Mechanistic Studies of Homo- and Heterodinuclear Zinc Phosphoesterase Mimics: What Has Been Learned?

Phosphoesterases hydrolyze the phosphorus oxygen bond of phosphomono-, di- or triesters and are involved in various important biological processes. Carboxylate and/or hydroxido-bridged dizinc(II) sites are a widespread structural motif in this enzyme class. Much effort has been invested to unravel the mechanistic features that provide the enormous rate accelerations observed for enzymatic phosphate ester hydrolysis and much has been learned by using simple low-molecular-weight model systems for the biological dizinc(II) sites. This review summarizes the knowledge and mechanistic understanding of phosphoesterases that has been gained from biomimetic dizinc(II) complexes, showing the power as well as the limitations of model studies

Ethyl N-[2-(4-phenoxyphenoxy)ethyl]-carbamate

peer-reviewedThe title compound, C17H19NO4, which is a non-toxic insect growth regulator with the common name fenoxycarb, contains two independent and conformationally different molecules in the asymmetric unit. Although the inter-ring dihedral angles are similar [62.21 (15) and 63.00 (14) ], the side-chain orientations differ. In the crystal, the molecules are linked through N—H O hydrogen-bonding associations, giving chains which extend along [110], while intra- and intermolecular aromatic C—H interactions give sheet structures parallel to [110].PUBLISHEDpeer-reviewe

Estrogens-functionalized metal complexes: selective anticancer and antibacterial activity

The abstract is included in the text

Crystalline adducts of the Lawsone molecule (2-hydroxy-1,4-naphthaquinone): optical properties and computational modelling

Four new crystalline adducts of the Lawsone molecule (2-hydroxy-1,4-naphthaquinone) with 4,4'-bipyridine, 4-(2-pyridine-4-ethyl)pyridine, 1,3-di.4-pyridyl)propane and 2-hydroxy pyridine are reported. Adduct formation leads to colour shifts, which are characterised by UV/visible spectroscopy. Complementary quantum-chemical calculations are used to study the energetics of the adduct formation, and to gain insight into the origin of the observed colour changes

Sulfamerazine:understanding the influence of slip-planes in polymorphic phase-transformation through X-ray crystallographic studies and <i>ab initio</i> lattice dynamics

Understanding the polymorphism exhibited by organic active-pharmaceutical ingredients (APIs), in particular the relationships between crystal structure and the thermodynamics of polymorph stability, is vital for the production of more stable drugs and better therapeutics, and for the economics of the pharmaceutical industry in general. In this article, we report a detailed study of the structure–property relationships among the polymorphs of the model API, Sulfamerazine. Detailed experimental characterization using synchrotron radiation is complemented by computational modeling of the lattice dynamics and mechanical properties, in order to study the origin of differences in millability and to investigate the thermodynamics of the phase equilibria. Good agreement is observed between the simulated phonon spectra and mid-infrared and Raman spectra. The presence of slip planes, which are found to give rise to low-frequency lattice vibrations, explains the higher millability of Form I compared to Form II. Energy/volume curves for the three polymorphs, together with the temperature dependence of the thermodynamic free energy computed from the phonon frequencies, explains why Form II converts to Form I at high temperature, whereas Form III is a rare polymorph that is difficult to isolate. The combined experimental and theoretical approach employed here should be generally applicable to the study of other systems that exhibit polymorphism

The RNA workbench: Best practices for RNA and high-throughput sequencing bioinformatics in Galaxy

