better electron
donating groups, that is, larger alkyl chains at the para positions,
cause extended conjugation, and this is reflected as improved
hyperconjugation, and results in increased molar absorptivity co-
efficients of the derivatives.
2
55
275
295
315
335
355
375
395
415
435
Wavelength (nm)
Fig. 2. UVeVis spectra of (4-alkyl-1-naphthyl)-quinolin-3-ylamide derivatives (6e9)
and 3-aminoquinolin (5).
benzenoid ring. The 344 nm absorption describes the n-p* transi-
tion in the precursor quinoline ring. Thus, the existence of two
peaks in the spectrum of the precursor quinoline ring implicates
the presence of two types of chemically nonequivalent rings of the
precursor ring structure, specifically, the benzenoid and quinoline
rings. Fig. 2 indicates that the 3-aminoquinoline derivatives are in
totally different forms due to the absorption band observed, with
3.6. Fourier transform infrared spectroscopy (FTIR) measurements
The FTIR spectra of the synthesized compounds (6e9) and the
precursor compound 3-aminoquinoline (5) are shown in Fig. 3. A
comparison of 3-aminoquinoline and its derivatives showed that
the intensity of all the peaks changed dramatically; the intensity of
the peaks for all the derivatives increased, becoming more sharper
than that of the 3-aminoquinoline compound. Further, new peaks
appeared upon the formation of derivatives, indicating that all the
reactions were carried out successfully.
l
max at 292 nm. In spectra, the absorption at 292 nm is described as
p-p
the * transition in the benzenoid rings of the 3-aminoquinoline
derivatives. Also, the 3-aminoquinoline derivatives showed two
large shoulder peaks at 282 and 302 nm, in addition to the main
peak at 292 nm. However, the absorption peak observed at 344 nm
for 3-aminoquinoline compound disappeared for all the 3-
aminoquinoline derivatives. This indicates that there were no n-
It can be seen from the FTIR spectrum of the compound 3-
aminoquinoline (5, Fig. 3), that all the expected peaks observed
were consistent with the chemical structure of 3-aminoquinoline.
p
* transitions in the 3-aminoquinoline derivatives. In other words,
all the electronic energy level transitions converted to * tran-
sitions in the 3-aminoquinoline derivatives. It can be seen from the
spectra of the 3-aminoquinoline derivatives that the intensity of
p-p
ꢁ
1
For example, the peaks at 3457 and 3323 cm
different modes of NeH stretching for the primary amine group
-NH ) of 3-aminoquinoline [21,22]. The weak peaks at 3190 and
988 cm belong to CeH stretching [21,22]. The aromatic ring
belong to the
the
p-p* transition peak increased as a result of the formation of
(
2
2
larger cyclic structural molecules, compared to that of the precursor
compound. The reason for this increase may be because of these
organic molecules being structurally more cyclic, and thus are able
ꢁ1
to donate more
p electrons upon the formation of the 3-
aminoquinoline derivatives. Thus, these 3-aminoquinoline de-
rivatives have a rich electronic structure, causing a significant in-
crease in the maximum absorption intensity. However, this
maximum absorption intensity increase was very small. Also, this
maximum absorption intensity increase was due to the longer alkyl
chain, acting as a better electron donating group. Further, the
maximum absorption wavelength (292 nm) of all the 3-
aminoquinoline derivatives shifted to higher absorption wave-
lengths, compared to the maximum absorption wavelength
(
274 nm) of the precursor compound. These results indicated that
the more cyclic structural organic molecules donated more bond
electrons as for the 3-aminoquinoline derivatives. The increase in
number of bonds of these organic molecules reduced the band
gap between the * transition peak, and thus the transition of
p
p
p-p
electrons occurred at lower energies.
The UVeVis data for the 3-aminoquinoline derivatives (6e9)
and 3-aminoquinoline compound (5) are summarized in Table 3.
The molar absorptivity coefficient values of all the 3-
aminoquinoline derivatives increased as compared to that of the
precursor compound. The rich electronic structures of these mol-
ecules cause significant increases in the molar absorption capacity
for all the 3-aminoquinoline derivatives as compared to the
Fig. 3. FTIR spectra of (4-alkyl-1-naphthyl)-quinolin-3-ylamide derivatives (6e9) and
3-aminoquinoline (5).

