Bio-inorganic Chemistry

Subject: Chemistry (CH 1201)

B.Tech (Group II)
The presence of nearly 40 different elements has been established in living
bodies.

Among them some are most abundant elements e.g. H, O, C, N, Na, K etc.

Some are essential, some are beneficiary, some are trace and some are ultra-
trace elements.

Bulk and trace elements

– bulk elements: C, H, O, N, S, P
– maintaining the osmotic pressure body fluids
Na, K, Ca, Mg, Cl
– essential trace elements:
F, I, Se, Si, Sn (main group elements)
Fe, Zn, Cu, Mn, Mo, Co, V, Ni (transition metals)
– potential trace elements: B, Ti, As, Pb, Cd, W, ....
– toxic elements
Average abundance of Bulk elements (70 kg individual)
Average amount of trace elements (70 kg individual)

Elements Weight (gm) Percentage %

Trace elements
1. The abundance of elements in different living organisms is in a
given concentration range

2. The decreasing of abundance of elements causes physiological

changes (diseases)

3. Administration of missing trace elements improve the physiological

condition
They take part in the metabolism.

4. The elements have defined biochemical functions

Roles of trace elements
1. Transport of biological small molecules
O2-transport: hemoglobin (Fe), hemocianin (Cu) O2-storage:
myoglobin (Fe)

2. Activation of molecules: metalloenzymes, enzymes activated by

metal ions
a) catalysing of redox processes (Fe, Cu, Mn, Co, Mo, Ni) biological
oxidation, reduction of substrate
b) catalysing of acid-base processes (Zn)

3. Secunder conformation of macromolecules

– determination of conformation of enzymes
– determination of conformation of proteins, nucleic acids

4. Metabolism of microelements
– uptaking, transport, storage of trace elements
At biological pH (~ 7), all these biometals cannot exist as free ions.
They should form insoluble hydroxides and phosphates.

By using the bioligands, these biometals form soluble complexes and

they function accordingly.

The important bioligands are proteins , amino acids, peptides having

mostly N and O donor ligands with high molecular weight.

So, the biological growth depends on the concentration of these

elements in the body.

If the elements present at an amount more than the required amount,

they will function as toxic elements.
 Dependence of biological growth on the conc. of
essential and toxic elements

The above figure illustrates the effect of both essential elements on

growth.
The essential elements can show toxicity if there uptake is very high.

If the concn. is less than B , the system experiences their deficiency

but if their concn. exceed C, their beneficial role decreases.

Thus, the deficient concn. range A-B is responsible for retardation of

growth; the optimal concn. range (B-C) stands for optimal growth; the
excess conc. range (C-D) again exerts growth retardation and the
condition exceeding the limiting value D induces toxic effects.

For the different essential elements, the conc. values denoted by A, B,

C and D are different.
For the toxic elements like Cd, As, Hg, Pu, etc. the
effect is represented by the curve shown below.
The distribution of different elements in normal diet is given as follows (for a 70 Kg
human):
Na (5-10 gm) K (3-4 gm) Ca (0.8-1.0 gm)
P (0.8-1.0 gm) Mg (0.3-0.4 gm) Fe (10 mg for male, 15 mg for female)
Zn (15 mg) Cu (2-3 mg) Mn (3-5 mg)
I (150 μg) Cr (50-150 μg) F (1.5-3 mg)
Se (50-150 μg) Co (3 μg, Vit. B12) Mo (150-450 μg)
 Effects of some elements on human health

Metal Disease due to deficiency Disease due to excessive accumulation

Na Addison’s disease; hyponatremia hypernatremia (increase in blood pressure)
(reduced blood pressure)
K --------------- Addison’s disease, Cardiac failure
Ca Abnormalities in bone nerve function Cataracts, Stones in gall bladder and kidney
Fe Anemia Hemochromatosis, liver damage
Co Pernicious anemia Coronary failure
Cu Anemia Wilson’s disease, liver damage
Zn Dwarfism Metal-fume fever due to inhaled Zn fume
Pb Not known Impaired kidney function
Hg Not known Minamata disease, Encephalitis
Cd Not Known Itai-itai disease
Addison’s disease or chronic adrenal insufficiency is a rare, chronic endocrine
system (The endocrine system is the collection of glands, viz. pineal gland, pituitary
gland, pancreas, etc., that produce hormones that regulate metabolism, growth and
development, tissue function, reproduction, sleep, and mood, among other things.)
disorder in which the adrenal glands do not produce sufficient steroid hormones.

