Polyaminopolycarboxylic Acids Research Articles

Speciation of yttrium and the rare earth elements in seawater: Review of a 20-year analytical journey

This review describes a program that we have conducted for more than 20 years, first at the University of South Florida and then at the University of Maryland Center for Environmental Science, to systematically measure stability constants for solution complexes of yttrium and all rare earth elements (YREE), except Pm, at the ionic strength of seawater (I ~ 0.7). This effort informs our goal of better characterizing and understanding YREE speciation in the marine environment, in the presence of both inorganic and organic ligands (and sorbents). Since all YREE appear to show similar behavior as a function of ionic strength, patterns of stability constants for individual ligands have been extrapolated to I = 0 whenever sufficient data for at least one member of the series are available. Complexes with hydroxide, fluoride and chloride, carbonate, and sulfate, are treated in detail, being the most prominent inorganic YREE ligands. A natural siderophore (DFOB) and synthetic polyaminopolycarboxylic acids (NTA, EDTA, DTPA) are given as examples of strong organic YREE complexation which, while remaining poorly quantified, is thought to be important. Several YREE ligands that play a negligible role in seawater, or for which data are as yet scarce, are also briefly discussed. Many different and sometimes novel analytical approaches were used in our experiments and these are summarized in the introductory sections, along with a primer on the theory of chemical speciation. This paper is intended as a retrospective of our work, not as a critical review of all available data. Literature values are thus cited primarily for comparison with our results, to support specific arguments, or to highlight prior discrepancies that prompted our own studies.

Fluorescence and conformation in water-soluble bis(pyrenyl amide) receptors derived from polyaminopolycarboxylic acids

Fluorescent responses and conformational changes against pH were studied on four new water-soluble 1-pyrene and 1-methylpyrene bichromophores, (ttha1py)H 4, (edta1mpy)H 2, (dtpa1mpy)H 3 and (ttha1mpy)H 4, with the objective of modifying pH–fluorescence profiles and other solution properties of 1-pyrene bichromophores, (edta1py)H 2 and (dtpa1py)H 3, developed previously by our group; the abbreviations with acidic protons stand for pyrenyl moieties interlinked by an EDTA, DTPA (diethylenetriaminepentacetic acid) or TTHA (triethylenetetraminehexaacetic acid) chain through amide linkages. The new derivatives exhibit emission bands of monomeric pyrene and an intense structureless excimer band; the latter responds to pH sensitively. The pH dependence of the emission intensity of the DTPA and TTHA derivatives is well correlated with species distribution determined by potentiometry. In every derivative, the completely deprotonated species L n− is the most efficient for excimer emission, followed by the corresponding monoprotonated species LH ( n−1)− . In the latter, the acidic hydrogen is located on the central amine, as confirmed by 1H NMR. The resulting hydrogen bond between amino nitrogen atoms makes the aliphatic chain rigid. Further protonation stretches the interlinking chain due to electrostatic repulsion. These conformational changes with protonation result in fluorescent on–off cycles against pH window. The switching cycles of the methylpyrene derivatives are reverse to those of the corresponding pyrene derivatives, as the CH 2 spacer between the amide and aromatic groups defines the orientation of pyrene rings. The sensitiveness of amide group to environment leads to a sharp change in excimer emission above pH ∼11. The combined functions of amide and amino groups lead to the novel pH-responses.

Stevens rearrangement as a tool for the structural modification of polyaminopolycarboxylic ligands

Polyaminopolycarboxylic acids are a well known class of ligands employed for metal ion complexation. Despite the large commercial availability, reports of their use as substrates for direct structural modifications are rare. Herein we report a simple and efficient protocol for the preparation of substituted polyaminopolycarboxylic ligands relying on a one-pot N-alkylation-Stevens rearrangement cascade.

Experimental and Theoretical Study of Lanthanide Complexes Based on Linear and Macrocyclic Polyaminopolycarboxylic Acids Containing Pyrazolylethyl Arms

We report the synthesis of two novel Gd(III)-complexes derived from linear and macrocyclic polyaminopolycarboxylic acids 1 and 2, which contain a 3,5- dimethylpyrazolyl-ethyl arm, and a study of their relaxivity properties. The relationships between the experimental and theoretical results have provided interesting information about the kinetic and thermodynamic stability of these complexes.

