Current Methods for Synthesis

of Gold Nanoparticles

CD

Metal nanoparticles possess quantum size effect and thus have specific electronic structures, which
makes them exhibit unique physical and chemical properties different from those of the bulk materials
or atoms. Among them, gold nanoparticles (AuNPs) may be the most remarkable members of the
metal nanoparticle groups. They have attracted plenty of researchers' interests and driven a diversity
of potential applications in catalysis, biology, drug delivery, and optics. Here we are specifically
focusing on the principles and most recent improvements disclosed in the literature on various types of
AuNPs synthesis.

Physical Methods:
Chemical Methods: γ- irradiation method, UV-induced
Turkevich method, Brust method, photochemical method, ultrasound-
seeded growth method, etc. assisted method, laser ablation
e.g. reduction of HAuCl4 method, etc.

Synthetic Routes
of AuNPs

Biological Methods:
Microbial mediated method,
extracellular method, intracellular
method, plant mediated method,
etc.

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Chemical Methods

In chemical methods, AuNPs are usually produced by reduction of (hydro)chloroauric acid (HAuCl4),
using some sort of stabilizing agents. The first step is to dissolve HAuCl4 and then stir the solution
quickly and add a reducing agent at the same time to reduce the Au3+ ions to neutral gold ions.

• Turkevich method

This method involves the reaction of small amounts of hot HAuCl4

in the presence of reducing agents such as citrate, amino acids,
Key Features:
ascorbic acid or UV light. The AuNPs will form due to the presence
of citrate ions as both a reducing agent and a capping agent. Produce modestly
When producing larger particles, the amount of sodium citrate monodisperse spherical
should be reduced to 0.05% and thus there would not be enough AuNPs (10-20 nm) in water;

citrate ions to reduce all the gold. Since the citrate ions are
When producing larger
responsible for stabilizing the particles, less sodium citrate will particles, the monodispersity
cause the small particles to aggregate into larger ones until the will be lost.
total surface area of all particles is small enough to be covered
by the existing citrate ions in solution. Finally, the larger particles
are produced.

• Brust method

It can be used to produce AuNPs in organic liquids that are

normally not miscible with water (e.g. toluene). It involves the Key Features:

reduction of HAuCl4 solution with tetraoctylammonium bromide

A method of two-phase
(TOAB, an anti-coagulant) solution in toluene and sodium synthesis and stabilization with
borohydride (NaBH4, a reducing agent). The diameter of AuNPs thiol;
here will be 2 to 6 nm and TOAB is both the phase transfer
Particle diameter and
catalyst and the stabilizing agent. The gold ions are then reduced grain-size distribution
using NaBH4 in presence of an alkanethiol. The alkanethiols controllable;
stabilize the AuNPs, resulting in a color change of the reaction
Functionalization of the particle
from orange to brown.
surface with alkanethiols.

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• Seeded growth method Key Features:

Seed mediated growth is the most widely used method to Used for producing other
produce AuNPs in other shapes. Firstly, the seed particles will be shaped gold particles (e.g.
produced by reducing gold salts with a strong reducing agent rods, cubes, tubes);

such as NaBH4. Then, the seed particles will be added to a

By using reducing agents,
solution of metal salt in presence of a weak reducing agent (e.g. structure-directing agents
ascorbic acid) and a structure-directing agent to prevent further and varying the
concentration of seeds, the
nucleation and accelerate the anisotropic growth of AuNPs.
geometry of AuNPs can be
altered.

Physical Methods

• γ- irradiation method

The γ- irradiation method is adopted to synthesize AuNPs with 2 Key Features:

to 40 nm in diameter. In this method, the natural polysaccharide

Proved to be the best
alginate solution is used as a stabilizer. Akhavan A. et. al. gave a method for the synthesis of
single step γ-irradiation method to synthesize AuNPs of size 2 to 7 AuNPs with controllable
size and high purity.
nm by using bovine serum albumin protein as a stabilizer.

