Novel marine-based gold nanocatalyst in solvent-free synthesis of polyhydroquinoline derivatives: Green and sustainable protocol

Article abstract of DOI:10.1002/aoc.6000

We report an ecofriendly synthetic approach for the fabrication of biogenic gold nanoparticles (AuNPs) using electron-rich sea cucumber extract as a bio-reductant and stabilizing agent in reducing gold cations into AuNPs at the optimal conditions. The produced AuNPs are spherical in shape with an average particle size of 11 ± 1.5 nm in transmission electron microscopy (TEM) and exhibited a crystal structure of face-centered cubic in X-ray diffraction (XRD) analyses. Our results indicated that bioinspired AuNPs demonstrate superior catalytic activity in the safe and facile one-pot synthesis of polyhydroquinoline derivatives under solvent-free reaction conditions. This green route encompasses multiple benefits including highly recyclable bioinspired catalyst (5 cycles), short reaction times, convenient workout, high to excellent product yields (82%–97%), and nonhazardous conditions.

Full text of DOI:10.1002/aoc.6000

Received: 21 May 2020
DOI: 10.1002/aoc.6000
Revised: 7 August 2020
Accepted: 15 August 2020
F U L L P A P E R
Novel marine-based gold nanocatalyst in solvent-free
synthesis of polyhydroquinoline derivatives: Green and
sustainable protocol
Mahsa Sepahvand1
| Foad Buazar1
| Mohammad Hosein Sayahi2
1Department of Marine Chemistry,
Khorramshahr University of Marine
Science and Technology, PO Box 669,
Khorramshahr, Iran
2Department of Chemistry, Payame Noor
University, PO Box 19395-3697, Tehran,
Iran
We report an ecofriendly synthetic approach for the fabrication of biogenic
gold nanoparticles (AuNPs) using electron-rich sea cucumber extract as a bio-
reductant and stabilizing agent in reducing gold cations into AuNPs at the
optimal conditions. The produced AuNPs are spherical in shape with an aver-
age particle size of 11 1.5 nm in transmission electron microscopy (TEM)
and exhibited a crystal structure of face-centered cubic in X-ray diffraction
(XRD) analyses. Our results indicated that bioinspired AuNPs demonstrate
superior catalytic activity in the safe and facile one-pot synthesis of poly-
hydroquinoline derivatives under solvent-free reaction conditions. This green
route encompasses multiple benefits including highly recyclable bioinspired
catalyst (5 cycles), short reaction times, convenient workout, high to excellent
product yields (82%–97%), and nonhazardous conditions.
Correspondence
Foad Buazar, Department of Marine
Chemistry, Khorramshahr University of
Marine Science and Technology, PO Box
669, Khorramshahr, Iran.
Email: fb@kmsu.ac.ir
K E Y W O R D S
biosynthesis, gold nanocatalyst, polyhydroquinoline, sea cucumber extract
1 | INTRODUCTION
biosynthesis of a wide range of NP. In fact, there are
plenty of publications, for example, articles, books, and
Green synthesis is a developing area in the field of chem-
istry, which aims to design clean products and sustain-
able processes through whether curtailing or eliminating
the implementation of unsafe solvents as well as toxic
reagents.[1,2] Because the growing innovative green
processing and synthesis utilizes nontoxic precursors and
mild reaction conditions, they are considered as a valu-
able alternative option for promoting environmental sus-
tainability.[3] Moreover, ecofriendly synthesis reactions
essentially comply with 12 principals of green chemistry,
providing cost-effective, facile, stable, and relatively
reproducible nanomaterial. Hence, over the past decade,
diverse biological methods have been developed in the
biosynthesis of nanoparticles (NPs) including plants,[4,5]
microorganisms (bacteria, yeast, and fungi),[6] and
marine algae extracts[7–9] among many others. Both
marine and land sources are applicable in the
reviews, that have been reported in the literature using
those methodologies. They present green downstream
processing in NP production; nevertheless, it is prema-
ture to demonstrate which one is more preferential.[10]
Compared with the fairly complicated and harsh
operational conditions of physical and chemical synthetic
procedures, the biocompatible peers are environmentally
friendly and fiscal substitutes for scaling up to large
production of NPs.
Over the past years, noble metal NPs have gained
popularity from researchers owing to their considerably
physicochemical and biological properties. In particular,
gold NPs (AuNPs) extensively preferred and synthesized
via green synthesis[11,12] because of its unique intrinsic
properties[13] and broad-spectrum application scopes
in areas such as biomedicine,[14] environmental
remediation,[15] organic photovoltaics,[16] sensors,[17]
Appl Organomet Chem. 2020;e6000.
wileyonlinelibrary.com/journal/aoc
© 2020 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.6000