The adrenal glands (also known as suprarenal glands) are endocrine glands that
produce a variety of hormones including adrenaline and the steroids aldosterone and
cortisol. They are found above the kidneys.

Addison’s disease is characterized by a number of relatively nonspecific symptoms,

such as abdominal pain and weakness, but under certain circumstances, these may
progress to Addisonian crisis, a severe illness which may include very low blood
pressure and coma.

Addison's disease affects about 0.9 to 1.4 per 10,000 people in the developed
world. Without treatment, an adrenal crisis can result in death.
Wilson’s disease or hepatolenticular degeneration is an autosomal
recessive genetic disorder. Autosomal recessive is one of several ways
that a trait, disorder, or disease can be passed down through families.

An autosomal recessive disorder means two copies of an abnormal

gene must be present in order for the disease or trait to develop.

Recessive is a quality found in the relationship between two versions

of a gene. Individuals receive one version of a gene, called an allele,
from each parent. If the alleles are different, the dominant allele will be
expressed, while the effect of the other allele, called recessive, is
masked.) in which copper accumulates in tissues; this manifests as
neurological or psychiatric symptoms and liver damage. Medication
reduces copper absorption or removes the excess copper from the
body, but occasionally a liver transplant is required.
 Pernicious anemia (also known as vitamin B12 deficiency
anemia, Biermer's anemia, Addison's anemia, or Addison–Biermer
anemia) is one of many types of the larger family of megaloblastic
anemias. One way pernicious anemia can develop is by loss of gastric
parietal cells, which are responsible, in part, for the secretion of
intrinsic factor, a protein essential for subsequent absorption of vitamin
B12 in the ileum.
Anemia, also spelled anaemia, is usually defined as a decrease in
the amount of red blood cells (RBCs) or hemoglobin in the blood.[1][2]
It can also be defined as a lowered ability of the blood to carry oxygen.
When anemia comes on slowly the symptoms are often vague and may
include: feeling tired, weakness, shortness of breath or a poor ability to
exercise. Anemia that comes on quickly often has greater symptoms
which may include: confusion, feeling like one is going to pass out,
and increased thirst. Anemia must be significant before a person
becomes noticeably pale.
Itai-itai disease ("it hurts-it hurts disease") was the name given to the
mass cadmium poisoning of Toyama Prefecture, Japan, starting around
1912. The term "itai-itai disease" was coined by locals for the severe
pains (Japanese: itai) people with the condition felt in the spine and
joints. Cadmium poisoning can also cause softening of the bones and
kidney failure.

One of the main effects of cadmium poisoning is weak and brittle

bones. Spinal and leg pain is common, and a waddling gait often
develops due to bone deformities caused by the cadmium. The pain
eventually becomes debilitating, with fractures becoming more
common as the bone weakens. Permanent deformation in bones can
occur.

Other complications include coughing, anemia, and kidney failure,

leading to death.
Minamata disease, sometimes referred to as Chisso-Minamata
disease, is a neurological syndrome caused by severe mercury
poisoning. Symptoms include ataxia, numbness in the hands and
feet, general muscle weakness, narrowing of the field of vision and
damage to hearing and speech. In extreme cases, insanity, paralysis,
coma and death follow within weeks of the onset of symptoms. A
congenital form of the disease can also affect foetuses.

Minamata disease was first discovered in Minamata City in Kumamoto

prefecture, Japan in 1956. It was caused by the release of
methylmercury in the industrial wastewater from the Chisso
Corporation's chemical factory, which continued from 1932 to 1968.
This highly toxic chemical bioaccumulated in shellfish and fish in
Minamata Bay and the Shiranui Sea, which when eaten by the local
populace resulted in mercury poisoning. While cat, dog, pig and human
deaths continued over more than 30 years, the government and
company did little to prevent the pollution.
Arsenic poisoning is a medical condition that occurs due to elevated levels
of arsenic in the body.

If arsenic poisoning occurs over a brief period of time, symptoms may

include vomiting, abdominal pain, encephalopathy, and watery diarrhea
that contains blood. Long-term exposure can result in thickening of the
skin, darker skin, abdominal pain, diarrhea, heart disease, numbness,
and cancer.

The most common reason for long-term exposure is contaminated

drinking water. Groundwater most often becomes contaminated
naturally; however, contamination may also occur from mining or
agriculture. Recommended levels in water are less than 10–50 µg/L (10–
50 parts per billion).

Arsenic acts by changing the functioning of around 200 enzymes.

