J. Appl. Cryst.の発刊に際して

I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

Methods in Enzymology.

N-Heterocyclic Carbenes in Late Transition Metal Catalysis

The quest for alternative drugs to the well-known cisplatin and its derivatives, which are still used in more than 50% of the treatment regimes for patients suffering from cancer, is highly needed.1,2 Despite their tremendous success, these platinum compounds suffer from two main disadvantages: they are inefficient against platinum-resistant tumors, and they have severe side effects such as nephrotoxicity. The latter drawback is the consequence of the fact that the ultimate target of these drugs is ubiquitous: It is generally accepted that Pt anticancer drugs target DNA, which is present in all cells.3,4 Furthermore, as a consequence of its particular chemical structure, cisplatin in particular offers little possibility for rational improvements to increase its tumor specificity and thereby reduce undesired side effects.

In this context, organometallic compounds, which are defined as metal complexes containing at least one direct, covalent metal−carbon bond, have recently been found to be promising anticancer drug candidates. Organometallics have a great structural variety (ranging from linear to octahedral and even beyond), have far more diverse stereochemistry than organic compounds (for an octahedral complex with six different ligands, 30 stereoisomers exist!), and by rational ligand design, provide control over key kinetic properties (such as hydrolysis rate of ligands). Furthermore, they are kinetically stable, usually uncharged, and relatively lipophilic and their metal atom is in a low oxidation state. Because of these fundamental differences compared to “classical coordination metal complexes”, organometallics offer ample opportunities in the design of novel classes of medicinal compounds, potentially with new metal-specific modes of action. Interestingly, all the typical classes of organometallics such as metallocenes, half-sandwich, carbene-, CO-, or π-ligands, which have been widely used for catalysis or biosensing purposes, have now also found application in medicinal chemistry (see Figure ​Figure11 for an overview of these typical classes of organometallics).



Figure 1

Summary of the typical classes of organometallic compounds used in medicinal chemistry.



In this Perspective, we report on the recent advances in the discovery of organometallics with proven antiproliferative activity. We are emphasizing those compounds where efforts have been made to identify their molecular target and mode of action by biochemical or cell biology studies. This Perspective covers more classes of compounds and in more detail than a recent tutorial review by Hartinger and Dyson.(5) Furthermore, whereas recent reviews and book contributions attest to the rapid development of bioorganometallic chemistry in general,6,7 this Perspective focuses on their potential application as anticancer chemotherapeutics. Another very recent review article categorizes inorganic anticancer drug candidates by their modes of action.(8) It should be mentioned that a full description of all currently investigated types of compounds is hardly possible anymore in a concise review. For example, a particularly promising class of organometallic anticancer compounds, namely, radiolabeled organometallics, has been omitted for space limitations. Recent developments of such compounds have been reviewed in detail by Alberto.(9)

http://pubs.acs.org/doi/pdf/10.1021/jm100020w

Organometallic Anticancer Compounds

Ionic liquids are defined today as liquids which solely consist of cations and anions and which by definition must have a melting point of 100 °C or below. Originating from electrochemistry in AlCl3 based liquids an enormous progress was made during the recent 10 years to synthesize ionic liquids that can be handled under ambient conditions, and today about 300 ionic liquids are already commercially available. Whereas the main interest is still focussed on organic and technical chemistry, various aspects of physical chemistry in ionic liquids are discussed now in literature. In this review article we give a short overview on physicochemical aspects of ionic liquids, such as physical properties of ionic liquids, nanoparticles, nanotubes, batteries, spectroscopy, thermodynamics and catalysis of/in ionic liquids. The focus is set on air and water stable ionic liquids as they will presumably dominate various fields of chemistry in future.

