Din et al.

Nanoscale Research Letters (2017) 12:638

DOI 10.1186/s11671-017-2399-8

NANO REVIEW Open Access

Green Adeptness in the Synthesis and

Stabilization of Copper Nanoparticles:
Catalytic, Antibacterial, Cytotoxicity, and
Antioxidant Activities
Muhammad Imran Din1*, Farhan Arshad1, Zaib Hussain1 and Maria Mukhtar2

Abstract
Copper nanoparticles (CuNPs) are of great interest due to their extraordinary properties such as high surface-to-volume
ratio, high yield strength, ductility, hardness, flexibility, and rigidity. CuNPs show catalytic, antibacterial, antioxidant, and
antifungal activities along with cytotoxicity and anticancer properties in many different applications. Many physical and
chemical methods have been used to synthesize nanoparticles including laser ablation, microwave-assisted process,
sol-gel, co-precipitation, pulsed wire discharge, vacuum vapor deposition, high-energy irradiation, lithography, mechanical
milling, photochemical reduction, electrochemistry, electrospray synthesis, hydrothermal reaction, microemulsion, and
chemical reduction. Phytosynthesis of nanoparticles has been suggested as a valuable alternative to physical and
chemical methods due to low cytotoxicity, economic prospects, environment-friendly, enhanced biocompatibility, and
high antioxidant and antimicrobial activities. The review explains characterization techniques, their main role, limitations,
and sensitivity used in the preparation of CuNPs. An overview of techniques used in the synthesis of CuNPs, synthesis
procedure, reaction parameters which affect the properties of synthesized CuNPs, and a screening analysis which is used
to identify phytochemicals in different plants is presented from the recent published literature which has been reviewed
and summarized. Hypothetical mechanisms of reduction of the copper ion by quercetin, stabilization of copper
nanoparticles by santin, antimicrobial activity, and reduction of 4-nitrophenol with diagrammatic illustrations are given.
The main purpose of this review was to summarize the data of plants used for the synthesis of CuNPs and open a new
pathway for researchers to investigate those plants which have not been used in the past.

Keywords: Phytosynthesis, Copper nanoparticles, Phytochemicals, Cytotoxicity, Catalytic activity, Antibacterial activity

Background Indeed, the properties of NPs, which may considerably

Nanoparticles (NPs) have a number of interesting appli- differ from those observed for fine particles, are higher
cations in the industrial field such as space technology, specific surface area, specific optical properties, lower
magnetism, optoelectronics and electronics, cosmetics, melting points, specific magnetizations, mechanical
and catalytic, pharmaceutical, biomedical, environmen- strength, and numerous industrial applications [4].
tal, and energy applications [1, 2]. The extraordinary Copper nanoparticles (CuNPs) are of great interest due
properties of NPs such as ductility, high yield strength, to easy availability, low cost, and their similar properties
hardness, flexibility, rigidity, high surface-to-volume to those of noble metals [5–9]. CuNPs can also be used
ratio, macroquantum tunneling effect, and quantum size in sensors, heat transfer systems [10–12], and electronics
are attributable as compared to properties of bulk (fuel cell and solar cell), as catalysts in many reactions
materials having the same chemical composition [3]. and as bactericidal and antimicrobial agents used to coat
hospital equipment [13–19].
* Correspondence: imrandin2007@gmail.com
1
Many physical and chemical methods including laser
Institute of Chemistry, University of Punjab, Lahore 54590, Pakistan
Full list of author information is available at the end of the article
ablation [20], microwave-assisted process, sol-gel [21],

© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made.
Din et al. Nanoscale Research Letters (2017) 12:638 Page 2 of 15

co-precipitation [22], pulsed wire discharge [23], vacuum preparation of plant extracts, and secondly, dry leaves
vapor deposition [24], high-energy irradiation [25], and roots in powder form are used.
lithography [26], mechanical milling [27], photochemical
reduction, electrochemistry [28–32], electrospray syn- Procedure for the Synthesis of CuNPs
thesis [33], hydrothermal reaction [34], microemulsion For the synthesis of CuNPs, plant extract was prepared by
[35], and chemical reduction are used to synthesize using different parts of different plants. For synthesis of
nanoparticles. Although physical and chemical methods the extract part of the plant of interest, leaves are
produce well-defined and pure nanoparticles, these collected and washed with tap water and then with dis-
methods are neither cost-effective nor eco-friendly due tilled water to remove dust particles. The washed leaves
to the use of toxic chemicals. One of the most important are used further in two ways. First, these leaves are sun
criteria of nanotechnology is the development of eco- dried for 1–2 h to remove the residual moisture. Known
friendly, nontoxic, and clean green chemistry procedures weights of these sun-dried leaves are divided into small
[36]. Hence, biosynthesis of nanoparticles contains a parts and soaked in deionized water or ethanol solution.
green chemistry-based method which employs different This mixture is stirred for 24 h at room temperature by
biological bodies such as plants [37, 38], actinomycetes using a magnetic stirrer and then filtered for further use.
[39, 40], fungus [41–44], bacteria [45–49], yeast [50–52], Second, these leaves are sun dried for 4–7 days or dried in
and viruses [53, 54]. Biological entities offer a nontoxic, an oven at 50 °C for 1 day and powdered using a domestic
clean, and environment-friendly approach to synthesize blender. Known weight of plant powder is mixed in water
the NPs with a wide range of size, physicochemical or ethanol solution and then stirred and filtered.
properties, shapes, and compositions [55]. For the synthesis of CuNPs, aqueous solution of pre-
Copper nanoparticles were synthesized and stabilized in cursor salts such as copper sulfate, copper chloride,
the literature by using different plants such as Euphorbia copper acetate, and copper nitrate with different concen-
esula [56], Punica granatum [57], Ocimum sanctum [58], trations is mixed with plant extract. Aqueous solution of
Ginkgo biloba [59], Calotropis procera [60], Lawsonia iner- sodium hydroxide is also prepared and added to the re-
mis [61], Citrus medicalinn [62], Camellia sinensis [63], action mixture to control the pH medium. The reaction
Datura innoxia [64], Syzygium aromaticum [65], Sesamum mixture is strongly shaken for different time intervals in
indicum [66], Citrus limon, Turmeric curcumin [67], an electric shaker and heated in an oven at different
Gloriosa superba L. [68], Ficus carica [69], Aegle marmelos time intervals and at different temperatures. The forma-
[70], Caesalpinia pulcherrima [71], Cassia fistula [72], tion of CuNPs can also take place at room temperature
Leucas aspera, Leucas chinensis [73], Delonix elata [74], and is confirmed by changing the color of the reaction
Aloe barbadensis Miller [75], Thymus vulgaris [76], Phyl- mixture. At the end, nanoparticles were centrifuged and
lanthus emblica [77], Magnolia kobus [78], Eucalyptus [79], dried at different temperatures. Reaction optimizations
Artabotrys odoratissimus [80], Capparis zeylanica [81], Vitis take place by changing the pH of the mixture, concen-
vinifera [82], Hibiscus rosa-sinensis [83], Zingiber officinale tration of precursor salt, heating time, and temperature
[84], Datura metel [85], Zea mays [86], Urtica, Matricaria of reaction mixture. In the literature, different plants
chamomilla, Glycyrrhiza glabra, Schisandra chinensis, have been used for the formation of copper nanoparti-
Inula helenium, Cinnamomum [87], Dodonaea viscosa [88], cles by using different precursor salts with different reac-
Cassia auriculata [89], Azadirachta indica, Lantana cam- tion conditions as shown in Table 1. From the table, it
era, Tridax procumbens [90], Allium sativum [91], Aspara- can be seen that the different reaction conditions affect
gus adscendens, Bacopa monnieri, Ocimum bacilicum, the shape and size of copper nanoparticles.
Withania somnifera [92], Smithia sensitiva, Colocasia escu-
lenta [93], Nerium oleander [94], and Psidium guajava Effect of Reaction Parameters on Properties of NPs
[95]; by using different algae/fungi such as Phaeophyceae The concentration of plant extract plays a main role in
[96], Stereum hirsutum [97], and Hypocrea lixii [98]; and by reducing and stabilizing the CuNPs. It has been reported
using some microorganisms such as Pseudomonas fluores- that by increasing the concentration of plant extract, the
cens [99] and Enterococcus faecalis [100] cultures. number of particles increased [88]. By increasing the
concentration of plant extract, the concentration of phy-
tochemicals increased and the reduction of copper salt
Biosynthesis of Copper Nanoparticles also increased. Due to the fast reduction of the metal
Parts of Plant Used for Extract salt, the size of the nanoparticles also decreased [101].
Different parts of plants are used for the preparation of The size and structure of CuNPs are highly affected by
plant extracts such as leaves, seeds, barks, fruits, peel, the copper salt. The morphology of nanoparticles
coir, roots, and gum. Leaves and roots are used in two changes when the salt (e.g., copper chloride, copper acet-
ways. Firstly, fresh leaves and roots are used for the ate, copper nitrate, or copper sulfate) is used in the
Table 1 Data for synthesis of copper nanoparticles under different reaction conditions
Plants Part of Active compounds in plant Precursor salt Concentration Reaction conditions Characterization Size Shape References
plant of salt
Euphorbia esula Leaves Flavonoids and phenolic acids Copper 5 mM Temp 120 °C, pH 9, time UV, FTIR, XRD, TEM 20– Spherical [56]
chloride 20 min 110 nm
Punica granatum Peels – Copper 50 mM Temp 80 °C for 10 min and UV, FTIR, PSA, TEM 15– Spherical [57]
sulfate 40 °C for 4 h 20 nm
Ocimum sanctum Leaves Terpenoids, alcohols, ketones, Copper 1 mM Room temp UV, FTIR, PSA, TEM, MZS 25 nm Rod, cylindrical, [58]
esters, aldehydes, and carboxylic sulfate elliptical
acids
Leaves Copper 1 mM Room temp UV, FTIR, EDX, SEM 150– Spherical [115]
sulfate 200 nm
Ginkgo biloba Leaves Polyphenols, quercetin Copper 5 mM Temp 80 °C, pH 9, time UV, FTIR, EDS, TEM 15– Spherical [59]
chloride 30 min 20 nm
Calotropis procera Latex Cysteine proteases Copper 3 mM Room temp UV, FTIR, XRD, TEM, EDAX 15 ± Spherical [60]
Din et al. Nanoscale Research Letters (2017) 12:638