Hemochromatosis is a disorder where too much iron builds up in our
body. Sometimes it’s called “iron overload.”

Normally, our intestines absorb just the right amount of iron from the
foods we eat. But in hemochromatosis, our body absorbs too much,
and it has no way to get rid of it. So, our body stores the excess iron in
our joints and in organs like our liver, heart, and pancreas. This
damages them. If it’s not treated, hemochromatosis can make your
organs stop working.
Metal fume fever (MFF) is a well-documented acute disease induced
by intense inhalation of metal oxides. MFF is primarily associated with
the inhalation of zinc oxide fumes that are produced when zinc-oxide
coated steel (galvanized) or zinc containing alloys (eg, brass) is
exposed to high temperatures. MFF is a self-limited syndrome
characterized by fever, myalgias, headache, and nausea. Symptoms
develop 4-12 hours after exposure and typically last several hours;
severe cases generally resolve in 1-2 days
 Removal of toxic metal ions by chelation therapy
The basic requirements of a chelating antidote in metal
detoxification
 Conditional stability constant: bind the toxic metal sufficiently strongly
to compete with the endogenous biological ligands such as proteins

 Lipophilicity of the chelating drugs: be sufficiently lipophilic

(Lipophilicity refers to the ability of a chemical compound to dissolve in
fats, oils, lipids, and non-polar solvents such as hexane or toluene.) to
penetrate the lipid membranes to reach the body compartment where the
toxic metal is accumulated.

 HSAB (hard and soft acids and bases) theory and selection of
chelating drugs: The HSAB concept is an initialism for "hard and soft
(Lewis) acids and bases". Also known as the Pearson acid base concept,
HSAB is widely used in chemistry for explaining stability of compounds,
reaction mechanisms and pathways.
It assigns the terms 'hard' or 'soft', and 'acid' or 'base' to chemical species.
'Hard' applies to species which are small, have high charge states (the charge
criterion applies mainly to acids, to a lesser extent to bases), and are weakly
polarizable. 'Soft' applies to species which are big, have low charge states and
are strongly polarizable. The concept is a way of applying the notion of orbital
overlap to specific chemical cases.
The gist of this theory is that soft acids react faster and form stronger bonds
with soft bases, whereas hard acids react faster and form stronger bonds with
hard bases, all other factors being equal. The classification in the original
work was mostly based on equilibrium constants for reaction of two Lewis
bases competing for a Lewis acid.
Hard acids and hard bases tend to have the following characteristics:
• small atomic/ionic radius
• high oxidation state
• low polarizability
• high electronegativity (bases)
• hard bases have highest-occupied molecular orbitals (HOMO) of low
energy, and hard acids have lowest-unoccupied molecular orbitals (LUMO)
of high energy.
Examples of hard acids are: H+, light alkali ions (Li through K all have
small ionic radius), Ti4+, Cr3+, Cr6+, BF3.
(Smaller ions from Gr. 1, 2 and the left hand side of the transition metals,
particularly when in high O.S. and these form the most stable complexes
with N and O donors.)
Examples of hard bases are: OH–, F–, Cl–, NH3, H2O, CH3COO–, CO32–. The
affinity of hard acids and hard bases for each other is mainly ionic in nature.
Soft acids and soft bases tend to have the following characteristics:
 large atomic/ionic radius
 low or zero oxidation state bonding
 high polarizability
 low electronegativity
 soft bases have HOMO of higher energy than hard bases, and soft acids
have LUMO of lower energy than hard acids. (However the soft-base
HOMO energies are still lower than the soft-acid LUMO energies.)
Examples of soft acids are: CH3Hg+, Pt2+, Pd2+, Cu+, Ag+, Au+, Hg2+, Hg22+,
BH3.
(These include ions from R.H.S. of the transition series, and also transition
metal complexes with low O.S. These form the most stable complexes with
ligands such as I-, SCN-, CN-)
Examples of soft bases are: H–, R3P, SCN–, I–. The affinity of soft acids and
bases for each other is mainly covalent in nature.
According to this theory, to remove a hard toxic metal ion, a chelating drug
with hard donor sites is preferred, and to detoxify a soft metal, the chelating
drug should have the soft binding sites.
 Designing of antidotes with the binding sites mimicking the
endogeneous binding sites: The binding sites of the chelaing drugs should
be similar to endogeneous binding sites

 Toxic effect of the chelating drug: The administered should not be toxic
and must have higher LD50 value

