Pentetic acid or diethylenetriaminepentaacetic acid (DTPA) is an
aminopolycarboxylic acid consisting of a
diethylenetriamine
Diethylenetriamine (abbreviated and also known as 2,2’-Iminodi(ethylamine)) is an organic compound with the formula HN(CH2CH2NH2)2. This colourless hygroscopic liquid is soluble in water and polar organic solvents, but not simple hydrocarbon ...
backbone with five carboxymethyl groups. The molecule can be viewed as an expanded version of
EDTA and is used similarly. It is a white solid with limited solubility in water.
Coordination properties
The
conjugate base
A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compound formed when an acid donates a proton () to a base—in other words, it is a base with a hydrogen ion added to it, as in the reverse reaction it loses a ...
of DTPA has a high affinity for metal cations. Thus, the penta-anion DTPA
5− is potentially an
octadentate ligand assuming that each nitrogen centre and each –COO
− group counts as a centre for coordination. The
formation constants for its complexes are about 100 greater than those for EDTA.
[J. Roger Hart "Ethylenediaminetetraacetic Acid and Related Chelating Agents" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2005.] As a
chelating agent
Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These ligands a ...
, DTPA wraps around a metal ion by forming up to eight bonds. Its complexes can also have an extra water molecule that coordinates the metal ion.
Transition metals, however, usually form less than eight
coordination bonds. So, after forming a complex with a metal, DTPA still has the ability to bind to other reagents, as is shown by its derivative
pendetide. For example, in its complex with copper(II), DTPA binds in a hexadentate manner utilizing the three amine centres and three of the five carboxylates.
Chelating applications
Like the more common
EDTA, DTPA is predominantly used as
chelating
Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These ligands ar ...
agent for complexing and
sequestering metal ions.
DTPA has been considered for treatment of radioactive materials such as
plutonium,
americium
Americium is a synthetic radioactive chemical element with the symbol Am and atomic number 95. It is a transuranic member of the actinide series, in the periodic table located under the lanthanide element europium, and thus by analogy was named ...
, and other
actinide
The actinide () or actinoid () series encompasses the 15 metallic chemical elements with atomic numbers from 89 to 103, actinium through lawrencium. The actinide series derives its name from the first element in the series, actinium. The info ...
s.
In theory, these complexes are more apt to be eliminated in
urine
Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra.
Cellular m ...
. It is normally administered as the
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...
or
zinc salt (Ca or Zn-DTPA), since these ions are readily displaced by more highly charged cations and mainly to avoid to deplete them in the organism. DTPA forms complexes with
thorium(IV),
uranium(IV),
neptunium
Neptunium is a chemical element with the symbol Np and atomic number 93. A radioactive actinide metal, neptunium is the first transuranic element. Its position in the periodic table just after uranium, named after the planet Uranus, led to it bein ...
(IV), and
cerium
Cerium is a chemical element with the symbol Ce and atomic number 58. Cerium is a soft, ductile, and silvery-white metal that tarnishes when exposed to air. Cerium is the second element in the lanthanide series, and while it often shows the +3 ...
(III/IV).
In August, 2004 the
US Food and Drug Administration (USFDA) determined zinc-DTPA and calcium-DTPA to be safe and effective for treatment of those who have breathed in or otherwise been contaminated internally by plutonium, americium, or curium. The recommended treatment is for an initial dose of calcium-DTPA, as this salt of DTPA has been shown to be more effective in the first 24 hours after internal contamination by plutonium, americium, or curium. After that time has elapsed both calcium-DTPA and zinc-DTPA are similarly effective in reducing internal contamination with
plutonium,
americium
Americium is a synthetic radioactive chemical element with the symbol Am and atomic number 95. It is a transuranic member of the actinide series, in the periodic table located under the lanthanide element europium, and thus by analogy was named ...
or
curium
Curium is a transuranic, radioactive chemical element with the symbol Cm and atomic number 96. This actinide element was named after eminent scientists Marie and Pierre Curie, both known for their research on radioactivity. Curium was first inte ...