Chelators as Antidotes of Metal Toxicity: Therapeutic and Experimental Aspects

The effects of chelating drugs used clinically as antidotes to metal toxicity are reviewed. Human exposure to a number of metals such as lead, cadmium, mercury, manganese, aluminum, iron, copper, thallium, arsenic, chromium, nickel and platinum may lead to toxic effects, which are different for each metal. Similarly the pharmacokinetic data, clinical use and adverse effects of most of the chelating drugs used in human metal poisoning are also different for each chelating drug. The chelating drugs with worldwide application are dimercaprol (BAL), succimer (meso-DMSA), unithiol (DMPS), D-penicillamine (DPA), N-acetyl-D-penicillamine (NAPA), calcium disodium ethylenediaminetetraacetate (CaNa(2)EDTA), calcium trisodium or zinc trisodium diethylenetriaminepentaacetate (CaNa(3)DTPA, ZnNa(3)DTPA), deferoxamine (DFO), deferiprone (L1), triethylenetetraamine (trientine), N-acetylcysteine (NAC), and Prussian blue (PB). Several new synthetic homologues and experimental chelating agents have been designed and tested in vivo for their metal binding effects. These include three groups of synthetic chelators, namely the polyaminopolycarboxylic acids (EDTA and DTPA), the derivatives of BAL (DMPS, DMSA and mono- and dialkylesters of DMSA) and the carbodithioates. Many factors have been shown to affect the efficacy of the chelation treatment in metal poisoning. Within this context it has been shown in experiments using young and adult animals that metal toxicity and chelation effects could be influenced by age. These findings may have a bearing in the design of new therapeutic chelation protocols for metal toxicity.

Stereochemistry of Pb(II) Complexes with Aminopolycarboxylic Ligands. The Role of a Lone Electron Pair

The structures of complex anions of Pb(II) coordination compounds (complexonates) with monoamino-, diamino-, and polyaminopolycarboxylic acids as ligands were interpreted in terms of a model of the valence shell electron pair repulsion. A lone electron pair (E) in all structurally studied Pb(II) complexonates with carboxyl-containing complexones was shown to be stereochemically active, and the structure of Pb coordination polyhedron was found to depend on both the ligand dentate number and on its degree of protonation. As the ligand dentate number increased, the coordination number (C.N.) of a central atom changed from 4 + E for monoamine complexonates to 6 + E for diamine and triamine complexonates. With allowance for secondary bonds in the structure, the C.N. of the Pb atom increased to 7–9. The Pb(II) complexonates with nitrilotriacetic acid exhibit the formation of a new type of coordination polyhedron for post-transition elements in a low-valent state with five electron pairs in a valence shell (including one lone electron pair), i.e., the ψ-trigonal bipyramid with E in the axial position.

TAME‐Hex A — A Novel Bifunctional Chelating Agent for Radioimmunoimaging.

AbstractFor Abstract see ChemInform Abstract in Full Text.

TAME‐Hex A − A Novel Bifunctional Chelating Agent for Radioimmunoimaging

AbstractTwo novel (bifunctional) chelating agents, TAME‐Hex A and B, which are polyaminopolycarboxylic acids based on the tripodal TAME [tris(aminomethyl)ethane] structure, have been designed and synthesized. The chelators show very good stability with gallium(III) ions and thus are highly effective candidates for use in radioimmunoimaging (RII), especially in positron emission tomography (PET). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Carbonic anhydrase inhibitors. A general approach for the preparation of water-soluble sulfonamides incorporating polyamino-polycarboxylate tails and of their metal complexes possessing long-lasting, topical intraocular pressure-lowering properties.

Reaction of polyamino-polycarboxylic acids or their dianhydrides with aromatic/heterocyclic sulfonamides possessing a free amino/imino/hydrazino/hydroxy group afforded mono- and bis-sulfonamides containing polyamino-polycarboxylic acid moieties in their molecule. The acids/anhydrides used in synthesis included IDA, NTA, EDDA, EDTA and EDTA dianhydride, DTPA and DTPA dianhydride, EGTA and EGTA dianhydride, and EDDHA, among others. All the newly prepared derivatives showed strong affinity toward isozymes I, II, and IV of carbonic anhydrase (CA). Metal complexes of the new compounds have also been prepared. Metal ions used in such preparations included di- and trivalent main-group and transition cations, such as Zn(II), Cu(II), Al(III), etc. Some of the new sulfonamides/disulfonamides obtained in this way, as well as their metal complexes, behaved as nanomolar CA inhibitors against isozymes II and IV, being slightly less effective in inhibiting isozyme I. Some of these sulfonamides as well as their metal complexes strongly lowered intraocular pressure (IOP) when applied topically, directly into the normotensive/glaucomatous rabbit eye, as 1-2% water solutions/suspensions. The good water solubility of these sulfonamide CA inhibitors, correlated with the neutral pH of their water solutions used in the ophthalmologic applications and the long duration of action of the IOP-lowering effect, makes them interesting candidates for developing novel types of antiglaucoma drugs devoid of serious topical side effects.

