For the combined diphtheria-tetanus-acellular pertussis vaccine used in Australia, see DTPa.
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 and is used similarly. It is a white solid with limited solubility in water.
The conjugate base 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.[3] As a chelating agent, 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.[4] 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.[5]
Chelating applications
Like the more common EDTA, 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, americium, and other actinides.[4] In theory, these complexes are more apt to be eliminated in urine. It is normally administered as the calcium 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(IV), and cerium(III/IV).[6]
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 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 for those who have breathed in contamination, and by intravenous injection for those contaminated by other routes.[7]
DTPA is also used as MRIcontrasting agent. DTPA improves the resolution of magnetic resonance imaging (MRI) by forming a soluble complex with a gadolinium (Gd3+) ion, which alters the magnetic resonance behavior of the protons of the nearby water molecules and increases the images contrast.[8]
DTPA under the form of iron(II) chelate (Fe-DTPA, 10 – 11 wt. %) is also used as aquarium plantsfertilizer. The more soluble form of iron, Fe(II), is a micronutrient needed by aquatic plants. By binding to Fe2+ ions DTPA prevents their precipitation as Fe(OH)3, or Fe2O3 · n H2O poorly soluble oxy-hydroxides after their oxidation by dissolved oxygen. It increases the solubility of Fe2+ and Fe3+ ions in water, and therefore the bioavailability 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 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 decomposition of hydrogen peroxide (H2O2 reduction by Fe2+ ions according to the Fenton reaction mechanism).[9] 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.[10] Several thousands tons of DTPA are produced annually for this purpose in order to limit the non-negligible losses of H2O2 by this mechanism.[3]
DTPA chelating properties are also useful in deactivating calcium and magnesium ions in hair products. DTPA is used in over 150 cosmetic products.[11]
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 cells by superoxide and hydrogen peroxide.[12][9] DTPA is also used in bioassays involving redox-active metal ions.
Environmental impact
An unexpected negative environmental impact of chelating agents, as DTPA, is their toxicity for the activated sludges in the treatment of Kraft pulping effluents.[13] Most of the DTPA worldwide production (several thousands of tons)[3] 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 (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.[14]
^Moeller, T.; Thompson, L. C. Observations on the rare earths—LXXV(1): The stabilities of diethylenetriaminepentaacetic acid chelates. Journal of Inorganic and Nuclear Chemistry 1962, 24, 499.
^ abcJ. Roger Hart "Ethylenediaminetetraacetic Acid and Related Chelating Agents" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2005.doi:10.1002/14356007.a10_095
^ abDeblonde, Gauthier J.-P.; Kelley, Morgan P.; Su, Jing; Batista, Enrique R.; Yang, Ping; Booth, Corwin H.; Abergel, Rebecca J. (2018). "Spectroscopic and Computational Characterization of Diethylenetriaminepentaacetic Acid/Transplutonium Chelates: Evidencing Heterogeneity in the Heavy Actinide(III) Series". Angewandte Chemie International Edition. 57 (17): 4521–4526. doi:10.1002/anie.201709183. ISSN 1521-3773. OSTI 1426318. PMID 29473263.
^V. V. Fomenko, T. N. Polynova, M. A. Porai-Koshits, G. L. Varlamova and N. I. Pechurova Crystal structure of copper (II) diethylenetriaminepentaacetate monohydrate Journal of Structural Chemistry, 1973, Vol. 14, 529. doi:10.1007/BF00747020
^(2) Brown, M. A.; Paulenova, A.; Gelis, A. V. "Aqueous Complexation of Thorium(IV), Uranium(IV), Neptunium(IV), Plutonium(III/IV), and Cerium(III/IV) with DTPA" Inorganic Chemistry 2012, volume 51, 7741-7748. doi:10.1021/ic300757k
^""FDA Approves Drugs to Treat Internal Contamination from Radioactive Elements" (press release)". United States Food and Drug Administration. 19 June 2015 [4 August 2004]. Retrieved 2 August 2016.