acetate 1.7 nm
Lawsonia inermis Leaves – Copper 10 mM Temp 100 °C, pH 11, time UV, FTIR, HRTEM, SEM, DMOM – [61]
sulfate 30 min
Citrus medicalinn Fruit Ascorbic acid, saponins, and Copper 100 mM Temp 60–100 °C UV, FTIR, NTA, XRD 33 nm – [62]
juice flavonoids sulfate
Camellia sinensis Leaves Flavonoids, phenolic acids, terpenoids, Copper 1 mM Temp 100 °C, time 3 h UV, FTIR, EDX, TEM, SEM 15– Spherical [63]
and polysaccharides chloride 25 nm
Leaves – Copper 10 mM Temp 90 °C FTIR, EDX, TEM, SEM, XRD, NTA 10– Spherical [104]
chloride 40 nm
Datura innoxia Leaves – Copper 1 mM – UV, FTIR, EDX, FESEM 90– Spherical [64]
sulfate 200 nm
Syzygium Flowers Eugenol Copper 1 mM Room temp, pH 3.43 UV, FTIR, XRD, TEM, SEM 5–40 nm – [65]
aromaticum sulfate
Sesamum Seeds – Copper 10 mM – UV – – [66]
indicum sulfate
Citrus limon and Fruit Curcuminanilineazomethine Copper 1 mM – UV, FTIR, XRD, HRTEM, SEM 60– Spherical [67]
Turmeric curcumin chloride 100 nm
Gloriosa superba Leaves – Copper 1 mM Room temp UV, FTIR – – [68]
L. sulfate
Gossypium Gum Hydroxyl, acetyl, carbonyl, and Copper 40 mM Room temp, pH 12 TEM, SAXS, UV, XRD 19 nm Spherical [116]
carboxylic groups nitrate
Ficus carica Leaves – Copper 10 mM Temp 25 °C, pH 8, time UV, SEM, XRD 50– – [69]
chloride 30 min 120 nm
Aegle marmelos Leaves Polyphenols, alkenoids, Copper 1 mM – UV, FTIR, XRD 48 nm Spherical [70]
phenylpropanoid, and chloride
terpenoids
Caesalpinia Flowers – Copper 1 mM – UV, FTIR, XRD, SEM, EDAX 18– Spherical [71]
pulcherrima nitrate 20 nm
Cassia fistula Flowers – 1 mM Room temp UV, FTIR, XRD, SEM 20 – [72]
Page 3 of 15
Table 1 Data for synthesis of copper nanoparticles under different reaction conditions (Continued)
Plants Part of Active compounds in plant Precursor salt Concentration Reaction conditions Characterization Size Shape References
plant of salt
Copper
sulfate
Leucas aspera Leaves – Copper 1 mM – UV – – [73]
sulfate
Leucas chinensis Leaves – Copper 1 mM – XRD, FESEM, EDX 60.23 nm – [117]
sulfate
Delonix elata Flowers – Copper 1 mM – UV, FTIR, XRD, SEM 20 – [74]
sulfate
Aloe barbadensis Flowers – Copper 5 mM Temp 50 °C, time 30 min UV, FTIR, FESEM 40 nm Spherical [75]
Miller acetate
Thymus vulgaris Leaves – Copper 0.2 M Temp 80 °C, time 4 h BET, TEM, SAED, FTIR, XRD, – – [76]
sulfate XRF, FESEM, EDS
Din et al. Nanoscale Research Letters (2017) 12:638

Phyllanthus Fruit Tannin, saponin, flavonoid, Copper 20 mM Temp 60–80 °C, pH 10 UV, FTIR, XRD, SEM, EDAX 15– Flakes [77]
emblica alkaloid, quinone, sulfate 30 nm
anthraquinone, anthocyanosides,
phenols
Magnolia kobus Leaves Copper 1 mM Temp 25–95 °C ICP, EDS, XPS, SEM, HRTEM 40– Spherical [78]
sulfate 100 nm
Eucalyptus Leaves Flavonoids and phenolic acids Copper 1 mM – UV, FTIR, XRD 38.62 nm – [79]
sulfate
Artabotrys Leaves – Copper 1 mM Temp 95 °C PSA 35 nm – [80]
odoratissimus sulfate
Capparis Leaves – Copper – UV, FTIR, SEM, EDX, XRD, TEM 50– Cubical [81]
zeylanica sulfate 100 nm
Vitis vinifera Leaves – Copper 1% – UV, FTIR, XRD 3–6 nm – [82]
acetate
Hibiscus rosa- Leaves Polyphenols, flavonoids, proteins, Copper 50 mM – UV, FTIR, TEM – – [83]
sinensis lignins, xanthones nitrate
Zingiber officinale – – – – – FTIR, XRD, EDX, TEM, SAED 10.13 nm Cubical [84]
Datura metel Leaves Alkaloids, terpenoids, and – – Time 10 min UV, PSA, TEM, EDX, FTIR – – [85]
phenolic groups
Zea mays Leaves – Copper 10 mM Room temp, time 1 h UV, XRD, EDAX, FTIR 40 nm Mixed [86]
sulfate
Urtica Leaves Flavonoids, quercetin, rutin, Copper – Temp 70 °C UV, SEM, XRD 6.5 nm – [87]
morin sulfate
Matricaria Leaves Flavonoids Copper – Temp 70 °C UV, SEM, XRD 58.77 nm – [87]
chamomilla sulfate
Glycyrrhiza glabra Leaves Flavonoids Copper – Temp 70 °C UV, SEM, XRD 28.21 nm – [87]
sulfate
Schisandra Leaves Quercetin, rutin, morin Copper – Temp 70 °C UV, SEM, XRD 32 nm – [87]
chinensis sulfate
Page 4 of 15
Table 1 Data for synthesis of copper nanoparticles under different reaction conditions (Continued)
Plants Part of Active compounds in plant Precursor salt Concentration Reaction conditions Characterization Size Shape References
plant of salt
Inula helenium Leaves Flavonoids Copper – Temp 70 °C UV, SEM, XRD 32.41 nm – [87]
sulfate
Cinnamomum Leaves Flavonoids Copper – Temp 70 °C UV, SEM, XRD 48.8 nm – [87]
sulfate
Dodonaea viscosa Leaves Santin, penduletin, alizarin, Copper 1 mM Temp 50 °C, pH 10 UV, XRD, AFM, HRTEM, SAED 30– Spherical [88]
pinocembrin, tannins, saponins chloride 40 nm
Cassia auriculata Leaves – Copper 1 mM – FESEM, XRD, FTIR 38– Spherical [89]
sulfate 43 nm
Azadirachta Leaves – Fehling – – UV – – [90]
indica solution
Lantana camera Leaves – Fehling – – UV – – [90]
solution
Din et al. Nanoscale Research Letters (2017) 12:638

