Reactivity Study of Unsymmetrical ß-Diketiminato Copper(I) Complexes: Effect of the Chelating Ring.

ß-Diketiminato copper(I) complexes play important roles in bioinspired catalytic chemistry and in applications to the materials industry. However, it has been observed that these complexes are very susceptible to disproportionation. Coordinating solvents or Lewis bases are typically used to prevent disproportionation and to block the coordination sites of the copper(I) center from further decomposition. Here, we incorporate this coordination protection directly into the molecule in order to increase the stability and reactivity of these complexes and to discover new copper(I) binding motifs. Here we describe the synthesis, structural characterization, and reactivity of a series of unsymmetrical N-aryl-N'-alkylpyridyl ß-diketiminato copper(I) complexes and discuss the structures and reactivity of these complexes with respect to the length of the pyridyl arm. All of the aforementioned unsymmetrical ß-diketiminato copper(I) complexes bind CO reversibly and are stable to disproportionation. The binding ability of CO and the rate of pyridyl ligand decoordination of these copper(I) complexes are directly related to the competition between the degree of puckering of the chelate system and the steric demands of the N-aryl substituent.

Ligand Degradation Study of Unsymmetrical ß-Diketiminato Copper Dioxygen Adducts: The Length Chelating Arm Effect.

An investigation on the reactivity of O2 binding to unsymmetrical ß-diketiminato copper(I) complexes by spectroscopic and titration analysis was performed. The length of chelating pyridyl arms (pyridylmethyl arm vs pyridylethyl arm) leads to the formation of mono- or di-nuclear copper-dioxygen species at -80 °C. The pyridylmethyl arm adduct (L1CuO2) forms mononuclear copper-oxygen species and shows ligand degradation, resulting in the formation of (2E,3Z)-N-(2,6-diisopropylphenyl)-4-(((E)-pyridin-2-ylmethylene)amino)pent-3-en-2-imine, which slowly converts to its cyclization isomer 1-(2,6-diisopropylphenyl)-4,6-dimethyl-2-(pyridin-2-yl)-1,2-dihydropyrimidine after addition of NH4OH at room temperature. On the other hand, the pyridylethyl arm adduct [(L2Cu)2(µ-O)2] forms dinuclear species at -80 °C and does not show any ligand degradation product. Instead, free ligand formation was observed after the addition of NH4OH. These experimental observations and product analysis results indicate that the chelating length of pyridyl arms governs the Cu/O2 binding ratio and the ligand degradation behavior.

Chicken HSP70 DNA vaccine inhibits tumor growth in a canine cancer model.

Immunization with xenogeneic DNA is a promising cancer treatment to overcome tolerance to self-antigens. Heat shock protein 70 (HSP70) is over-expressed in various kinds of tumors and is believed to be involved in tumor progression. This study tested a xenogeneic chicken HSP70 (chHSP70) DNA vaccine in an experimental canine transmissible venereal tumor (CTVT) model. Three vaccination strategies were compared: the first (PE) was designed to evaluate the prophylactic efficacy of chHSP70 DNA vaccination by delivering the vaccine before tumor inoculation in a prime boost setting, the second (T) was designed to evaluate the therapeutic efficacy of the same prime boost vaccine by vaccinating the dogs after tumor inoculation; the third (PT) was similar to the first strategy (PE), with the exception that the electroporation booster injection was replaced with a transdermal needle-free injection. Tumor growth was notably inhibited only in the PE dogs, in which the vaccination program triggered tumor regression significantly sooner than in control dogs (NT). The CD4(+) subpopulation of tumor-infiltrating lymphocytes and canine HSP70 (caHSP70)-specific IFN-γ-secreting lymphocytes were significantly increased during tumor regression in the PE dogs as compared to control dogs, demonstrating that specific tolerance to caHSP70 has been overcome. In contrast, no benefit of the therapeutic strategy (T) could be noticed and the (PT) strategy only led to partial control of tumor growth. In summary, antitumor prophylactic activity was demonstrated using the chHSP70 DNA vaccine including a boost via electroporation. Our data stressed the importance of DNA electroporation as a booster to get the full benefit of DNA vaccination but also of cancer immunotherapy initiation as early as possible. Xenogeneic chHSP70 DNA vaccination including an electroporation boost is a potential vaccine to HSP70-expressing tumors, although further research is still required to better understand true clinical potential.