 Urinary and bilary excretion: To remove the toxic metal from an interior
compartment, the drug must form a lipophilic complex in the body
compartment, and then it must change to a hydrophilic complex (Having an
affinity for water; readily absorbing or dissolving in water.) upon reacting
with the blood plasma so that elimination of metal complex is possible
through urinary excretion rather than its redistribution back in the tissues.
2,3-dimarcapto-1-propanol (British anti-Lewisite or British
antilewisite (abbreviated BAL): The drug was developed by the British
scientist Sir Rudolph Peters during the Second World War II to treat the
patients affected by the poison gas Lewisite. Lewisite can block the –SH
groups of different enzymes to cause the toxicity but BAL can remove the
enzyme bound As-compound to restore the activity of the enzymes, and
As-BAL complex is excreted through urine. The detoxification process is
presented as:
For Cu- poisoning (Wilson’s disease), BAL can show its antidotal
activity (remedy). In fact BAL is recommended for the treatment of
poisoning by different heavy metals like Hg, Au, Tl, Bi. But in
detoxification of methyl mercury, the neutral chelate (CH3Hg)2
BALH2 formed can pass through the biological membrane to enhance
the toxicity by its redistribution. BAL is found to increase the toxicity
of Cd and Pb in experimental animals:
2CH3Hg+ + BAL → (CH3Hg)2 + BALH2 + 2H+
 D-Penicillamine (DPA)
N-acetyl D-penicillamine (NAPA)

D-Penicillamine (DPA) or 3, 3-dimethyl cysteine with binding sites

containing N, S and O, can bind with CH3Hg+, Hg(II), Cu(II), Au(I),
Pb(II) etc. In NAPA, acetyl group (Ac, COCH3) makes the chelating
ligand more lipophilic.
Polycarboxylic acid based chelating drugs
 Calcium salts are used intravenously or intramuscularly

 Polycarboxylic acid ligands forms strong complex with Ca(II) salts

 Na-salts causes calcium depletion

 Thus, to avoid depletion of Ca(II) or Zn(II) from human body,

Na2Ca(edta) types of salts are used
Deferoxamine (DFO), also known as desferrioxamine is a chelating
ligand that binds iron and aluminium.

It is specifically used in iron overdose, hemochromatosis either due to

multiple blood transfusions or an underlying genetic condition, and
aluminium toxicity in people on dialysis.

It is used by injection into a muscle, vein, or under the skin.

Desferroxamine B
Desferroxamine E
 Rheumatoid arthritis (RA) is an autoimmune disease that can cause
joint pain and damage throughout your body. Rheumatoid arthritis
affects joint linings, causing painful swelling. Over long periods of
time, the inflammation associated with rheumatoid arthritis can
cause bone erosion and joint deformity.

An autoimmune disease is a condition in which your immune

system mistakenly attacks your body. The immune system normally
guards against germs like bacteria and viruses. When it senses these
foreign invaders, it sends out an army of fighter cells to attack them.
 Few gold(I) salts are primarily found effective to reduce
inflammation and to slow disease progression in patients with
rheumatoid arthritis. The gold salts stop cells from releasing
chemicals that can harm tissues.

 The use of gold compounds has decreased since the 1980s

because of numerous side effects and monitoring requirements,
limited efficacy, and very slow onset of action.

 Most chemical compounds of gold, including some of the drugs

discussed below, are not salts, but are examples of metal thiolate
complexes.

 A procedure that uses gold salts (a salt form of the metal element
gold) to treat diseases, such as rheumatoid arthritis is known as
called chrysotherapy or aurotherapy.
 Sodium aurothiomalate

Solganol Aurafin
Silver based antimicrobial materials
Therapeutic use of simple silver salts or complex species for the
treatment of local infections, mental illness, epilepsy, nicotine
addiction and gastroenteritis is known for long.

Silver sulfadiazine is used as a topical broad-spectrum antibiotic to

treat bacterial infections in severe burns or chronic wounds.
AgNO3 has been utilized in eye drops to prevent gonococcal
ophthalmic neonatorum in newborns.

Ag NPs are widely used in wound dressings, for the treatment of

burns, as water disinfectants, in antiseptic sprays, and as coatings on
medical devices such as synthetic implants and urinary tract and
intravenous catheters to prevent infections.
Vanadium based insulin mimetic agents
Several vanadium complexes are now known to mimic the role of the
signalling hormone insulin required in glucose metabolism

Sodium orthovanadate (Na3VO4), Vanadyl sulfate (VOSO4),

peroxovanadium complexes.

