Electronic Appendix

Introduction to Silver

A Brief History of Silver

The chemical symbol for silver, Ag, is derived from the Latin argentum, meaning shiny or
glistening. It is commonly found throughout nature as the metal and as sulfide ores,
usually accompanied by sulfides of Fe, Cu and Ni83. Its abundance in the Earth’s crust
is 0.07 ppm and it is isolated as a by-product in theprocessing of certain metal ores,
such as galena (PbS) and copper pyrite (CuFeS2), as well as cyanide leaching from
silver ores. The final purification of silver is generally carried out by electrolysis. It
has been widely used throughout history, in jewellery, ornaments and coinage
material, and also hasmedicinal, photographic and catalytic applications.

Synthesis and Evaluation of Silver(I) Complexes for Antimicrobial and Anticancer

Potential

Introduction:

This thesis delves into the synthesis and characterization of silver(I) complexes incorporating 9-
anthracenecarboxylic acid (9-acaH) and imidazoles. The goal is to explore their potential as
antimicrobial and anticancer agents.

Synthesis and Characterization:

Various complexes, including polymeric carboxylates and imidazole derivatives, were meticulously
synthesized and characterized using IR, NMR spectroscopy, and X-ray crystallography.

Antimicrobial Screening:

In vitro screening against Candida albicans, Escherichia coli, and methicillin-resistant Staphylococcus
aureus (MRSA) demonstrated the superior antimicrobial activity of certain silver(I) complexes,
surpassing established prescription drugs. Notably, [Ag4(9-aca)4(NH3)2] exhibited remarkable
efficacy, outperforming Ketoconazole and silver sulfadiazine.

In Vivo Evaluation:

In vivo tests on Galleria mellonella larvae showcased the complexes' effectiveness against Candida
albicans and their ability to enhance survival rates.

Anticancer Activity:

The silver(I) complexes displayed promising anticancer activity, particularly against breast cancer cells,
offering potential for further therapeutic development.

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Biological Activity of Silver: Absorption and Antimicrobial Properties

Absorption and Elimination:

Silver is absorbed primarily as silver protein complexes and can be tolerated at higher concentrations
without cumulative toxicity. The body eliminates silver through urine and feces, suggesting a non-
cumulative nature.
Antimicrobial Properties:
Certain silver(I)-coumarin complexes exhibit antimicrobial activity, disrupting microbial respiration and
inhibiting the synthesis of cytochromes. These properties highlight silver's potential in combating
microbial infections.
Cytotoxicity to Cancer Cells:
Some silver(I) carboxylate complexes have demonstrated high cytotoxicity against cancer cells.
Unfortunately, they also exhibit damaging effects on normal cells, posing a challenge for their selective use
in cancer therapy.

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Microbial Resistance to Silver

Overview:
Microbial resistance to silver, while not yet a significant clinical concern, is a recognized phenomenon.
Understanding the mechanisms of resistance is essential for anticipating potential future challenges.
Mechanisms:
Resistance often involves energy-dependent efflux mechanisms or plasmid-mediated binding of toxins,
preventing the accumulation of silver ions within microbial cells.
Historical Context:
Instances like Pseudomonas stutzeri AG259 isolated from a silver mine in 1984 highlighted early
cases of silver resistance, with the bacterium carrying a plasmid encoding silver resistance.
Recent Discoveries:
Studies on a silver-resistant strain of Salmonella typhimurium revealed specific mechanisms,
including a plasmid-encoded silver-specific binding protein (SilE) and parallel efflux pumps (SilA, SilB,
SilC, SilP, SilR, and SilS) that remove silver ions.

Other Resistant Strains:

Rare instances of resistance have been observed in bacterial species like E. coli, Enterobacter
cloacae, Klebsiella pneumonia, and Acinetobacter baumannii, with a currently low risk of silver
resistance gene transfer.

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Understanding of Silver Nanoparticles (AgNPs)

The usual quantity of silver in human plasma is less than 2 µg/mL, and this concentration comes
from diet and particulate matter inhalation. Oral exposure to silver can also come via dietary
supplements, contaminated water, or from eating fish and other aquatic species . Ionic silver can be
ingested orally, inhaled, or absorbed through wounds to enter the body. AgNP’s are believed to be
transported inside the body by two processes: pinocytosis and Endocytosis
Pinocytosis (Cell Drinking)
Pinocytosis (“pino” means “to drink”) is a process by which the cell takes in the fluids along with
dissolved small molecules. In this process, the cell membrane folds and creates small pockets and
captures the cellular fluid and dissolved substances.
Endocytosis
Endocytosis is a cellular process by which a cell internalizes any material (liquid as well as solid)
from the external environment
SYNTHESIS OF AgNPs
It should be known, what happens in a nanoparticle synthesis process? As mentioned above
requires a precise control in the synthesis to control the size and shape in order to obtain a set of
particles with a certain property. In a synthesis by the general we have the following components which
must be known to manipulate and work them: metallic precursor, reducing agent (solvent) and
stabilizing agent

