How accurately can we predict the melting points of drug-like compounds?

© 2014 American Chemical Society. This article contributes a highly accurate model for predicting the melting points (MPs) of medicinal chemistry compounds. The model was developed using the largest published data set, comprising more than 47k compounds. The distributions of MPs in drug-like and drug lead sets showed that >90% of molecules melt within [50,250]°C. The final model calculated an RMSE of less than 33 °C for molecules from this temperature interval, which is the most important for medicinal chemistry users. This performance was achieved using a consensus model that performed calculations to a significantly higher accuracy than the individual models. We found that compounds with reactive and unstable groups were overrepresented among outlying compounds. These compounds could decompose during storage or measurement, thus introducing experimental errors. While filtering the data by removing outliers generally increased the accuracy of individual models, it did not significantly affect the results of the consensus models. Three analyzed distance to models did not allow us to flag molecules, which had MP values fell outside the applicability domain of the model. We believe that this negative result and the public availability of data from this article will encourage future studies to develop better approaches to define the applicability domain of models. The final model, MP data, and identified reactive groups are available online at http://ochem.eu/article/55638

Phylogeny, biogeography and diversification of the mining bee family Andrenidae

peer reviewedThe mining bees (Andrenidae) are a major bee family of over 3000 described species with a nearly global distribution. They are a particularly significant component of northern temperate ecosystems and are critical pollinators in natural and agricultural settings. Despite their ecological and evolutionary significance, our knowledge of the evolutionary history of Andrenidae is sparse and insufficient to characterize their spatiotemporal origin and phylogenetic relationships. This limits our ability to understand the diversification dynamics that led to the second most species-rich genus of all bees, Andrena Fabricius, and the most species-rich North American genus, Perdita Smith. Here, we develop a comprehensive genomic dataset of 195 species of Andrenidae, including all major lineages, to illuminate the evolutionary history of the family. Using fossil-informed divergence time estimates, we characterize macroevolutionary dynamics, incorporate paleoclimatic information, and present our findings in the context of diversification rate estimates for all other bee tribes. We found that diversification rates of Andrenidae steeply increased over the past 15 million years, particularly in the genera Andrena and Perdita. This suggests that these two groups and the brood parasites of the genus Nomada Scopoli (Apidae), which are the primary cleptoparasitic counterparts of Andrena, are similar in age and represent the fastest diversifying lineages of all bees. Using our newly developed time frame of andrenid evolution, we estimate a late Cretaceous origin in South America for the family and reconstruct the past dispersal events that led to its present-day distribution.15. Life on lan

National records of 3000 European bee and hoverfly species: A contribution to pollinator conservation

Pollinators play a crucial role in ecosystems globally, ensuring the seed production of most flowering plants. They are threatened by global changes and knowledge of their distribution at the national and continental levels is needed to implement efficient conservation actions, but this knowledge is still fragmented and/or difficult to access. As a step forward, we provide an updated list of around 3000 European bee and hoverfly species, reflecting their current distributional status at the national level (in the form of present, absent, regionally extinct, possibly extinct or non-native). This work was attainable by incorporating both published and unpublished data, as well as knowledge from a large set of taxonomists and ecologists in both groups. After providing the first National species lists for bees and hoverflies for many countries, we examine the current distributional patterns of these species and designate the countries with highest levels of species richness. We also show that many species are recorded in a single European country, highlighting the importance of articulating European and national conservation strategies. Finally, we discuss how the data provided here can be combined with future trait and Red List data to implement research that will further advance pollinator conservation

The wild bees (Hymenoptera: Apoidea) of Morocco

peer reviewedCliPS - Fédération Wallonie Bruxelle

Open Source Drug Discovery: Highly Potent Antimalarial Compounds Derived from the Tres Cantos Arylpyrroles

The development of new antimalarial compounds remains a pivotal part of the strategy for malaria elimination. Recent large-scale phenotypic screens have provided a wealth of potential starting points for hit-to-lead campaigns. One such public set is explored, employing an open source research mechanism in which all data and ideas were shared in real time, anyone was able to participate, and patents were not sought. One chemical subseries was found to exhibit oral activity but contained a labile ester that could not be replaced without loss of activity, and the original hit exhibited remarkable sensitivity to minor structural change. A second subseries displayed high potency, including activity within gametocyte and liver stage assays, but at the cost of low solubility. As an open source research project, unexplored avenues are clearly identified and may be explored further by the community; new findings may be cumulatively added to the present work

Versatile synthesis of Boc protected hydrazinoacetic acid and its application to the chemoselective ligation of TASP molecules

This paper describes a convenient synthesis of protected hydrazine derivatives, i.e. 1,2-bis-Boc-hydrazinoacetic acid, and its application for hydrazone ligation techniques in convergent template assembled synthetic protein (TASP) synthesis