^Caravan, Peter; Ellison, Jeffrey J.; McMurry, Thomas J. ; Lauffer, Randall B. "Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications" Chem. Revs. 1999, volume 99, pp. 2293–2342.
^ abCohen, Gerald; Lewis, David; Sinet, Pierre M. (1981). "Oxygen consumption during the Fenton-type reaction between hydrogen peroxide and a ferrous-chelate (Fe2+-DTPA)". Journal of Inorganic Biochemistry. 15 (2): 143–151. doi:10.1016/S0162-0134(00)80298-6. ISSN 0162-0134.
^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).
^Burnett, L. C. "Final Report on the Safety Assessment of Pentasodium Pentetate and Pentetic Acid as Used in Cosmetics" International Journal of Toxicology 2008, 27, 71-92.
^Fisher, Anna E.O.; Maxwell, Suzette C.; Naughton, Declan P. (2004). "Superoxide and hydrogen peroxide suppression by metal ions and their EDTA complexes". Biochemical and Biophysical Research Communications. 316 (1): 48–51. doi:10.1016/j.bbrc.2004.02.013. ISSN 0006-291X. PMID 15003509.
^Larisch, B.C.; Duff, S.J.B. (1997). "Effect of H2O2 and DTPA on the characteristics and treatment of TCF (totally chlorine-free) and ECF (elementally chlorine-free) kraft pulping effluents". Water Science and Technology. 35 (2–3). doi:10.1016/S0273-1223(96)00928-6. ISSN 0273-1223.
^Milenic, Diane E.; Erik D. Brady; Martin W. Brechbiel (June 2004). "Antibody-targeted radiation cancer therapy". Nat Rev Drug Discov. 3 (6): 488–99. doi:10.1038/nrd1413. ISSN 1474-1776. PMID 15173838. S2CID 22166498.
^Kahn, Daniel; J. Christopher Austin; Robert T Maguire; Sara J Miller; Jack Gerstbrein; Richard D Williams (1999). "A Phase II Study of [90Y] Yttrium-Capromab Pendetide in the Treatment of Men with Prostate Cancer Recurrence Following Radical Prostatectomy". Cancer Biotherapy & Radiopharmaceuticals. 14 (2): 99–111. doi:10.1089/cbr.1999.14.99. PMID 10850293.
^Liu, Shuang (2008-09-15). "Bifunctional coupling agents for radiolabeling of biomolecules and target-specific delivery of metallic radionuclides". Advanced Drug Delivery Reviews. 60 (12): 1347–70. doi:10.1016/j.addr.2008.04.006. ISSN 0169-409X. PMC2539110. PMID 18538888.
^Chowdhury, Rajat; Wilson, Iain; Rofe, Christopher; Lloyd-Jones, Graham (2013-07-08). Radiology at a Glance. John Wiley & Sons. p. 109. ISBN9781118691083.