Tridax Leaves – Fehling – – UV – – [90]

procumbens solution
Allium sativum – Copper 10 mM – UV, FTIR, SEM, XRD, TEM 100 nm Spherical [91]
sulfate
Asparagus Leaves – copper 1 mM – UV, FTIR, TEM, SAED 10– Spherical [92]
adscendens sulfate 15 nm
Bacopa monnieri Leaves – copper 1 mM – UV, FTIR, TEM, SAED 50– Spherical [92]
sulfate 60 nm
Ocimum Leaves – copper 1 mM – UV, FTIR, TEM, SAED 40– Spherical [92]
bacilicum sulfate 60 nm
Withania Leaves – copper 1 mM – UV, FTIR, TEM, SAED 50– Mixed [92]
somnifera sulfate 60 nm
Smithia sensitiva Leaves Tannin, saponin, flavonoid, Copper 1 mM – UV, FTIR, SEM, NTA 136 nm – [93]
anthraquinone glycoside, sulfate
steroids
Leaves Tannin, saponin, flavonoid, Copper 1% – UV, FTIR, SEM, NTA 50 nm – [93]
anthraquinone glycoside, acetate
steroids
Colocasia Leaves Tannin, flavonoid, alkaloid, Copper 1 mM – UV, FTIR, SEM, NTA 57 nm – [93]
esculenta cardiac glycoside, terpenoids, sulfate
phenols
Leaves Tannin, flavonoid, alkaloid, cardiac Copper 1% – UV, FTIR, SEM, NTA 44 nm – [93]
glycoside, terpenoids, phenols acetate
Nerium oleander Leaves Copper 1 mM – UV, FTIR – – [94]
sulfate
Psidium guajava Fruit Flavonoid, alkaloid, steroids, glycoside, Copper 20 mM Room temp, pH 10 UV, FTIR, XRD, EDAX, TEM, SEM 15– Flakes [95]
terpenoids, phenols sulfate 30 nm
Page 5 of 15
Din et al. Nanoscale Research Letters (2017) 12:638 Page 6 of 15

presence of sodium hydroxide. It was reported that the Phytochemicals for Reduction of Metal and Stabilizing the
shape was triangular and tetrahedron in the case of cop- NPs
per chloride, rod-shaped in the case of copper acetate, Green synthesis of CuNPs by the use of phytochemicals
and spherical in the case of copper sulfate [102]. By in- offers more flexible control over the shape and size of
creasing the concentration of the precursor salt, the size the NPs (i.e., by changing reaction temperature, concen-
of the CuNPs also increased. tration of plant extract, metal salt concentration, reac-
The synthesis of CuNPs gives best results by varying the tion time, and pH of reaction mixture). Color change of
pH of the reaction medium within the preferred range. the reaction medium indicates reduction of the metal
The size of nanoparticles was controlled by changing the ion and formation of NPs. The green reduction of the
pH value of the reaction mixture. At higher pH, smaller- copper salts starts instantly, and the formation of copper
sized nanoparticles were obtained compared to those ob- nanoparticles is indicated by the color change of the re-
tained at low pH value. This difference can be attributed action mixture. Phytochemicals have a main role in first
to the difference in reduction rate of the metal salts by reducing the metal ions and then stabilizing the metal’s
plant extract. The inverse relation between the value of nuclei in the form of nanoparticles as shown in Fig. 2.
pH and the size of nanoparticle showed that an increase The interaction of phytochemicals with metal ions and
in pH value enables us to obtain small-sized spherical the concentration of these phytochemicals control the
nanoparticles while a decrease in pH value gives large- shape and size of CuNPs.
sized (rod-shaped and triangular) nanoparticles. The effect Flavonoids contain polyphenolic compounds, e.g.,
on absorption spectra of different values of pH (4, 6, 8, 10, quercetin, catechins, flavanones, isoflavones, santin, pen-
and 12) is represented in Fig. 1 [36]. It was reported that duletin, alizarin, pinocembrin, anthocyanins, flavones,
the addition of plant extract to CuCl2 did not lead to the tannins, and saponins, which are present in different
formation of CuNPs but, instead, the CuNPs were ob- plants such as Ginkgo biloba [59], Citrus medicalinn
tained by changing the pH of the reaction mixture to basic [62], Phyllanthus emblica [77], Hibiscus rosa-sinensis
medium. The same behavior was observed by Wu and [83], and Dodonaea viscosa [93]. These compounds play
Chen, and it was concluded that pH plays an important a main role in reducing and chelating the metal. Various
role in the synthesis of CuNPs [103]. functional groups present in the flavonoids are respon-
sible for the reduction of the copper ion. It has been as-
Mechanism for Phytosynthesis of Copper sumed that a reactive hydrogen atom in the flavonoids
Nanoparticles may be released during the tautomeric alterations of the
Phytochemical Screening: a Qualitative Analysis enol form to the keto form which can reduce copper
Phytochemical screening analysis is a chemical analysis ions to form copper nuclei or CuNPs. For example, it is
carried out for the detection of phytochemicals in different assumed that in the case of Ginkgo biloba plant extracts,
plants. Fresh plant extract with chemicals or chemical it is the transformation of quercetin (flavonoid) which
reagents is used for this analysis [77] as shown in Table 2. plays a main role in the reduction of copper metal ions
into copper nuclei or CuNPs due to the change of enol
form to keto form as shown in Fig. 3.
During the synthesis process of CuNPs, metal ions with
monovalent or divalent oxidation states are converted into
zero-oxidation copper nuclei and these nuclei are merged
to obtain different shapes. During the nucleation, nuclei
aggregate to form different shapes such as wires, spheres,
cubes, rods, triangles, pentagons, and hexagons. Some fla-
vonoids have an ability to chelate the CuNPs with their π
electrons and carbonyl groups. Quercetin and santin are
flavonoids with strong chelating activity due to the pres-
ence of two functional groups involving the hydroxyls and
carbonyls. These groups chelate with copper nanoparticles
by following the previous mechanism and also explain the
ability of adsorption of santin (flavonoid) on the surface of
CuNPs as shown in Fig. 4.
It was assumed that the protein molecules (superoxide
dismutase, catalase, glutathione) in different plants such
as Hibiscus rosa-sinensis [83] and Camellia sinensis
Fig. 1 Parts of the plant used for the preparation of plant extract
[104] display a high reducing activity for the formation
Din et al. Nanoscale Research Letters (2017) 12:638 Page 7 of 15

Table 2 Phytochemical screening analysis

Test for phytochemicals Amount of plant extract Chemicals used End point for confirmation of phytochemical
Carbohydrate 2 mL Few drops of concentrated sulfuric Reddish or purple color
acid and 1 mL of Molisch’s reagent
Tannins 2 mL 4 mL of 5% ferric chloride Greenish black or dark blue color
Saponins 2 mL 2 mL of distilled water and shake Layer of foam on surface
for 15 min
Flavonoids 2 mL 1 mL of 2 N sodium hydroxide Yellow color
Alkaloids 2 mL Few drops of Mayer’s reagent and White precipitate or green color
2 mL of concentrated HCl
Anthraquinone 1 mL Few drops of 10% ammonia solution Pink color precipitates
Anthocyanosides 1 mL of filtrate 5 mL HCl Pale pink color

of nanoparticles from metal ions but their chelating and anthocyanoside in Phyllanthus emblica [77]; lignins
activity is not excessive. Sugars such as monosaccharides and xanthones in Hibiscus rosa-sinensis [83]; and cardiac
(glucose), disaccharides (maltose and lactose), and glycoside, triterponoid, carotenoid glycoside, and anthra-
polysaccharides in Camellia sinensis plant [63] can act quinone glycoside in Colocasia esculenta plant [93] are
as reducing agents or antioxidants and have a series of also phytochemicals which are present in extracts of
tautomeric transformations from ketone to aldehyde. different plants and act as reducing and stabilizing
Other phytochemicals such as polyphenols (e.g., ellagic agents. Examples of certain phytochemicals with struc-
acid and gallic acid) which are present in Hibiscus rosa- tures are shown in Fig. 5.
sinensis [40], phenylpropanoids (phenylalanine, tyrosine)
in Aegle marmelos [70], terpenoids in Ocimum sanctum Characterization Techniques
and Asparagus adscendens [58, 92], cysteine proteases in For characterization of synthesized nanoparticles, differ-
Calotropis procera [60], curcuminanilineazomethine in ent techniques were used such as ultraviolet-visible spec-
Turmeric curcumin [67], ascorbic acid in Citrus medica- troscopy (UV-vis), transmission electron microscopy
linn [62], eugenol in Syzygium aromaticum [65], and al- (TEM), small-angle X-ray scattering (SAXS), Fourier
kaloids in Aegle marmelos [70] play the same role of transform infrared spectroscopy (FTIR), X-ray fluores-
reducing the copper ions and stabilizing the copper cence spectroscopy (XRF), X-ray diffraction (XRD),
nanoparticles. Carbohydrates, anthraquinone, quinone, X-ray photoelectron spectroscopy (XPS), scanning