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SEPAHVAND ET AL.
optical imaging,[18] and therapeutic agents.[19] In addi-
tion, they are widely used as a catalyst in a number of
chemical reactions.[20]
antitumor and vasodilator[26,27]
attempts have been devoted to innovating straightfor-
ward synthetic methods targeting compounds possessing
the PHQ core.
;
hence, significant
Multicomponent reactions (MCRs) as powerful syn-
thetic methodology have attracted a surge of interest in
modern organic synthesis and medicinal chemistry
because they create strategic organic molecules and vari-
ation of structures in a one-pot single fashion.[21] They
not only reduce the amount of energy and solvent
required for separation and purification of intermediates
but also generate highly selective products that maintain
large quantities of the starting material. Owing to multi-
ple benefits of MCRs process including atom-economy,
efficiency, diversity, and environmental sustainability,
the development of new NP-catalyzed MCRs based on
eco-friendly procedures has been established as an area
of growing interest in organic chemistry.[22]
Therefore, in the present research, we illustrate an
innovative biogenic procedure to fabricate Au NPs using
the natural extract of sea cucumber[28] under optimized
reaction conditions. Then, the bioprepared AuNPs were
utilized as a novel biogenic catalyst in the solvent-free
synthesis of environmentally benign PHQ derivatives by
one-pot four-component designed in time-efficient MCRs
manner. Apart from full compliance with green chemis-
try rules, solvent-free reactions manifest ample benefits
in industrial applications mainly due to facile workout
technique, low cost, and pollution reduction.[26]
The ocean covers more than 70% of the surface of our
planet. Hence, the surging popularity of marine routes in
synthesis of NPs mainly relies on their abundance, rea-
sonable costs, sustainability, and less contamination.
However, the large-scale production of green NPs from
lab scale to pilot-plant level using an eco-friendly and
biocompatible process still at its early stage in compari-
son with conventional methods.[23] In this connection,
sea cucumbers are a high value of nutrients marine ani-
mals that widely used as food and traditional medicine
especially in Asia. These edible sea cucumbers are rich
sources of nutritional ingredients such as high-quality
proteins, vitamins, minerals, and fatty acids. It is also
home of broad spectrum of isolated electron-rich bioac-
tive compounds including alkaloid, sulfated polysaccha-
rides, terpenoids, phenols, flavonoids, saponins,
carbohydrates, glycosides, tannins, and steroids.[24]
Polyhydroquinoline (PHQ) compounds are consid-
ered as a privileged skeleton for various N-heterocyclic
derivatives, and because of their promising pharmacolog-
ical and biological activities, they were broadly investi-
gated as neurotropic, anticancer, antitubercular, and
antidiabetic activities[25] (Scheme 1). Owing to these
distinct features, PHQ nucleus unites have received
considerable attention in medicinal chemistry such as
2 | EXPERIMENTAL
All chemicals used in this study were purchased from
Sigma-Aldrich and utilized as received. Produced NPs were
analyzed using a UV–vis (Analytic Jena-Germany) spectro-
photometer covered the spectral range 200–700 nm. X-ray
diffraction (XRD) diffractometer (Cu Ka, radiation,
λ = 1.5405 Å) was operated at a scanning speed of 2/min
from 10 to 80 (2θ). Fourier transform infrared (FTIR) spec-
tra of the compounds were recorded on Nicolet MAGNA-
IR 550 spectrometer (Madison, WI, USA) by a KBr pellet.
To explore the surface of the NPs, thermogravimetric
analysis (TGA; PerkinElmer, Pyris 1, USA) experiment was
run under inert argon gas flow. Transmission electron
microscopy (TEM) was performed with a Leo 912 AB at
an accelerating voltage 200 kV. For organic product
characterization, melting points were recorded using the
electrothermal IA9200 apparatus. 1H and 13C NMR spectra
were recorded on a Brucker (Rheinstetten, Germany)
NMR spectrometer at 250 and 63 MHz using tetra-
methylsilane (TMS) as the internal standard. The progress
of the reactions and determination of the purity of the sub-
strates were monitored using thin-layer chromatography
(TLC) on silica gel SILG/UV 254 and 365 plates. Sea
cucumber (Holothuria parva) was collected during low tide
from the coasts of the Bushehr Province, Iran.
2.1 | Preparation of sea cucumber extract
The organic extract was obtained by mixing 3 g of
thoroughly washed air-dried powder of body wall of sea
cucumber organ sample with 10 ml of extraction solvent
mixtures of methanol and distilled water (3:1, v:v) and
97 m; of distilled water in a 150-ml Erlenmeyer flask
under vigorous stirring with a magnetic stirrer. The
SCHEME 1 Selected biologically active polyhydroquinoline
products[25]

