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Angew. Chem. Int. Ed, 2010, early view (DOI: 10.1002/anie.201002721)

A Potent Trans-Diimine Platinum Anticancer Complex Photoactivated by Visible Light

N. J. Farrer, J. A. Woods, L. Salassa, Y. Zhao, K. S. Robinson, G. Clarkson, F. S. Mackay, P. J. Sadler

Angew. Chem. Int. Ed, 2010, early view. DOI: 10.1002/anie.201003399

Activating platinum with light: An inert platinum(IV) diazido complex trans,trantrans,trans-[Pt(N₃)₂(OH)₂(py)₂] becomes potently cytotoxic to cancer cells when activated by low doses of visible light.

Sarah Crosby, working in Jon Rourke's group, has identified a number of new Pt(IV) complexes containg dmso ligands.

Oxidation of cyclometalated Pt(II) complexes with S-bound DMSO ligands initially results in Pt(IV) complexes which retain the S-bound DMSO ligands in the same relative position. Isomerisation reactions result in a rearrangement of the ligands to give O-bound DMSO complexes, with the DMSO trans to a cyclometalated carbon. X-ray structures representing the only two known examples of Pt(IV) complexes with O-bound DMSO ligands have been solved. The rate of isomerisation of complexes without a pendant alkyl chain is strongly solvent dependent, consistent with the need to stabilise a coordinatively unsaturated intermediate. Pt(IV) complexes with a pendant alkyl chain show little dependence on isomerisation rate with solvent, with solution NMR data strongly suggesting the presence of agostic complexes. DFT calculations provide support for the presence of agostic complexes, with the same interactions being used to account for the loss of DMSO from the O-bound DMSO complexes.

See

Jon Rourke and collaborators report in ACS nano on the structural analysis of graphene oxide (GO) by transmission electron microscopy (TEM). Electron diffraction shows that on average the underlying carbon lattice maintains the order and lattice-spacings of graphene; a structure that is clearly resolved in 80 kV aberration-corrected atomic resolution TEM images. These results also reveal that single GO sheets are highly electron transparent and stable in the electron beam, and hence ideal support films for the study of nanoparticles and macromolecules by TEM. We demonstrate this through the structural analysis of physiological ferritin, an iron-storage protein.

The team studied the binding mode adopted by picolinamide derivatives in organometallic Os^II and Ru^II half-sandwich complexes and showed that it can lead to contrasting cancer cell cytotoxicity. N-Phenyl picolinamide derivatives (XY) in Os^II (1, 3−5, 7, 9) and Ru^II (2, 6, 8, 10) complexes [(η⁶-arene)(Os/Ru)(XY)Cl]ⁿ⁺, where arene = p-cymene (1−8, 10) or biphenyl (9), can act as N,N- or N,O-donors. Electron-withdrawing substituents on the phenyl ring resulted in N,N-coordination and electron-donating substituents in N,O-coordination. Dynamic interconversion between N,O and N,N configurations can occur in solution and is time- and temperature- (irreversible) as well as pH-dependent (reversible). The neutral N,N-coordinated compounds (1−5 and 9) hydrolyzed rapidly (t_1/2 ≤ min), exhibited significant (32−70%) and rapid binding to guanine, but no binding to adenine. The N,N-coordinated compounds 1, 3, 4, and 9 exhibited significant activity against colon, ovarian, and cisplatin-resistant ovarian human cancer cell lines (3 4 > 1 > 9). In contrast, N,O-coordinated complexes 7 and 8 hydrolyzed slowly, did not bind to guanine or adenine, and were nontoxic.

2-tert-Butyl-6-(4-fluorophenyl)pyridine reacts with K₂PtCl₄ via the activation of an sp² C−H bond to give a cyclometalated complex that contains a bifurcated agostic interaction. Rearrangement of this complex results in the activation of an sp³ C−H bond, and reaction eventually leads to a doubly cyclometalated complex where both sp² and sp³ C−H bonds have been activated. Deuterium exchange studies show that a delicate balance exists between the two cyclometalations.