We report the preparation and thermal reactivities of unique Cu(I) and Cu(I
I) metalloenediyne complexes of the flexible 1,8-bis(pyridine-3-oxy)oct-4-e
ne-2,6-diyne ligand (bpod, 1). The thermal reactivities of these metalloene
diynes are intimately modulated by metal oxidation state. Using differentia
l scanning calorimetry (DSC), we demonstrate that the [Cu(bpod)(2)](+) comp
lex (2) undergoes Bergman cyclization at 203 degrees C, whereas the Cu(II)
analogue (3) is substantially more reactive and cyclizes at 121 OC. Similar
results are also observed for mixed ligand [Cu(bpod)(pyridine)2](+/2+) ana
logues 4 (194 degrees C) and 5 (116 degrees C), suggesting that both comple
xes of a given oxidation state have comparable structures. The Cu(bpod)Cl-2
compound (6) exhibits a cyclization temperature (152 degrees C) midway bet
ween the those of Cu(I) and Cu(II) complexes, which can be explained by the
propensity for cis-CuN2Cl2 structures to exhibit dihedral angle distortion
. The oxidation-state-dependent thermal reactivity is unprecedented and ref
lects the influence of the ligand field geometry on the barrier to enediyne
cyclization. On the basis of X-ray structures of Cu(pyridine)lt complexes,
2 and 4 are proposed to be tetrahedral. In contrast, the electronic absorp
tion spectra of 3 and 5 each show a broad envelope that can be Gaussian res
olved into three ligand field transitions characteristic of a Cu(II) center
in a tetragonal octahedral environment. This structural assignment is conf
irmed by the EPR spin Hamiltonian parameters (g(parallel to)/A(parallel to)
(cm) = 134 (3), 138 (5)) and is consistent with crystallographically chara
cterized Cu(pyridine)(4)X-2 structures. Molecular mechanics calculations ha
ve independently derived comparable tetrahedral and tetragonal structures f
or 2 and 3, respectively, and determined the average alkyne termini separat
ion to be [a] = 4.0 Angstrom for 2 and 3.6 Angstrom for 3. Thus, the tetrah
edral geometries of the copper centers in 2 and 4 increase the distance bet
ween alkyne termini relative to the tetragonal Cu(II) geometries of 3 and 5
, and are therefore responsible for the increase in the thermal cyclization
temperatures. The DSC and spectroscopic data for 6 support these conclusio
ns, as the latter suggests a distorted four-coordinate structure in the sol
id state, and a six-coordinate geometry in solution, which gives rise to an
intermediate Bergman cyclization temperature. Overall, our results emphasi
ze the utility of newly emerging metalloenediyne complexes for controlling
thermal Bergman cyclization reactions and provide insights into designing n
ovel, pharmacologically useful metalloenediyne compounds.