Fig. 2 A protocol for reducing the metal ions and then stabilizing the metal’s nuclei
Din et al. Nanoscale Research Letters (2017) 12:638 Page 8 of 15

Fig. 3 Reduction of copper ions by quercetin

electron microscopy (SEM), field emission scanning antibacterial activity, cytotoxicity or anticancer activity,
electron microscopy (FESEM), particle size analysis antioxidant activity, and antifungal activity in different
(PSA), Malvern Zetasizer (MZS), energy-dispersive X-ray applications. In catalytic activity, copper nanoparticles
spectroscopy (EDX/EDS), nanoparticle tracking analysis are used for the Huisgen [3 + 2] cycloaddition of alkynes
(NTA), X-ray reflectometry (XRR), Brunauer-Emmett- and azides in many solvents under ligand-free conditions
Teller analysis (BET), selected area electron diffraction [59], 1-methyl-3-phenoxy benzene, 3,3-oxybis(methyl-
(SAED), and atomic force microscopy (AFM) (Table 3). benzene) [94], synthesis of 1-substituted 1H-1,2,3,4-
tetrazole [76], adsorption of nitrogen dioxide, and
Applications of Copper Nanoparticles adsorption of sulfur dioxide [66]. In most of the transi-
Due to their outstanding chemical and physical proper- tion metals catalyzed, Ullmann coupling-reaction li-
ties, large surface-to-volume ratio, constantly renewable gands, such as phosphines, are reported in the literature
surface, low cost, and nontoxic preparation, CuNPs have and most ligands are expensive, difficult to prepare, and
been of great interest for applications in different fields. moisture sensitive. For this work, synthesized copper
Copper nanoparticles show catalytic activity, nanoparticles are used for ligand-free Ullmann coupling

Fig. 4 Stabilization of copper nanoparticles by santin

Din et al. Nanoscale Research Letters (2017) 12:638 Page 9 of 15

of diphenyl ether. Different dyes and toxic organic com- oxysporum f.sp. ciceris, Macrophomina phaseolina, Fu-
pounds and pesticides present in industrial waste are sarium oxysporum f.sp. udum, Rhizoctonia bataticola
very harmful for the environment and living organisms. [58], Candida albicans, Curvularia, Aspergillus niger,
Copper nanoparticles are used for degradation of differ- and Trichophyton simii [67]. In cytotoxicity, copper
ent dyes such as methylene blue [73], degradation of nanoparticles are used for a study on HeLa, A549,
atrazine [86], and reduction of 4-nitrophenol [76]. MCF7, MOLT4, and BHK21 cell lines (cancer tumors)
Among the antimicrobial agents, copper compounds [60, 104].
have been commonly used in agriculture as herbicides
[105], algaecides [106], fungicides [107], and pesticides Hypothetical Mechanism of Antimicrobial Activity
as well as in animal husbandry as a disinfectant [108] It was observed that CuNPs have an excellent antimicro-
(shown in Table 4). The biogenic copper nanoparticles bial activity and only limited reports presented the
showed powerful antibacterial activity against gram- mechanism of the antibacterial activity of copper nano-
positive and gram-negative pathogens such as Pseudo- particles in the literature, but these mechanisms were
monas aeruginosa (MTCC 424), Micrococcus luteus hypothetical. It was observed that bacteria and enzymes/
(MTCC 1809), Enterobacter aerogenes (MTCC 2832) proteins were destroyed due to the interaction of CuNPs
[57], Salmonella enterica (MTCC 1253), Rhizoctonia with –SH (sulfhydryl) group [109, 110]. It was also re-
solani, Xanthomonas axonopodis pv. citri, Xanthomonas ported that the helical structure of DNA molecules be-
axonopodis pv. punicea [58], Escherichia coli (ATCC come disturbed by the interaction of CuNPs [111]. The
14948) [62], Staphylococcus aureus (ATCC 25923), Ba- interaction of CuNPs with the cell membrane of bacteria
cillus subtilis (ATCC 6633), Pediococcus acidilactici [69], decreased the transmembrane electrochemical potential,
and Klebsiella pneumoniae (MTCC 4030). In antifungal and due to the decrease in transmembrane electrochem-
activity, copper nanoparticles are used against Alterneria ical potential, it affected the membrane integrity [112]. It
carthami, Colletotrichum gloeosporioides, Colletotrichum was assumed that metal NPs release their respective
lindemuthianum, Drechslera sorghicola, Fusarium oxy- metal ions. Copper nanoparticles and copper ions accu-
sporum f.sp. carthami, Rhizopus stolonifer, Fusarium mulate on the cell surface of the bacteria and form pits

Fig. 5 Phytochemicals with their structures

Din et al. Nanoscale Research Letters (2017) 12:638 Page 10 of 15

Table 3 Characterization techniques and limitations

Technique Main role Limitations Sensitivity Ref.
Ultraviolet-visible spectroscopy Concentration and shape of NPs can Only for liquid samples UV-visible regions [22]
(UV-vis) be measured 200–800 nm
Fourier transform infrared Nature of bonds and functional groups Structure and size of NPs cannot be 20 Å–1 μm [22]
spectroscopy (FTIR) can be determined measured
X-ray diffraction (XRD) Size and crystallinity of nanoparticles Composition of NPs and plasmon 1 nm [36]
can be measured cannot be found
Scanning electron microscopy Shape and size of nanostructures can Samples must be solid and cannot < 1 nm [115]
(SEM) be determined detect elements with atomic number
< 11
Field emission scanning electron All structural and morphological Does not give a concentration of NPs < 1 nm [117]
microscopy (FESEM) investigations are carried out by this
technique
Transmission electron microscopy Shape and size of nanostructures can Particles with size < 1.5 nm cannot be < 1.5 nm [92]
(TEM) be determined determined
Particle size analysis (PSA) Measured the distribution of size in – 1 nm–1 μm [57,
the sample of solid or liquid 58]
particulate materials
Malvern Zetasizer (MZS) Measured the size of NPs, zeta In nanorange – [58]
potential, and protein mobility
Energy-dispersive X-ray Composition of NPs can be analyzed Particles with size < 2 nm cannot be < 2 nm [59,
spectroscopy (EDX/EDS) analyzed 60]
Nanoparticle tracking analysis Visualize and measure particle size, – 30–10 nm [62]
(NTA) concentration, and fluorescent
properties of a nanoparticle
Small-angle X-ray scattering Size and shape conformation Lower resolution range 50–10 Å [116]
(SAXS)
X-ray reflectometry (XRR) Determination of thickness, density, Layer thickness 0.1–1000 nm – [116]
and roughness
X-ray fluorescence spectroscopy Chemical composition and Limited in their ability to measure – [76]
(XRF) concentration can be measured precisely and accurately
X-ray photoelectron spectroscopy Elemental composition of Decomposition of samples occurred 3–92 nm [78]
(XPS) nanoparticles can be analyzed
Brunauer-Emmett-Teller analysis Specific surface area is measured 0.35–2 nm [76]
(BET)
Selected area electron diffraction Technique that can be performed Cannot be recommended for – [76]
(SAED) inside a TEM quantitative identification techniques
Atomic force microscopy (AFM) Particle size and characterization For gas and liquid samples 1 nm–8 μm [88]

in the membrane, causing leakage of the cellular compo- Catalytic activity of the synthesized CuNPs has been
nent from the cell and inside the cell, causing oxidative studied in the reduction of 4-nitrophenol in aqueous
stress which leads to cell death [112–114]. A hypothet- medium at room temperature in the presence of aque-
ical mechanism of antibacterial activity representing the ous solution of sodium borohydride [56]. The reduction
above possibilities is shown in Fig. 6. of 4-NP by using CuNPs is a simple and environment-
friendly process. Catalytic efficiency of CuNPs for the re-
Catalytic Activity for Reduction of 4-Nitrophenol duction of 4-NP was examined by using a UV-vis spec-
4-Nitrophenol (4-NP) which is usually found in agricul- trometer. It was observed that the maximum absorption
tural wastewaters and industrial products is hazardous peak for 4-NP in aqueous medium was at 317 nm and
and not environment-friendly. Hydrogenation or reduc- the adsorption peak shifted to 403 nm by adding sodium
tion of 4-NP, which is converted into 4-aminophenol (4- borohydride due to the formation of 4-nitrophenolate
AP), takes place in the presence of CuNPs. CuNPs can ions. A peak at 403 nm remained unaffected even after
catalyze the reaction to overcome the kinetic barrier by 2 days, which indicated that the reduction of 4-NP can-
assisting electron transfer from the donor borohydrate not take place in the absence of a catalyst. After adding
ions to the acceptor 4-NP. the CuNPs, the absorption peak of the solution shifted
Din et al. Nanoscale Research Letters (2017) 12:638 Page 11 of 15

