Synthesis and structural characterization of novel cyclam-based zirconium complexes and their use in the controlled ROP of rac-lactide: access to cyclam-functionalized polylactide materials

Abstract

Novel Bn(2)Cyclam-based zirconium complexes of the type (Bn(2)Cyclam)Zr(X)(X') (3, X = X' = OPh; 4, X = X' = SPh; 5, X = Cl, X' = O(i)Pr) were synthesized in good yields via metathesis routes involving the reaction of the dichloro precursor (Bn(2)Cyclam)Zr(Cl)(2) and the appropriate lithium salts. The molecular structures of compounds 3, 4 and 5, as determined by X-ray crystallographic studies, all confirmed the effective chelation of the Bn(2)Cyclam ligand in a κ(4)-N(2)N(2)' fashion, with the hexa-coordinated Zr center adopting a trigonal prismatic geometry. Complexes 3-5 as well as the diisopropoxide derivative (Bn(2)Cyclam)Zr(O(i)Pr)(2) (2) were all found to initiate the ring-opening polymerization (ROP) of rac-lactide in a controlled manner, as deduced from SEC data and linear correlations between molecular weight numbers (M(n)) and monomer conversion as the ROP proceeds. While initiator 2 polymerizes rac-lactide to afford, as expected, an O(i)Pr-ester-end PLA, the ROP of rac-lactide by species 3 or 4 affords an unusual cyclam-end group PLA, as deduced from MALDI-TOF data. The bonding and the electronic structures of the dialkoxides 2 and 3 were assessed by DFT and their possible influence on the polymerization mechanism is discussed.

Recent Advances in Zirconium-89 Chelator Development

“…It provided irrefutable proof of an octadentate coordination environment where all four macrocycle nitrogen atoms and acetate pendant arms participated in Zr 4+ ion coordination. Furthermore, the compressed, square anti-prismatic geometry and low-symmetry saddle-like ligand conformation displayed by Zr- 37 was consistent with the limited number of reports describing Zr-catalysts containing analogous ligands with a Zr(IV) metal center that lacks crystal-field stabilization [ 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 ].…”

Zirconium tetraazamacrocycle complexes display extraordinary stability and provide a new strategy for zirconium-89-based radiopharmaceutical development

“…This is not unusual, since Zr tetraazamacrocycle complexes exhibit varying geometries dictated by the additional ligands that occupy the coordination sites not occupied by the nitrogen atoms of the macrocycle. 25,26,28 The perpendicular distance from the metal center to the plane described by the 4 acetate-containing pendant arms of the macrocycle is 1.004(3) Å, and the perpendicular distance from the metal center to the plane described by the 4 nitrogens of the macrocycle is 1.310(4) Å. The DOTA ligand displays a low-symmetry saddle-like conformation similar to that of metal–dibenzotetramethytetraaza[14]annulene complexes described by De Angelis and co-workers.…”

“…29 The average Zr–ligand bond lengths and bond angles are comparable to those observed in structurally characterized Zr complexes containing hydroxamate, phenoxyamine, salophen, or cyclam ligands. 25,26,28,30–33 …”

“…Despite well-reasoned arguments to the contrary, 20,22–24 it seemed reasonable to posit that tetraazamacrocycles would be useful in 89 Zr-radiopharmaceutical applications, since several Zr–cyclam complexes have been described previously. 25,26 Additionally, we reasoned that their use would be advantageous since (1) they demonstrate enhanced stability over acyclic ligands due to the macrocyclic effect; (2) various functional groups can be introduced into the macrocycle's backbone or pendant arms to modulate the ligand's stereo- and coordination chemistry; (3) bifunctional chelators derived from these ligands allow them to be conjugated to various peptides, proteins, and antibodies; and (4) they have been used successfully in a number of radiopharmaceutical applications and clinical trials.…”

End‐functionalized polylactides using a calcium‐based precatalyst: Synthesis and insights by mass spectrometry

“…Apart from a pioneering study by Montaudo et al from 1996, similar observations are mostly only briefly reported for other alkoxide complexes used as catalysts for lactide polymerization. Apparently, the metal ion does not have a large impact, since these complexes described in literature are based on actinoides, alkali metals, alkaline earth metals, titanium, zirconium, and zinc . The only exceptions from this trend seems to be an aluminum catalyst with a sterically demanding multidentate salen‐type ligand and a zinc catalyst that was applied without addition of an alcohol as co‐initiator.…”