Mg²⁺-Induced Thermal Enediyne Cyclization at Ambient Temperature

Metal-mediated diradical tuning for DNA replication arrest via template strand scission

“…2). Overall, the proposed Cu(N 2 )(N′ 2 )Cl ligand field environment for both constructs is supported by these spectroscopic signatures, as well as the previously reported, energy-minimized structure for the Mg(II)-pyridine metalloenediyne (36).…”

“…Our current approach toward the development of small molecule, chelationinduced diradical generators capable of DNA damage is influenced by metal-mediated therapeutics such as Fe-BLM and hydroxyl radical footprinting reagents that act via Fenton chemistry or Hatom abstraction, leading to oxidative DNA strand scission (34,35). From this conceptual platform, we have prepared the versatile tetradentate ligand (Z)-N,N-bis[1-pyridin-2-yl-meth(E)-ylidene]oct-4-ene-2,6-diyne-1,8-diamine (PyED), which demonstrates facile Bergman cyclization and 1,4-benzenoid diradical formation within 2.5 h at room temperature upon chelation of Mg(II) in methanolic solution (36).…”

A Unique Approach to Metal‐Induced Bergman Cyclization: Long‐Range Enediyne Activation by Ligand‐to‐Metal Charge Transfer

“…[1][2][3][4][5] Computational [9,10] and experimental [11] evaluations of the Bergman cyclization reaction coordinate show that s acceptor/p donor functionalities at the alkyne termini reduce the activation barrier to diradical formation. In an effort to extend this model, we questioned whether binding of a strong Lewis acid in the vicinity of the alkyne termini would induce sufficient electron polarization to promote enediyne cyclization in an analogous manner.…”

“…Metals have been shown to thermally activate stable enediynes by both s-donor coordination [1][2][3][4][5] and p complexation, [6,7] which induce a marked reduction in the thermal barrier to Bergman cyclization. Despite these advances, the scope of the metal-activated Bergman cyclization remains poorly defined.…”

Microwave assisted synthesis of symmetrically and asymmetrically substituted acyclic enediynes

“…12 In order to improve the biological activity of the enediynes, efforts are being made to synthesize analogous compounds with better efficacy. [13][14][15][16][17][18][19] Sonogashira coupling has been one of the reactions extensively used in the synthesis of enediyne framework. [20][21][22] Lot of work has been done recently in the development of Sonogashira coupling and one of the development was the use of microwaves in order to promote the C-C bond formation.…”