The Deceptively Similar Ruthenium(III) Drug Candidates KP1019 and NAMI-A Have Different Actions. What Did We Learn in the Past 30 Years?

The general interest in anticancer metal-based drugs and some encouraging pharmacological results obtained at the beginning of the investigations on innovative Ru-based drugs triggered a lot of attention on NAMI-A and KP1019, the two Ru(III) coordination compounds that are the subject of this review. This great attention led to a considerable amount of scientific results and, more importantly, to their eventual admission into clinical trials. Both complexes share a relatively low systemic toxicity that allows reaching rather high dosages, comparable to those of carboplatin. Soon it became evident that NAMI-A and KP1019, in spite of their structural similarity, manifest very distinct chemical and biological properties. The pharmacological performances qualified KP1019 mainly as a cytotoxic drug for the treatment of platinum-resistant colorectal cancers, whereas NAMI-A gained the reputation of a potential anticancer drug with negligible effects on the primary tumor but a pronounced ability to affect metastases. We believe that a strictly comparative exam of NAMI-A and KP1019, based on the substantial body of studies accomplished since their discovery almost 30 years ago, might be an useful exercise, both for assessing the state of the art in terms of biological and clinical profiles, and of the inherent mechanisms, and for envisaging possible future developments in the light of past achievements.

Environmental Impact of Alkyl Lead(IV) Derivatives: Perspective after Their Phase-out.

The use of alkyl lead derivatives as antiknock agents in gasoline can be considered as one of the main pollution disasters of the 20th century because of both the global character of the pollution emitted and the seriousness of the impact on human health. Alkyl lead derivatives in themselves cannot be considered to be persistent pollutants because they readily degrade either before being released from the tailpipes or soon afterwards in the atmosphere. However, the inorganic lead they produced has been deposited in soils all over the planet, largely, but not exclusively in urban areas and along motorways, since the direct emission of lead into the atmosphere favored its dispersal over great distances: The signal of the massive use of alkyl lead derivatives has been found all over the world, including in remote sites such as polar areas. The short residence time of lead in the atmosphere implies that this compartment is highly responsive to changes in emissions. This was demonstrated when leaded gasoline was phased-out and is in striking contrast to the very long permanence of inorganic lead in soils, where resuspension is a permanent source of toxic lead.

Alfred Werner's chemistry of dinuclear complexes--a test case of Werner's intuition.

The re-investigation of four original tris-bridged dinuclear dicobalt complexes from the Werner collection of the University of Zurich by X-ray diffraction studies is described. The complex [Co2(NH3)6(µ-NH2) (µ-OH)(µ-O2)](NO3)3 was studied recently. As the most interesting feature it was found to contain a µ-superoxo bridge, recognized by Alfred Werner and his coworker as an asymmetric peroxo bridge. The newly established µ-mono- and diacetato structures from crystals of the Werner collection, [Co2(NH3)6(µ-OH)2(µ-O2CMe)](NO3)3·H2O and [Co2(NH3)6(µ-OH)(µ-O2CMe)2](NO3)3·H2O, were assigned by Alfred Werner and his co-workers as mono- or di-bridged systems with the water functioning as η(1)-aqua ligands and not, as revealed by the X-ray diffraction studies, as solvate molecules. Similarly the exact nature of the µ(N, O) nitrito bridge in the structure of the [Co2(NH3)6(µ-OH)2(µ-O2N)](NO3)3·H2O complex from the Werner collection was left open in Werner's and his coworker's description. Only the accuracy of the X-ray diffraction study could ascertain any earlier 'good guess'. The assignment of the bridges of bridged dinuclear structures at Werner's time are well conceived considering the lack of appropriate analytical tools. The structural assignments of Alfred Werner for the discussed dinuclear complexes are therefore considered to deviate only marginally from the real structures. They are testimonies of Alfred Werner's predictive abilities in coordination chemistry supported by his prepared mind, his great abilities of intuition and conceptual thinking.

The race to discover the insect vector of kala-azar: a great saga of tropical medicine 1903-1942.

In the 19(th) century, a devastating epidemic of visceral leishmaniasis (kala-azar) swept through northeast India. After identification of the pathogenic agent, Leishmania donovani, in 1903, the question of its transmission remained to be resolved. In 1904, thanks to work by L. Rogers on cultures of this parasite it became probable that a haematophagous arthropod was responsible for transmission. J.A. Sinton suggested, in 1925, the distribution of the sand fly Phlebotomus argentipes was similar to that of the disease and, thereafter, two independent teams led by H.E. Shortt in Assam and R. Knowles and L. Napier in Calcutta concentrated on this potential vector. Parallel work was in progress in China, directed by E. Hindle and W. S. Patton for the Royal Society Kala-azar Commission, on another species of sand fly. In 1942 the Assam workers transmitted L. donovani to five human volunteers by the bites of colonised P. argentipes and the race was over.

[History of chemical radicals: the part of Auguste Cahours (1813-1891)]. / Histoire des radicaux: contribution d'Auguste Cahours (1813-1891).

Auguste Cahours succeeded Dumas, as professor to Ecole centrale, and Chevreul, as examiner to Ecole polytechnique. He was connected with many french and foreign chemists. His works relating to vapour densities, radicals and organometallic compounds were conclusive for acceptance of the Avogadro's law and setting up valency by chemists about 1860.

A quarter of a century of explorations in organozirconium chemistry.

Systematic explorations of organozirconium chemistry over the past quarter of a century have led to the discoveries and development as well as structural and mechanistic clarifications of novel Zr-catalyzed and -promoted carbon-carbon bond-forming reactions including (i) Ni- or Pd-catalyzed cross-coupling reaction of organozirconiums, (ii) Zr-catalyzed carboalumination of alkynes, (iii) Zr-catalyzed asymmetric carboalumination of alkenes, (iv) generation and carbometallative ring expansion of zirconacyclopropanes and zirconacyclopropenes and a myriad of their transformations and (v) various organozirconium migratory insertion reactions.