Anion Control of Lanthanoenediyne Cyclization

Abstract

A suite of lanthanoenediyne complexes of the form Ln(macrocycle)X 3 (Ln = La 3+ , Ce 3+ , Eu 3+ , Gd 3+ , Tb 3+ , Lu 3+ ; X = NO 3 − , Cl − , OTf −) was prepared by utilizing an enediyne-containing [2 + 2] hexaaza-macrocycle (2). The solid-state Bergman cyclization temperatures, measured via DSC, decrease with the denticity of X (bidentate NO 3 − , T = 267−292 °C; monodentate Cl − , T = 238-262 °C; noncoordinating OTf − , T = 170-183 °C). 13 C NMR characterization shows that the chemical shifts of the acetylenic carbon atoms also rely on the anion identity. The alkyne carbon closest to the metal binding site, C A , exhibits a Δδ > 3 ppm downfield shift, while the more distal alkyne carbon, C B , displays a concomitant Δδ ≤ 2.5 ppm upfield shift, reflecting a depolarization of the alkyne on metal inclusion. For all metals studied, the degree of perturbation follows the trend 2 < NO 3 − < Cl − < OTf −. This belies a greater degree of electronic rearrangement in the coordinated macrocycle as the denticity of X and its accompanying shielding of the metal's Lewis acidity decrease. Computationally modeled structures of LnX 3 show a systematic increase in the lanthanide-2 coordination number (CN La-mc = 2 (NO 3 −), 4 (Cl −), 5 (H 2 O, model for OTf −)) and a decrease in the mean Ln−N bond length (La−N average = 2.91 Å (NO 3 −), 2.78 Å (Cl −), 2.68 Å (H 2 O)), further suggesting that a decrease in the anion coordination number correlates with an increase in the metal-macrocycle interaction. Taken together, these data illustrate a Bergman cyclization landscape that is influenced by the bonding of metal to an enediyne ligand but whose reaction barrier is ultimately dominated by the coordinating ability of the accompanying anion.

Bergman cyclization of main-chain enediyne polymers for enhanced DNA cleavage

“…To firstly probe the desired polycondensation of EDY-II with aldehydes, we focused on the model reaction shown in Scheme 2 to precisely adjust the stoichiometric ratios as required according to the Carother's equation to reach adjustable chain lengths. We have used (Z)-octa-4-en-2,6-diyne-1,8diamine 28 for which several synthetic approaches are known 29,31 to embed the ene-diynes into the main chain of the polymers. For initial protection, the tert-butyloxy carbonyl (Boc) group was installed within the terminal alkyne via classical Sonogashira coupling reaction between (Z)-1,2-dichloroethene and tert-butyl prop-2-yn-1-ylcarbamate, thus affording EDY-I.…”

“…See DOI: https://doi.org/ In this context (Z)-octa-4-en-2,6-diyne-1,8-diamine, 28 designed and synthesized by the Zaleski group in 2000, caught our interests, as the primary amine groups, displaying reduced steric hindrance and intramolecular hydrogen bonding, can contribute to its active cyclization performance. Since its first synthesis in 2000, the diamino enediyne has been only applied scarcely [29][30][31] and not in polymers yet, displaying an only limited stability as such and thus being not useful for a direct use in DNA cleavage.…”