Bis(maltolato)oxovanadium(IV)
Anticancer Activity of Pt - complexes
The discovery of the powerful anticancer properties of Cis-platin (cis-
diamine dichloro Pt (II), known as cis-DDP) by Rosenberg et al in the
mid 1960 is a landmark in the discipline of anti metal complexes.

Several Pt-complexes like cis-[Pt(NH3)2X2], [Pt(en)X2] (X = Cl─, Br─,

NO2─, etc); [Pt(NH3)2X], [Pt(enX)], (X = malonate, oxalate) are now
established to have anticancer properties. The NH3 group may be
replaced by different amines like CH3NH2, etc. Some important
anticancer Pt(II) complexes are,
Spiroplatin
It is interesting to note that though cis-platin is active, the trans-platin
is inactive and toxic. Though cis-platin is quite effective for various
types of cancers, it is specially effective for testicular and ovarian
tumors. It is also used in the treatment of bronchogenic carcinoma,
osteosarcoma, etc. In fact, cis-platin is one of the three most widely
used anticancer drugs in the world.
From the knowledge of activity of the above mentioned neutral Cis-Pt
(II) complexes, it has been concluded that:

(1) the compound should be neutral to allow its passive diffusion into
the cells
(2) it should have cis configuration
(3) the non-leaving groups should [have poor trans-labilising power
and they] should be amines.
Among the different neutral Pt(II) complexes, the two compounds
Cis-platin and Carboplatin i.e., cis-diammine(1,1-
cyclobutanedicarboxylato)Pt(II) have been approved worldwide for
clinical use.

It may be noted that the anticancer activity is not only confined

within the non-electrolytic Pt(II) complexes. The charge complexes
called platinum pyrimidine blues, having structures,
Pt(NH3)2(pyrimidine)]Xn (where X = CH3CO2─, Cl─, etc) are known
to have the therapeutic activity against some cancers. Some Pt (V)
complexes like cis-[Pt(NH3)2Cl4], [Pt(en)Cl4] are also known to have
anticancer activity.
 Mechanism
Cis-platin or cis-DDP is both thermodynamically and kinetically stable with respect to
hydrolysis in blood.
In blood the concentration of Cl is sufficiently high ( 0.1 M) to prevent the
hydrolysis of cis-DDP Cis-DDP enters through the cell membrane by passive diffusion
In cytoplasm Cl concentration is low ( 0.04 M) and hydrolysis is possible

The mechanism of action of cisplatin is mediated by the interaction of cisplatin with

DNA in order to for DNA adducts. The principle of action involves exerting its
cytotoxicity upon cancer cells through the formation of DNA adducts that include
mono-, inter, and intrastrand cisplatin DNA cross-links
Cis-platin becomes activated once it enters the cell. In the cytoplasm
the chloride atoms on cis-platin are displaced by water molecules.

Cis-platin, under low intracellular chloride ion concentrations, has

been shown to hydrolyze into variously charged reactive species
including [cis-(NH3)2Pt(OH2)(HO)]+ and diaquated [cis-
(NH3)2Pt(OH2)2]2+ forms

This hydrolyzed product is a potent electrophile that can react with any
nucleophile, including the sulfhydryl groups on proteins and nitrogen
donor atoms on nucleic acids.

Cis-platin binds to the N7 reactive center on purine residues and as

such can cause deoxyribonucleic acid (DNA) damage in cancer cells,
blocking cell division and resulting in apoptotic cell death.
Apoptosis is a controlled type of cell death which is energy-dependent
leading to cell shrinkage, chromatin condensation, membrane
budding, phosphatidylserine externalization

The 1,2-intrastrand cross-links of purine bases with cisplatin are the

most notable among the changes in DNA. These include the 1,2-
intrastrand d(GpG) adducts 1,2-intrastrand d(ApG) adducts
representing about 90% and 10% of adducts, respectively.

1,3-intrastrand d(GpXpG) adducts and other adducts such as inter-

strand crosslinks and nonfunctional adducts have been reported to
contribute to cisplatin's toxicity.

The intrastrand adducts, ApG and GpG in particular, are responsible

for the cytotoxic effects of cisplatin and account for 85–90% of the
bound platinum. These adducts block DNA replication and
transcription.
Trans-platin is kinetically more labile (due to trans effect) and
undergoes rapid and non-specific binding.

