1,4,7‐Triazacyclononane‐Based Bifunctional Picolinate Ligands for Efficient Copper Complexation

Abstract

International audienceThree 1,4,7-triazacyclononane-based (tacn-based) ligands containing picolyl and picolinate pendant arms (no3py, no2pa1py, and no3pa) were synthesized, and their copper(II) complexation properties were studied to evaluate their potentials as chelators for copper radioisotopes. The thermodynamic stability constants of the complexes were determined by potentiometric titrations. These studies evidenced the formation of mononuclear species for no3py and mono- and dinuclear species for no2pa1py and no3pa. The pCu values decreased as the number of carboxypicolyl arms increased. The [Cu(no3py)]2+ complex presented a very high stability constant (log KCuL = 27.4) and a very high selectivity towards Zn2+ ions (log KZnL = 17.25). Vis/NIR (NIR = near-infrared) absorption and electron paramagnetic resonance (EPR) spectroscopy indicated that the three complexes present distorted octahedral geometries with two paramagnetic species, which were identified as the Δ(δδδ) and Λ(δδδ) isomers [and their corresponding enantiomeric forms Λ(λλλ) and Δ(λλλ)] by DFT calculations. The electrochemical properties were investigated by cyclic voltammetry, which revealed quasireversible behavior for the [Cu(no3py)]2+ complex but irreversible Cu2+/Cu+ systems for [Cu(no2pa1py)] and [Cu(no3pa)]–

Comparative Study of Macrocyclic and Acyclic Picolinate Derivatives for Chelation of Copper Cations

“…The treatment of the data obtained with the HypSpec software taking into account the data for 1 : 1 species from potentiometric titration confirmed the formation of Cu 2 L form with logβ(Cu 2 L) = 21.4 � 0.1. This situation is similar to complex formation of picolinate analog of NOTA -no3pa [32] (Scheme 1) with copper: in acidic pH range Cu 2 L can be identified. Moreover the overall constant logβ(Cu 2 no3pa) = 21.3 is almost equal to the value for Cu 2 L2, that can be attributed to the structural similarity between L2 and no3pa.…”

Is Less More? Influence of the Coordination Geometry of Copper(II) Picolinate Chelate Complexes on Metabolic Stability

“…Similar picolinate binding modes were also observed by Tripier and co-workers in their modeling studies of the mixed picolinate−picolyl triazacyclononane systems Cu(NO3PA) − , Cu(NO2PA1PY), and Cu(NO1PA2PY) + . 43 The base of the square pyramid is comprised of three nitrogen donors [N(2), N(3), and N( 4 The introduction of two pendant acetate arms presents several potential structures for [Cu(mpatcn)] − . Geometry optimization of [Cu(mpatcn)] − revealed two low-energy axially distorted six-coordinate structures that differed by ∼1.1 kcal mol −1 (Figure 5C).…”

A Bispidol Chelator with a Phosphonate Pendant Arm: Synthesis, Cu(II) Complexation, and 64Cu Labeling

“…NOTA 35,36 and TETA 37,38,39 and their derivatives are easily accessible but often suffer from low kinetic inertness. Variations of the substituent are being explored in order to improve the in vivo stability of the Cu complexes (see HTE1PA, 40,41,42,43 NO1PA2PY 44 and its derivatives, 45 Chart 2). Very stable and inert cyclen-based cross-bridged systems (such as PycupBn 46 and CB-TE2A, 47 Chart 2) and macrobicycles such as L 7 48 are being developed but their slow kinetic of complexation is hampering their use for the labeling of antibodies.…”