Debate over the electronic structure of CuIII complexes has intensified in recent years, focusing primarily on whether the [Cu(CF3)4]- moiety should be desc Show more
Debate over the electronic structure of CuIII complexes has intensified in recent years, focusing primarily on whether the [Cu(CF3)4]- moiety should be described as a classical Werner-type 3d8 CuIII complex or as a 3d10 CuI inverted ligand field framework. The copper periodate complex [Cu(HIO6)2]5-, discovered in 1937, has long been regarded as a 3d8 CuIII species and sometimes used as a reference 3d8 CuIII complex in oxidation state assignments for Cu-containing metalloenzymes. Nevertheless, its detailed electronic structure remains unexplored. Herein, we revisit the oxidation state of [Cu(HIO6)2]5- by means of X-ray photoelectron spectroscopy, X-ray absorption spectroscopy, and density functional theory calculations. The obtained results show that the oxidation state of the Cu center in [Cu(HIO6)2]5- lies at the boundary between the classical Werner-type and inverted ligand field regimes. This study thus demonstrates that categorizing the oxidation state of CuIII complexes as either 3d8 or 3d10 configurations is often inadequate; instead, the existence of electronic states at the boundary between these two limiting cases should be recognized. Show less
Developing novel therapeutics often follows three steps: target identification, design of strategies to suppress target activity and drug development to implement the strategies. In this review, we re Show more
Developing novel therapeutics often follows three steps: target identification, design of strategies to suppress target activity and drug development to implement the strategies. In this review, we recount the evidence identifying the basic leucine zipper transcription factors ATF5, CEBPB, and CEBPD as targets for brain and other malignancies. We describe strategies that exploit the structures of the three factors to create inhibitory dominant-negative (DN) mutant forms that selectively suppress growth and survival of cancer cells. We then discuss and compare four peptides (CP-DN-ATF5, Dpep, Bpep and ST101) in which DN sequences are joined with cell-penetrating domains to create drugs that pass through tissue barriers and into cells. The peptide drugs show both efficacy and safety in suppressing growth and in the survival of brain and other cancers in vivo, and ST101 is currently in clinical trials for solid tumors, including GBM. We further consider known mechanisms by which the peptides act and how these have been exploited in rationally designed combination therapies. We additionally discuss lacunae in our knowledge about the peptides that merit further research. Finally, we suggest both short- and long-term directions for creating new generations of drugs targeting ATF5, CEBPB, CEBPD, and other transcription factors for treating brain and other malignancies. Show less