Using remote substituents to control solution structure and anion binding in lanthanide complexes.

A study of the anion-binding properties of three structurally related lanthanide complexes, which all contain chemically identical anion-binding motifs, has revealed dramatic differences in their anion affinity. These arise as a consequence of changes in the substitution pattern on the periphery of the molecule, at a substantial distance from the binding pocket. Herein, we explore these remote substituent effects and explain the observed behaviour through discussion of the way in which remote substituents can influence and control the global structure of a molecule through their demands upon conformational space. Peripheral modifications to a binuclear lanthanide motif derived from α,α′-bis(DO3 Ayl)-m-xylene are shown to result in dramatic changes to the binding constant for isophthalate. In this system, the parent compound displays considerable conformational flexibility, yet can be assumed to bind to isophthalate through a well-defined conformer. Addition of steric bulk remote from the binding site restricts conformational mobility, giving rise to an increase in binding constant on entropic grounds as long as the ideal binding conformation is not excluded from the available range of conformers

Using Remote Substituents to Control Solution Structure and Anion Binding in Lanthanide Complexes

A study of the anion-binding properties of three structurally related lanthanide complexes, which all contain chemically identical anion-binding motifs, has revealed dramatic differences in their anion affinity. These arise as a consequence of changes in the substitution pattern on the periphery of the molecule, at a substantial distance from the binding pocket. Herein, we explore these remote substituent effects and explain the observed behaviour through discussion of the way in which remote substituents can influence and control the global structure of a molecule through their demands upon conformational space. Peripheral modifications to a binuclear lanthanide motif derived from α,α′-bis(DO3 Ayl)-m-xylene are shown to result in dramatic changes to the binding constant for isophthalate. In this system, the parent compound displays considerable conformational flexibility, yet can be assumed to bind to isophthalate through a well-defined conformer. Addition of steric bulk remote from the binding site restricts conformational mobility, giving rise to an increase in binding constant on entropic grounds as long as the ideal binding conformation is not excluded from the available range of conformers

Gemcitabine-mediated tumour regression and p53-dependent gene expression: implications for colon and pancreatic cancer therapy

Gemcitabine is a chemotherapeutic that is widely used for the treatment of a variety of haematological malignancies and has become the standard chemotherapy for the treatment of advanced pancreatic cancer. Combinational gemcitabine regimes (e.g. with doxorubicin) are being tested in clinical trials to treat a variety of cancers, including colon cancer. The limited success of these trials has prompted us to pursue a better understanding of gemcitabine's mechanism of cell killing, which could dramatically improve the therapeutic potential of this agent. For comparison, we included gamma irradiation that triggers robust cell cycle arrest and Cr(VI), which is a highly toxic chemical that induces a robust p53-dependent apoptotic response. Gemcitabine induced a potent p53-dependent apoptosis that correlated with the accumulation of pro-apoptotic proteins such as PUMA and Bax. This is accompanied by a drastic reduction in p2l and 14-3-3 sigma protein levels, thereby significantly sensitizing the cells to apoptosis. In vitro and in vivo studies demonstrated that gemcitabine required PUMA transcription to instigate an apoptotic programme. This was in contrast to Cr(VI)-induced apoptosis that required Bax and was independent of transcription. An examination of clinical colon and pancreatic cancer tissues shows higher p53, p21, 14-3-3 sigma and Bax expression compared with matched normal tissues, yet there is a near absence of PUMA protein. This may explain why gemcitabine shows only limited efficacy in the treatment of these cancers. Our results raise the possibility that targeting the Bax-dependent cell death pathway, rather than the PUMA pathway, could result in significantly improved patient outcome and prognosis for these cancers.Fundacao para a Ciencia e a Tecnologia (FCT) [SFRH/BPD/84634/2012]; European Union [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Canadian Institute of Health Researchinfo:eu-repo/semantics/publishedVersio

Homes of the London poor

Cottage property in London.--Four years management of a London court.--Landlords and tenants in London.--The work of volunteers in the organization of charity.--Co-operation of volunteers and poor-law officials.--Why the Artisans dwellings bill was wanted.--Space for the people.Mode of access: Internet

Octavia Hill & open spaces

Lecture delivered at Wisbech (GB), 4 Oct 1993Available from British Library Document Supply Centre-DSC:2250.0522(3) / BLDSC - British Library Document Supply CentreSIGLE2. ed.GBUnited Kingdo

Mulheres praticantes de skate e de rugby no Brasil : histórias a serem narradas

The self-assembly of higher order structures in water is realised by using the association of 1,3-biscarboxylates to binuclear meta-xylyl bridged DO3A complexes. Two dinicotinate binding sites are placed at a right-angle in a rhenium complex, which is shown to form a 1 : 2 complex with α,α'-bis(Eu·DO3A)-5-amino-m-xylene

The relationship between Bordetella pertussis genotype and clinical severity in Australian children with pertussis

Abstract not availableMichelle Clarke, Peter B. McIntyre, Christopher C. Blyth, Nick Wood, Sophie Octavia, Vitali Sintchenko, Lynne Giles, Helen Quinn, Verity Hill, Gabrielle Hanly, Ruiting Lan, Helen S. Marshal