, and zinc-DTPA is less likely to deplete the body's normal levels of zinc and other metals essential to health. Each drug can be administered by
nebulizer
In medicine, a nebulizer (American English) or nebuliser (British English) is a drug delivery device used to administer medication in the form of a mist inhaled into the lungs. Nebulizers are commonly used for the treatment of asthma, cystic fibr ...
for those who have breathed in contamination, and by
intravenous injection for those contaminated by other routes.
DTPA is also used as
MRI
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...
contrasting agent. DTPA improves the resolution of magnetic resonance imaging (MRI) by forming a soluble complex with a
gadolinium (Gd
3+) ion, which alters the
magnetic resonance
Magnetic resonance is a process by which a physical excitation (resonance) is set up via magnetism.
This process was used to develop magnetic resonance imaging and Nuclear magnetic resonance spectroscopy technology.
It is also being used to d ...
behavior of the
protons of the nearby
water molecules and increases the images contrast.
DTPA under the form of iron(II) chelate (Fe-DTPA, 10 – 11 wt. %) is also used as
aquarium plants fertilizer. The more soluble form of iron, Fe(II), is a
micronutrient needed by
aquatic plant
Aquatic plants are plants that have adapted to living in aquatic environments (saltwater or freshwater). They are also referred to as hydrophytes or macrophytes to distinguish them from algae and other microphytes. A macrophyte is a plant that g ...
s. By binding to Fe
2+ ions DTPA prevents their
precipitation as Fe(OH)
3, or Fe
2O
3 · n H
2O poorly soluble oxy-hydroxides after their
oxidation by dissolved
oxygen. It increases the
solubility of Fe
2+ and Fe
3+ ions in water, and therefore the
bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...
of iron for aquatic plants. It contributes so to maintain iron under a dissolved form (probably a mix of Fe(II) and Fe(III) DTPA complexes) in the
water column. It is unclear to what extent does DTPA really contribute to protect dissolved Fe
2+ against air oxidation and if the Fe(III)-DTPA complex cannot also be directly assimilated by aquatic plants simply because of its enhanced solubility. Under natural conditions, ''i.e.'', in the absence of complexing DTPA, Fe
2+ is more easily assimilated by most organisms, because of its 100-fold higher solubility than that of Fe
3+.
In
pulp and paper mills
Pulp may refer to:
* Pulp (fruit), the inner flesh of fruit
Engineering
* Dissolving pulp, highly purified cellulose used in fibre and film manufacture
* Pulp (paper), the fibrous material used to make paper
* Molded pulp, a packaging material
* ...
DTPA is also used to remove dissolved ferrous and ferric ions (and other redox-active metal ions, such as
Mn or
Cu) that otherwise would accelerate the
catalytic decomposition of
hydrogen peroxide (H
2O
2 reduction by Fe
2+ ions according to the
Fenton reaction
Fenton's reagent is a solution of hydrogen peroxide (H2O2) with ferrous iron (typically iron(II) sulfate, FeSO4) as a catalyst that is used to oxidize contaminants or waste waters as part of an advanced oxidation process. Fenton's reagent can be u ...
mechanism).
This helps preserving the
oxidation capacity of the hydrogen peroxide stock which is used as
oxidizing agent to
bleach pulp in the chlorine-free process of paper making.
[Colodette, J. L. (1987). Factors affecting hydrogen peroxide stability in the brightening of mechanical and chemi-mechanical pulps (Doctoral dissertation, State University of New York College of Environmental Science and Forestry).] Several thousands tons of DTPA are produced annually for this purpose in order to limit the non-negligible losses of H
2O
2 by this mechanism.
DTPA chelating properties are also useful in deactivating
calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...
and
magnesium ions in
hair products
Hairstyle products are used to change the texture and/or shape of hair.
History
Hairstyling products have had a significant impact on the creation of various hairstyles and trends throughout history. For the ancient Egyptians, physical appearance ...
. DTPA is used in over 150 cosmetic products.