Paper chromatography of hafnium complexes

Complexes of Hf with polyaminopolycarboxylic acids viz. diethylene-triamine-penta-acetic acid (DTPA) and its dimethoxy derivative DMDTPA have been studied using paper chromatography at different acidities. Kinetic stabilities of the complexes have also been looked at. Behaviors of these two ligands in complexing with Hf(IV) have been found to be similar. The extent of complexation reduces slowly with acidity and increase with time and reaches a maximum around 70-80% after about 24 hours.

In vitro and in vivo studies on chelation of manganese.

This work deals with new chelating agents of manganese (Mn). Out of 24 compounds chosen for their chemical structure supposed to be favorable for Mn complexation, six polyaminopolycarboxylic acids proved to be efficient for displacing Mn bound to serum bovine proteins in vitro: TTHA, DTPA, DPTA, DPTA-OH, HBED, EDTA (mobilization > or =50%). The first five compounds were then tested in vivo on rats pretreated with MnCl2. They exhibited only slight to moderate efficacy to diminish Mn in tissues and were ineffective on increased Mn concentration in whole blood; in addition, they had different and specific mobilizing effects on other essential elements (Fe, Zn, Cu). Their limited efficacy in vivo could be due to the formation of very stable complexes between Mn2+ and different molecules such as hemoglobin and certain cytochromes, instead of Fe2+. This could disturb the functioning of the cellular respiratory chain, leading to an incomplete reduction of O2 with formation of free oxygenated radicals, reduction in the energy supply, and disturbance of the cytochromes renewal mechanism. All of these phenomena could accelerate cellular aging and explain the lack of efficacy of the chelating agents towards Mn neurotoxicity (Parkinson's syndrome).

Determination of the solubility products of nitrilotriacetic acid, ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid

A method is described for the determination of solubility products for polyaminopolycarboxylic acids. The neutral protonated species of NTA (nitrilotriacetic acid), EDTA (ethylenediaminetetraacetic acid) and DTPA (diethylenetriaminepentaacetic acid) were precipitated at low pH values. The amount of precipitate was quantified by gravimetry and complexometric titrations with a standard zinc(II) solution. The following solubility products were obtained: S H 3NTA =10 −16.36, S H 4EDTA =10 −24.66 and S H 5DTPA =10 −30.43. Those values were used for theoretical calculation and optimization of the precipitation processes of NTA, EDTA and DTPA at different pH values in the absence and presence of the metal ions Fe 3+ and Mn 2+.

Capillary zone electrophoretic and micellar electrokinetic capillary chromatographic separations of polyaminopolycarboxylic acids as their copper complexes

Capillary zone electrophoretic (CZE) and micellar electrokinetic capillary chromatographic (MECC) separations with UV absorbance detection at 290 nm were developed for separation and detection of the negatively-charged copper complexes of the polyaminopolycarboxylic acids. A standard mixture that contained ethylenediaminetetraacetic (EDTA), nitrilotriacetic (NTA), ethylenediaminetriacetic (ED3A), diethylenetriaminepentaacetic (DPTA) and hydroxyethylenediaminetriacetic (HEDTA) acids was utilized to demonstrate these separation methods. MECC techniques were performed with either cationic (cetyltrimethylammonium bromide, CTAB) or anionic (sodium dodecyl sulfate, SDS) surfactants. All three separation techniques achieved separation of the standard components with baseline resolution. A fast separation (7.5 min) was obtained with CTAB surfactant that provided a detection limit of 38 pg for HEDTA. The cationic micellar strategy was also extended to separations of mixed-metal EDTA complexes.

Capillary electrophoresis in speciation analysis. Investigations of metal-polyaminopolycarboxylate complexes and effects of metals on proteins

Model substances of metal species composed of organic ligands and heavy metals were separated and detected by capillary electrophoresis. The effect of metal addition to polyaminopolycarboxylic acids on their electrophoretic mobility was studied. Metal-ligand complexation reactions changed the mobilities of polyaminopolycarboxylic acids which decreased their migration times (with the exception of nitrilotriacetic acid) and increased detection sensitivities. The separation time is less than 10 min. The use of this type of reaction in metal-protein speciation is described and demonstrated with both model protein mixtures and cereal protein extracts, based on studies of 11 metal ions.

Isoelectric focusing of proteins in ultra-thin polyacrylamide gels.

