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BRAFV600EKis a frequent mutationally active tumor-specific kinase in melanomas that is currently targeted for therapy by the specific inhibitor PLX4032. Our studies with melanoma tumor cells that are BRAFV600EKand BRAFWTshowed that, paradoxically, while PLX4032 inhibited ERK12 in the highly sensitive BRAFV600EK, it activated the pathway in the resistant BRAFWTcells, via RAF1 activation, regardless of the status of mutations in NRAS or PTEN. The persistently active ERK12 triggered downstream effectors in BRAFWTmelanoma cells and induced changes in the expression of a wide-spectrum of genes associated with cell cycle control. Furthermore, PLX4032 increased the rate of proliferation of growth factor-dependent NRAS Q61L mutant primary melanoma cells, reduced cell adherence and increased mobility of cells from advanced lesions. The results suggest that the drug can confer an advantage to BRAFWTprimary and metastatic tumor cells in vivo and provide markers for monitoring clinical responses.

A study of a series of six-coordinate Co(III) complexes has been carried out to quantify spectroscopic parameters for a range of ligands that are commonly employed to realize strong charge-transfer absorptions in low-spin, d6systems. Identification of any three ligand-field transitions allows for the determination of the splitting parameter (10 Dq) as well as the Racah Band Cparameters for a given compound. The data revealed a relatively small spread in the magnitude of 10 Dq, ranging from ca. 23 000 cm–1in the case of [Co(pyrro-bpy)3]3+(where pyrro-bpy is 4,4′-dipyrrolidinyl-2,2′-bipyridine) to ca. 26 000 cm–1for [Co(terpy)2]3+(where terpy is 2,2′:6′,2″-terpyridine). Significantly, trends across the series suggest that polypyridyl ligands behave as net π-donors when interacting with Co(III), in contrast to the net π-accepting character they exhibit when bound to second- and third-row metals. The influence of strong σ donation associated with carbene-based ligands was evident from the data acquired for [Co(BMeImPy)2]3+(where BMeImPy is 3,3′-(pyridine-2,6-diyl)bis(1-methyl-1H-3-imidazolium)), where a 10 Dq value of ca. 30 000 cm–1was determined. Spectroscopic data were also analyzed for [Fe(bpy)3]2+using the results on [Co(bpy)3]3+as a reference point. A value for 10 Dq of 21 000 cm–1was estimated, indicating a reduction in the ligand-field strength of ca. 3000 cm–1upon replacing Co(III) with Fe(II). We suggest that this approach of taking advantage of the blueshift of the charge-transfer feature in Co(III) complexes to reveal otherwise obscured ligand-field bands can be a useful tool for the development of new ligand systems to expand the photofunctionality of first-row transition-metal-based chromophores.

The electron injection dynamics of dye-sensitized TiO 2-based solar cells have been investigated to determine the effects of replacing the I 3−/I −redox system by non-redox-active supporting electrolytes. TiO 2films were sensitized with Ru(dcbpy) 2(NCS) 2, where dcbpy = 4,4′-dicarboxylic acid-2,2′-bipyridine (the “N3” dye), and placed in contact with either M(ClO 4) or M(I 3−/I −) solutions (M = Li +or (n-C 4H 9) 4N +); cells that contained I 3−/I −were fully functional solar cells whose steady-state photocurrents were directly measured. In (n-C 4H 9) 4N +-containing solutions, significant differences were observed between the measured kinetics when ClO 4−was replaced by the redox-active I 3−/I −system. In particular, a ps time scale loss of the metal-to-ligand charge-transfer excited-state of the N3 dye, associated with electron injection, that was observed in cells containing either LiClO 4or [(n-C 4H 9) 4N]ClO 4was absent in fully functional solar cells that contained [(n-C 4H 9) 4N]I/I 2. These results underscore the importance of performing kinetics measurements on this class of solar cells under operational conditions if one is to obtain reliable correlations between the dynamics data and the steady-state performance metrics of the solar cell devices.

A variety of synthetic procedures have been employed that allow access to three new tetranuclear [M4(µ3-O)2]8+ (M 4;= 4;MnIII or FeIII) complexes. The complex [Fe4O2Cl2(O2CMe)6(bpy)2] displays an unusual structural asymmetry in its core that can be described as a hybrid of the bent (butterfly) and planar dispositions of four M atoms seen previously in such compounds. Magnetochemical and 57Fe Mössbauer studies on this compound showed that its structural asymmetry has little influence on these properties compared with the more symmetric types. The complex [NBun4][Fe4O2(O2CMe)7(pic)2] has been prepared by an unusual chelate substitution in [NBun4][Fe4O2(O2CMe)7(bpy)2] that does not disrupt the core or the bridging carboxylate groups.

The rapid synthesis of 4-aryl-2,2'-bipyridines is described leading to some previously reported compounds in good yields in addition to some new functionalized bipyridines.

Renal artery stenosis causing hypertension may be the sequel of blunt nonpenetrating abdominal trauma. Early recognition of such renal artery injury is essential. In the case reported, late recognition of unilateral traumatic renal artery stenosis led to surgical correction of the lesion and lasting cure of hypertension.

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