Pentetic acid or diethylenetriaminepentaacetic acid (DTPA) is an aminopolycarboxylic acid consisting of a diethylenetriamine backbone with five carboxymethyl groups. The molecule can be viewed as an expanded version of

EDTA Ethylenediaminetetraacetic acid (EDTA), also called EDTA acid, is an aminopolycarboxylic acid with the formula . This white, slightly water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-solubl ...

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 gives a proton () to a base—in other words, it is a base with a hydrogen ion added to it, as it loses a hydrogen ion in the reve ...

of DTPA has a high affinity for metal

cations An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

. 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 their 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 l ...

, 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. The distinction between H₅DTPA, "DTPA", and DTPA⁵⁻ is often not explicit.

Chelating applications

Like the more common

, DTPA is predominantly used as

chelating Chelation () is a type of bonding of ions and their 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 l ...

agent for complexing and sequestering metal ions. DTPA has been considered for treatment of radioactive materials such as

plutonium Plutonium is a chemical element; it has symbol Pu and atomic number 94. It is a silvery-gray actinide metal that tarnishes when exposed to air, and forms a dull coating when oxidized. The element normally exhibits six allotropes and four ...

americium Americium is a synthetic element, synthetic chemical element; it has Chemical symbol, symbol Am and atomic number 95. It is radioactive and a transuranic member of the actinide series in the periodic table, located under the lanthanide element e ...

, and other

actinide The actinide () or actinoid () series encompasses at least the 14 metallic chemical elements in the 5f series, with atomic numbers from 89 to 102, actinium through nobelium. Number 103, lawrencium, is also generally included despite being part ...

s. In theory, these complexes are more apt to be eliminated in

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

. It is normally administered as the

calcium Calcium is a chemical element; it has 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 to it ...

zinc Zinc is a chemical element; it has symbol Zn and atomic number 30. It 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 periodic tabl ...

salt (Ca or Zn-DTPA), since these ions are readily displaced by more highly charged cations and mainly to avoid to depleting them in the organism. DTPA forms complexes with

thorium Thorium is a chemical element; it has symbol Th and atomic number 90. Thorium is a weakly radioactive light silver metal which tarnishes olive grey when it is exposed to air, forming thorium dioxide; it is moderately soft, malleable, and ha ...

(IV),

uranium Uranium is a chemical element; it has chemical symbol, 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. Ura ...

(IV),

neptunium Neptunium is a chemical element; it has chemical symbol, symbol Np and atomic number 93. A radioactivity, radioactive actinide metal, neptunium is the first transuranic element. It is named after Neptune, the planet beyond Uranus in the Solar Syste ...

(IV), and

cerium Cerium is a chemical element; it has Chemical symbol, symbol Ce and atomic number 58. It is a hardness, soft, ductile, and silvery-white metal that tarnishes when exposed to air. Cerium is the second element in the lanthanide series, and while it ...

(III/IV). In August, 2004 the U.S.

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

or curium, 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 (English language, 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, c ...

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 nutr ...

for those contaminated by other routes.

Gadolinium Gadolinium is a chemical element; it has Symbol (chemistry), symbol Gd and atomic number 64. It is a silvery-white metal when oxidation is removed. Gadolinium is a malleable and ductile rare-earth element. It reacts with atmospheric oxygen or moi ...

(Gd³⁺)-DTPA compounds are

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...

contrasting agents. DTPA under the form of iron(II) chelate (Fe-DTPA, 10 – 11 wt. %) is also used as aquarium plants

fertilizer A fertilizer or fertiliser 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 liming materials or other non-nutrient soil amendments. Man ...

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

micronutrient Micronutrients are essential chemicals required by organisms in small quantities to perform various biogeochemical processes and regulate physiological functions of cells and organs. By enabling these processes, micronutrients support the heal ...

needed by

aquatic plant Aquatic plants, also referred to as hydrophytes, are vascular plants and Non-vascular plant, non-vascular plants that have adapted to live in aquatic ecosystem, aquatic environments (marine ecosystem, saltwater or freshwater ecosystem, freshwater ...

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 from clouds due to gravitational pull. The main forms of precipitation include drizzle, rain, rain and snow mixed ("sleet" in Commonwe ...

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

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

by dissolved

oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...

. It increases the

solubility In chemistry, solubility is the ability of a chemical substance, substance, the solute, to form a solution (chemistry), solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form su ...

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%. 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 The (oceanic) water column is a concept used in oceanography to describe the physical (temperature, salinity, light penetration) and chemical ( pH, dissolved oxygen, nutrient salts) characteristics of seawater at different depths for a defined ...

. 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 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 increase in reaction rate, rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst ...

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 viscosity, viscous than Properties of water, water. It is used as an oxidizer, bleaching agent, and antiseptic, usua ...

(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 ''electron donor''). In ot ...

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; it has Symbol (chemistry), 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 ...

ions in hair products. 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 damages induced in cells 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 potency or effect of a substance by its effect on animal testing, living animals or plants (''in vivo''), or on living cells or tissues (''in vitro''). A bioassay can be either quantal or quantit ...

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 wastewater treatment, industrial wastewaters using aeration and a biological floc (biofilm), floc composed of bacteria and protozoa ...

s in the treatment of Kraft pulping 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; it has symbol Fe () 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, forming much of Earth's o ...

and

manganese Manganese is a chemical element; it has Symbol (chemistry), symbol Mn and atomic number 25. It is a hard, brittle, silvery metal, often found in minerals in combination with iron. Manganese was first isolated in the 1770s. It is a transition m ...

ions in the chlorine-free Kraft pulping processes (total chlorine free (TCF) and environmental chlorine free (ECF) processes). DTPA decreases the biological oxygen demand (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 (whereas normal methane has the formula ). In formulas, the group is often abbreviated a ...

. *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. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

linker used to connect the chelate to an

antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

. *Pentetreotide is a modified DTPA attached to a

segment. *DTPA and derivatives are used to chelate

gadolinium Gadolinium is a chemical element; it has Symbol (chemistry), symbol Gd and atomic number 64. It is a silvery-white metal when oxidation is removed. Gadolinium is a malleable and ductile rare-earth element. It reacts with atmospheric oxygen or moi ...

to form an

contrast agent, such as

Magnevist Gadopentetic acid, sold under the brand name Magnevist, is a gadolinium-based MRI contrast agent. It is usually administered as a salt of a complex of gadolinium with DTPA (''d''iethylene''t''riamine''p''ent''a''cetate) with the chemical formul ...

. *

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 Radiophar ...

is chelated with DTPA for ventilation perfusion (V/Q) scans and radioisotope renography

nuclear medicine Nuclear medicine (nuclear radiology, nucleology), is a medical specialty involving the application of radioactivity, radioactive substances in the diagnosis and treatment of disease. Nuclear imaging is, in a sense, ''radiology done inside out'', ...

scans.

References

:''This article incorporates material fro
Facts about DTPA
a

fact sheet A factsheet or fact sheet, also called fact file, is a single-page document containing essential information about a product, substance, service or other topic. Factsheets are frequently used to provide information to an end user, consumer or ...

produced by the United States

Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...