SEPAHVAND ET AL.
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combination was heated for 20 min, then cooled and
filtered using standard Whatman Grade 1 filter paper.
The resultant was stored in the refrigerator for fulfilling
the additional experiments demand.
830, 733, 620. 1H NMR (250 MHz, DMSO-d6) (Figure S1):
δ 9.70 (s, 1H, NH), 8.27 (d, J = 7.5 Hz, 1H, Ar–H), 7.58
(m, 1H, Ar–H), 7.22–7.40 (m, 6H, Ar–H), 4.90 (s, 1H,
CH), 2.48 (s, 2H, CH2), 2.24 (d, J = 16 Hz, 1H, CH2), 2.04
(d, J = 16 Hz, 1H, CH2),1.03 (s, 3H, CH3), 0.90. (s, 3H,
CH3), 13C NMR (63 MHz, DMSO-d6) (Figure S2): δ 196.1,
161.7, 153.5, 151.3, 146.2, 143.7, 133.5, 132.2, 131.0, 129.4,
125.5, 124.5, 118.3, 114.4, 111.9, 102.8, 51.5, 35.6, 33.6,
30.4, 28.0. Anal. calcd for C24H20NO3Cl: C 71.02, H 4.97,
N 3.45. Found: C 71.04, H 4.92, N 3.47.
2.2 | Biosynthesis of AuNPs
AuNPs were synthesized by adding 30 ml of an aqueous
solution of HAuCl4Á3H2O (1 mM) to 10 ml of sea cucum-
ber extract. The reaction mixture containing sea cucum-
ber extract and tetrachloroauric acid solution was
incubated at 70ꢀC for 24 h on a shaker at 600 rpm. The
purification of obtained solution accomplished by reiter-
ated centrifugation at 15,000 rpm for 15 min followed by
decanting and dried at 70ꢀC in an oven overnight.
2.5 | 7-(4-Bromophenyl)-10,10-dimethyl-
7,10,11,12-tetrahydro-6H-chromeno[4,3-b]
quinoline-6,8(9H)-dione (5l)
MP: 283–285ꢀC; FTIR (KBr, ν, cm−1): 3,309, 2,949, 2,939,
2,876, 1,669, 1,462, 1,362, 1,235, 1,192, 1,145, 1,041,
851, 758, 621. 1H NMR (250 MHz, DMSO-d6) (Figure S3):
δ 9.70 (s, 1H, NH), 8.28 (d, J = 7.5 Hz, 1H, Ar–H), 7.60 (t,
J = 7.5 Hz, 1H, Ar–H), 7.32–7.43 (m, 4H, Ar–H),
7.15–7.18 (m, 2H, Ar–H), 4.88 (s, 1H, CH), 2.62 (s, 2H,
CH2), 2.24 (d, J = 16 Hz, 1H, CH2), 2.04 (d, J = 16 Hz,
1H, CH2),1.04 (s, 3H,CH3), 0.90. (s, 3H, CH3), 13C NMR
(63 MHz, DMSO-d6) (Figure S4): δ 196.1, 161.6, 153.5,
151.2, 146.6, 143.7, 133.5, 132.3, 131.5, 125.5, 124.5, 120.7,
118.3, 114.3, 111.8, 102.7, 51.5, 35.7, 33.6, 30.4, 28.0. Anal.
calcd for C24H20NO3Br: C 64.01, H 4.48, N 3.11. Found: C
64.04, H 4.45, N 3.14.
2.3 | Synthesis of PHQ derivatives in the
presence of Au nanocatalyst
A mixture of 4-hydroxy coumarin (1, 1 mmol) and
ammonium acetate (4, 2 mmol) was heated with stirring
at 100ꢀC for half an hour. Then, dimedone (2, 1 mmol),
aldehyde (3, 1 mmol), and Au nanocatalyst (1.5 mg) were
added, and the reaction was continued for 20 min under
solvent-free conditions (Scheme 2). After completion of
the reaction indicated via TLC monitoring, the solution
was cooled down to room temperature, and then the pre-
cipitated product was diluted with cold H2O and filtered.
The crude precipitate dissolved in DMF (5 ml), and the
catalyst was then separated by simple centrifugation,
washed with large amounts of anhydrous ethanol, dried
at 60ꢀC overnight, and recycled. After the separation of
Au nanocatalyst, 12 ml of water was added to the mixture
of reaction to precipitate of the product. Then, the precip-
itate was filtered, washed with water, and recrystallized
by ethanol to afford pure products.
3 | RESULTS AND DISCUSSION
3.1 | UV–visible spectroscopy analysis
The preliminary visual confirmation of AuNPs formation
was observed when the solution color turned from light
yellow to dark brown. Further, in contrast to pristine sea
cucumber extract, the generated biogenic AuNPs were
determined spectrophotometrically in the UV–vis spec-
trum, which appears distinctive plasmon peak at 550 nm
2.4 | 7-(4-Chlorophenyl)-10,10-dimethyl-
7,10,11,12-tetrahydro-6H-chromeno[4,3-b]
quinoline-6,8(9H)-dione (5k)
−
(Figure 1a,b). Monitoring the reaction kinetics of AuCl4
reduction by UV–vis absorption spectrum as a function
of time (5 min, 15 min, 45 min, 1 h, and 4 h) revealed the
completion of the reaction after 1 h and the stability of
the absorbance peak, with no significant change beyond
MP: (256–258ꢀC); FTIR (KBr, ν, cm−1): 3,308, 2,959,
2,933, 1,682, 1,670, 1,464, 1,363, 1,225, 1,194, 1,147, 1,042,
SCHEME 2 The synthesis of
polyhydroquinoline derivatives catalyzed by a
novel sea cucumber extract-mediated
biosynthesized gold nanoparticles (AuNPs)