pentetic, acid, combined, diphtheria, tetanus, acellular, pertussis, vaccine, used, australia, dtpa, diethylenetriaminepentaacetic, acid, dtpa, aminopolycarboxylic, acid, consisting, diethylenetriamine, backbone, with, five, carboxymethyl, groups, molecule, vi. For the combined diphtheria tetanus acellular pertussis vaccine used in Australia see DTPa 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 and is used similarly It is a white solid with limited solubility in water Pentetic acid NamesPreferred IUPAC name 2 2 2 2 Carboxymethyl azanediyl bis ethane 2 1 diylnitrilo tetraacetic acidOther names DTPA H5dtpa Diethylenetriaminepentaacetic acid Penta carboxymethyl diethylenetriamine 1 IdentifiersCAS Number 67 43 6 Y3D model JSmol Interactive imageChEBI CHEBI 35739 YChEMBL ChEMBL780 YChemSpider 2945 YECHA InfoCard 100 000 593KEGG D05422 YPubChem CID 30536441444 Zinc DTPA RTECS number MB8205000UNII 7A314HQM0I NCompTox Dashboard EPA DTXSID2023434InChI InChI 1S C14H23N3O10 c18 10 19 5 15 1 3 16 6 11 20 21 7 12 22 23 2 4 17 8 13 24 25 9 14 26 27 h1 9H2 H 18 19 H 20 21 H 22 23 H 24 25 H 26 27 YKey QPCDCPDFJACHGM UHFFFAOYSA N YSMILES C CN CC O O CC O O N CCN CC O O CC O O CC O OPropertiesChemical formula C 14H 23N 3O 10Molar mass 393 349 g mol 1Appearance White crystalline solidMelting point 220 C 428 F 493 K Boiling point decomposes at a higher temp Solubility in water lt 0 5 g 100 mLAcidity pKa 1 80 20 C 2 HazardsFlash point Non flammableRelated compoundsRelated compounds EDTA NTAExcept where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N verify what is Y N Infobox references Contents 1 Coordination properties 2 Chelating applications 3 Biochemistry 4 Environmental impact 5 Related compounds 6 See also 7 ReferencesCoordination properties EditThe conjugate base 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 3 As a chelating agent 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 4 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 5 Chelating applications EditLike the more common EDTA 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 americium and other actinides 4 In theory these complexes are more apt to be eliminated in urine It is normally administered as the calcium 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 IV and cerium III IV 6 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 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 for those who have breathed in contamination and by intravenous injection for those contaminated by other routes 7 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 Gd3 ion which alters the magnetic resonance behavior of the protons of the nearby water molecules and increases the images contrast 8 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 plants By binding to Fe2 ions DTPA prevents their precipitation as Fe OH 3 or Fe2O3 n H2O poorly soluble oxy hydroxides after their oxidation by dissolved oxygen It increases the solubility of Fe2 and Fe3 ions in water and therefore the bioavailability 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 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 decomposition of hydrogen peroxide H2O2 reduction by Fe2 ions according to the Fenton reaction mechanism 9 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 10 Several thousands tons of DTPA are produced annually for this purpose in order to limit the non negligible losses of H2O2 by this mechanism 3 DTPA chelating properties are also useful in deactivating calcium and magnesium ions in hair products DTPA is used in over 150 cosmetic products 11 Biochemistry EditDTPA 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 cells by superoxide and hydrogen peroxide 12 9 DTPA is also used in bioassays involving redox active metal ions Environmental impact EditAn unexpected negative environmental impact of chelating agents as DTPA is their toxicity for the activated sludges in the treatment of Kraft pulping effluents 13 Most of the DTPA worldwide production several thousands of tons 3 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 BOD of activated sludges and therefore their microbial activity Related compounds EditCompounds 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 14 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 15 Pentetreotide is a