Unusual DNA binding modes for metal anticancer complexes

DNA is believed to be the primary target for many metal-based drugs. For example, platinum-based anticancer drugs can form specific lesions on DNA that induce apoptosis. New platinum drugs can be designed that have novel modes of interaction with DNA, such as the trinuclear platinum complex BBR3464. Also it is possible to design inert platinum(IV) pro-drugs which are non-toxic in the dark, but lethal when irradiated with certain wavelengths of light. This gives rise to novel DNA lesions which are not as readily repaired as those induced by cisplatin, and provides the basis for a new type of photoactivated chemotherapy. Finally, newly emerging ruthenium(II) organometallic complexes not only bind to DNA coordinatively, but also by H-bonding and hydrophobic interactions triggered by the introduction of extended arene rings into their versatile structures. Intriguingly osmium (the heavier congener of ruthenium) reacts differently with DNA but can also give rise to highly cytotoxic organometallic complexes

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

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

Photoactivation of trans diamine platinum complexes in aqueous solution and effect on reactivity towards nucleotides

We show that UVA irradiation (365 nm) of the Pt-IV complex trans,trans,trans-[(PtCl2)-Cl-IV(OH)(2)(dimethylamine) (isopropylamine)] (1), induces reduction to Pt-II photoproducts. For the mixed amine Pt-II complex, trans[(PtCl2)-Cl-II(isopropylamine)(methylamine)] (2), irradiation at 365 nm increases the rate and extent of hydrolysis, triggering the formation of diaqua species. Additionally, irradiation increases the extent of reaction of complex 2 with guanosine-5'-monophosphate and affords mainly the bis-adduct, while reactions with adenosine-5'-monophosphate and cytidine-5'-monophosphate give rise only to mono-nucleotide adducts. Density Functional Theory calculations have been used to obtain insights into the electronic structure of complexes 1 and 2, and their photophysical and photochemical properties. UVA-irradiation can contribute to enhanced cytotoxic effects of diamine platinum drugs with trans geometry

Classroom assessment and education: challenging the assumptions of socialisation and instrumentality

The opportunity offered by the Umea Symposium to probe the intersection of quality and assessment immediately brings into focus a wider issue – that of the quality of education which assessment aspires to support. Prompted by recent research into formative assessment in Scottish primary school contexts, the paper explores how formative assessment has become associated with an overly benign understanding of learning which misrecognises the possibility of undesirable learning and does not seem to address the inherently political nature of education. Having illuminated the potential inequities of formative assessment practices, the paper then asks what role formative assessment might play to support an understanding of education that is not simply about the transmission of traditional social norms, but also aspires to illuminate their social construction and their political nature

Allosteric modulation of zinc speciation by fatty acids

Background: Serum albumin is the major protein component of blood plasma and is responsible for the circulatory transport of a range of small molecules that include fatty acids, hormones, metal ions and drugs. Studies examining the ligand-binding properties of albumin make up a large proportion of the literature. However, many of these studies do not address the fact that albumin carries multiple ligands (including metal ions) simultaneously in vivo. Thus the binding of a particular ligand may influence both the affinity and dynamics of albumin interactions with another. Scope of review: Here we review the Zn2 + and fatty acid transport properties of albumin and highlight an important interplay that exists between them. Also the impact of this dynamic interaction upon the distribution of plasma Zn2 +, its effect upon cellular Zn2 + uptake and its importance in the diagnosis of myocardial ischemia are considered. Major conclusions: We previously identified the major binding site for Zn2 + on albumin. Furthermore, we revealed that Zn2 +-binding at this site and fatty acid-binding at the FA2 site are interdependent. This suggests that the binding of fatty acids to albumin may serve as an allosteric switch to modulate Zn2 +-binding to albumin in blood plasma. General significance: Fatty acid levels in the blood are dynamic and chronic elevation of plasma fatty acid levels is associated with some metabolic disorders such as cardiovascular disease and diabetes. Since the binding of Zn2 + to albumin is important for the control of circulatory/cellular Zn2 + dynamics, this relationship is likely to have important physiological and pathological implications. This article is part of a Special Issue entitled Serum Albumin

Anti-colorectal cancer activity of an organometallic osmium arene azopyridine complex

This first in vivo antitumour activity for an organometallic osmium arene complex, [Os(eta(6)-p-cym)(4-(2-pyridylazo)-N,N-dimethylaniline)I]PF(6), is reported. The complex delays the growth of HCT116 human colon cancer xenografts in mice, with negligible toxicity. Its activity appears to involve redox mechanisms and its potency towards A2780 ovarian and A549 lung cancer cells is increased significantly in combination with L-buthionine-sulfoximine

SN1997cy/GRB970514 - A New Piece in the GRB Puzzle?

We present observations of SN1997cy, a supernova discovered as part of the Mount Stromlo Abell Cluster SN Search, which does not easily fit into the traditional classification scheme for supernovae. This object's extraordinary optical properties and coincidence with GRB970514, a short duration gamma ray burst, suggest a second case, after SN1998bw/GRB980425, for a SN-GRB association. SN1997cy is among the most luminous SNe yet discovered and has a peculiar spectrum. We present evidence that SN1997cy ejected approximately 2 solar masses of 56Ni, supported by its late-time light curve, and FeII/[FeIII] lines in its spectrum, although it is possible that both these observations can be explained via circumstellar interaction. While SN1998bw and SN1997cy appear to be very different objects with respect to both their gamma ray and optical properties, SN1997cy and the optical transient associated with GRB970508 have roughly similar late-time optical behavior. This similarity may indicate that the late-time optical output of these two intrinsically bright transient events have a common physical process. Although the connection between GRB970514 and SN1997cy is suggestive, it is not conclusive. However, if this association is real, followup of short duration GRBs detected with BATSE or HETE2 should reveal objects similar to SN1997cy.Comment: 26 pages including 6 postscript figures and 3 tables. Submitted to ApJ. Re-calibrated photometry - objects are about 0.3mags brighter than in original versio