Recent structural insight into mitochondria gained by microscopy

Novel applications of microscopy have recently provided new insights into mitochondrial structures. Diverse techniques such as high resolution scanning electron microscopy, transmission electron microscopy, electron microscope tomography and light microscopy have contributed a better understanding of mitochondrial compartmentalization, dynamic networks of mitochondria, intermembrane bridges, segregation of mitochondrial DNA and contacts with the endoplasmic reticulum among other aspects. This review focuses on advances reported in the last five years concerning aspects of mitochondrial substructure or dynamics gained through new techniques, whether they be novel microscope methods or new ways to prepare or label specimens. Sometimes these advances have produced surprising results and more often than not, they have challenged current conceptions of how mitochondria work.     

A computer-aided drug discovery system for chemistry teaching

The Schools Malaria Project (http://emalaria.soton.ac.uk/) brings together school students with university researchers in the hunt for a new antimalaria drug. The design challenge being offered to students is to use a distributed drug search and selection system to design potential antimalaria drugs. The system is accessed via a Web interface. This e-science project displays the results of the trials in an accessible manner, giving students an opportunity for discussion and debate both with peers and with the university contacts. The project has been implemented by using distributed computing techniques, spreading computer load over a network of machines that cross institutional boundaries, forming a grid. This provides access to greater computing power and allows a much more complex and detailed formulation of the drug design problem to be tackled for research, teaching, and learning.     

Gold catalysis: no steric limitations in the phenol synthesis

Different dihydroisoindol-4-ols and 8-hydroxytetrahydroisoquinolines were prepared by the gold-catalyzed phenol synthesis. The reaction was investigated with several sterically demanding groups in the 5-position of the furan starting material. The influence of the reaction time and the catalyst on the yield was investigated.     

13C solid-state NMR chromatography by magic angle spinning 1H T1 relaxation ordered spectroscopy

An efficient method to separate the ¹³C NMR spectra of solid mixtures is introduced. The ¹H longitudinal (T₁) relaxation time is used to separate the overlapping ¹³C chemical shift spectra of solid mixtures via an inverse Laplace transform (ILT) of the relaxation dimension. The resulting 2D spectrum of the mixture contains separate ¹³C spectra for each component of the mixture that are identical to ¹³C spectra of the isolated materials. The separation is based on the equalization of ¹H T₁ values in a single domain by rapid ¹H spin diffusion and on the ¹H T₁ value differences between different domains. The introduction of a general ILT scheme enables efficient and reduced data acquisition time. The method is demonstrated on a mixture of two disaccharides and on a commercial drug containing several compounds.     

2-pyridone: The role of out-of-plane vibrations on the S1<-->S0 spectra and S1 state reactivity

The S(1)<-->S(0) vibronic spectra of supersonic jet-cooled 2-pyridone [pyridin-2-one (2PY)] and its N-H deuterated isotopomer (d-2PY) have been recorded by two-color resonant two-photon ionization, laser-induced fluorescence and emission, and fluorescence depletion spectroscopies. By combining these methods, the B origin of 2PY at 0(0) (0)+98 cm(-1) and the bands at +218 and +252 cm(-1) are identified as overtones of the S(1) state out-of-plane vibrations nu(1) (') and nu(2) ('), as are the analogous bands of d-2PY. Anharmonic double-minimum potentials are derived for the respective out-of-plane coordinates that predict further nu(1) (') and nu(2) (') overtones and combinations, reproducing approximately 80% of the vibronic bands up to 600 cm(-1) above the 0(0) (0) band. The fluorescence spectra excited at the electronic origins and the nu(1) (') and nu(2) (') out-of-plane overtone levels confirm these assignments. The S(1) nonplanar minima and S(1)<--S(0) out-of-plane progressions are in agreement with the determination of nonplanar vibrationally averaged geometries for the 0(0) (0) and 0(0) (0)+98 cm(-1) upper states by Held et al. [J. Chem. Phys. 95, 8732 (1991)]. The fluorescence lifetimes of the S(1) state vibrations show strong mode dependence: Those of the out-of-plane levels decrease rapidly above 200 cm(-1) excess vibrational energy, while the in-plane vibrations nu(5) ('), nu(8) ('), and nu(9) (') have longer lifetimes, although they are above or interspersed with the "dark" out-of-plane states. This is interpreted in terms of an S(1) (') state reaction with a low barrier towards a conical intersection with a prefulvenic geometry. Out-of-plane vibrational states can directly surmount this barrier, whereas in-plane vibrations are much less efficient in this respect. Analysis of the fluorescence spectra allows to identify nine in-plane S(0) (') state fundamentals, overtones of the S(0) state nu(1) (") and nu(2) (") out-of-plane vibrations, and >30 other overtones and combination bands. The B3LYP6-311++G(d,p) calculated anharmonic wave numbers are in very good agreement with the observed fundamentals, overtones, and combinations, with a deviation Delta(rms)=1.3%.     