RNA-based regulation has become a major research topic in molecular biology. The analysis of epigenetic and expression data is therefore incomplete if RNA-based regulation is not taken into account. Thus, it is increasingly important but not yet standard to combine RNA-centric data and analysis tools with other types of experimental data such as RNA-seq or ChIP-seq. Here, we present the RNA workbench, a comprehensive set of analysis tools and consolidated workflows that enable the researcher to combine these two worlds. Based on the Galaxy framework the workbench guarantees simple access, easy extension, flexible adaption to personal and security needs, and sophisticated analyses that are independent of command-line knowledge. Currently, it includes more than 50 bioinformatics tools that are dedicated to different research areas of RNA biology including RNA structure analysis, RNA alignment, RNA annotation, RNA-protein interaction, ribosome profiling, RNA-seq analysis and RNA target prediction. The workbench is developed and maintained by experts in RNA bioinformatics and the Galaxy framework. Together with the growing community evolving around this workbench, we are committed to keep the workbench up-to-date for future standards and needs, providing researchers with a reliable and robust framework for RNA data analysis

Community-Driven Data Analysis Training for Biology

The primary problem with the explosion of biomedical datasets is not the data, not computational resources, and not the required storage space, but the general lack of trained and skilled researchers to manipulate and analyze these data. Eliminating this problem requires development of comprehensive educational resources. Here we present a community-driven framework that enables modern, interactive teaching of data analytics in life sciences and facilitates the development of training materials. The key feature of our system is that it is not a static but a continuously improved collection of tutorials. By coupling tutorials with a web-based analysis framework, biomedical researchers can learn by performing computation themselves through a web browser without the need to install software or search for example datasets. Our ultimate goal is to expand the breadth of training materials to include fundamental statistical and data science topics and to precipitate a complete re-engineering of undergraduate and graduate curricula in life sciences. This project is accessible at https://training.galaxyproject.org. We developed an infrastructure that facilitates data analysis training in life sciences. It is an interactive learning platform tuned for current types of data and research problems. Importantly, it provides a means for community-wide content creation and maintenance and, finally, enables trainers and trainees to use the tutorials in a variety of situations, such as those where reliable Internet access is unavailable

Investigation of non-covalent interactions of metal complexes with DNA in cell-free systems

Non-covalent interactions of metallo compounds with DNA range from the simple, unspecific electrostatic binding of a positively charged metal complex to the sequence-selective recognition of DNA binding sites due to shape, size, symmetry and hydrogen bonding complementarity of a rationally designed system. Metal complexes that recognize and target specific DNA sequences or particular structures are of considerable interest as therapeutics, diagnostics or structural probes. To gain molecular level insight into DNA metal complex interactions, binding studies are carried out in cell-free systems using isolated DNA or short oligonucleotides. For this, a powerful toolbox of complementary spectroscopic and biophysical techniques is available. This review focuses on the most frequently applied spectroscopic methods; UVNis, CD, LD, fluorescence emission and NMR spectroscopy and is aimed at giving the reader an overview of the qualitative and/or quantitative information that can be obtained. After a short introduction into DNA structures and non-covalent metal complex DNA interactions, each spectroscopic method will be discussed. In the last section a few selected studies will be described as illustrative examples for the potential of the various spectroscopic methods.peer-reviewe

Investigation of Non-covalent Interactions of Metal Complexes with DNA in Cell-free Systems

Non-covalent interactions of metallo compounds with DNA range from the simple, unspecific electrostatic binding of a positively charged metal complex to the sequence-selective recognition of DNA binding sites due to shape, size, symmetry and hydrogen bonding complementarity of a rationally designed system. Metal complexes that recognize and target specific DNA sequences or particular structures are of considerable interest as therapeutics, diagnostics or structural probes. To gain molecular level insight into DNA–metal complex interactions, binding studies are carried out in cell-free systems using isolated DNA or short oligonucleotides. For this, a powerful toolbox of complementary spectroscopic and biophysical techniques is available. This review focuses on the most frequently applied spectroscopic methods; UV/Vis, CD, LD, fluorescence emission and NMR spectroscopy and is aimed at giving the reader an overview of the qualitative and/or quantitative information that can be obtained. After a short introduction into DNA structures and non-covalent metal complex–DNA interactions, each spectroscopic method will be discussed. In the last section a few selected studies will be described as illustrative examples for the potential of the various spectroscopic methods