Dicarba-closo-dodecarborane-containing half-sandwich complexes of ruthenium, osmium, rhodium and iridium : biological relevance and synthetic strategies

This review describes how the incorporation of dicarba-closo-dodecarboranes into half-sandwich complexes of ruthenium, osmium, rhodium and iridium might lead to the development of a new class of compounds with applications in medicine. Such a combination not only has unexplored potential in traditional areas such as Boron Neutron Capture Therapy agents, but also as pharmacophores for the targeting of biologically important proteins and the development of targeted drugs. The synthetic pathways used for the syntheses of dicarba-closo-dodecarboranes-containing half-sandwich complexes of ruthenium, osmium, rhodium and iridium are also reviewed. Complexes with a wide variety of geometries and characteristics can be prepared. Examples of addition reactions on the metal centre, B–H activation, transmetalation reactions and/or direct formation of metal–metal bonds are discussed (103 references)

Photoactivatable metal complexes : from theory to applications in biotechnology and medicine

This short review highlights some of the exciting new experimental and theoretical developments in the field of photoactivatable metal complexes and their applications in biotechnology and medicine. The examples chosen are based on some of the presentations at the Royal Society Discussion Meeting in June 2012, many of which are featured in more detail in other articles in this issue. This is a young field. Even the photochemistry of well-known systems such as metal–carbonyl complexes is still being elucidated. Striking are the recent developments in theory and computation (e.g. time-dependent density functional theory) and in ultrafast-pulsed radiation techniques which allow photochemical reactions to be followed and their mechanisms to be revealed on picosecond/nanosecond time scales. Not only do some metal complexes (e.g. those of Ru and Ir) possess favourable emission properties which allow functional imaging of cells and tissues (e.g. DNA interactions), but metal complexes can also provide spatially controlled photorelease of bioactive small molecules (e.g. CO and NO)—a novel strategy for site-directed therapy. This extends to cancer therapy, where metal-based precursors offer the prospect of generating excited-state drugs with new mechanisms of action that complement and augment those of current organic photosensitizers

Controlling platinum, ruthenium, and osmium reactivity for anticancer drug design

The main task of the medicinal chemist is to design molecules that interact specifically with derailed or degenerating processes in a diseased organism, translating the available knowledge of pathobiochemical and physiological data into chemically useful information and structures. Current knowledge of the biological and chemical processes underlying diseases is vast and rapidly expanding. In particular the unraveling of the genome in combination with, for instance, the rapid development of structural biology has led to an explosion in available information and identification of new targets for chemotherapy. The task of translating this wealth of data into active and selective new drugs is an enormous, but realistic, challenge. It requires knowledge from many different fields, including molecular biology, chemistry, pharmacology, physiology, and medicine and as such requires a truly interdisciplinary approach. Ultimately, the goal is to design molecules that satisfy all the requirements for a candidate drug to function therapeutically. Therapeutic activity can then be achieved by an understanding of and control over structure and reactivity of the candidate drug through molecular manipulation

Kinetic Monte Carlo simulations of the growth of polymer crystals

Based upon kinetic Monte Carlo simulations of crystallization in a simple polymer model we present a new picture of the mechanism by which the thickness of lamellar polymer crystals is constrained to a value close to the minimum thermodynamically stable thickness, l_{min}. The free energetic costs of the polymer extending beyond the edges of the previous crystalline layer and of a stem being shorter than l_{min} provide upper and lower constraints on the length of stems in a new layer. Their combined effect is to cause the crystal thickness to converge dynamically to a value close to l_{min} where growth with constant thickness then occurs. This description contrasts with those given by the two dominant theoretical approaches. However, at small supercoolings the rounding of the crystal profile does inhibit growth as suggested in Sadler and Gilmer's entropic barrier model.Comment: 12 pages, 13 figures, revte

Microfluidic integration of photonic crystal fibers for online photochemical reaction analysis

Liquid-filled hollow-core photonic crystal fibers (HC-PCFs) are perfect optofluidic channels, uniquely providing low-loss optical guidance in a liquid medium. As a result, the overlap of the dissolved specimen and the intense light field in the micronsized core is increased manyfold compared to conventional bioanalytical techniques, facilitating highly-efficient photoactivation processes. Here we introduce a novel integrated analytical technology for photochemistry by microfluidic coupling of a HC-PCF nanoflow reactor to supplementary detection devices. Applying a continuous flow through the fiber, we deliver photochemical reaction products to a mass spectrometer in an online and hence rapid fashion, which is highly advantageous over conventional cuvette-based approaches

Speciation of precious metal anti-cancer complexes by NMR spectroscopy

Understanding the mechanism of action of anti-cancer agents is of paramount importance for drug development. NMR spectroscopy can provide insights into the kinetics and thermodynamics of the binding of metallodrugs to biomolecules. NMR is most sensitive for highly abundant I = 1/2 nuclei with large magnetic moments. Polarization transfer can enhance NMR signals of insensitive nuclei at physiologically-relevant concentrations. This paper reviews NMR methods for speciation of precious metal anti-cancer complexes, including platinum-group and gold-based anti-cancer agents. Examples of NMR studies involving interactions with DNA and proteins in particular are highlighted

The elements of life and medicines

Which elements are essential for human life? Here we make an element-by-element journey through the periodic table and attempt to assess whether elements are essential or not, and if they are, whether there is a relevant code for them in the human genome. There are many difficulties such as the human biochemistry of several so-called essential elements is not well understood, and it is not clear how we should classify elements that are involved in the destruction of invading microorganisms, or elements which are essential for microorganisms with which we live in symbiosis. In general, genes do not code for the elements themselves, but for specific chemical species, i.e. for the element, its oxidation state, type and number of coordinated ligands, and the coordination geometry. Today, the biological periodic table is in a position somewhat similar to Mendeleev's chemical periodic table of 1869: there are gaps and we need to do more research to fill them. The periodic table also offers potential for novel therapeutic and diagnostic agents, based on not only essential elements, but also non-essential elements, and on radionuclides. Although the potential for inorganic chemistry in medicine was realized more than 2000 years ago, this area of research is still in its infancy. Future advances in the design of inorganic drugs require more knowledge of their mechanism of action, including target sites and metabolism. Temporal speciation of elements in their biological environments at the atomic level is a major challenge, for which new methods are urgently needed

The physical determinants of the thickness of lamellar polymer crystals

Based upon kinetic Monte Carlo simulations of crystallization in a simple polymer model we present a new picture of the mechanism by which the thickness of lamellar polymer crystals is constrained to a value close to the minimum thermodynamically stable thickness. This description contrasts with those given by the two dominant theoretical approaches.Comment: 4 pages, 4 figures, revte