Synthesis and NMR Studies of Three Pyridine-Containing Triaza Macrocyclic Triacetate Ligands and Their Complexes with Lanthanide Ions

Abstract

The synthesis of three triazamacrocycles containing the pyridine moiety and three acetate pendant arms (PCTA) is reported. The three systems differ due to the number of carbon atoms in the macrocyclic ring forming ligands PCTA-[12], -[13], and -[14], endowed with different coordination capabilities toward lanthanide(III) ions. Microscopic protonation sequences for the three ligands have been investigated by (1)H NMR spectroscopy. Complexes of PCTA-[12], -[13], and -[14] with La(III), Gd(III), and Lu(III) have been prepared. Relaxometric measurements on the aqueous solutions of the paramagnetic Gd(III) complexes in the presence of competitive ligands gave the following stability constants: log K(f) = 20.8 for Gd-PCTA-[12], log K(f) = 19.3 for GdPCTA-[13], and log K(f) = 12.5 for GdPCTA-[14]. The measurement of water relaxation rates indicated a tendency to decrease the degree of hydration upon increasing the ring size. The VT (1)H and (13)C-NMR spectra of the diamagnetic La(III) and Lu(III) complexes exhibit a large variability of the solution structures dictated by the matching of the size of the lanthanide ion and the macrocyclic cavity. This results in noticeable differences in their stereochemical nonrigidity, hydration state, and thermodynamic stability. To some extent the changes observed in continuing from the 12-14-membered ring macrocyclic complexes parallels the behaviors shown by the octacoordinated lanthanide(III) complexes with DOTA and TETA. GdPCTA-[12] and -[13] feature promising properties in view of their possible use as contrast agents for magnetic resonance imaging.

Henry reaction catalyzed by copper(I) complexes of a new pyridine‐containing macrocyclic ligand

“…[8] By reacting 2 with the commercially available 2,6-bis(chloromethyl) pyridine in refluxing anhydrous MeCN in the presence of anhydrous K 2 CO 3 , the macrocycle 1 was obtained in 85% yield after purification. The experimental conditions adopted here represent a modification [9] of the Richman-Atkins protocol. Crystals suitable for an X-ray structural determination were obtained by crystallization of 1 from a dichloromethane-toluene solution (Fig.…”

Impact of rigidification on relaxometric properties of a tricyclic tetraazatriacetic gadolinium chelate

“…Nevertheless, the fitted value of t M 310 is smaller for Gd-cyclo-PCTA12 (34 ns), indicating that the rigidification and consequently the crowding of the ligand around the gadolinium induced a shortening of the residence lifetime of the inner-sphere water (14,15). It is worth mentioning that the introduction of the pyridine moiety in the macrocycle skeleton already resulted in a first shortening of the residence lifetime of the inner-sphere water, as demonstrated by comparing the t M value of two q ¼ 2 complexes, Gd-DO3A (t M 298 ¼ 160 ns) and Gd-PCTA12 (t M 298 ¼ 70 ns) (24), and that the introduction of a second cycle induces a further shortening of the residence lifetime of the inner-sphere water, probably by elongating of the Gd-H 2 O bond. A theoretical calculation based on the Solomon-Bloembergen-Morgan theory of paramagnetic relaxation has shown that the optimal residence lifetime of the inner-sphere water to attain the highest relaxivities is around few tenths of a nanosecond (2).…”

“…It is generally assumed that this improvement is due to the presence of two water molecules (q ¼ 2) in the inner sphere as demonstrated by relaxivity study, variable-temperature NMR studies of the lanthanum and lutetium complexes (24,25) and luminescence lifetime measurement of europium and terbium complexes (25). Although PCTA12 is a heptadentate macrocyclic ligand, its gadolinium complex is characterized by a high thermodynamic stability (logK Gd 3þ ¼ 20.8) (25).…”

Modulation of the Prototropic Exchange Rate at the Water Molecule Coordinated to a GdIII Ion

“…III Complexes: The general procedure for the synthesis of the gadolinium complexes consists of the addition of equimolar amounts of the corresponding ligand (2 mmol) and GdCl 3 ·6H 2 O (2 mmol) in deionized water (20 cm 3 ), followed by adjustment of the pH to 6.0 by adding KOH.…”