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SEPAHVAND ET AL.
this time, as shown in Figure 1b. These results are in
accordance with earlier reports showing absorption peak
around 525–540 which is attributed to the noble
AuNPs.[29]
3.2 | XRD analysis
The XRD pattern of gold NPs fabricated by sea cucumber
extract is depicted in Figure 2. The XRD spectrum reveals
four characteristic Bragg diffraction peaks including
38.10ꢀ, 45.15ꢀ, 65.37ꢀ, and 78.24ꢀ, which related to the
(111), (200), (220), and (311) lattice planes, respec-
tively[30] (Figure 2). As a result, the produced green
AuNPs are highly crystalline in nature with the face cen-
ter cubic (FCC) crystal structure. Moreover, the obtained
results of bio-assisted AuNPs are in good agreement with
XRD reference pattern of the Joint Committee on Powder
Diffraction Standards (JCPDS) for the bulk gold (card no:
04-0784)[31] as well as biological AuNPs synthesized uti-
lizing other eco-friendly synthetic procedures.[11,32]
According to the line width of the intensive peak at
38.10ꢀ (111), the average crystallite size of biogenic
AuNPs calculated by Debye–Scherrer's equation is found
to be 10 nm.[33]
FIGURE 2 X-ray diffraction (XRD) pattern of marine-based
gold nanoparticles (AuNPs) arranged in crystalline face center
cubic (FCC) lattice structure
achieved through counting 300 particles by ImageJ
software.[34]
After characterizations, we examined the catalytic
efficiency of the AuNPs in the one-pot synthesis of novel
PHQ derivatives using a four-component condensation
reaction of aldehyde 1a, 4-hydroxy coumarin 2b,
dimedone 3c, and ammonium acetate 4d as a model reac-
tion under solvent-free condition (Scheme 2). To the best
of our knowledge, this is the first report on the applica-
tion of biosynthesized AuNPs as an efficient catalyst in
this type of organic reactions.
3.3 | TEM characterization
The morphology and particle size of AuNPs were ana-
lyzed using the TEM technique. As can be seen in
Figure 3, the morphology of the NPs is spherical in
nature, with the slight aggregation of particles occurred
haphazardly due to inappropriate preparation of the sam-
ple. Additionally, the TEM image demonstrated that the
AuNPs have a mean diameter of about 11
1.5 nm
3.4 | FTIR analysis
FTIR spectrum of the pristine sea cucumber extract and
bio-mediated AuNPs is depicted in Figure 4. The results
demonstrate the availability of various sea cucumber-
derived functional groups on the surface of NPs, which
involved in bioreduction and proficient stabilization of
fresh AuNPs (Figure 4b). This postulation can be fortified
because the position and intensity of some peaks, in par-
ticular, carbonyl and phenolic hydroxy groups, have
changed in the biological AuNPs spectrum rather than
corresponding raw sea cucumber extract. The noticeably
abroad peak appeared in the range of 3,423 cm−1 is asso-
ciated with O H and/or N H stretching, resulting from
the multiple intramolecular hydrogen-bonding interac-
tions. The presence of an aliphatic symmetric C H
stretching mode of the methylene and methyl groups can
be assigned at 2,945 and 2,885 cm−1. The vibrational
FIGURE 1 UV–visible spectra of (a) ethanolic sea cucumber
extract, (b) biogenic gold nanoparticles (AuNPs), and impact of
different time intervals on AuNPs absorbance peak; inset illustrates
photographic images of visual color changes upon the formation of
AuNPs

