Scaffold searching: automated identification of similar ring systems for the design of combinatorial libraries

Rigid ring systems can be used to position receptor-binding functional groups in 3D space and they thus play an increasingly important role in the design of combinatorial libraries. This paper discusses the use of shape-similarity methods to identify ring systems that are structurally similar to, and aligned with, a user-defined target ring system. These systems can be used as alternative scaffolds for the construction of a combinatorial library

Come-back of phenanthridine and phenanthridinium derivatives in 21st century

Phenanthridine derivatives are one of the most intensively studied families of biologically active compounds with efficient DNA binding ; attracting attention about time of DNA structure discovery (1960ies), early recognized as a symbol of DNA intercalative binding, for many decades applied as gold-standard DNA- and RNA-fluorescent markers (ethidium bromide), probes for cell viability (propidium iodide), but also “ill-famed” for various toxic (genotoxic) and mutagenic effects. After two decades of low interest, the discovery of phenanthridine alkaloids and new studies of antiparasitic/antitumour properties of phenanthridine derivatives resulted in the strong increase of the scientific interest about the turn of this century. Here are summarized phenanthridine-related advances in the 21st century (2000-present period) with emphasis on the supramolecular interactions and bioorganic chemistry, as well as novel or improved synthetic approaches

Organofluorine chemistry : difluoromethylene motifs spaced 1,3 to each other imparts facial polarity to a cyclohexane ring

This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) and the European Research Council (ERC). The authors acknowledge the EPSRC National Mass Spectrometry Facility (Swansea). D.O’H. thanks the Royal Society for a Wolfson Research Merit Award.2,2-Dimethyl-5-phenyl-1,1,3,3-tetrafluororocyclohexane has been prepared and characterised as an example of a facially polarised cyclohexane containing 1,3 related CF2 groups. The dipolar nature of the ring arises from the axial orientation of two of the C-F bonds pointing in the same direction, and set by the chair conformation of the cyclohexane. This electrostatic profile is revealed experimentally both in the solid-state (X-ray) packing of the rings and by solution (NMR) in different solvents. A computationally derived electrostatic profile of this compound is consistent with a more electronegative and a more electropositive face of the cyclohexane ring. This placing of CF2 groups 1,3 to each other in a cyclohexane ring is introduced as a new design strategy which could be applicable to the preparation of polar hydrophobic cyclohexane motifs.Publisher PDFPeer reviewe

Using natural language processing techniques to inform research on nanotechnology

Literature in the field of nanotechnology is exponentially increasing with more and more engineered nanomaterials being created, characterized, and tested for performance and safety. With the deluge of published data, there is a need for natural language processing approaches to semi-automate the cataloguing of engineered nanomaterials and their associated physico-chemical properties, performance, exposure scenarios, and biological effects. In this paper, we review the different informatics methods that have been applied to patent mining, nanomaterial/device characterization, nanomedicine, and environmental risk assessment. Nine natural language processing (NLP)-based tools were identified: NanoPort, NanoMapper, TechPerceptor, a Text Mining Framework, a Nanodevice Analyzer, a Clinical Trial Document Classifier, Nanotoxicity Searcher, NanoSifter, and NEIMiner. We conclude with recommendations for sharing NLP-related tools through online repositories to broaden participation in nanoinformatics

Storing the wisdom: chemical concepts and chemoinformatics

The purpose of the paper is to examine the nature of chemical concepts, and the ways in which they are applied in chemoinformatics systems. An account of concepts in philosophy and in the information sciences leads to an analysis of chemical concepts, and their representation. The way in which concepts are applied in systems for information retrieval and for structure–property correlation are reviewed, and some issues noted. Attention is focused on the basic concepts or substance, reaction and property, on the organising concepts of chemical structure, structural similarity, periodicity, and on more specific concepts, including two- and three-dimensional structural patterns, reaction types, and property concepts. It is concluded that chemical concepts, despite (or perhaps because of) their vague and mutable nature, have considerable and continuing value in chemoinformatics, and that an increased formal treatment of concepts may have value in the future

Biological evaluations of novel 2,3,3-Trisphosphonate in osteoclastic and osteoblastic activities