Biochemistry
DTPA is more effective than
EDTA to deactivate redox-active metal ions such as Fe(II)/(III), Mn(II)/(IV) and Cu(I)/(II) perpetuating
oxidative damages induced in
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
s by
superoxide
In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of th ...
and
hydrogen peroxide.
DTPA is also used in
bioassay
A bioassay is an analytical method to determine the concentration or potency of a substance by its effect on living animals or plants (''in vivo''), or on living cells or tissues(''in vitro''). A bioassay can be either quantal or quantitative, dir ...
s involving redox-active metal ions.
Environmental impact
An unexpected negative environmental impact of chelating agents, as DTPA, is their toxicity for the
activated sludge
The activated sludge process is a type of biological wastewater treatment process for treating sewage or industrial wastewaters using aeration and a biological floc composed of bacteria and protozoa. It uses air (or oxygen) and microorganisms to ...
s in the treatment of
Kraft pulping
The kraft process (also known as kraft pulping or sulfate process) is a process for conversion of wood into wood pulp, which consists of almost pure cellulose fibres, the main component of paper. The kraft process involves treatment of wood chip ...
effluents.
Most of the DTPA worldwide production (several thousands of tons)
is intended to avoid
hydrogen peroxide decomposition by redox-active
iron and
manganese ions in the chlorine-free Kraft pulping processes (total chlorine free (TCF) and environmental chlorine free (ECF) processes). DTPA decreases the
biological oxygen demand
Biochemical oxygen demand (BOD) is the amount of dissolved oxygen (DO) needed (i.e. demanded) by aerobic biological organisms to break down organic material present in a given water sample at a certain temperature over a specific time period. T ...
(BOD) of activated sludges and therefore their microbial activity.
Related compounds
Compounds that are structurally related to DTPA are used in medicine, taking advantage of the high affinity of the triaminopentacarboxylate scaffold for metal ions.
*In
ibritumomab tiuxetan
Ibritumomab tiuxetan (pronounced ), sold under the trade name Zevalin, is a monoclonal antibody radioimmunotherapy treatment for non-Hodgkin's lymphoma. The drug uses the monoclonal mouse IgG1 antibody ibritumomab in conjunction with the chelator ...
, the chelator tiuxetan is a modified version of DTPA whose carbon backbone contains an isothiocyanatobenzyl and a
methyl group.
*In
capromab pendetide and
satumomab pendetide, the chelator
pendetide (GYK-DTPA) is a modified DTPA containing a
peptide linker used to connect the chelate to an
antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
.
*Pentetreotide is a modified DTPA attached to a
peptide segment.
*DTPA and derivatives are used to chelate
gadolinium to form an
MRI
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...
contrast agent, such as
Magnevist.
*
Technetium-99m
Technetium-99m (99mTc) is a metastable nuclear isomer of technetium-99 (itself an isotope of technetium), symbolized as 99mTc, that is used in tens of millions of medical diagnostic procedures annually, making it the most commonly used Radiopharm ...
is chelated with DTPA for
ventilation perfusion (V/Q) scans and
radioisotope renography
Radioisotope renography is a form of medical imaging of the kidneys that uses radiolabelling. A renogram, which may also be known as a MAG3 scan, allows a nuclear medicine physician or a radiologist to visualize the kidneys and learn more about how ...
nuclear medicine
Nuclear medicine or nucleology is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging, in a sense, is "radiology done inside out" because it records radiation emitting ...
scans.
See also
*
Nuclear medicine
Nuclear medicine or nucleology is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging, in a sense, is "radiology done inside out" because it records radiation emitting ...
*
Radiopharmaceutical
Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which i ...
*
Hydrogen peroxide decomposition
*
DTPA in chlorine-free Kraft pulping
References
:''This article incorporates material fro
Facts about DTPA a
fact sheet produced by the United States
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
.
{{Chelating agents
Chelating agents
Acetic acids
Tertiary amines
Nuclear medicine
Magnetic resonance imaging