Table 4 Catalytic, antibacterial, cytotoxicity or anticancer, antioxidant, and antifungal activities of copper nanoparticles
Biological entity Activity In/against Concentration of NPs References
Euphorbia esula Catalytic Reduction of 4-nitrophenol 25 μL [56]
Catalytic Ligand-free Ullmann coupling of diphenyl ether, 1-methyl-3-phenoxy 1 mL [56]
benzene, and 3,3-oxybis(methylbenzene)
Punica granatum Antibacterial Enterobacter aerogenes, Micrococcus luteus, Salmonella enterica, and 100 μg/L [57]
Pseudomonas aeruginosa
Ocimum sanctum Antibacterial Rhizoctonia solani, Xanthomonas axonopodis pv. citri, Xanthomonas – [58]
axonopodis pv. punicea
Antifungal Alterneria carthami, Colletotrichum gloeosporioides, Colletotrichum – [58]
lindemuthianum, Drechslera sorghicola, Fusarium oxysporum f.sp.
carthami, Rhizopus stolonifer, Fusarium oxysporum f.sp. ciceris,
Macrophomina phaseolina, Fusarium oxysporum f.sp. udum, and
Rhizoctonia bataticola
Ginkgo biloba Catalytic Huisgen [3 + 2] cycloaddition of azides and alkynes 10 mol% [59]
Calotropis procera Cytotoxicity Study on HeLa, A549, and BHK21 cell lines (cancer tumors) 120 μM [60]
Citrus medicalinn Antibacterial Propionibacterium acnes (MTCC 1951), Salmonella typhi 20 μL [62]
(ATCC 51812),
K. pneumoniae (MTCC 4030), P. aeruginosa, and Escherichia coli
Antifungal Fusarium culmorum (MTCC 349) and Fusarium oxysporum 20 μL [62]
(MTCC 1755)
Camellia sinensis Antibacterial Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, 2, 4, 6, and [63]
and Bacillus subtilis 8 μg/L
Anticancer HT-29, MCF7, and MOLT4 cell lines 80 μg/mL [104]
Datura innoxia Antibacterial Xanthomonas oryzae pv. oryzae [64]
Sesamum indicum Catalytic Adsorption of nitrogen dioxide and sulfur dioxide 0.01–0.06 g [66]
Citrus limon and Antibacterial Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, – [67]
Turmeric curcumin and Bacillus subtilis
Antifungal Candida albicans, Curvularia, Aspergillus niger, Trichophyton simii – [67]
Ficus carica Antibacterial Pediococcus acidilactici 10 μg/mL [69]
Leucas aspera Catalytic Degradation of methylene blue 1 mL [73]
Thymus vulgaris Catalytic Reduction of 4-nitrophenol and synthesis of 1-substituted 50 g and 15 [76]
1H-1,2,3,4-tetrazole mg, respectively
Phyllanthus emblica Antibacterial Staphylococcus aureus and Escherichia coli – [77]
Magnolia kobus Antibacterial Escherichia coli (ATCC 25922) – [78]
Capparis zeylanica Antibacterial Gram-positive and gram-negative pathogens – [81]
Vitis vinifera Antibacterial Bacillus subtilis and Escherichia coli (ATCC 25922) – [82]
Hibiscus rosa-sinensis Antibacterial Bacillus subtilis and Escherichia coli (ATCC 25922) – [83]
Antioxidant Hydrogen peroxide scavenging assay was assessed – [83]
Zingiber officinale Antibacterial Staphylococcus aureus (ATCC 25923), Bacillus subtilis, and – [84]
Escherichia coli
Zea mays Catalytic Degradation of atrazine 30 mg [86]
Dodonaea viscosa Antibacterial Staphylococcus aureus (ATCC 25923), Bacillus subtilis, – [88]
Escherichia coli, and K. pneumoniae (MTCC 4030)
Azadirachta indica Antibacterial Escherichia coli – [90]
Lantana camera Antibacterial Escherichia coli – [90]
Antifungal Aspergillus niger – [90]
Tridax procumbens Antibacterial Escherichia coli – [90]
Antifungal Aspergillus niger – [90]
Allium sativum Antibacterial Escherichia coli, Bacillus subtilis 75 and 50 μL, [91]
respectively
Asparagus adscendens Antibacterial Staphylococcus aureus – [92]
Bacopa monnieri Antibacterial Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa – [92]
Nerium oleander Antibacterial Escherichia coli, Staphylococcus aureus, Bacillus subtilis, K. 35 μL [94]
pneumoniae, Salmonella typhi
Psidium guajava Antibacterial Escherichia coli, Staphylococcus aureus – [95]
Din et al. Nanoscale Research Letters (2017) 12:638 Page 12 of 15

Fig. 6 Mechanism for antibacterial activity of copper nanoparticles

to 300 nm and the peak at 403 nm completely disappeared protons and 4-nitrophenolate ion, CuNPs overcome the
which indicated the reduction of 4-NP to 4-AP without kinetic barrier of reactants and 4-nitrophenolate ion is
any side product. A hypothetical mechanism for the re- converted into 4-aminophenolate ion. After conversion,
duction of 4-NP is shown in Fig. 7. In the mechanism, 4- desorption of the 4-aminophenolate ion takes place and it
NP and sodium borohydride are present in the solution in is converted into 4-aminophenol.
the form of ions. The protons of the borohydride ion are
adsorbing on the surface of the copper nanoparticles and Conclusions
BO2 produced. 4-Nitrophenolate ions also adsorb on the This paper has reviewed and summarized recent infor-
surface of the CuNPs. Due to the adsorption of both mation of biological methods used for the synthesis of

Fig. 7 Mechanism for the reduction of 4-nitrophenol

Din et al. Nanoscale Research Letters (2017) 12:638 Page 13 of 15

copper nanoparticles (CuNPs) using different plants. Authors’ Information

Green synthesis of CuNPs has been proposed as a MID received his PhD in Physical Chemistry from the Islamia University of
Bahawalpur in 2013. He joined the Institute of Chemistry, University of the
valuable alternative to physical and chemical methods Punjab, Lahore, Pakistan, in November 2009. His field of interest is adsorption
with low cytotoxicity, economic prospects, environment- by activated carbon, theoretical chemistry, computational chemistry, and
friendly, enhanced biocompatibility, feasibility, and high material chemistry. Currently, he is working on high-surface-area activated
carbon. His research work is published in different international journals and
antioxidant activity and high antimicrobial activity of presented at various international conferences held worldwide. He has pub-
CuNPs. The mechanism of biosynthesis of NPs is still lished over 42 research articles in leading international journals. This review
unknown, and more research needs to be focused on the article is a 3-year effort of MID.