50
G. Zengin et al. / Journal of Molecular Structure 1103 (2016) 45e55
Fig. 4. 1H NMR spectrum of (4-ethyl-1-naphthyl)-quinolin-3-ylamide (7).
Fig. 5. 13C NMR spectrum of (4-ethyl-1-naphthyl)-quinolin-3-ylamide (7).

G. Zengin et al. / Journal of Molecular Structure 1103 (2016) 45e55
51
Fig. 6. 1H NMR spectrum of (4-propyl-1-naphthyl)-quinolin-3-ylamide (8).
Fig. 7. 13C NMR spectrum of (4-propyl-1-naphthyl)-quinolin-3-ylamide (8).

52
G. Zengin et al. / Journal of Molecular Structure 1103 (2016) 45e55
ꢁ
1
stretching, NeH deformation and the C]C, CeC, C]N and CeN
mid-strength new peaks appearing at 1707 and 1632 cm for all
the 3-aminoquinoline derivatives had amide bonds, observed as
C]O carbonyl group vibrational stretching in the 3-
aminoquinoline derivatives [21,22]. Also, the intensity of the peak
vibrational stretches all give absorptions in the region 1600-
ꢁ
1
1
1
240 cm . The strong peaks at about 1219 1188, 1148, 1124 and
ꢁ1
015 cm belong to the CeN vibrational stretching between the
ꢁ
1
aromatic ring and primary amine group [21,22].
at about 1707 cm increased upon changing the para substituted
methyl group to a butyl alkyl chain. The appearance of these new
peaks can be interpreted as additional evidence for new amide
bond formation, hence successfully occurring reactions. The mid-
strength peaks at 2953 cm indicate the different modes of NeH
vibrational stretching in the amide group of the 3-aminoquinoline
derivatives. The appearance of these new peaks can be accepted as
additional evidence for amide bond formation, thus successfully
occurring reactions. Further, new peaks also appeared after deriv-
atization, and these peaks can be expressed as below. The peak at
It can be seen from the FTIR spectra of the 3-aminoquinoline
derivatives (6e9, Fig. 3), that all the expected peaks were
observed, and were in accordance with the chemical structures of
the 3-aminoquinoline derivatives. The peaks at 3457 and
ꢁ1
ꢁ1
3
323 cm belong to the different modes of NeH stretching in the
primary amine group (-NH ) of 3-aminoquinoline (5) which dis-
2
appeared for all the 3-aminoquinoline derivatives (6e9). The
disappearance of these peaks indicated that the primary amine
2
group (-NH ) of 3-aminoquinoline reacted, and new amide bonds
ꢁ
1
formed, thus being indicative of successful reactions. Further, the
about 2928 cm belongs to the CeH stretching of the aliphatic
Fig. 8. Mass spectrum of (4-ethyl-1-naphthyl)-quinolin-3-ylamide (7).

G. Zengin et al. / Journal of Molecular Structure 1103 (2016) 45e55
53
ꢁ
1
alkane [21,22]. The peak at about 1458 cm belongs to the CeH
bending modes of the aliphatic eCH - chain. The peak at about
397 cm belongs to the CeH bending modes in the eCH chain
terminal of the aliphatic structure. The mid-strength peak at
are for the CeH out-of-plane bending modes, in particular, para
substitution being observed with the peak at 767 cm . This is
ꢁ
1
2
ꢁ
1
1
3
ascribed as the out-of-plane CeH bending. This peak shifted
ꢁ
1
ꢁ1
slightly from 760 cm to 767 cm , from the para substituted
methyl group through to the butyl chain. The bands at about 609,
ꢁ
1
2
868 cm
belongs to the CeH stretching. The aromatic ring
stretching, NeH deformation and the C]C, CeC, C]N and CeN
vibrational stretches all give absorptions in the region
600e1240 cm [21,22]. The strong peaks at about 1191, 1168,
ꢁ1
511 and 486 cm are the aromatic ring deformation peaks. The
medium and strong absorption modes at about 1027, 641 and
460 cm belong to the CeH vibrational stretching of the aromatic
ꢁ1
ꢁ1
1
ꢁ
1
1
128, 1104 and 1057 cm belong to the CeN vibrational stretching
ring or AreH cyclic structure [21,22].