SEPAHVAND ET AL.
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FIGURE 3 (a) The transmission electron
microscopy (TEM) image and (b) the histogram
demonstrating particle size distribution of gold
nanoparticles (AuNPs) biosynthesized using sea
cucumber extract
FIGURE 4 Fourier transform infrared (FTIR) spectra of
(a) original sea cucumber extract and (b) bio-mediated gold
nanoparticles
FIGURE 5 Thermogravimetric analysis (TGA) plot of
biocapped gold nanoparticle (AuNPs) fabricated using sea
cucumber extract
band observed at 1,731 cm−1 is corresponded to the
stretching vibration of the carbonyl group (C O). The
absorption band centered at 1,639 cm−1 is attributed to
N H bending vibrations of residual amide. The quite dis-
tinctive absorption band at 1,336 cm−1 is corresponded to
C N stretching of amino and/or amid entity. The charac-
teristic absorption peaks at 1,246 and 823 cm−1 can be
assigned to S O and C O S stretching modes of sul-
fated polysaccharide. Finally, carbohydrates etheric and
phenolic O H vibration bands appear at 1,132 and
1,048 cm−1, respectively.[35]
due to the evaporation of the absorbed water. The second
weight loss with a proximate proportion of 45% is mainly
attributed to the decomposition of bioorganic compounds
that were compassed the AuNPs. As a result, TGA analy-
sis reveals that copious bioactive phytochemicals present
in the marine cucumber extract such as phenolic and
polysaccharides could coat the surface of the
nanoparticles and function as steric and/or electrostatic
stabilizing agent.[36] This result is in accordance with
FTIR findings and other reports of green synthesized
AuNPs,[37] exhibiting multiple functions of marine-
derived biomolecules in reduction gold cations, shielding
fresh AuNPs, and curb aggregation/agglomeration of
biocompatible NPs.
3.5 | TGA examination of
biocapped AuNPs
In order to determine the proportional amount of the bio-
functional groups adsorbed on the surface of NPs, the
TGA technique was used. Figure 5 shows two steps of
steady weight loss in the TGA curve of the freshly bio-
produced AuNPs. First, an initial weight loss rate of 10%
occurs in the temperature range of 80–110ꢀC high likely
3.6 | Biogenic AuNPs catalytic activity
Our investigation commenced with an optimization
study of the different catalytic concentrations for the
solvent-free synthesis of PHQ derivatives in the presence
of AuNPs as a robust catalyst at 60ꢀC. The practicability