• UV-induced photochemical method

Using photochemistry, AuNPs with controllable size were

successfully synthesized. The presence of UV radiation with
different wavelengths will encourage chemical reactions in Key Features:
aqueous Au solution. For example, with γ-rays irradiation, the
Used for the formation of
aqueous solution of chloroauric acid can form 80 nm AuNPs.
single crystallite-based
Moreover, the presence of surfactant/polymer reagent will AuNPs;
impact the particle dimensions, namely the particle size will
decrease by increasing the polymerization degree. Particle size and shape
controllable.
Macromolecular polymers, dendrimers, and surfactants can
provide the required steric hindrance effect and thus prevent the
aggregate formation, which acts as soft templates during AuNPs
fabrication.

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• Ultrasound-assisted method

Using an ultrasound wave generator in a water bath with

Key Features:
constant temperature, gold ions can be reduced with
ultrasonic-assisted in the presence of 2-propanol. For Eco-friendly and rapid
reproducibility and tunability reasons, various stabilizers have synthesis of AuNPs;
been used during the conventional ultrasound-assisted synthesis
Ideal for various
method, such as citrate, poly (N-vinyl-2-pyrrolidone),
biotechnological applications.
triphenylphosphine, disulphide, and several dendrimers.

• Laser ablation method

This method is based on the photo-induced effects of a 532 nm

wavelength laser beam which reduces the gold (III)
tetrachloroaurate metallic precursor to produce nanogold Key Features:
particles with a size range lower than 5 nm. During this process,
Accurate and reproducible
aqueous solutions of sodium dodecyl sulfate (SDS) have been
results;
used as a template agent and the researchers have studied the
influence of both SDS concentrations and laser influences on the A full-fledged physical
approach to produce AuNPs
dimensions of the synthesized AuNPs. Gold nanospheres,
with tunable features.
silica-gold nanoshells and gold nanorods synthesized by this
method have been widely used in biological, cell imaging and
photothermal therapeutic applications.

Biological Methods

Given the versatility of both physical and chemical synthesis strategies used for AuNPs fabrication,
various technologies have been successfully used during the latest research studies, including
aerosol-based synthesis, ultraviolet, and ultrasound radiation, lithography, laser ablation and
photochemical reduction of metallic gold. However, these physicochemical synthesis approaches often
require using hazardous chemicals, expensive equipment, and technologies, so the attention of the
research community recently turned into the bio-inspired methodologies for AuNPs synthesis.

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• Microbial mediated method

Both the eukaryotes and prokaryotes can synthesize gold colloids

from inorganic precursors due to the specific activity of their
secondary metabolites produced either intracellular or
Key Features:
extracellular. For example, the fungus Penicillium crustosum
isolated from soil involved in success full synthesis of AuNPs Eco-friendly and
mediated by extracellular proteins. Enzymes such as ligninases, cost-effective;
laccases, reductases, and peptides are involved in growth and
No hazardous chemicals and
nucleation of NPs, while free cysteine/amino and surface-bound
toxic derivatives.
protein of microbes involve in the stabilization of these colloids.
Moreover, several factors including temperature, pH, substrate
concentration and static condition also affect the synthesis and
stability of AuNPs.

Mechanism of extracellular and intracellular synthesis of AuNPs.

• Extracellular method Key Features:

This approach refers to the reduction of chloroauric ions in the

Eco-friendly and
presence of cells to produce AuNPs. The biosynthesis is cost-effective;
successfully accomplished due to the key role of the cell wall and
Easy to synthesize;
cell wall proteins. It has been shown that the Enterobacteriaceae
culture supernatants are enriched in nitroreductase enzyme Reduction and surface
content that is subsequently involved in bacterial mediated accretion of metals may be
synthesis of colloidal gold. processed, by which bacteria
keep themselves from the toxic
effects of metallic ions.

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• Intracellular method
Many reports have shown that plants have the tremendous ability
to in situ produce inorganic nanoparticles within the vegetal cells. Key Features:
For example, growing Sesbania drummondii seedlings in
Reliable;
chloroaurate solution resulted in the accumulation of stable
AuNPs within various plant tissues, as a consequence of Eco-friendly reducing and
shoot-guided transport phenomena of the root-located capping agents.

reduction processes. The obtained intracellular monodispersed

and immobilized gold nanoparticles may act as stable catalysts
for future applications. Moreover, the intracellular biosynthesized gold clusters capped with organic
ligands possess the ability to covalently attach to biological substances and structures and protein
molecules, indicating that they are promising tools with biological labeling potential applications.