between the aromatic ring and secondary amine group [21,22]. The
ꢁ1
3
.7. Nuclear magnetic resonance spectroscopy ( H and 13C NMR)
1
region from 1200 to 500 cm is the region for the in-plane and
out-of-plane bending of CeH bonds of the aromatic rings [21,22].
The main absorption bands for the 3-aminoquinoline derivatives
1H and 13C NMR spectra for the synthesized (4-alkyl-1-
naphthyl)-quinolin-3-ylamide derivatives (6e9) were recorded,
and the data obtained are given in the materials and method
ꢁ
1
are located at 1027, 888, 839, 767 and 696 cm , and some weak
ꢁ
1
bands can be seen. The peaks at about 888, 839, 767 and 696 cm
Fig. 9. Mass spectrum of (4-propyl-1-naphthyl)-quinolin-3-ylamide (8).

54
G. Zengin et al. / Journal of Molecular Structure 1103 (2016) 45e55
reveals that the predominant decomposition pathway was
a-
cleavage [23], with the formation of the corresponding acylium
þ
cation fragment ([C12
H
11C^O:] , m/z 183), via loss of the quinolin-
.
3
-ylamino alkyl group ([C
9
H
7
N
2
] , m/z 143). The molecular ion peak
þ
[
Mꢁ1] for derivative 8 was observed at m/z 339, with the highest
intensity peaks observed at m/z 339 and 183 (100 and 82%,
respectively). Derivative 8 gave the m/z 197 fragment, indicating an
a
-cleavage decomposition pathway [23], with the formation its
þ
corresponding acylium cation fragment ([C13
via loss of the quinolin-3-ylamino alkyl group ([C
All the derivatives seemed to follow the
H
13C^O:] , m/z 197),
.
H
9 7
N
2
] , m/z 143).
a
-cleavage decomposition
pathway except for derivative 9, which seemed to follow a different
pattern of decomposition. This may be because it being a more
larger and labile structure than the other derivatives (6e8). De-
þ
rivative 9 gave the molecular ion peak [Mþ1] at m/z 355 (8%), with
the highest intensity peak for the derivative being observed at m/z
278 (100%).
Fig. 10. Photoluminescence spectra of (4-alkyl-1-naphthyl)-quinolin-3-ylamide de-
rivatives (6e9) and 3-aminoquinoline (5) in DCM; samples were excited at 266 nm.
3.9. Photoluminescence measurements
section. As representative examples, the NMR spectra of derivatives
Photoluminescence is an invaluable tool regularly used in me-
dicinal science. Photophysical properties of the compounds syn-
thesized were examined for possible uses in medical imaging. The
excitation and emission spectra for (4-alkyl-1-naphthyl)-quinolin-
1
7
and 8 are given in Figs. 4e7. In the H NMR spectra of the de-
rivatives, the aliphatic protons were observed in the region
d
d
0.92e3.12 ppm, and the aromatic protons in the region
7.30e8.15 ppm, as commonly given in the literature [21]. The
3
-ylamide derivatives (6e9) and 3-aminoquinoline (5) solutions
were studied, with excitation at 266 nm.
-Aminoquinoline (5) showed weak emission, while its de-
region
d 7.54e7.64 ppm shows an overlapping multiplet, repre-
senting the aromatic protons of both the naphthyl and quinoline
rings. There are four doublets representing four aromatic CeH
protons of the naphthyl and quinoline rings. The two singlets ex-
pected for two quinoline CeH protons are probably masked by
other low field naphthyl and quinoline CeH protons. The quinoline
NeH proton was observed as a singlet about at 6.85 ppm.
