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 Ethylenediaminetetraacetic acid (EDTA) is an aminopolycarboxylic acid with the formula H2N(CH2CO2H)2sub>2. This white, water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-soluble complexes ev ...

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 DTPA⁵⁻ 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

, DTPA is predominantly used as chelating agent for complexing and sequestering metal ions. DTPA has been considered for treatment of radioactive materials such as

plutonium Plutonium is a radioactive chemical element with the symbol Pu and atomic number 94. It is an actinide metal of silvery-gray appearance that tarnishes when exposed to air, and forms a dull coating when oxidized. The element normally exh ...

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 n ...

, 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. Cellul ...

. 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 ...

zinc Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...

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 Thorium is a weakly radioactive metallic chemical element with the symbol Th and atomic number 90. Thorium is silvery and tarnishes black when it is exposed to air, forming thorium dioxide; it is moderately soft and malleable and has a high ...

(IV),

uranium Uranium is a chemical element with the symbol U and atomic number 92. It is a silvery-grey metal in the actinide series of the periodic table. A uranium atom has 92 protons and 92 electrons, of which 6 are valence electrons. Uranium is weak ...

(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 The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(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

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 in ...

, 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 fibro ...

for those who have breathed in contamination, and by

intravenous injection Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutri ...

for those contaminated by other routes. DTPA is also used as MRI contrasting agent. DTPA improves the resolution of magnetic resonance imaging (MRI) by forming a soluble complex with a

gadolinium Gadolinium is a chemical element with the symbol Gd and atomic number 64. Gadolinium is a silvery-white metal when oxidation is removed. It is only slightly malleable and is a ductile rare-earth element. Gadolinium reacts with atmospheric oxygen ...

(Gd³⁺) 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

proton A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the proton–electron mass ...

s 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 An aquarium (plural: ''aquariums'' or ''aquaria'') is a vivarium of any size having at least one transparent side in which aquatic plants or animals are kept and displayed. Fishkeepers use aquaria to keep fish, invertebrates, amphibians, aqu ...

fertilizer A fertilizer (American English) or fertiliser (British English; see spelling differences) is any material of natural or synthetic origin that is applied to soil or to plant tissues to supply plant nutrients. Fertilizers may be distinct from ...

. The more soluble form of iron, Fe(II), is a

micronutrient Micronutrients are essential dietary elements required by organisms in varying quantities throughout life to orchestrate a range of physiological functions to maintain health. Micronutrient requirements differ between organisms; for example, huma ...

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 ...

s. By binding to Fe²⁺ ions DTPA prevents their

precipitation In meteorology, precipitation is any product of the condensation of atmospheric water vapor that falls under gravitational pull from clouds. The main forms of precipitation include drizzle, rain, sleet, snow, ice pellets, graupel and hail. ...

as Fe(OH)₃, or Fe₂O₃ · n H₂O poorly soluble oxy-hydroxides after their

oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or ...

by dissolved

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements ...

. It increases the

solubility In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solubi ...

of Fe²⁺ and Fe³⁺ 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%. Ho ...

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 A water column is a conceptual column of water from the surface of a sea, river or lake to the bottom sediment.Munson, B.H., Axler, R., Hagley C., Host G., Merrick G., Richards C. (2004).Glossary. ''Water on the Web''. University of Minnesota-D ...

. It is unclear to what extent does DTPA really contribute to protect dissolved Fe²⁺ 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, Fe²⁺ is more easily assimilated by most organisms, because of its 100-fold higher solubility than that of Fe³⁺. 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 Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

decomposition of

hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3 ...

(H₂O₂ reduction by Fe²⁺ ions according to the Fenton reaction mechanism). This helps preserving the

capacity of the hydrogen peroxide stock which is used as

oxidizing agent An oxidizing agent (also known as an oxidant, oxidizer, electron recipient, or electron acceptor) is a substance in a redox chemical reaction that gains or " accepts"/"receives" an electron from a (called the , , or ). In other words, an oxi ...

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 H₂O₂ by this mechanism. DTPA chelating properties are also useful in deactivating

and

magnesium Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ...

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

to deactivate redox-active metal ions such as Fe(II)/(III), Mn(II)/(IV) and Cu(I)/(II) perpetuating

oxidative damage Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal r ...

s 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 ...

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 t ...

and

. 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 microorganism ...

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

decomposition by redox-active

iron Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in ...

and

manganese Manganese is a chemical element with the Symbol (chemistry), symbol Mn and atomic number 25. It is a hard, brittle, silvery metal, often found in minerals in combination with iron. Manganese is a transition metal with a multifaceted array of ...

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, the chelator tiuxetan is a modified version of DTPA whose carbon backbone contains an isothiocyanatobenzyl and a

methyl group In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ma ...

. *In capromab pendetide and satumomab pendetide, the chelator pendetide (GYK-DTPA) is a modified DTPA containing a

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

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 t ...

. *Pentetreotide is a modified DTPA attached to a

segment. *DTPA and derivatives are used to chelate

to form an MRI 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 medica ...

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 emi ...

scans.

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 ...