Ethylenediaminetetraacetic acid

ethylenediaminetetraacetic acid, also called EDTA or less frequently EDTA, is a substance used as a chelating agent that can create complexes with a metal having an octahedral coordination structure. It coordinates to heavy metals reversibly through four acetate and two amino positions, which makes it a hexadentate ligand, and the most important of the chelate ligands. It was first synthesized in 1935 by Ferdinand Münz.

Biomedical importance

EDTA and its derivatives have the valuable chemical property of combining with polyvalent metal ions in solution to form nonionic, water-soluble, virtually non-dissociable coordinated cyclic complexes. These complexes are known as chelates.

In addition, the chelating capacity of EDTA is used in biochemical and biotechnological laboratories to deactivate metalloproteins (since these cannot act without the metal ion that serves as a catalytic center), either to study the kinetics of these enzymes, or well to deactivate them so as not to damage DNA (nucleases), proteins or polysaccharides in a solution.

Chemical Importance

Assessment of complexes

EDTA, ethylenediaminetetraacetic acid, has four carboxyl and two amino groups; groups that can act as donors of electron pairs, or Lewis bases. EDTA's ability to potentially donate its six pairs of electrons for coordinate covalent bond formation to metal cations makes EDTA a hexadentate ligand. However, in practice EDTA is usually partially ionized, and therefore forms fewer than six coordinate covalent bonds with metal cations.

Disodium EDTA is commonly used to standardize aqueous solutions of transition metal cations. Noting that the abbreviated form of Na_4-xH_xY can be used to represent any EDTA species, with the designation of x number of acidic protons attached to the EDTA molecule.

EDTA forms an octahedral complex with most 2+ metal cations, M²⁺, in aqueous solution. The main reason that EDTA is widely used in the standardization of metal cations in solutions is that the formation constant for most metal cation complexes with EDTA is very high, which means that the equilibrium of the reaction:

M²⁺ + H₄Y → MH₂And + 2H⁺

is now on the right. Carrying out the reaction in a basic buffer solution removes H⁺ when it is formed, which also favors the formation of EDTA complexes with metal cations as the reaction product. For most purposes the formation of EDTA complexes with metal cations can be considered to be complete, and this is the main reason why EDTA is used in titrations/standardizations of this type [1].

Pharmacology

EDTA and its derived sodium salts are used to precipitate toxic heavy metals so that they can be excreted in the urine. The fixation of lead, cadmium, and nickel by EDTA shows a favorable relationship in the human body, however, the binding to copper, iron, and cobalt is not so strong.

To be useful, EDTA and any other chelating agent must have a certain degree of pH so that its fixing activity for each metal is optimal. EDTA specifically acts in a narrow pH range, within which the pH of blood and tissue fluids are found, so that EDTA can work optimally within the human body.

Pharmacokinetics and mode of action

Quelato metal-EDTA

EDTA can be applied intravenously or topically. It can be given orally and its absorption in the digestive tract is good, although intravenous administration is preferred because it is more effective in increasing the rate of urinary excretion of chelates.

After administration, the drug is absorbed and after 6 hours 60 to 90% of the administered amount can be detected in urine. At 25 hours it can recover up to 99%. The rest appears in the feces.

The pharmacological effects of EDTA result from the formation of chelates with divalent and trivalent metals in the body. In the form of calcium disodium edetate it is applied to chelate metals with a high affinity for the chelator rather than ionic calcium.

It is very useful for chelating lead found in bone. In blood, the drug can be found in plasma and because it is excreted in the urine, the patient must be carefully evaluated and certify that he has adequate renal function. A small percentage has been detected in spinal fluid.

Toxicity

EDTA toxicity is rare if well-established doses and application protocols are used. And in doses equal to or less than 2 g diluted in 450 mL of saline solution once a week, it is extremely rare to observe adverse effects. Especially when used as monotherapy (no other active ingredients, nutrients or other chelating agents are added).

EDTA derivatives

EDTA derivatives include hydroxyethylenediaminetriacetic acid (HEDTA), dihydroxyethylenediaminediacetic acid, diethylenetriaminepentaacetic acid (DTPA), triethylenetetraminehexaacetic acid (TTHA), and calcium disodium ethylenediaminetetraacetate (CaNa₂EDTA). The use of CaNa₂EDTA in children for the treatment of lead encephalopathy has given good results.

Therapeutic indications

EDTA Ampoule

EDTA is widely used for lead chelation in poisoning by this metal. It is commonly used in the form of CaNa₂EDTA because sodium EDTA, when used alone, can cause hypocalcemic tetany.

In Dentistry, EDTA is used as a chemical stretcher in Endodontics, widely spread among the most frequently used solutions for irrigation and taking advantage of its chelating property, it captures Calcium from dental tissues. It can also be combined with Cetrimide to form EDTAC (a quaternary ammoniated bromide is added to the composition to reduce surface tension and thus favor penetration), thus removing the smear layer or smear layer.

In the food industry it is useful to prevent the enzymatic browning reaction since it is a powerful copper chelating agent, substrate of the Polyphenoloxidase Enzyme (PPO) responsible for the appearance of color in vegetables and fruits. However, it is more effective when used in combination with ascorbic acid or citric acid.

There are also applications in the agricultural industry. This compound is present in agricultural products that contribute to the effectiveness of herbicides, insecticides, among others. EDTA is used in water conditioners and acidifiers to correct the hardness of the water or mixture.