Pentetic acid explained

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.

Coordination properties

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.[1] 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.[2] 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.[3]

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.[2] 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 depleting them in the organism. DTPA forms complexes with thorium(IV), uranium(IV), neptunium(IV), and cerium(III/IV).[4]

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.[5]

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.[6]

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).[7] 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.[8] 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 calcium and magnesium ions in hair products. DTPA is used in over 150 cosmetic products.[9]

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.[10] 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.[11] 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 (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.

See also

References

This article incorporates material from Facts about DTPA, a fact sheet produced by the United States Centers for Disease Control and Prevention.

Notes and References

  1. J. Roger Hart "Ethylenediaminetetraacetic Acid and Related Chelating Agents" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, 2005.
  2. 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. en. 57. 17. 4521–4526. 10.1002/anie.201709183. 29473263. 1426318. 1521-3773. free.
  3. 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.
  4. (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.
  5. Web site: "FDA Approves Drugs to Treat Internal Contamination from Radioactive Elements" (press release) . United States Food and Drug Administration . 4 August 2004. 19 June 2015 . 2 August 2016.
  6. 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.
  7. Cohen. Gerald. Lewis. David. Sinet. Pierre M.. Oxygen consumption during the Fenton-type reaction between hydrogen peroxide and a ferrous-chelate (Fe2+-DTPA). Journal of Inorganic Biochemistry. 15. 2. 1981. 143–151. 0162-0134. 10.1016/S0162-0134(00)80298-6.
  8. 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).
  9. 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.
  10. Fisher. Anna E.O.. Maxwell. Suzette C.. Naughton. Declan P.. Superoxide and hydrogen peroxide suppression by metal ions and their EDTA complexes. Biochemical and Biophysical Research Communications. 316. 1. 2004. 48–51. 0006-291X. 10.1016/j.bbrc.2004.02.013. 15003509 .
  11. Larisch. B.C.. Duff. S.J.B.. 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. 1997. 0273-1223. 10.1016/S0273-1223(96)00928-6.
  12. 10.1038/nrd1413. 1474-1776. 3. 6. 488–99. Milenic. Diane E.. Erik D. Brady . Martin W. Brechbiel . Antibody-targeted radiation cancer therapy. Nat Rev Drug Discov. June 2004. 15173838. 22166498.
  13. 14. 2. 99–111. Kahn. Daniel. J. Christopher Austin . Robert T Maguire . Sara J Miller . Jack Gerstbrein . Richard D Williams . A Phase II Study of [90Y] Yttrium-Capromab Pendetide in the Treatment of Men with Prostate Cancer Recurrence Following Radical Prostatectomy. Cancer Biotherapy & Radiopharmaceuticals. 1999. 10.1089/cbr.1999.14.99. 10850293.
  14. 10.1016/j.addr.2008.04.006. 0169-409X. 60. 12. 1347–70. Liu. Shuang. Bifunctional coupling agents for radiolabeling of biomolecules and target-specific delivery of metallic radionuclides. Advanced Drug Delivery Reviews. 2008-09-15. 18538888. 2539110.
  15. Book: Chowdhury. Rajat. Wilson. Iain. Rofe. Christopher. Lloyd-Jones. Graham. Radiology at a Glance. John Wiley & Sons. 9781118691083. 109. en. 2013-07-08.