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SEPAHVAND ET AL.
TABLE 1 Impact of catalytic concentration of green gold
nanoparticle (AuNPs) in the solvent-free synthesis of
polyhydroquinoline 5a
products in record time rather than counterparts includ-
ing chemical-based AuNPs. In addition, in the absence of
catalyst and after even lengthy reaction time only
neglectable yield of product was produced. Apart from
using bioinspired methods in the biogenic synthesis of
NPs, this type of green nanomaterial genuinely takes
advantage of controllable, well-defined size, shape, and
particle distribution because they are encompassed by a
diverse range of biomolecules during both reduction and
stabilization process. As a result, in nano-catalyzed
organic reactions, it would remarkably enhance their
catalysis efficiency rather than corresponding chemical
ones.[38] According to these results, it can be noted that
the use of eco-friendly AuNPs would offer substantial
benefits for the sake of environmental sustainability
when compared with commercial ones.
During the green synthetic reactions, the recyclability
of the catalyst is of paramount importance. Hence, for
the recovery of bioinspired AuNPs-based catalyst, it was
filtered off from the reaction mixture via centrifugation
and washed with a mixture of water and ethanol to elimi-
nate the residual product. Once dried, it was devoted to
another reaction. We examined the reusability of the
AuNPs in subsequent experiments up to 5 cycles without
appreciable loss in its catalytic activity as illustrated in
Figure 6.
To scrutinize the scope and limits of bioproduced gold
nanocatalyst activities, more functionalized PHQ deriva-
tives were prepared, and experiments were accomplished
by creating an array of arylaldehydes holding a collection
of different functional groups (Table 3). All products were
produced in high to excellent yields and high purity.
Based on results, both electron-withdrawing and
electron-donating substituents increase the yield of prod-
ucts, advocating the great potency of designed reaction in
this study. Furthermore, 4-nitrobenzaldehyde (Table 3,
Entry 6) afforded the target product (5e) in the higher
Entry
Catalytic conc. (mg)
Time (min)
Yield (%)
1
2
3
4
5
0.5
1
50
50
50
50
50
68
79
95
91
80
1.5
2
2.5
TABLE 2 Comparison of various catalysts in the synthesis of
5a
Entry
Catalyst
Time (min)
Yield (%)
1
2
3
4
5
Bulk gold
160
120
140
50
53
75
Chemical AuNPs
Acetic acid
Biogenic AuNPs
None
≤60
95
24 h
15
Abbreviation: AuNPs, gold nanoparticles.
of the various catalytic concentrations is depicted in
Table 1. It is found that 1.5-mg loading of AuNPs (Entry
3) is the optimal amount of choice in the model reaction
of four components according to yield as presented in
Table 1. It can be noted that sensible changes in the yield
were observed using larger quantities of green Au
nanocatalyst.
Afterward, in order to compare the catalytic activity
of biprepared AuNPs with other catalysts, different types
of catalysts have addressed in the model reaction under
free solvent conditions as a function of end reaction time.
As can be shown from Table 2, the biological AuNPs rela-
tively afford higher yield (Entry 4) of the related PHQ
FIGURE 6 Recyclability of biosynthesized
gold nanocatalyst for the synthesis of 5a

SEPAHVAND ET AL.
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TABLE 3 polyhydroquinoline derivatives synthesized in the presence of biological gold nanocatalyst
Entry
R
Product
Yield (%)a
Mp (ꢀC)
Reported Mp (ꢀC)
272[41]
1
H
5a
5b
5c
5d
5e
95
271–273
2
3
4
5
2-Cl
89
90
95
97
300–302
330–332
283–285
277–279
300[41]
2,4-DiCl
333–334[42]
282–284[42]
279[41]
3-NO2
4-NO2
(Continues)

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SEPAHVAND ET AL.
TABLE 3 (Continued)
Entry
R
Product
Yield (%)a
Mp (ꢀC)
Reported Mp (ꢀC)
6
4-OCH3
5f
82
243–245
242[41]
7
4-Me
5 g
94
251–253
250[41]
8
4-N(CH3)2
5 h
95
159–161
160–161[42]
9
4-F
5i
83
219–220
220[41]
10
4-OH
5j
95
295–297
295[41]
(Continues)