Trans-platin, is known to be biologically inactive because of the

diversity of qualitative and quantitative DNA adducts that it forms
compared with cisplatin

Toxic effects of Anticancer Pt-complexes

Pt is not biologically involved and the living system does not have any
efficient mechanism to cope with the toxic effects pf Pt-complexes. Pt
(II) being soft can interact like other heavy metals with the soft and
border tissue sites (e.g. –SH, -NH2, etc.) of different enzymes.
However, the toxicity largely depends on the nature of amine and acid
ligands present in the Pt (II) complex.
 Radioisotopes as therapeutic and in diagnostic
Metal complexes having radioactive nuclei find many applications in
medicine, such as tumor, organ and tissue imaging. Early detection of cancer,
e.g., by selective uptake and imaging of the tumor using a radioactive metal
complex can facilitate surgical removal or chemotherapeutic treatment before
the disease reaches an advanced stage. Ideally, radioisotopes used for
diagnostic purposes should be short lived, emit high energy γ photons and
emit no α or β particles.

Diagnostic radiopharmaceuticals
 Isotope must emit high energy particle such as -ray
 Emitted particle must have high penetrating power
 Isotope must have short half-life, preferably few hours

Therapeutic radiopharmaceuticals
 Isotope preferably emit low energy particle
 Emitted particle must have low penetrating power
 Isotope must have high half-life, few days to few years
Radionuclides most commonly employed in
diagnostic nuclear medicine
Radionuclide t½ Energy (KeV)
57Co 271d 836
67Ga 78h 1,001
99mTc 6h 140
111In 67h 172, 247
113mIn 104m 392
123I 13h 1,230
169Yb 32d 207
197Hg 64h 159
201Tl 72h 135, 167
Positron emission tomography (PET scan): Positron emission
tomography (PET) is a nuclear medicine, functional imaging technique
that is used to observe metabolic processes in the body. The system
detects pairs of gamma rays emitted indirectly by a positron-emitting
radionuclide (tracer), which is introduced into the body on a biologically
active molecule. The biologically active molecule chosen for PET is
fludeoxyglucose (FDG), an analogue of glucose, the concentrations of
tracer imaged will indicate tissue metabolic activity as it corresponds to
the regional glucose uptake. One of the main differences between PET
scans and other imaging tests like CT scan or magnetic resonance
imaging (MRI) is that the PET scan reveals the cellular level metabolic
changes occurring in an organ or tissue. This is important and unique
because disease processes often begin with functional changes at the
cellular level. A PET scan can often detect these very early changes
whereas a CT or MRI detect changes a little later as the disease begins
to cause changes in the structure of organs or tissues.
Fludeoxyglucose (18F) also commonly called fluorodeoxyglucose (18F-
FDG) is a radiopharmaceutical used in the medical imaging modality
positron emission tomography (PET). Chemically, it is 2-deoxy-2-
(18F)fluoro-D-glucose, a glucose analog, with the positron-emitting
radionuclide fluorine-18 substituted for the normal hydroxyl group at the
C-2 position in the glucose molecule. The labeled 18F-FDG compound
has a relatively short shelf life which is dominated by the physical decay
of 18F with a half-life of 109.8 minutes, or slightly less than 2 hours. It
decays by positron emission 97% of the time and electron capture 3% of
the time. PET tracers emit positrons that annihilate with electrons up to a
few millimeters away, causing two gamma photons to be emitted in
opposite directions. A PET scanner detects these emissions "coincident"
in time, which provides more radiation event localization information.
18F-FDG, as a glucose analog, is taken up by high-glucose-using cells
such as brain, brown adipocytes, kidney, and cancer cells, where
phosphorylation prevents the glucose from being released again from the
cell, once it has been absorbed. The 2-hydroxyl group (—OH) in normal
glucose is needed for further glycolysis (metabolism of glucose by
splitting it), but 18F-FDG is missing this 2-hydroxyl. Thus, in common
with its sister molecule 2-deoxy-D-glucose, FDG cannot be further
metabolized in cells. The 18F-FDG-6-phosphate formed when 18F-FDG
enters the cell thus cannot move out of the cell before radioactive decay.
As a result, the distribution of 18F-FDG is a good reflection of the
distribution of glucose uptake and phosphorylation by cells in the body.
After 18F-FDG decays radioactively, however, its 2-fluorine is converted
to 18O−, and after picking up a proton H+ from a hydronium ion in its
aqueous environment, the molecule becomes glucose-6-phosphate
labeled with harmless nonradioactive "heavy oxygen" in the hydroxyl at
the C-2 position. The new presence of a 2-hydroxyl now allows it to be
metabolized normally in the same way as ordinary glucose, producing
non-radioactive end-products.
 Cancer
 heart problems
 brain disorders
 problems with the central
nervous system

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