mechanism of formation of nanoparticles and under-

Competing Interests
standing of the role of phytochemicals in the formation The authors declare that they have no competing interests.
of NPs. This review gives data of plants used in the
synthesis of copper nanoparticles, synthesis procedure,
Publisher’s Note
and the reaction parameters which affect the properties Springer Nature remains neutral with regard to jurisdictional claims in
of synthesized CuNPs. A phytochemical screening ana- published maps and institutional affiliations.
lysis is a chemical analysis used to identify the phyto-
Author details
chemicals such as detection of carbohydrates, tannins, 1
Institute of Chemistry, University of Punjab, Lahore 54590, Pakistan.
saponins, flavonoids, alkaloids, anthraquinones, and 2
Department of Zoology, University of Punjab, Lahore 54590, Pakistan.
anthocyanosides in different plants. The mechanism of
Received: 5 October 2017 Accepted: 1 December 2017
reduction of copper ion by quercetin and stabilization of
copper nanoparticles by santin is described in this paper.
Characterization techniques used in the literature for References
copper nanoparticles are UV-vis, FTIR, XRD, SEM, 1. Puzyn T, Leszczynska D, Leszczynski J (2009) Toward the development of
“nano-QSARs”: advances and challenges. Small 5:2494–2509
FESEM, TEM, PSA, MZS, EDX, NTA, SAXS, XRR, XRF, 2. Leszczynski J (2010) Bionanoscience: nano meets bio at the interface. Nat
XPS, BET, SAED, and AFM. Copper nanoparticles show Nanotechnol 5:633–634
catalytic activity, antibacterial activity, cytotoxicity or 3. Puzyn T, Leszczynski J, Cronin MT: Recent Advances in QSAR Studies:
Methods and Applications. Springer Science & Business Media; 2010.
anticancer activity, antioxidant activity, and antifungal 4. Raigond P, Raigond B, Kaundal B, Singh B, Joshi A, Dutt S. Effect of zinc
activity in different applications. Hypothetical mecha- nanoparticles on antioxidative system of potato plants. J Env. Biol. 2017;38:435.
nisms of antimicrobial activity and reduction of 4-nitro- 5. Ahmadi SJ, Outokesh M, Hosseinpour M, Mousavand T. A simple
granulation technique for preparing high-porosity nano copper oxide (II)
phenol with diagrams are shown in this paper. catalyst beads. Particuology. 2011;9:480–5.
CuNPs with different structural properties and effect- 6. Ramgir N, Datta N, Kaur M, Kailasaganapathi S, Debnath AK, Aswal D, Gupta
ive biological effects can be fabricated using new green S. Metal oxide nanowires for chemiresistive gas sensors: issues, challenges
and prospects. Colloid Surface A. 2013;439:101–16.
protocols in the coming days. The control over particle 7. Ruparelia JP, Chatterjee AK, Duttagupta SP, Mukherji S. Strain specificity in
size and, in turn, the size-dependent properties of antimicrobial activity of silver and copper nanoparticles. Actabiomaterialia.
CuNPs will open the new doors of their applications. 2008;4:707–16.
8. Ren G, Hu D, Cheng EW, Vargas-Reus MA, Reip P, Allaker RP.
This study provides an overview of synthesis of CuNP Characterisation of copper oxide nanoparticles for antimicrobial
by using plant extract, microbial extract, and naturally applications. Int J Antimicrob AG. 2009;33:587–90.
occurring biomolecules. Although all these green proto- 9. T. Theivasanthi, M. Alagar, arXiv preprint arXiv (2011) Studies of copper
nanoparticles effects on microorganisms:1110.1372
cols for CuNP synthesis have their own advantages and 10. Eranna G, Joshi B, Runthala D, Gupta R. Oxide materials for development of
limitations, the use of plant extract as a reductant is integrated gas sensors—a comprehensive review. Crit Rev Solid State. 2004;
more beneficial as compared to the use of microbial 29:111–88.
11. Guo Z, Liang X, Pereira T, Scaffaro R, Hahn HT. CuO nanoparticle filled vinyl-
extract because of the rapid rate of production of nano- ester resin nanocomposites: Fabrication, characterization and property
particles with former green reductant. analysis. Compos Sci Technol. 2007;67:2036–44.
12. Padil VVT, Černík M. Green synthesis of copper oxide nanoparticles using
Funding gum karaya as a biotemplate and their antibacterial application. Int J
The authors confirmed that they did not receive any funding for this article. Nanomedicine. 2013;
13. Stoimenov PK, Klinger RL, Marchin GL, Klabunde KJ. Metal oxide
nanoparticles as bactericidal agents. Langmuir. 2002;18:6679–86.
Availability of Data and Materials 14. Gabbay J, Borkow G, Mishal J, Magen E, Zatcoff R, Shemer-Avni Y. Copper
The authors agreed to share data to any recommended repositories. oxide impregnated textiles with potent biocidal activities. J Ind Textiles.
2006;35:323–35.
Authors’ Contributions 15. Borkow G, Zatcoff RC, Gabbay J. Reducing the risk of skin pathologies in
MID collected all the data and write the whole manuscript. FA also contributes diabetics by using copper impregnated socks. Med Hypotheses. 2009;73:883–6.
to this article by studying more than 100 relevant articles and also helped in 16. Borkow G, Gabbay J, Dardik R, Eidelman AI, Lavie Y, Grunfeld Y, Ikher S,
collecting some data. ZH helped in the writing of this manuscript. She is a Huszar M, Zatcoff RC, Marikovsky M. Molecular mechanisms of enhanced
native speaker of English from UK. She revised the whole manuscript and wound healing by copper oxide-impregnated dressings. Wound Repair
improved its English language. MM helped in the writing of the interpretation Regen. 2010;18:266–75.
of antimicrobial effect. She also helped in explaining the green mechanism. All 17. Umer A, Naveed S, Ramzan N, Rafique MS. Selection of a suitable method
authors read and approved the final manuscript. for the synthesis of copper nanoparticles. Nano. 2012;7:1230005.
Din et al. Nanoscale Research Letters (2017) 12:638 Page 14 of 15