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In addition, two very important formation processes are taken into account, one is nucleation, in which a
high activation energy is required for the agglomeration of the atoms and the other is that of growth
where, on the contrary, a low energy of Activation for ordering in the formation of particles, is in these
points of the synthesis where the shape and size are totally dependent on the speed of both processes
which are controlled by parameters such as concentration, temperature, reducing power and the pH.7 On
the other hand, the stabilizing agent plays a very important role in the synthesis because with its help the
nanoparticles are protected in such a way that an unexpected agglomeration is prevented in the step of
controlling their size and shape.
USES OF SILVER IN MEDICAL SCIENCE
When we think of silver, we think about jewelry and coins. But did you know that silver is actually used in
medicine and healthcare, as well? Since the discovery of nano silver, silver has been integrated into
common medical and healthcare practices. Here are a few uses of silver in medicine and healthcare, which
you might not have heard of:
LAB COATS
Doctors and lab technicians use lab coats which have antimicrobial properties, because this helps protect
the coat from the growth of harmful microorganisms. Now, doctors don’t have to worry about their coats
smelling bad, either -- silver contains properties which fight odor-causing bacteria. Talk about smelling
good naturally!
IMMUNE BUILDER
Colloidal silver has been used to remedy homeopathic conditions, as well as treat several diseases.
Specifically, colloidal silver has been known to fight against the flu and colds, treat bronchial complications,
and even treat ear infections.
SURGERY
Silver is used as a cauterizing agent for openings during surgery. This works because silver nitrate can
close cuts which were purposely performed in surgery. Silver nitrate is a great cauterizing agent because it
can prevent infections and further damage to these bodily openings.

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BIOSENSORS
Today, silver nano wires are being developed into biosensors, in order for them to assist in various disease
diagnostics. The silver nano wire can be used as electronic bio-sensing mechanisms.
ANTIBIOTICS
Silver salts are very effective against E. Coli. When infused with antibiotics, the silver salts can kill bacteria
up to 1,000 more effective than your standard antibiotic. This works because silver can neutralize the
defenses of bacteria, making them easier to target and eliminate.
MERCURY POISONING
Silver chloride has been used as an antidote for mercury poisoning. Silver can flush out the toxin inside the
body, which aids in the healing process.
SMOKING
Rather, the prevention of smoking. Silver acetate in gum, mouth sprays and lozenges has been found to aid
people in their addiction to smoking. This was first observed in the 1970s, when a gum called Tabmint was
used to help people deal with their smoking habits.
DISINFECTANT
Silver acts as a surface disinfectant commonly used in hospitals and other medical establishments. For
instance, Nanosil is an EPA-approved surface disinfectant because it doesn’t use toxic chemicals. This is
especially important if they’re being used in hospitals, where sanitation is the prime concern.
NAILS
Podiatrists frequently utilize silver nitrate to kill fungus found in their patients’ nail beds. Silver in its
nitrate form can effectively eliminate fungus growing on the toes.
SURGICAL MASKS
The FDA has approved of surgical masks that contain silver woven into the fiber to be used in healthcare.
These surgical masks, such as Spectrashield, contain copper and silver ions which have been woven into
the fiber. These masks can eliminate up to 99.99% of bacteria, eliminating foul odors.
BED MATS
Long-term patients who have to stay in bed for an extended period of time can now stay in sanitary bed
mats which contain silver. These mats have been proven to prevent bedsores. In addition, nanosilver in
these bed mats is naturally hydrophilic, which means that each time the nanosilver comes in contact with
moisture such as sweat and other bodily fluids, its antibacterial property increases.
ENDOTRACHEAL TUBES
These tubes can be found in ventilators. Patients who use these ventilators are at risk of developing
pneumonia and other diseases. Tubes which have been coated with silver reduce this possibility by around
40 percent. This is because silver has been known to fight against bacteria and infection.

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CONCLUTION:
Today, silver’s reach has extended beyond the medical world. It wouldn’t be surprising to see silver
in different industries, since developments are still in their early stages. We have yet to see the full reach of
silver in terms of their medical implications. With silver and medicine being two of the most studied areas
today, we should be seeing improvements in the near future.