SEPAHVAND ET AL.
9 of 11
TABLE 3 (Continued)
Entry
R
Product
Yield (%)a
Mp (ꢀC)
Reported Mp (ꢀC)
—
11
4-Cl
5 k
91
256–258
12
4-Br
5 l
93
283–285
—
Note: Reaction conditions: 4-hydroxy coumarin (1 mmol), ammonium acetate (2 mmol), dimedone (1 mmol), aldehyde (1 mmol), and AuNPs
(1.5 mg).
Abbreviation: AuNPs, gold nanoparticles.
aIsolated yeild.
yield (97%) rather than counterpart products under the
same reaction conditions. Experimentally, aliphatic alde-
hydes were presented products with a lower yield than
corresponding aromatic peers in the multicomponent
synthesis of PHQ. Furthermore, a significant proportion
of the by-products also were obtained along with target
compounds when aliphatic aldehydes were involved in
the synthesis reaction.
(2) reacts with the catalyst-activated carbonyl of
arylaldehyde (3) to produce the α,β-unsaturated com-
pound 7. Third, compound 7 converts to intermediate
8 via Michael addition of enamine (6). Lastly, products
5a–l were achieved through an intramolecular ring cycli-
zation process from compound 8, followed by the elimi-
nation of a molecule of water. The Lewis acidic character
of bioinspired AuNPs catalyst could act an essential role
in both enhancing the electrophilicity of the reactants as
well as intermediates stability. These results are consis-
tent with the concept that indicates that in Lewis acid-
catalyzed organic reaction, a metal-based Lewis acid
serves as an electron pair acceptor that in turn increases
the reactivity of an organic substrate toward nucleophilic
attack.[39,40] Moreover, it is presumably expected that
electron-withdrawing groups afford products with better
yields than electron-donating ones; however, because of
the appropriate effect of biogenic Au nanocatalyst in the
synthesis of PHQ derivatives, interestingly both electron-
donating and withdrawing groups of benzaldehyde lead
to an approximately excellent yield of products.
3.7 | PHQ synthesis mechanism
Whereas no experimental proof established concerning
the mechanistic pathway of four-component reaction, a
reasonable mechanism could be elucidated by the reac-
tion sequence in Scheme 3 according to literature prece-
dent of alike MCRs. First, the reaction perhaps proceeds
via a reaction between the in situ generated NH3 from
ammonium acetate (4) and 4-hydroxy coumarin (4) to
yield 4-amino coumarin (6) at 100ꢀC. Second, based on
Knoevenagel condensation, the enolic form of dimedone

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SEPAHVAND ET AL.
SCHEME 3 A putative mechanism route for the synthesis of polyhydroquinolines using marine-mediated Au nanocatalyst
4 | CONCLUSION
supervision; visualization. Mohammad Hosein Sayahi:
Formal analysis; methodology; project administration;
validation.
In summary, we have established a novel marine-based
biocompatible and a straight forward synthetic route for the
biofabrication of AuNPs via the direct interaction of gold
nitrate with extract of the sea cucumber body wall. In the
aqueous reaction mixture, the extract-derived electron-rich
biomolecules not only reduced the Au ions to zero-valent
metallic atoms but also stabilized and protected the freshly
formed NPs from agglomeration. Our results indicated that
highly recyclable biogenic AuNPs demonstrated superior
catalytic activity in the one-pot synthesis of poly-
hyroquinline derivatives, producing higher yields of desired
products in record time under solvent-free conditions.
Owing to compliance with green chemistry principles, this
novel sea cucumber-mediated biosynthesized AuNPs
could consider as a sustainable and environmentally
friendly protocol in broad-spectrum applications such as
organic synthesis, medicinal chemistry, and environmental
remediation. In the context of NP biofabrication following
future prospects should be addressed: (a) comparison of
viable marine organisms as sources of electron-rich
molecules advantageous in the synthetic processes of NPs,
(b) recognizing controlled and optimized conditions for
large-scale production of green NPs, and (c) investigation of
the various parts of marine creature for highly efficient syn-
thesis of NPs including organ, tissue, leaves, stem, and cell.
ORCID
Mahsa Sepahvand https://orcid.org/0000-0002-6011-
5120
Foad Buazar https://orcid.org/0000-0002-8937-9402
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DATA AVAILABILITY STATEMENT
Data sharing is not applicable; no new data are
generated.
AUTHOR CONTRIBUTIONS
Mahsa Sepahvand: Investigation; project administra-
tion; software; visualization. Foad Buazar: Methodology;

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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
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How to cite this article: Sepahvand M, Buazar F,
Sayahi MH. Novel marine-based gold nanocatalyst
in solvent-free synthesis of polyhydroquinoline
derivatives: Green and sustainable protocol. Appl
Organomet Chem. 2020;e6000. https://doi.org/10.
1002/aoc.6000
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