Air and water stable ionic liquids in physical chemistry

Electrochemical synthesis of polypyrrole in ionic liquids

A combined experimental/quantum chemical investigation of the transition metal-mediated dehydrocoupling reaction of H(3)B center dot NMe(2)H to ultimately give the cyclic dimer [H(2)BNMe(2)](2) is reported Intermediates and model complexes have been isolated, including examples of amine-borane sigma-complexes of Rh(I) and Rh(III) These come from addition of a suitable amine-borane to the crystallographically characterized precursor [Rh(eta(6)-1,2-F(2)C(6)H(4))(P(i)Bu(3))(2)][BAr(4)(F)] [Ar(F)= 3,5-(CF(3))(2)C(6)H(3)] The complexes [Rh(eta(2)-H(3)B center dot NMe(3))(P(i)Bu(3))(2)][BAr(F)4] and [Rh(H)(2)(eta(2)-H(3)B center dot NHMe(2))(P(i)Bu(3))(2)][BAr(4)(F)] have also been crystallographically characterized Other intermediates that stem from either H(2) loss or gain have been characterized in solution by NMR spectroscopy and ESI-MS These complexes are competent in the catalytic dehydrocoupling (5 mol %) of H(3)B center dot NMe(2)H During catalysis the linear dimer amine-borane H(3)B center dot NMe(2)BH(2)center dot NHMe(2) is observed which follows a characteristic intermediate time/concentration profile The corresponding amine-borane sigma-complex, [Rh(P(i)Bu(3))(2)(eta(2)-H(3)B center dot NMe(2)BH(2)center dot NHMe(2))][BAr(4)(F)], has been isolated and crystallographically characterized A Rh(I) complex of the final product, [Rh(P(i)Bu(3))(2){eta(2)-(H(2)BNMe(2))(2)}][BAr(4)(F)], is also reported, although this complex lies outside the proposed catalytic cycle DFT calculations show that the first proposed dehydrogenation step, to give H(2)B=NMe(2), proceeds via two possible routes of essentially the same energy barrier: BH or NH activation followed by NH or BH activation, respectively Subsequent to this, two possible low energy routes that invoke either H(2)/H(2)B=NMe(2) loss or H(2)B=NMe(2)/H(2) loss are suggested For the second dehydrogenation step, which ultimately affords [H(2)BNMe(2)](2), a number of experimental observations suggest that a simple intramolecular route is not operating: (i) the isolated complex [Rh(P(i)Bu(3))(2)(eta(2)- H(3)B center dot NMe(2)BH(2)center dot NHMe(2))][BAr(4)(F)] is stable in the absence of amine-boranes; (ii) addition of H(3)B center dot NMe(2)BH(2)center dot NHMe(2) to [Rh(P(i)Bu(3))(2)(eta(2)-H(3)B center dot NMe(2)BH(2 center dot)NHMe(2))][BAr(4)(F)] initiates dehydrocoupling; and (iii) H(2)B=NMe(2) is also observed during this process

Monomeric and Oligomeric Amine−Borane σ-Complexes of Rhodium. Intermediates in the Catalytic Dehydrogenation of Amine−Boranes

Natural bond orbital (NBO) and topological electron density analyses have been used to investigate the electronic structure of phosphazenes [N3P3R6] (R = H, F, Cl, Br, CH3, CF3, N(C2H4); 2R = O2C6H4), [N4P4Cl8], and H[NPCl2]4H. Using the former, the two most likely phosphazene bonding alternatives, negative hyperconjugation and ionic bonding have been critically evaluated. Ionic bonding, as suggested by topological analysis, was found to be the dominant bonding feature, although contributions from negative hyperconjugation are necessary for a more complete bonding description. Substituent effects on the P-N bond have been assessed and cases of bond length alternation have been rationalized using this combined bonding model, which supersedes previous models involving d-orbital participation, leading to an explanation for the observed bond length alternation found in some linear polyphosphazenes. In addition, common aromaticity indicators, nucleus independent chemical shifts (NICS) and para-delocalization indices (PDI), have been determined for the cyclophosphazenes.

Revisiting the electronic structure of phosphazenes.

The antitumour activity of the organometallic ruthenium(II)–arene mixed phosphine complexes, [Ru(η6-p-cymene)Cl(PTA)(PPh3)]BF41b and [Ru(η6-C6H5CH2CH2OH)Cl(PTA)(PPh3)]BF42b (PTA = 1,3,5-triaza-7-phosphaadamantane), have been evaluated in vitro and compared to their RAPTA analogues, [Ru(η6-p-cymene)Cl2(PTA)] 1a and [Ru(η6-C6H5CH2CH2OH)Cl2(PTA)] 2a. The results show that the addition of the PPh3 ligand to 2a increases the cytotoxicity towards the TS/A adenocarcinoma cancer cells, which correlates with increased uptake, but also increases cytotoxicity to non-tumourigenic HBL-100 cells, thus decreasing selectivity. The decrease in selectivity has been correlated to increased DNA interactions relative to proteins, demonstrated by reactivity of the compounds with a 14-mer oligonucleotide and the model proteins ubiquitin and cytochrome-c.

Tuning the hydrophobicity of ruthenium(II)–arene (RAPTA) drugs to modify uptake, biomolecular interactions and efficacy

Rhodium amine-borane σ-complexes of H3BNHMe2 have been isolated which are potential intermediates in the catalytic dehydrogenation of H3B·NHMe2.

Adrian B. Chaplin

Papers

Electrochemical synthesis of polypyrrole in ionic liquids

Monomeric and Oligomeric Amine−Borane σ-Complexes of Rhodium. Intermediates in the Catalytic Dehydrogenation of Amine−Boranes

Revisiting the electronic structure of phosphazenes.

Tuning the hydrophobicity of ruthenium(II)–arene (RAPTA) drugs to modify uptake, biomolecular interactions and efficacy

Amine-Borane σ-Complexes of Rhodium. Relevance to the Catalytic Dehydrogenation of Amine-Boranes