Expanding the Family of Pyclen-Based Ligands Bearing Pendant Picolinate Arms for Lanthanide Complexation

Abstract

We report a detailed characterization of lanthanide complexes with two azaligands based on the pyclen macrocycle containing two picolinate and one acetate pendant arms. The two picolinate arms are attached to either opposite (L3) or adjacent (L4) amine nitrogen atoms of the macrocyclic platform. The X-ray structures of the Yb complexes show nine coordination of the ligand to the metal ion, a situation that is also observed for EuL4 in the solid state. The EuL3 complex forms centrosymmetric dimers in the solid state joined by μ-η:η carboxylate groups, which results in 10-coordinate Eu ions. The emission spectra of EuL3 measured in HO and DO solution reveal the presence of a hydration equilibrium involving a nine-coordinate species lacking inner-sphere water molecules and a monohydrated 10-coordinate species. The Eu complexes present modest emission quantum yields in buffered aqueous solution (Φ = 16 and 22% for EuL3 and EuL4, 0.1 M tris buffer, pH 7.4), while the corresponding Tb complexes present very high emission quantum yields under the same conditions (∼90%). H NMR studies show that the complexes of L3 present a fluxional behavior in DO solution, while those of L4 are more rigid. The analysis of the Yb-induced NMR shifts of YbL4 indicates that the complex presents a structure in solution similar to that observed in the solid state. The Gd complexes present very high thermodynamic stability constants (log K = 23.56(2) and 23.44(2) for GdL3 and GdL4, respectively). The corresponding pGd values (pGd = -log[Gd] with c = 1 × 10 M and c = 1 × 10 at pH 7.4) of 20.69 (GdL3) and 21.83 (GdL4) are higher than that of Gd(dota) (pGd = 19.21). The Gd complexes also show remarkable inertness with respect to their proton-assisted dissociation, with dissociation half-life times of 50 min (GdL3) and 20 h (GdL4) in 1 M HCl.

A novel DOTA-like building block with a picolinate arm for the synthesis of lanthanide complex-peptide conjugates with improved luminescence properties

“…Hence, due to the DO3Apic chelate, LZF4 ACD|Eu allows ratiometric detection of Zn 2+ upon double wavelength excitation at 402 nm (responsive channel) and 283 nm (selfcalibration channel). Comparatively, Φ Eu pic is lower than the values reported for nonadentate Eu 3+ complexes with picolinate arms such as DO3Apic chelators (9-24%) [69] or other recently described pyclen-based chelators (23-38%) [92]. In the case of LZF4 ACD|Eu , selective excitation of the picolinamide chromophore cannot be achieved due to the overlap of its absorption and that of the acridone chromophore.…”

Ligand design strategies to increase stability of gadolinium-based magnetic resonance imaging contrast agents

“…The introduction of pyridine into the ligand backbone was expected to rigidify this ligand, compensating for any potential reduction in thermodynamic stability or kinetic inertness associated with the reduction in denticity 93 . Indeed, the reported range of log K values for the [Gd(OH 2 ) 2 (pcta)] complex was from 18.3 to 21.0, indicating comparable thermodynamic stability to the Gd 3+ complexes of the octadentate ligands H 5 dtpa and H 4 cdta 93–95 . H 3 pcta also exhibited promising complex formation kinetics: the pyridine moiety introduces an additional degree of pre-organisation into the macrocyclic ring, resulting in formation rates of Ln 3+ species that are an order of magnitude greater than those of H 4 dota 94 .…”

“…However, it was only stable above pH 3 97 . More recently, Le Fur et al have had success with the substitution of H 3 pcta’s acetic acid donor groups for picolinic acid 95,98 . Picolinic acid moieties are bidentate, and the synthesis of octadentate and nonadentate H 3 pcta derivatives incorporating this functionality have been reported.…”

The Use of the Macrocyclic Chelator DOTA in Radiochemical Separations

“…The k OH values of the Ln III complexes formed with DOTA derivatives possessing mixed carboxylate‐phosphonate pendant arms decrease with the gradual replacement of the carboxylate arms by the phosphonate groups, which can be explained by the stabilization of the # Ln(H 2 L) intermediate due to the higher negative charge on the pendant arm. The kinetic studies of PCTA‐like complexes possessing with mixed carboxylate and picolinate side chains reveal that the formation rates of the Ln III complexes with the non‐symmetric monoacetate ‐ dipicolinate and monopicolinate ‐ diacetate derivatives is significantly faster than the formation rates of the complexes of symmetrical regioisomers . These findings were explained in terms of labile capping bond effect in lanthanide complexes.…”

“…The dissociation rate of Ln III complexes with octadentate DOTA derivatives are slower than those of the heptadentate DO3A and PCTA complexes due to the easy protonation on the secondary and pyridine nitrogen of DO3A and PCTA ligand than on the tertiary nitrogen of DOTA ,. [59a], On the other hand, the kinetic studies on PCTA‐like complexes with mixed carboxylate‐picolinate side chains reveal that the acid‐catalyzed dissociation of the Gd III complexes with the non‐symmetric and symmetric monoacetate ‐ dipicolinate pendants are significantly slower than the complexes formed with the non‐symmetric and symmetric monopicolinate ‐ diacetate regioisomers . The replacement of the carboxylate group by the weaker coordinating –OH group results in the lower kinetic inertness of the [Gd(BT‐DO3A)] and [Gd(HP‐DO3A)] complexes.…”