Biosynthesis
Biological Source Nanoparticles Morphology Size (nm)
Location
Bacteria
Bacillus subtillus Octahedral 5-30 Intracellular
Pseudomonas aeruginosa Spherical 5–30 Extracellular
Escherichia coli Triangular 25–33 Intracellular
Rhodopseudomonas
Spherical 10–20 Extracellular
capsulata
Stenotrophomonas
Spherical 40 Extracellular
maltophilia
Brevibacterium casei Spherical 10–50 Extracellular
Bacillus licheniformis Cubic 10–100 Intracellular
Pseudomonas veronii Different shapes 5–25 Extracellular
Klebsiella pneumoniae Spherical 35–65 Extracellular
Marinobacter pelagius Spherical > 20 Extracellular
Geobacillus sp. strain ID17 quasi-hexagonal 5–50 Intracellular
Fungi
Fusarium oxysporum Spherical and Triangular 8–40 Intracellular
Rhizopus oryzae Different shapes (rod, triangle, hexagon) 9–10 Intracellular
Algae
Shewanella algae Different shapes (triangular, hexagonal, nanoplates) ~10 Extracellular
Sargassum wightii Greville Spherical 8–12 Extracellular
Different shapes (triangular, truncated triangular,
Chlorella vulgari 800–2000 Extracellular
hexagonal)
Plant
Aloe vera Triangular 2–8 Extracellular
Cassia auriculata Triangular, hexagonal 15–25 Extracellular
Hibiscus rosa-sinensis Spherical 16–30 Extracellular
Ananas comosus Spherical 10–11 Extracellular

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• Plant mediated method
Plant extract
solution
Alkaloids
Terpenoids
Phenolics
Proteins
Vitamins
Sugars
Co-enzymes
Naphthoquinones
Anthraquinones
Nitrate reductase

Green synthesis

AuNPs Gold salt

solution

This method involves in revaluing the polyphenol-based

Key Features:
secondary metabolites from plants as efficient reducing agents
for metallic precursors. The hydroxyl groups within the Spontaneous, eco-friendly and
plant-derived polyphenols would be successfully taken part in cost-effective synthesis;

gold ions reducing process via encouraging the oxidation

Suitable for large scale
reaction and the specific formation of quinine forms. Moreover, production;
when a hard ligand specifically binds soft metals, e.g. Au+, no
Avoidance of time-consuming
complex compounds will be encouraged to form. However, the
maintenance of cell cultures;
concerned soft metal will undergo reduction processes and
finally form AuNPs. Many leaves and fruits have been successfully Particle size and shape
used to produce AuNPs, such as Jatropa curcas L. (Barbados controllable.

nut), Tridax procumbens L. (Coat buttons), Solanum melongena

L. (Eggplant), Calotropis gigantea L. (Calotropis), Carica papaya L. (Papaya), Datura metel L. (Datura),
Citrus reticulate, Citrus limon, Citrus sinensis and banana peel powder. In addition to leaves and fruits, bark
or stem extract and seed extract are also applied to the synthesis of AuNPs.

Creative Diagnostics provides a comprehensive list of gold nanoparticles including spherical gold
nanoparticles, gold nanorods and special shape gold particles, which meets various research and
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References:
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(2012). Conjugation of curcumin with PVP capped gold nanoparticles for improving bioavailability.
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applications-A review. Indian Journal of Pharmaceutical and Biological Research, 3(2), 13.
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characterization of protein stabilized gold nanoparticles. Chemical Engineering Journal, 159(1-3), 230-235.
7. Mafuné, F., Kohno, J. Y., Takeda, Y., Kondow, T., & Sawabe, H. (2001). Formation of gold nanoparticles
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8. Barabadi, H., Honary, S., Ebrahimi, P., Mohammadi, M. A., Alizadeh, A., & Naghibi, F. (2014). Microbial
mediated preparation, characterization and optimization of gold nanoparticles. Brazilian Journal of
Microbiology, 45(4), 1493-1501.
9. Sengani, M., Grumezescu, A. M., & Rajeswari, V. D. (2017). Recent trends and methodologies in gold
nanoparticle synthesis–a prospective review on drug delivery aspect. OpenNano, 2, 37-46.
10. Ramezani, F., Ramezani, M., & Talebi, S. (2010). Mechanistic aspects of biosynthesis of nanoparticles
by several microbes. Nanocon, 10(12-14), 1-7.
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