Isoelectric focusing (IEF) is an electrophoretic method for the separation of proteins, according to their isoelectric points (pI), in a stabilized pH gradient. The method involves casting a layer of support media (usually a polyacrylamide gel but agarose can also be used) containing a mixture of carrier ampholytes (low-mol-wt synthetic polyamino-polycarboxylic acids). When an electric field is applied across such a gel, the carrier ampholytes arrange themselves in order of increasing pi from the anode to the cathode. Each carrier ampholyte maintains a local pH corresponding to its pi and thus a uniform pH gradient is created across the gel. If a protein sample is applied to the surface of the gel, it will also migrate under the influence of the electric field until it reaches the region of the gradient where the pH corresponds to its isoelectric point. At this pH, the protein will have no net charge and will therefore become stationary at this point. Should the protein diffuse slightly toward the anode from this point, it will gain a weak positive charge and migrate back to its position of zero charge. Similarly diffusion toward the cathode results in a weak negative charge that will direct the protein back to the same position. The protein is therefore trapped or “focused” at the pH value where it has zero charge.

Separation of scandium(III) and lanthanides(III) by polyaminopolycarboxylic acids using the capillary tube isotachophoretic method

The separation of scandium(III) and lanthanides(III) by polyaminopolycarboxylic acids (EDTA, DTPA, TTHA and TPHA) is described. The satisfactory separation of scandium from lathanides in an acetone-water medium (50%, v/v) was accomplished using 10 mM (M = mol dm −3) citric acid and 3 mM Na 2EDTA as the terminating electrolyte with the leading solution containing 5 mM hydrochloric acid, buffered (pH 2.6) 3 mM β-alanine and hydroxypropyl methyl cellulose (additive). The migration order with the EDTA complexes was in accord with the order of increasing stability constant ( K f). The migration order was Sc > Gd > Eu > Sm > Nd > La. When TPHA was used, separation of scandium from dysprosium, gadolinium, neodymium and lanthanum but not from europium and samarium was accomplished.

Kinetics of zinc and cadmium dissociation of metallothionein in the presence of chelating agents

AbstractThe dissociation kinetics of metal ions from native metallothionein (Cd5Zn2‐MT) of rat liver has been studied in the presence of external ligands including amino acids, peptide and polyamino polycarboxylic acids at 25°C. The study shows that the solution pH affects the metal dissociation process. Different ligands present different multiphasic kinetics. The possible mechanism of metal dissociation from metallothionein has been proposed.

Coordination of Copper(II) to Polyaminopolycarboxylic Acids in Aqueous Solution

Abstract The formation of copper(II) complexes in aqueous solution has been followed by EPR and electronic absorption spectroscopy for a series of polyaminopolycarboxylic ligands, namely ethylenediaminotetra-acetic (EDTA), N-(2-hydroxyethyl)ethylenediamino-N,N′,N′-triacetic (HEDTA), ethylenediaminodiacetic (EDDA), iminodiacetic (IDA), and nitrilotriacetic (NTA) acids. The species in complex formation have been identified and structures proposed by previous studies have been examined and discussed on the basis of the spectroscopic data.

Capillary isotachophoretic determinations of metal ions by use of complexation equilibria in acetone—water medium

The determination of metal ions by capillary isotachophoresis and the complexation equilibria between metal ions and polyaminopolycarboxylic acids has been investigated. A seven-component mixture of metal ions can be separated in 45% v/v acetone—water medium when EDTA or DCTA is used as the terminating ion. Linear calibration graphs are obtained for a standard mixture of Mn +, Cu 2+, Zn 2+, Cd 2+, Pb 2+ and Fe 3+ in the range 0.5–5.0 nmole, with relative standard deviations of 1.0% or better. The effective mobilities of the Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes increase in parallel with the stability constants, except for the Cu(II) complexes. It is concluded that the abnormal behaviour of the Cu(II) complexes may be attributed to a difference in steric configuration.

Isotachophoretic separation of trivalent metal complexes of some polyaminopolycarboxylic acids in acetone-water solvent

The isotachophoretic separation of trivalent metal complexes of some polyaminopolycarboxylic acids in acetone-water solvent has been carried out. The variation of the qualitative index, RE, obtained by analysis of the isotachopherograms resulted in a classification into two groups: FeIII, CoIII, InIII and BiIII complexes, and AlIII, CrIII and GaIII complexes. The satisfactory separation of trivalent metal ions was accomplished by employing a polyaminopolycarboxylic acid as the terminating electrolyte. Linear calibration graphs were obtained in the range 2 × 10–5–2 × 10–4 mol dm–3, the injection volume being kept constant at 25 µl.