3
rivatives gave an intense emission upon irradiation by UV light. The
photoluminescence spectra of these compounds are shown in
Fig. 10. A weak maximum luminescent intensity was observed at
366 nm. The full width at half maximum (FWHM) was 93 nm for
compound 3-aminoquinoline (5). Compound 3-aminoquinoline (5)
revealed 18% QYand 1.70 ns lifetime of the excited-state. Maximum
emission was observed at 396 nm and the FWHM was 74 nm for (4-
methyl-1-naphthyl)-quinolin-3-ylamide (6). Compound (4-
methyl-1-naphthyl)-quinolin-3-ylamide (6) revealed 22% QY and
In the 13C NMR spectra of the derivatives the aliphatic carbons
were observed at
d 14.2e34.6 ppm and the aromatic carbons were
observed at 123.7e170.0 ppm, as commonly given in the litera-
d
ture [21]. Several carbon signals had exactly the same NMR signal,
either as a result of symmetry or by coincidence. In general, carbons
having hydrogens are observed as larger peaks than those carbons
without hydrogens [21].
2.05 ns lifetime of the excited-state. The luminescence intensity of
the peaks and the QYs of (4-alkyl-1-naphthyl)-quinolin-3-ylamides
(6e9) increased significantly compared to that of the precursor
compound 3-aminoquinoline (5) as a result of more bulkier cyclic
molecules. Further, attachments of more electron donating groups
onto the rings at the para-position of the derivatives leads to
extended conjugation, and thus improved hyperconjugation, and
this results in increased intensities of the main peaks, shifting to
3.8. Mass spectra (LC-MS-MS)
The mass spectra for the synthesized (4-alkyl-1-naphthyl)-qui-
nolin-3-ylamide derivatives (6e9) were recorded, and the data
obtained are given in materials and method section. All spectra
observed were in accordance with the molecular structures of the
greater wavelengths of emission. High QY is a result of extensive
electron delocalization in large molecular structural systems.
Therefore, as a result increasing bonds or electron rich cyclic
p-
þ
compounds. The molecular ions [M] of the derivatives were
p
þ
þ
observed as [Mꢁ1] or [Mþ1] .
molecular systems, the fluorescence emission intensity increases;
cyclic molecular systems increase electron delocalization and/or
energy transfer from the excited state of the (4-alkyl-1-naphthyl)-
quinolin-3-ylamide. This leads to an increase in the non-radiated
transition of the (4-alkyl-1-naphthyl)-quinolin-3-ylamide excited
state, and an increase in fluorescence emission.
As representative examples, the mass spectra of derivatives 7
and 8 are given in Figs. 8 and 9, respectively. The molecular ion peak
þ
[
Mꢁ1] for derivative 7 was observed at m/z 325, while the highest
intensity peaks for the derivative was observed at m/z 325 and 183
100 and 99%, respectively). The m/z 183 fragment of 99% intensity
(
Table 4
Photoluminescence data for (4-alkyl-1-naphthyl)-quinolin-3-ylamide derivatives (6e9) and 3-aminoquinoline (5).
Compound
lmax Ex (nm)
In Ex
max Em (nm)
In Em
f
f
(%)
f
t (ns)
5
6
7
8
9
274 (230; 248; 263; 281)
276 (235; 254; 285)
278 (241; 259; 287)
279 (244; 261; 289)
280 (246; 262; 292)
332
411
506
589
692
366 (348; 393; 425; 464)
396 (366; 426; 467)
398 (371; 427; 469)
401 (368; 429; 472)
404 (371; 432; 478)
326
403
496
577
678
18
22
26
30
34
1.70
2.05
2.44
2.76
3.15
l
l
max Ex: maximum excitation wavelength; In Ex: maximum excitation intensity.
max Em: maximum emission wavelength; In Em: maximum emission intensity.
f f
f : quantum yield; t : excited-state lifetime.

G. Zengin et al. / Journal of Molecular Structure 1103 (2016) 45e55
55
The photoluminescence data for (4-alkyl-1-naphthyl)-quinolin-
-ylamides (6e9) and 3-aminoquinoline (5) are summarized in
Table 4. The luminescene properties of these derivatives may pro-
vide great potential for numerous optical applications and for
medicinal biomarkers.
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