Cyclometallated Palladium(II) Complexes: An Approach to the First Dinuclear Bis(iminophosphorane)phosphane-[C,N,S] Metallacycle.

Treatment of bis(iminophosphorane)phosphane ligands 2a-2e with Li2PdCl4 gave a set of novel diphosphane-derived complexes bearing two metallacycle rings, each one enclosing a P=N double bond: the unprecedented bis(iminophosphorane)phosphane-[C,N,S] palladacycles. In the case of the ligand derived from bis(diphenylphosphino)methane, 2a, both the single and the double palladacycle complexes were obtained. Reaction of 3a with bis(diphenylphosphino)ethane did not yield the expected product with the diphosphane bonded to both palladium atoms, but rather the novel coordination compound 5. The crystal structures of 3c and 5 are described.

In Vitro and In Vivo Effect of Palladacycles: Targeting A2780 Ovarian Carcinoma Cells and Modulation of Angiogenesis.

Palladacycles are versatile organometallic compounds that show potential for therapeutic use. Here are described the synthesis and characterization of mono- and dinuclear palladacycles bearing diphosphines. Their biological effect was investigated in A2780, an ovarian-derived cancer line, and in normal dermal fibroblasts. The compounds displayed selective cytotoxicity toward the A2780 cell line. Compound 3 decreased the cell viability through cell cycle retention in G0/G1, triggered apoptosis through the intrinsic pathway, and induced autophagy in A2780 cells. Compound 9 also induced cell cycle retention, apoptosis, and cellular detachment. Notably, compound 9 induced the production of intracellular reactive oxygen species (ROS). Our work demonstrated that compound 3 enters A2780 cells via active transport, which requires energy, while compound 9 enters A2780 cells mostly passively. The potential effect of palladacycles in angiogenesis was investigated for the first time in an in vivo chorioallantoic membrane model, showing that while compound 3 displayed an antiangiogenic effect crucial to fighting cancer progression, compound 9 promoted angiogenesis. These results show that palladacycles may be used in different clinical applications where pro- or antiangiogenic effects may be desirable.

Chemistry of Tetradentate [C,N : C,N] Iminophosphorane Palladacycles: Preparation, Reactivity and Theoretical Calculations.

A theoretical and experimental study of tetradentate [C,N : C,N] iminophosphorane palladacycles was carried out for the purpose of elucidating their behavior as compared to the parent Schiff base analogues to determine the prospect of encountering new A-frame structures for the iminophosphorane derivatives. The DFT calculations were in agreement with the experimental results regarding the performance of these ligands. New insights into the chemistry of the related dinuclear species have been obtained.

From Chemical Serendipity to Translational Chemistry: New Findings in the Reactivity of Palladacycles.

In the world of science, in particular the section concerning the field of chemistry, when the results encountered during the experiment do not meet our expectations, our shrewdness may play an important role to open up new unexplored fields that could be much more interesting than what we were seeking. In those cases, our research undergoes an unforeseen shift, delivering novel and challenging results that may altogether alter our point of view and our future work. We have then struck serendipity. Specifically, in our investigation linked to palladacycles we have found that the new trends in their reactivity, as well as in their structure, have been, in many cases, related to this experience, broadening our research scope within this field. Herein, we describe our most relevant findings, which have shed new light upon the reactivity of palladacycles, thus opening new routes that lead to novel unexpected structures.

The chelate-to-bridging shift of phosphane dipalladacycles: convenient synthesis of double A-frame tetranuclear complexes.

Palladacycles of the type [Pd2(Ph2PCH2PPh2-P,P)2(C,N:C,N)] (C,N:C,N = bis(N-2,3,4-trimethoxybenzylidene)-4,4'-sulfonyldianiline or -4,4'-oxydianiline) can undergo a spontaneous slow chelate-to-bridging diphosphane coordination shift in solution. Following this strategy a tailor-made synthetic procedure was devised that culminates in isolation of double A-frame tetranuclear palladium complexes.

Palladium iminophosphorane complexes: the pre-cursors to the missing link in triphenylphosphane chalcogenide metallacycles.

Herein we report on the synthesis, characterization and the ensuing chemistry of iminophosphorane palladacycles. Treatment of Ph3P[double bond, length as m-dash]N-(2-OHC6H4), 1, with sodium tetrachloropalladate gives 2 with the ligand as terdentate [C,N,O] allowing for only one µ-Cl ligand bonding the metal centers, resulting in a dinuclear complex. Treatment of 2 with PPh3 gives the mononuclear complex 3, whereas the reaction of 2 with diphosphanes Ph2P(CH2)nPPh2 in 1 : 2 ratio gives mixtures of 4 and 5 (n = 2) and 6 and 7 (n = 3). From them, the mononuclear complexes 4 and 6, and the dinuclear compounds, 5 and 7, were obtained with the parent ligand as bidentate [C,N]. The former two are of zwitterionic nature void of any counterion, with the phosphane ligand in the chelating mode. In a remarkable case of chemical serendipity, a solution of 2 left to stand produced crystals of complex 8: this is the missing link in the series of triphenylphosphane chalcogenide metallacycles. The experiment is repeatable; however, direct metallation of triphenylphosphane oxide was not possible.