H₄octapa: Highly Stable Complexation of Lanthanide(III) Ions and Copper(II)

Abstract

The acyclic ligand octapa 4− (H 4 octapa = 6,6′-((ethane-1,2-diylbis((carboxymethyl)azanediyl))bis-(methylene))dipicolinic acid) forms stable complexes with the Ln 3+ ions in aqueous solution. The stability constants determined for the complexes with La 3+ , Gd 3+ , and Lu 3+ using relaxometric methods are log K LaL = 20.13(7), log K GdL = 20.23(4), and log K LuL = 20.49(5) (I = 0.15 M NaCl). High stability constants were also determined for the complexes formed with divalent metal ions such as Zn 2+ and Cu 2+ (log K ZnL = 18.91(3) and log K CuL = 22.08 (2)). UV− visible and NMR spectroscopic studies and density functional theory (DFT) calculations point to hexadentate binding of the ligand to Zn 2+ and Cu 2+, the donor atoms of the acetate groups of the ligand remaining uncoordinated. The complexes formed with the Ln 3+ ions are nine-coordinated thanks to the octadentate binding of the ligand and the presence of a coordinated water molecule. The stability constants of the complexes formed with the Ln 3+ ions do not change significantly across the lanthanide series. A DFT investigation shows that this is the result of a subtle balance between the increased binding energies across the 4f period, which contribute to an increasing complex stability, and the parallel increase of the absolute values of the hydration free energies of the Ln 3+ ions. In the case of the [Ln(octapa)(H 2 O)] − complexes the interaction between the amine nitrogen atoms of the ligand and the Ln 3+ ions is weakened along the lanthanide series, and therefore the increased electrostatic interaction does not overcome the increasing hydration energies. A detailed kinetic study of the dissociation of the [Gd(octapa)(H 2 O)]− complex in the presence of Cu 2+ shows that the metal-assisted pathway is the main responsible for complex dissociation at pH 7.4 and physiological [Cu 2+ ] concentration (1 μM).

Influence of a Pre‐organized N‐Donor Group on the Coordination of Trivalent Actinides and Lanthanides by an Aminopolycarboxylate Complexant

“…The p K 7 value is also lower than the p K 8 value of DTPA and DTTA‐BuA (amide‐substituted DTPA) . This may indicate that the initial protonation occurs on the central amine, and is inhibited by the electron‐withdrawing influence of the picolinate group, as previously shown in the literature . Alternatively, the initial amine protonation may occur at the terminal iminodiacetate end, as implied by the results reported by Phukan et al .…”

“…Structures with variable denticity and nature of the substituents adhere to this linear relationship, including ligands recently investigated by our group . Figure shows a consistent departure from this linearity when the aminopolycarboxylate reagents contain pre‐organized motifs …”

“…In order of increasing chelate stability, the complexants adhering to the linear relationship are: (1) nitrilotriacetate, (2) ethylenediamine‐ N , N′ ‐di(acetylglycine)‐ N , N′ ‐diacetate, (3) N ‐hydroxyethane‐ N , N′ , N′ ‐triacetate, (4) ethylenediamine‐ N , N , N′ , N′ ‐tetraacetate, (5) diethylenetriamine‐ N , N′′ ‐di(acetylglycine)‐ N , N′ , N′′ ‐triacetate, (6) N ‐butyl‐2‐acetamide‐diethylenetriamine‐ N , N′ , N′′ , N′′ ‐tetraacetic acid, (7) diethylenetriamine‐ N , N , N′ , N′′ , N′′ ‐pentaacetic acid . Rigid complexants deviating from the linear correlation are: N ‐2‐methylpicolinate‐ethylenediamine‐ N , N′ , N′ ‐triacetic acid (EDTA‐Mpic), trans ‐1,2‐diaminocyclohexane‐ N , N , N′ , N′ ‐tetraacetate (CDTA), 4‐azido‐2,6‐{[bis(ethylcarboxymethyl)amino]methyl}pyridine (Py), N , N′ ‐bis(2‐methylpicolinate)‐ethylenediamine‐ N , N′ ‐diacetic acid (H 4 octapa), and 1,4,7,10‐tetraazacyclodecane (H 4 dota) …”

“…Accordingly, no migration of the first proton associated with the central amine site of EDTA‐Mpic occurs, and the acidity of the second proton is increased. The third protonation equilibrium, p K 5 , occurs on the pyridine nitrogen, rendered more acidic by the electron‐withdrawing substituents . The two lowest acid dissociation constants, p K 4 and p K 3 , describe the protonation of the carboxylate sites.…”

Pyclen-Based Ligands Bearing Pendant Picolinate Arms for Gadolinium Complexation

“…Different open-chain octadentate ligands were found to form very stable complexes with the Ln(III) ions, 10 though they generally yield fast dissociation kinetics. 11 The lability of the complexes can be alleviated by ligand rigidification, yet macrocyclic ligands often form, in return, more inert complexes. 12 The incorporation of picolinate groups also increase the macrocyclic rigidity and their insertion to crown ethers of different sizes was found to be a very robust approach to enhance the selectivity of the ligand to certain Ln(III) ions.…”