modified DTPA attached to a peptide segment 16 DTPA and derivatives are used to chelate gadolinium to form an MRI contrast agent such as Magnevist Technetium 99m is chelated with DTPA for ventilation perfusion V Q scans and radioisotope renography nuclear medicine scans 17 See also EditNuclear medicine Radiopharmaceutical Hydrogen peroxide decomposition DTPA in chlorine free Kraft pulpingReferences Edit Anonymous Pentetic Acid In Dictionary of Organic Compounds Sixth Edition Buckingham J Macdonald F Eds CRC Press 1996 Vol 5 pp 1188 Moeller T Thompson L C Observations on the rare earths LXXV 1 The stabilities of diethylenetriaminepentaacetic acid chelates Journal of Inorganic and Nuclear Chemistry 1962 24 499 a b c J Roger Hart Ethylenediaminetetraacetic Acid and Related Chelating Agents in Ullmann s Encyclopedia of Industrial Chemistry Wiley VCH Weinheim 2005 doi 10 1002 14356007 a10 095 a b Deblonde Gauthier J P Kelley Morgan P Su Jing Batista Enrique R Yang Ping Booth Corwin H Abergel Rebecca J 2018 Spectroscopic and Computational Characterization of Diethylenetriaminepentaacetic Acid Transplutonium Chelates Evidencing Heterogeneity in the Heavy Actinide III Series Angewandte Chemie International Edition 57 17 4521 4526 doi 10 1002 anie 201709183 ISSN 1521 3773 OSTI 1426318 PMID 29473263 V V Fomenko T N Polynova M A Porai Koshits G L Varlamova and N I Pechurova Crystal structure of copper II diethylenetriaminepentaacetate monohydrate Journal of Structural Chemistry 1973 Vol 14 529 doi 10 1007 BF00747020 2 Brown M A Paulenova A Gelis A V Aqueous Complexation of Thorium IV Uranium IV Neptunium IV Plutonium III IV and Cerium III IV with DTPA Inorganic Chemistry 2012 volume 51 7741 7748 doi 10 1021 ic300757k FDA Approves Drugs to Treat Internal Contamination from Radioactive Elements press release United States Food and Drug Administration 19 June 2015 4 August 2004 Retrieved 2 August 2016 Caravan Peter Ellison Jeffrey J McMurry Thomas J Lauffer Randall B Gadolinium III Chelates as MRI Contrast Agents Structure Dynamics and Applications Chem Revs 1999 volume 99 pp 2293 2342 a b Cohen Gerald Lewis David Sinet Pierre M 1981 Oxygen consumption during the Fenton type reaction between hydrogen peroxide and a ferrous chelate Fe2 DTPA Journal of Inorganic Biochemistry 15 2 143 151 doi 10 1016 S0162 0134 00 80298 6 ISSN 0162 0134 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 Burnett L C Final Report on the Safety Assessment of Pentasodium Pentetate and Pentetic Acid as Used in Cosmetics International Journal of Toxicology 2008 27 71 92 Fisher Anna E O Maxwell Suzette C Naughton Declan P 2004 Superoxide and hydrogen peroxide suppression by metal ions and their EDTA complexes Biochemical and Biophysical Research Communications 316 1 48 51 doi 10 1016 j bbrc 2004 02 013 ISSN 0006 291X PMID 15003509 Larisch B C Duff S J B 1997 Effect of H2O2 and DTPA on the characteristics and treatment of TCF totally chlorine free and ECF elementally chlorine free kraft pulping effluents Water Science and Technology 35 2 3 doi 10 1016 S0273 1223 96 00928 6 ISSN 0273 1223 Milenic Diane E Erik D Brady Martin W Brechbiel June 2004 Antibody targeted radiation cancer therapy Nat Rev Drug Discov 3 6 488 99 doi 10 1038 nrd1413 ISSN 1474 1776 PMID 15173838 S2CID 22166498 Kahn Daniel J Christopher Austin Robert T Maguire Sara J Miller Jack Gerstbrein Richard D Williams 1999 A Phase II Study of 90Y Yttrium Capromab Pendetide in the Treatment of Men with Prostate Cancer Recurrence Following Radical Prostatectomy Cancer Biotherapy amp Radiopharmaceuticals 14 2 99 111 doi 10 1089 cbr 1999 14 99 PMID 10850293 Liu Shuang 2008 09 15 Bifunctional coupling agents for radiolabeling of biomolecules and target specific delivery of metallic radionuclides Advanced Drug Delivery Reviews 60 12 1347 70 doi 10 1016 j addr 2008 04 006 ISSN 0169 409X PMC 2539110 PMID 18538888 Chowdhury Rajat Wilson Iain Rofe Christopher Lloyd Jones Graham 2013 07 08 Radiology at a Glance John Wiley amp Sons p 109 ISBN 9781118691083 This article incorporates material from Facts about DTPA a fact sheet produced by the United States Centers for Disease Control and Prevention Retrieved from https en wikipedia org w index php title Pentetic acid amp oldid 1095178429, wikipedia, wiki, book, books, library,
