In the next two decades, the world is expected to see around 20 million cases of cancer. Moreover, the types of cancer will vary considerably from country to other. Therefore, all efforts will be needed to face such a vast diversity of problems. With current annual sales of about $500 millions, the platinum(II) complex known as cisplatin [cis-(NH3)2PtCl2] is still one of the most effective drugs to treat testicular, ovarian, bladder and neck cancers. Since it was launched in 1978 there has been a rapid expansion in research to find new, more effective metal-based anticancer drugs and to study their interactions with biological systems. This study gives an up to date overview of the anticancer chemistry of the platinum group elements platinum, palladium, and nickel with an emphasis on the new strategies used in the development of new antitumor agents. Methodologies for application of bulky aromatic or aliphatic nitrogen ligands, chiral organic moieties, chelates containing other donor atoms than nitrogen, and biologically active ligands in the design of agents analogous to cisplatin are presented. The review also aims to highlight the class of the unconventional complexes that violate the empirical structure-activity rules (SAR) of platinum compounds and the common features and structural differences between the most successful anticancer complexes that are currently in human clinical trials.

Using a mouse model of neonatal respiratory distress syndrome (RDS), we demonstrate a central role for macrophage migration inhibitory factor (MIF) in lung maturation at the developmental stage when human neonates are most susceptible to RDS. We prematurely delivered mouse pups at embryonic day 18, during the early saccular stage of pulmonary development. Only 8% of the prematurely delivered pups genetically deficient in MIF survived 8 h vs 75% of wild-type controls (p < 0.001). This phenotype was corrected when pups of all genotypes were bred from dams heterozygote for MIF deficiency. Local production of MIF in the lung increased at embryonic day 18, continued until full-term at embryonic day 19.5, and decreased in adulthood, thus coinciding with this developmental window. The lungs of pups genetically deficient in MIF were less mature upon histological evaluation, and demonstrated lower levels of vascular endothelial growth factor and corticosterone – two factors that promote fetal lung maturation. In vitro studies support a role for MIF in surfactant production by pulmonary epithelial cells. In a cohort of human neonates with RDS, higher intrapulmonary MIF levels were associated with a lower likelihood of developing bronchopulmonary dysplasia, a sequelae of RDS (p < 0.03). This study demonstrates for the first time a role for MIF in lung maturation, and supports a protective role for MIF in newborn lung disease.

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A new class of iron(II) and cobalt(II) complexes with neutral, tetradentate bis(pyridylimine) chelate ligands bridged by a chiral 6,6Ј-dimethylbiphenyl backbone has been synthesized. Their dihalogen derivatives gave spectral, magnetic and X-ray diffraction results in agreement with a C 2 -symmetric, approximately octahedral geometry with cis-positioned halide ligands and high-spin d-electron configuration.1 H NMR signals of these paramagnetic complexes were assigned by correlating line widths with reciprocal proton-metal distances. Methyl substitution in 6-position of the pyridyl

Syntheses of new tetradentate ligands, containing a bianiline backbone and two additional heterocyclic N-donors, and of chiral zirconium complexes containing these ligands as dianions are reported. Crystal structures of some of these complexes show a preference for coordinating the two remaining ligands in a trans- rather than cis-orientation. Nevertheless, these complexes are moderately active in MAO-activated olefin polymerization in toluene solution at 50 °C. With propene, partly isotactic polypropene (55% mmmm) is obtained. These observations indicate that in cationic species generated in these reaction systems, the growing polymer chain and the olefin substrate occupy cis-coordination sites, while the heterocyclic N ligands adopt a screw-like trans orientation suitable to favor one of the enantiofacial orientations of the entering olefin substrate.