18. Nasirian A. Synthesis and Characterization of Cu Nanoparticles and Studying 45. Roh Y, Lauf R, McMillan A, Zhang C, Rawn C, Bai J, Phelps T. Microbial
of Their Catalytic Properties. Dimension. 2012;2:159–64. synthesis and the characterization of metal-substituted magnetites. Solid
19. Magaye R, Zhao J, Bowman L, Ding M. Genotoxicity and carcinogenicity of State Commun. 2001;118:529–34.
cobalt-, nickel- and copper-based nanoparticles. Exp Therapeutic Med. 2012; 46. Lengke M, Southam G. Bioaccumulation of gold by sulfate-reducing
4:551–61. bacteria cultured in the presence of gold (I)-thiosulfate complex.
20. Bajaj G, Chaudhary A, Naaz H, Kumar B, Soni R. Laser ablation synthesis of Geochimica Cosmochimica Acta. 2006;70:3646–61.
Zn/ZnO core-shell nanoparticles. IEEE. 2007:940–2. 47. Nair B, Pradeep T. Coalescence of nano-clusters and formation of
21. Jia F, Zhang L, Shang X, Yang Y. Non-aqueous sol–gel approach towards submicron crystallites assisted by Lactobacillus strains. Cryst Grow
the controllable synthesis of nickel nanospheres, nanowires, and Design. 2002;2:293–8.
nanoflowers. Adv Mater. 2008;20:1050–4. 48. Klaus-Joerger T, Joerger R, Olsson E, Granqvist C-G. Bacteria as workers in
22. Imran Din M, Rani A. Recent Advances in the Synthesis and Stabilization of the living factory: metal-accumulating bacteria and their potential for
Nickel and Nickel Oxide Nanoparticles: A Green Adeptness. Int J Ana Chem. materials science. Trend. Biotechnol. 2001;19:15–20.
2016;2016 49. Husseiny M, El-Aziz MA, Badr Y, Mahmoud M. Biosynthesis of gold
23. Tanori J, Pileni MP. Control of the shape of copper metallic particles by nanoparticles using Pseudomonas aeruginosa. Spectrochimica Acta Part A.
using a colloidal system as template. Langmuir. 1997;13:639. 2007;67:1003–6.
24. Lisiecki I, Pileni MP. Synthesis of copper metallic clusters using reverse 50. Dameron C, Reese R, Mehra R, Kortan A, Carroll P, Steigerwald M, Brus L,
micelles as microreactors. J Am Chem Soc. 1993;115:3887–96. Winge DR. Biosynthesis of cadmium sulphide quantum semiconductor
25. Treguer M, de Cointet C, Remita H, Khatouri J, Mostafavi M, Amblard J, crystallites. Nature. 1989;38:596–7.
Belloni J, De Keyzer R. Dose rate effects on radiolytic synthesis of gold− 51. Kowshik M, Ashtaputre S, Kharrazi S, Vogel W, Urban J, Kulkarni SK, Paknikar
silver bimetallic clusters in solution. J Phy Chem B. 1998;102:4310–21. K. Extracellular synthesis of silver nanoparticles by a silver-tolerant yeast
26. Zhang G, Wang D. Fabrication of heterogeneous binary arrays of strain MKY3. Nanotechnol. 2002;14:95.
nanoparticles via colloidal lithography. J Am Chem Soc. 2008;130:5616–7. 52. Mohanpuria P, Rana NK, Yadav SK. Biosynthesis of nanoparticles:
27. S-H W, Chen D-H. Synthesis of high-concentration Cu nanoparticles in technological concepts and future applications. Nano Res. 2008;10:507–17.
aqueous CTAB solutions. J Colloid Interf Sci. 2004;273:165–9. 53. Lee S-W, Mao C, Flynn CE, Belcher A. Ordering of quantum dots using
28. Chen W, Cai W, Zhang L, Wang G, Zhang L. Sonochemical processes and genetically engineered viruses. Science. 2002;296:892–5.
formation of gold nanoparticles within pores of mesoporous silica. J Colloid 54. Merzlyak A, Lee S-W. Phage as templates for hybrid materials and
Interf Sci. 2001;238:291–5. mediators for nanomaterial synthesis. Curr Opinion Chem Bio. 2006;10:
29. Eustis S, Hsu H-Y, El-Sayed MA. Gold Nanoparticle Formation from 246–52.
Photochemical Reduction of Au3+ by Continuous Excitation in Colloidal 55. Husen A, Khwaja SS. Phytosynthesis of nanoparticles: concept, controversy
Solutions. A Proposed Molecular Mechanism. J Phy Chem B. 2005;109:4811–5. and application. Nanoscale res let. 2014;9:229–52.
30. Khaydarov RA, Khaydarov RR, Gapurova O, Estrin Y, Scheper T. 56. Nasrollahzadeh M, Sajadi SM, Khalaj M. Green synthesis of copper
Electrochemical method for the synthesis of silver nanoparticles. Nano Res. nanoparticles using aqueous extract of the leaves of Euphorbia esula L and
2009;11:1193–200. their catalytic activity for ligand-free Ullmann-coupling reaction. RSC
31. Shanmugavadivu M, Kuppusamy S, Ranjithkumar R. Synthesis of Advance. 2014;4:47313–8.
pomegranate peel extract mediated silver nanoparticles and its antibacterial 57. Kaur P, Thakur R, Chaudhury A. Calotropis procera: A phytochemical and
activity. Drug Deliv. 2014;2:174–82. pharmacological review. Chem Lett Review. 2016;9:33–8.
32. Frattini A, Pellegri N, Nicastro D, De Sanctis O. Effect of amine groups in the 58. Shende S, Gaikwad N, Bansod S. Synthesis and evaluation of antimicrobial
synthesis of Ag nanoparticles using aminosilanes. Mater Chem Phys. 2005; potential of copper nanoparticle against agriculturally important
94:148–52. Phytopathogens. Synthesis. 2016;1:4.
33. Basak S, Chen D-R, Biswas P. Electrospray of ionic precursor solutions to 59. Nasrollahzadeh M, Sajadi SM. Green synthesis of copper nanoparticles using
synthesize iron oxide nanoparticles: modified scaling law. Chem Eng Sci. Ginkgo biloba L. leaf extract and their catalytic activity for the Huisgen [3 +
2007;62:1263–8. 2] cycloaddition of azides and alkynes at room temperature. J Colloid
34. Chen D, Xu R. hydrothermal synthesis and characterization of Interface Sci. 2015;457:141–7.
nanocrystallineγ-Fe2O3particles. J Solid State Chem. 1998;137:185–90. 60. Harne S, Sharma A, Dhaygude M, Joglekar S, Kodam K, Hudlikar M. Novel
35. Chen D-H, S-H W. Synthesis of nickel nanoparticles in water-in-oil route for rapid biosynthesis of copper nanoparticles using aqueous extract
microemulsions. Chem Mater. 2000;12:1354–60. of Calotropis procera L. latex and their cytotoxicity on tumor cells. Colloid
36. Din MI, Arshad F, Rani A, Aihetasham A, Mukhtar M, Mehmood H. Single Surface B. 2012;95:284–8.
step green synthesis of stable copper oxide nanoparticles as efficient photo 61. Cheirmadurai K, Biswas S, Murali R, Thanikaivelan P (2014) RSC Adv 4:19507–19511
catalyst material. Biomed Mater. 2017;9:41–8. 62. Shende S, Ingle AP, Gade A, Rai M. Green synthesis of copper nanoparticles
37. Philip D. Green synthesis of gold and silver nanoparticles using Hibiscus and conducting nanobiocomposites using plant and animal sources. W J
rosa sinensis. Phys E. 2010;42:1417–24. Microb Biotechnol. 2015;31:865–73.
38. Kumar P, Singh P, Kumari K, Mozumdar S, Chandra R. a green approach for 63. Keihan AH, Veisi H, Veasi H (2017) Green synthesis and characterization of
the synthesis of gold nanotriangles using aqueous leaf extract of spherical copper nanoparticles as organometallic antibacterial agent. Appl
Callistemon viminalis. Mater Lett. 2011;65:595–7. Organomet Chem
39. Ahmad A, Senapati S, Khan MI, Kumar R, Sastry M. Extracellular Biosynthesis 64. Kala A, Soosairaj S, Mathiyazhagan S, Raja P. Green synthesis of copper
of Monodisperse Gold Nanoparticles by a Novel Extremophilic bionanoparticles to control the bacterial leaf blight disease of rice. Curr Sci.
Actinomycete, Thermomonospora sp. Langmuir. 2003;19:3550–3. 2016;110:10.
40. Sastry M, Ahmad A, Khan MI, Kumar R. Biosynthesis of metal nanoparticles 65. Subhankari I, Nayak P. Synthesis of copper nanoparticles using Syzygium
using fungi and actinomycete. Current Sci. 2003;85:162–70. aromaticum (Cloves) aqueous extract by using green chemistry. World J
41. Mukherjee P, Ahmad A, Mandal D, Senapati S, Sainkar SR, Khan MI, Nano. Sci Technol. 2013;2:14–7.
Parishcha R, Ajaykumar P, Alam M, Kumar R. Fungus-mediated synthesis of 66. Nenavath G, Sirisha D, Hasheena M, Asthana S (2014) Adsorptive removal of
silver nanoparticles and their immobilization in the mycelial matrix: a novel aqueous SO2 by using Orange Peel Powder IJERT 12:39–51.
biological approach to nanoparticle synthesis. Nano Lett. 2001;1:515–9. 67. Jayandran M, Haneefa MM, Balasubramanian V. Green synthesis of copper
42. Ahmad A, Senapati S, Khan MI, Kumar R, Ramani R, Srinivas V, Sastry M. nanoparticles using natural reducer and stabilizer and an evaluation of
Intracellular synthesis of gold nanoparticles by a novel alkalotolerant antimicrobial activity. J Chem Pharm Res. 2015;7:251–9.
actinomycete, Rhodococcus species. Nanotechnol. 2003;14:824. 68. Rajanaika H, Lingaraju K, Manjunath K, Kumar D, Nagaraju G, Suresh D,
43. Ahmad A, Senapati S, Khan MI, Kumar R, Sastry M. Extra-/intracellular Nagabhushana H. Green Nanotechnology: Biomimetic Synthesis of Metal
biosynthesis of gold nanoparticles by an alkalotolerant fungus, Nanoparticles Using Plants and Their Application in Agriculture and
Trichothecium sp. J Biomed Nanotechnol. 2005;1:47–53. Forestry. JTUSCI. 2015;9:7–12.
44. Bhainsa KC, D’Souza S. Extracellular biosynthesis of silver nanoparticles using 69. Gültekin DD, Güngör AA, Önem H, Babagil A, Nadaroğlu H. Synthesis of
the fungus Aspergillus fumigatus. Colloid Surface B. 2006;47:160–4. Copper Nanoparticles Using a Different Method: Determination of Its
Din et al. Nanoscale Research Letters (2017) 12:638 Page 15 of 15

