Nuclear magnetic resonance and potentiometric studies of the protonation scheme of a triaza triacetic macrocycle and its complexes with lanthanum and lutetium

Abstract

The protonation constants of the macrocyclic ligand 1,4,7-triazacyclononane-N,N',N"-triacetic acid (NOTA) have been measured by potentiometry, and the protonation sequence of the various amino and carboxylate groups of NOTA has been studied in DzO as a function of pD from the chemical shifts of the nonlabile protons. Shielding constants for protonation of the amino groups were determined in a NMR study of the triaza macrocyclic amine, its trimethylated analogue, and NOTA and compared with values reported for linear polyamino polycarboxylates and cyclic tetraaza tetracarboxylate ligands. The results indicate that two nitrogens of NOTA are protonated at higher pH than the carboxylate groups. The last nitrogen is protonated only at very low pH. The sequence of protonation of NOTA supports the formation of hydrogen bonds between two protonated nitrogens and the adjacent two nonprotonated carboxylates. The 'H and I3C spectra of the La(N0TA) and Lu(N0TA) species were studied as a function of pH and temperature. The aqueous complexes show spectra characteristic of flexible triaza macrocycles, displaying fast interconversion between the two staggered 6 and X conformations of the ethylenediamine rings even at room temperature. Above pH 9.5, the La(N0TA) and Lu(N0TA) hydroxo complexes start to form and their spectra show evidence of greater rigidity as at room temperature the 6/X ethylenediamine ring conformational interconversions in the Lu(N0TA) hydroxo complex are slow on the NMR time scale.Current interest in the complexation properties of macrocycles showing remarkable cation-binding selectivity' has led to the synthesis and study of a large number of new macrocycles derived from cyclic polyaza and cyclic polyaza polyoxa ligands with ionizable functions such as @-diketonate,z d i p h e n o l~,~ or carboxylate groups.e7 Some of these macrocycles should be very useful as models of certain biological systems and as possible reagents for complexometric titrations. Increased selectivity to cation complexation should also be achieved by these ligands because of the combined effects of internal cavity size, rigidity, and nature of donor atoms and of pH-selective coordinating groups.The purpose of the present work is twofold. First, the protonation constants and the protonation scheme of the macrocyclic triaza ligand 1,4,7-triazacyclononane-N,N',N''-triacetic acid (1, NOTA) were obtained with use of potentiometric titrations and IH NMR pH titrations. To help interpret the NOTA NMR results, we also studied the cyclic triamine 2 and the N-methylated triaza macrocycle 3. The protonation shifts measured for these cyclic amines were used in a quantitative study of the proton distribution at the various basic sites of NOTA. The conclusions obtained for NOTA were compared with results for noncyclic polyamino polyacetic acidss-10 and for the cyclic tetraaza ligands 1,4~7,10-tetraazacyclododecane-N,N',N'',N"'-tetraacetic acid (DOTA) and 1,4,8,11 -tetraazacyclotetradecane-N,N',N'',N"'-tetraacetic acid (TETA).6,7-'1 The quantitative ...

Synthesis and Iron Sequestration Equilibria of Novel Exocyclic 3-Hydroxy-2-pyridinone Donor Group Siderophore Mimics

“…pK a1 and pK a5 correspond to the central ring system and are significantly separated due to electrostatic repulsion. 59 The third proton on the central ring has a pK a too low to be observed, also due to steric interactions and electrostatic repulsion from the 2+ doubly protonated ring system. As with the bishydroxypyridinone chelators, it is not possible to make an unambiguous assignment of protonation constants pK a2 , pK a3 , and pK a4 of the N 3 (etLH) 3 HOPO donor groups.…”

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

“…Protonation sequences of N-methylated cyclic polyamines have been derived from 1 H NMR titration data [179,180,181,182,183]. Linewidth variations of methylenic protons as a function of pH have also been observed for methylated cyclic triamines, caused by slow interconversion of various conformations of the partially protonated ring [179].…”

“…Here again, characteristic points of the 1 H NMR titration curve of the cyclic polyaminocarboxylate under study can help deriving C j,N coefficients [52,179,186], which often turn out to be pH-dependent [52,180,185]. In triaza, oxatriaza, and tetraaza macrocycles, the first two associating protons attach to ring nitrogens to form hydrogen bonds with pendant carboxylates.…”

“…In triaza, oxatriaza, and tetraaza macrocycles, the first two associating protons attach to ring nitrogens to form hydrogen bonds with pendant carboxylates. The subsequent acid equivalents protonate almost exclusively those carboxylates that are not involved in such hydrogen bonds and the remaining ring nitrogens protonate only in strong acidic medium [52,178,179,180,185,187,188]. Thus, internal hydrogen bonds connecting the ammonium and the side chain carboxylate groups act as additional key factors to determine protonation sequences [186,187,188,189,190], to cause protonation shift anomalies [52,179], to indicate redistribution of protons [190], to make C j,N coefficients pH-dependent [185], or to slow down the inversion of asymmetrically positioned nitrogen atoms [179].…”

Synthesis, structure and superoxide dismutase activity of a novel tetranuclear copper(II) complex Na2[Cu4Na2(TACNTA)4(H2O)6]·(H2O)26

“…The ligand 1,4,7-triazacyclononane-1,4,7-triacetate (TACNTA) was first synthesized by Takahashi and Takamoto [19] and able to coordinate with transition metals to form stable complexes [19][20][21]. Different crystal structures of Cu(II) complexes (Na[Cu(TACNTA)]· 2NaBr·8H 2 O, CuCl(TACNTAH 2 )) were also reported [22,23], indicative of the strong binding of TACNTA to Cu(II) ions.…”