Metal – Aminopolycarboxylic Acid Complexes. II. Studies of Triethylenetetraaminehexaacetic Acid and its Lead(II) Complexes in Aqueous Solution by Proton Magnetic Resonance Spectroscopy

Abstract

Nuclear magnetic resonance (n.m.r.) spectroscopy was used to determine the preferred protonation sites in TTHA. For its 1 :1 complex with PbOI) the following equilibrium constants for protonation were obtained (triethylenetetraaminehexaacetic acid = H6A)The non-protonated complex is considered to have four coplanar (or nearly coplanar) metal-nitrogen bonds with the center carboxylate groups coordinated above and below this plane, and with the terminal carboxylate groups playing only a small part in the coordinate bonding. The first and second protonations of the complex occur preferentially at the terminal and center nitrogen atoms, respectively, on the same side of the complex, accompanied by breaking of the respective metal-nitrogen bonds. This causes partial unwrapping of the complex from one side. Rapid interconversion between configurations in which unwrapping and rewrapping occurs first from one side of the molecule and then from the other leads to simplified n.m.r. spectra.La spectroscopie r.m.n. a 6td utilis6e pour determiner les sites prkfdrentiels de protonation dans le TTHA. Dans le cas d'une complexation 1 :1 avec le Pb(I1) les constantes d'dquilibre suivantes ont ttd obtenues pour la protonation (acide tri6thylenetdtraamineh6xaacdtique = H6A) PbA4-+ H + e PbHA3-log K = 8.25 + 0.2 PbHA3-+ H + PbH2A2-log K = 4.25 i-0.25Dans le complexe non protone, on considere que les quatre liaisons mdtal-azote sont coplanaires (ou presque coplanaires), que les groupes carboxylates centraux sont coordonnds au-dessus et en dessous du plan et que les groupes carboxylates terminaux n'interviennent que trks peu dans les liaisons coordonn6es. La premiere et la seconde protonation du complexe se font prdf6rentiellement et respectivement sur les atomes d'azote terminaux et centraux et sur le meme c6td du complexe provoquant ainsi la rupture respective des liaisons metal-azote. Ceci provoque un ddroulenient du complexe i partir d'un cdtC. L'interconversion rapide entre les configurations ou I'enroulement et le dCroulement sefait d'abord d'un c6td de la molkule puis de I'autre, conduit i simplifier les spectres r.m.n.

An nmr protonation study of metal diethylenetriaminepentaacetic acid complexes: An integrated senior chemistry experiment

“…Fortunately the literature (10)(11)(12) is consistent in labelling the non-labile protons of the anion of DTPA as follows where one expects singlets for (a) and (d) protons in the ratio of 4:1 and an AsB, pattern for the spin-coupled (b) and (c) protons as shown in Figure 1. If the experiment is performed in aqueous solutions then the resonance signals of the ionizable protons will merge with the water proton signal due to rapid exchange and the pmr spectra will indicate changes in the chemical environment surrounding the non-labile methylene protons.…”

“…As one adds acid to the fully basic form of DTPA, each site (carboxyls and nitrogens) is protonated for a certain average fraction of the time at any given pH. The pmr spectra indicate that the methylenic protons (type a, b, c, and d) are deshielded by protonation of a nearby basic site and by an amount which depends upon the nature of the basic site, its proximity to the particular methylene protons, and the fraction of time protonated (10)(11)(12)(13)(14). Since there are three basic nitrogen sites, two of which are equivalent by symmetry, a student might ask readily which sites are protonated at one, two, and three equivalents of acid per equivalent of the basic DTPA anion.…”

“…~,>B «Awhere i refers to the various donor sites, for example, two different nitrogen atoms and two different carboxyl groups. In this paper only the nitrogen donor sites will be considered since it does become somewhat complicated to bring in the carboxylate protonation as well (11,13). It is well known by now that the nitrogen sites are more basic than the carboxyl sites especially at pH's above 4. In following the chemical shifts of a particular signal one finds a point of inflection where 5 = 1/2(5a + 5b) or where the concentrations of the protonated and non-protonated forms are equal.…”

Determination of microscopic acid?base parameters from NMR?pH titrations

“…Fractional protonation of the "polyamine backbone" nitrogens has been determined by 1 H NMR titration for higher complexone homologues as triethylenetetraminehexaacetate (TTHA) [173] and its bis-butylamides as potential radiopharmaceuticals [168,169], tetraethylenepentamineheptaacetate (TPHA), and pentaethylenehexamineoctaacetate (PHOA) [173]. The protonation sequence is determined by the same factors as for DTPA discussed above.…”

“…The proton population of nitrogens is determined mainly by minimizing coulombic repulsion between neighboring NH + groups and by maximizing the hydrogen-bonded rings involving terminal carboxylates. Site-specific protonation can usually be assessed with a pH-independent set of C shielding constants, although small modifications to C coefficients proposed originally by Sudmeier and Reilly become necessary for higher homologues [173]. 1 H NMR-pH titration curves and protonation sequences of EDTA and ethylenediaminetetrakis(methylenephosphonate) (15) are very similar, albeit the nitrogens in the latter are approximately 3 log units more basic due to the double negative charge of phosphonate groups [174].…”