Bisphosphonates (BPs) are the first line treatment for many bone diseases including hypercalcimia associated with bone malignancies. In this paper, we introduce a new analogue of bisphosphonate called the 2,3,3-Trisphosphonate (2,3,3-TriPP) that was synthesised in a two steps reaction. In vitro investigations using a medically known bisphosphonate (Etidronate) and the 2,3,3-TrisPP were performed with an aim to evaluate biological effect of this novel compound in major bone cells. 2,3,3-TrisPP showed to have potential to supress the bone resorption process, as our data found that this novel compound exhibited cytotoxic effect in osteoclastic cells at a low concentration of 0.172 mg/mL (LC50). A molecular docking computational simulation calculated a high level of binding affinity between the human farnesyl pyrophosphate synthase (hFPPS) and 2,3,3-TrisPP. This calculation suggested 2,3,3TrisPP may have undergone the mevalonate pathway to prevent the prenylation step during biosynthesis and subsequently resulted in the deactivation of osteoclastic cells. Finally, high levels of osteoblast mineralisation potentials were recorded upon treatments with 2,3,3-TrisPP (0.01-0.1 mg/ml), which implied 2,3,3-TrsiPP may also facilitate bone regeneration.Peer reviewe

Storing the wisdom: chemical concepts and chemoinformatics

The purpose of the paper is to examine the nature of chemical concepts, and the ways in which they are applied in chemoinformatics systems. An account of concepts in philosophy and in the information sciences leads to an analysis of chemical concepts, and their representation. The way in which concepts are applied in systems for information retrieval and for structure–property correlation are reviewed, and some issues noted. Attention is focused on the basic concepts or substance, reaction and property, on the organising concepts of chemical structure, structural similarity, periodicity, and on more specific concepts, including two- and three-dimensional structural patterns, reaction types, and property concepts. It is concluded that chemical concepts, despite (or perhaps because of) their vague and mutable nature, have considerable and continuing value in chemoinformatics, and that an increased formal treatment of concepts may have value in the future

In search of lost time constants and of non-Michaelis–Menten parameters

SummaryUpon completing 100 years since it was published, the work Die Kinetik der Invertinwirkung by Michaelis and Menten (MM) was celebrated during the 6th Beilstein ESCEC Symposium 2013. As the 7th Beilstein ESCEC Symposium 2015 debates enzymology in the context of complex biological systems, a post-MM approach is required to address cell-like conditions that are well beyond the steady-state limitations. The present contribution specifically addresses two hitherto ambiguous constants whose interest was, however, intuited in the original MM paper: (i) the characteristic time constant τ∞, which can be determined using the late stages of any progress curve independently of the substrate concentration adopted; and (ii) the dissociation constant KS, which is indicative of the enzyme–substrate affinity and completes the kinetic portrayal of the Briggs–Haldane reaction scheme. The rationale behind τ∞ and KS prompted us to revise widespread concepts of enzyme's efficiency, defined by the specificity constant kcat/KM, and of the Michaelis constant KM seen as the substrate concentration yielding half-maximal rates. The alternative definitions here presented should help recovering the wealth of published kcat/KM and KM data from the criticism that they are subjected. Finally, a practical method is envisaged for objectively determining enzyme's activity, efficiency and affinity – (EA)2 – from single progress curves. The (EA)2 assay can be conveniently applied even when the concentrations of substrate and enzyme are not accurately known

Lattice thermal conductivity of graphene nanostructures

Non-equilibrium molecular dynamics is used to investigate the heat current due to the atomic lattice vibrations in graphene nanoribbons and nanorings under a thermal gradient. We consider a wide range of temperature, nanoribbon widths up to 6nm and the effect of moderate edge disorder. We find that narrow graphene nanorings can efficiently suppress the lattice thermal conductivity at low temperatures (~100K), as compared to nanoribbons of the same width. Remarkably, rough edges do not appear to have a large impact on lattice energy transport through graphene nanorings while nanoribbons seem more affected by imperfections. Furthermore, we demonstrate that the effects of hydrogen-saturated edges can be neglected in these graphene nanostructures