Antioxidant and Antimicrobial Activity. J Turkish Chem Soc A. 2016;3: 95. Caroling G, Priyadharshini MN, Vinodhini E, Ranjitham AM, Shanthi P.
623–36. biosynthesis of copper nanoparticles using aqueous guava extract. Int J
70. Kulkarni V, Kulkarni P. Synthesis of copper nanoparticles with aegle Pharm. BioSci. 2015;5:25–43.
marmelos leaf extract. Nanosci Nanotechnol. 2014;8:401–4. 96. Abboud Y, Saffaj T, Chagraoui A, El Bouari A, Brouzi K, Tanane O, Ihssane B.
71. Kurkure RV, Jaybhaye S, Sangle A. Synthesis of Copper/Copper Oxide Biosynthesis, characterization and antimicrobial activity of copper oxide
nanoparticles in ecofriendly and non-toxic manner from floral extract of nanoparticles (CONPs) produced using brown alga extract (Bifurcaria
Caesalpinia pulcherrima. IJRITCC. 2016;4:363–6. bifurcata). Appl Nanosci. 2014;4:571–6.
72. Valli G, Suganya M. GREEN SYNTHESIS OF COPPER NANOPARTICLES USING 97. Cuevas R, Durán N, Diez M, Tortella G, Rubilar O. Extracellular biosynthesis of
CASSIA FISTULA FLOWER EXTRACT. J.Bio.Innov. 2015;4:162–70. copper and copper oxide nanoparticles by Stereum hirsutum, a native
73. Hase J, Bharati G, Deshmukh K, Phatangre K, Rahane N, Dokhe Shital A. white-rot fungus from chilean forests. J Nanomater. 2015;16:57.
Synthesis and characterization of Cu nanoparticles of Leucas chinensis L 98. M.R. Salvadori, L.F. Lepre, R.M.A. Ando, C.A.O Nascimento, B. Correâ (2013)
plant. EJPMR. 2016;3:241–2. Biosynthesis and Uptake of Copper Nanoparticles by Dead Biomass of
74. Valli G, Suganya M. Biogenic synthesis of copper nanoparticles using Hypocrea lixii Isolated from the Metal Mine in the Brazilian Amazon Region.
Delonix elata flower extract. J Chem Pharm Research. 2015;7:776–9. 99. Shantkriti S, Rani P. Biological synthesis of copper nanoparticles using
75. Mohsenzadeh JKS. Rapid, Green, and Eco-Friendly Biosynthesis of Copper Pseudomonas fluorescens. Int J Curr Microb. Appl Sci. 2014;3:374–83.
Nanoparticles Using Flower Extract of Aloe Vera. Syn React Inorg Met. 2015; 100. Ashajyothi C, Jahanara K, Chandrakanth K. BIOSYNTHESIS AND
45:895–8. CHARACTERIZATION OF COPPER NANOPARTICLES FROM ENTEROCOCCUS
76. Rostami-Vartooni A, Alizadeh M, Bagherzadeh M. Rapid, Green, and Eco- FAECALIS. Int J PharmaBiosci. 2014;5:204–11.
Friendly Biosynthesis of Copper Nanoparticles Using Flower Extract of Aloe 101. Din MI, Rehan R. Synthesis, Characterization, and Applications of Copper
Vera. Beilstein. J Nanotechnol. 2015;6:2300–9. Nanoparticles. Analytical Lett. 2017;50:50–62.
77. Jyothi PG, Aishwarya B, Guruprasad R. GREEN SYNTHESIS OF COPPER 102. Shankar S, Rhim J-W. Effect of copper salts and reducing agents on
NANOPARTICLES FROM PHYLLANTHUS EMBLICA AND TO STUDY ITS UV- characteristics and antimicrobial activity of copper nanoparticles. Mater Lett.
PROTECTION PROPERTY BY DANIO RERIO (ZEBRAFISH) EMBRYOS. W. J 2014;132:307–11.
Pharm Pharmaceutical Sci. 2016;5(2016):1133–40. 103. SH W, Chen DH. Synthesis of high-concentration Cu nanoparticles in
78. Lee H-J, Lee G, Jang NR, Yun JH, Song JY, Kim BS. Biological synthesis of aqueous CTAB solutions. J Colloid Interface Sci. 2004;273:165–9.
copper nanoparticles using plant extract. Nanotechnol. 2011;1:371–4. 104. Keihan AH, Veisi H, Veasi H. Green synthesis and characterization of
79. Kolekar R, Bhade S, Kumar R, Reddy P, Singh R, Pradeepkumar K. spherical copper nanoparticles as organometallic antibacterial agent. Appl.
Biosynthesis of copper nanoparticles using aqueous extract of Eucalyptus Organometal Chem. 2017;31
sp. plant leaves. Curr Sci. 2015;109:255. 105. Mastin B, Rodgers JH Jr. Toxicity and bioavailability of copper herbicides
80. Kathad U, Gajera H. Synthesis of copper nanoparticles by two different (Clearigate, Cutrine-Plus, and copper sulfate) to freshwater animals. Arch
methods and size comparison. Int. J Pharm Bio Sci. 2014;5:533–40. Environ Con Tox. 2000;39:445–51.
81. Saranyaadevi K, Subha V, Ravindran RE, Renganathan S. Synthesis and 106. de Oliveira-Filho EC, Lopes RM, Paumgartten FJR. Comparative study on the
characterization of copper nanoparticle using Capparis zeylanica leaf extract. susceptibility of freshwater species to copper-based pesticides.
Int J Chem Technol Res. 2014;6:4533–41. Chemosphere. 2004;56:369–74.
82. Rozina SSM, Shaikh R, Sawant MR, Sushama B. Biosynthesis of Copper 107. Garcia PC, Rivero RM, Ruiz JM, Romero L. the role of fungicides in the
Nanoparticles using Vitis vinifera Leaf Extract and Its Antimicrobial Activity. physiology of higher plants: implications for defense responses. Bot Review.
Der Pharm Lett. 2016;8(2016):265–72. 2003;69:162–72.
83. Subbaiya R, Selvam M. Green synthesis of copper nanoparticles from 108. Mortazavi F, An J, Dubinett S. p120-catenin is transcriptionally
Hibicus rosa-sinensis and their antimicrobial, antioxidant activities. Res J downregulated by FOXC2 in nonsmall cell lung cancer cells. Molecular Canc
Pharm Biol. Chem Sci. 2015;6:1183–90. Res. 2010;8:762–74.
84. Chitra K, Manikandan A, Moortheswaran S, Reena K, Antony SA. Zingiber 109. Das R, Gang S, Nath SS, Bhattacharjee R. Linoleic acid capped copper
officinale extracted green synthesis of copper nanoparticles: structural, nanoparticles for antibacterial activity. J Bio-nanosci. 2010;4:82–6.
morphological and antibacterial studies. Adv Sci Eng. Medicine. 2015;7:710–6. 110. Schrand AM, Rahman MF, Hussain SM, Schlager JJ, Smith DA, Syed AF.
Metal-based nanoparticles and their toxicity assessment. Nano-med Nano-
85. Parikh P, Zala D, Makwana B. Biosynthesis of copper nanoparticles and their
biotechnol. 2010;2:544–68.
antimicrobial activity. Inst Post Studies Res KSV Uni. India. 2014:1–15.
111. Kim J-H, Cho H, Ryu S-E, Choi M-U. Effects of Metal Ions on the Activity of
86. Sriram T, Pandidurai V, Kuberan T. DEGRADATION OF ATRAZINE USING
Protein Tyrosine Phosphatase VHR: Highly Potent and Reversible Oxidative
COPPER NANOPARTICLES SYNTHESISED FROM THE LEAF EXTRACT OF Zea
Inactivation by Cu2+ Ion. Arch Biochem Biophys. 2000;382:72–80.
mays. J Sci. 2016;6:232–8.
112. Deryabin D, Aleshina E, Vasilchenko A, Deryabina T, Efremova L, Karimov I,
87. Shah M, Fawcett D, Sharma S, Tripathy SK, Poinern GEJ. Green synthesis of
Korolevskaya L. Investigation of Copper Nanoparticles Mechanisms Tested
metallic nanoparticles via biological entities. Material. 2015;11:7278–308.
by Luminescent Escherichia coli Strains. Nanotech Russia. 2013;8:402–8.
88. Daniel SK, Vinothini G, Subramanian N, Nehru K, Sivakumar M. Biosynthesis
113. Khursheed A, Ahmed B (2015) Microwave Accelerated Green Synthesis of
of Cu, ZVI, and Ag nanoparticles using Dodonaea viscosa extract for
Stable Silver Nanoparticles with Eucalyptus globulus Leaf Extract and Their
antibacterial activity against human pathogens. J. Nano Res. 2013;15:1319.
Antibacterial and Antibiofilm Activity on Clinical Isolates.
89. Dr A, Chandra M. SYNTHESIS OF COPPER NANOPARTICLES USING BIO METHOD
114. Samia S, Ahmed B, Khan MS, Al-Shaeri Musarrat M. Inhibition of growth and
IN CASSIA AURICULATA LEAVES EXTRACT. W. J Pharm Res. 2017:1058–65.
biofilm formation of clinical bacterial isolates by NiO nanoparticles
90. V. A. Mane, PATIL. N, S. S. Gaikwad (2016) EXTRACELLULAR SYNTHESIS OF
synthesized from Eucalyptus globulus plants. J. Microbial Pathogenesis.
COPPER NANOPARTICLES USING DIFFERENT PLANT EXTRACT. Int J Appl
2017;111:375–87.
Natural Sci (IJANS) 5: 33–38
115. Mekala J, Rajan M, Ramesh R. Synthesis and characterization of copper
91. Joseph AT, Prakash P, Narvi SS. phytofabrication and characterization of nanoparticles using Tridax procumbens and its application in degradation
copper nanoparticles using allium sativum and its antibacterial activity. of bismarck brown. Int. J ChemTech Res. 2016;9:498–507.
IJSET. 2016;4:463–73. 116. Suresh Y, Annapurna S, Bhikshamaiah G, Singh A. Green Luminescent
92. Thakur S, Rai R, Sharma S. STUDY THE ANTIBACTERIAL ACTIVITY OF COPPER Copper Nanoparticles. IJSER. 2014;5:156–60.
NANOPARTICLES SYNTHESIZED USING HERBAL PLANTS LEAF EXTRACTS. Int 117. Hase GJ, Bharati KT, Deshmukh KK, Phatangre ND, Rahane A, Dokhe S.
J Bio-Technol Res. 2014;4:21–34. Synthesis and Characterization of anthracite oxide nanoparticles of
93. Damle S, Sharma K, Bingi G, Shah H. A Comparative Study of Green anthracite coal. IJSER. 2016;7:638–41.
Synthesis of Silver and Copper Nanoparticles using Smithia sensitiva
(Dabzell), Cassia tora (L.) and Colocasia esculenta (L.). Int J Pure App. Biosci.
2016;4:275–81.
94. Gopinath M, Subbaiya R, Selvam MM, Suresh D. Synthesis of copper
nanoparticles from Nerium oleander leaf aqueous extract and its
antibacterial activity. Int J Curr Microbiol. Appl Sci. 2014;3:814–8.