Understanding and controlling organic-inorganic interfaces in mesostructured hybrid photovoltaic materials

The chemical compositions and structures of organic-inorganic interfaces in mesostructurally ordered conjugated polymer-titania nanocomposites are shown to have a predominant influence on their photovoltaic properties. Such interfaces can be controlled by using surfactant structure-directing agents (SDAs) with different architectures and molecular weights to promote contact between the highly hydrophobic electron-donating conjugated polymer species and hydrophilic electron-accepting titania frameworks. A combination of small-angle X-ray scattering (SAXS), scanning and transmission electron microscopy (SEM, TEM), and solid-state NMR spectroscopy yields insights on the compositions, structures, and distributions of inorganic and organic species within the materials over multiple length scales. Two-dimensional NMR analyses establish the molecular-level interactions between the different SDA blocks, the conjugated polymer, and the titania framework, which are correlated with steady-state and time-resolved photoluminescence measurements of the photoexcitation dynamics of the conjugated polymer and macroscopic photocurrent generation in photovoltaic devices. Molecular understanding of the compositions and chemical interactions at organic-inorganic interfaces are shown to enable the design, synthesis, and control of the photovoltaic properties of hybrid functional materials.     

Synthesis and DNA binding properties of novel benzo[b]isoquino[2,3-h]-naphthyridines

Several benzo[b]isoquino[2,3-h]-naphthyridines have been prepared via formal hetero-Diels Alder reaction of N-aryl imines as a key step. These compounds have different side chains at C-11, and a cis or trans configuration at the C-8a,C-14a ring junction. Binding constants for the interaction with oligonucleotides and polynucleotides were determined by UV absorption and melting experiments. NMR experiments (NOE) revealed that the cis isomers, showing a slightly folded structure, preferentially bind to the minor groove of AT-rich oligomers. In contrast, the trans isomers prefer the CG-rich sequences, leading to cap-complexes with the isoquinoline moiety stacked at the top of the double helix, in agreement with the flatter shape, and with a preference for the 3'-terminals, as found for camptothecins. Models of the complexes were built up by molecular dynamics (MD) calculations, by using the inter-proton distances derived from the NOE values. Cytotoxicity assays against human Ewing sarcoma cell lines RD-ES and CAD-ES1 were performed.     

The semantic smart laboratory: a system for supporting the chemical eScientist

One goal of eScience is to enable the end-to-end publication of experiments and results. In the Combechem project we have developed an innovative human-centred system which captures the process of a chemistry experiment from plan to execution. The system comprises an electronic lab book replacement, which has been successfully trialled in a synthetic organic chemistry laboratory, and a flexible back-end storage system. Working closely with the users, we found that a light touch and a high degree of flexibility was required in the user interface. In this paper, we concentrate on the representation and storage of human-scale experiment metadata, introducing an ontology to describe the record of an experiment, and a storage system for the data from our lab book software. Just as the interfaces need to be flexible to cope with whatever a chemist wishes to record, so the back end solutions need to be similarly flexible to store any metadata that may be created. The storage system is based on Semantic Web technologies, such as RDF, and Web Services. It gives a much higher degree of flexibility to the type of metadata it can store, compared to the use of rigid relational databases.