The expansion of chemical space in 1826 and in the 1840s prompted the convergence to the periodic system.

The periodic system, which intertwines order and similarity among chemical elements, arose from knowledge about substances constituting the chemical space. Little is known, however, about how the expansion of the space contributed to the emergence of the system-formulated in the 1860s. Here, we show by analyzing the space between 1800 and 1869 that after an unstable period culminating around 1826, chemical space led the system to converge to a backbone structure clearly recognizable in the 1840s. Hence, the system was already encoded in the space for about two and half decades before its formulation. Chemical events in 1826 and in the 1840s were driven by the discovery of new forms of combination standing the test of time. Emphasis of the space upon organic chemicals after 1830 prompted the recognition of relationships among elements participating in the organic turn and obscured some of the relationships among transition metals. To account for the role of nineteenth century atomic weights upon the system, we introduced an algorithm to adjust the space according to different sets of weights, which allowed for estimating the resulting periodic systems of chemists using one or the other weights. By analyzing these systems, from Dalton up to Mendeleev, Gmelin's atomic weights of 1843 produce systems remarkably similar to that of 1869, a similarity that was reinforced by the atomic weights on the years to come. Although our approach is computational rather than historical, we hope it can complement other tools of the history of chemistry.

Molecular basis of the anchoring and stabilization of human islet amyloid polypeptide in lipid hydroperoxidized bilayers.

The molecular structure of membrane lipids is formed by mono- or polyunsaturations on their aliphatic tails that make them susceptible to oxidation, facilitating the incorporation of hydroperoxide (R-OOH) functional groups. Such groups promote changes in both composition and complexity of the membrane significantly modifying its physicochemical properties. Human Langerhans islets amyloid polypeptide (hIAPP) is the main component of amyloid deposits found in the pancreas of patients with type-2 diabetes (T2D). hIAPP in the presence of membranes with oxidized lipid species accelerates the formation of amyloid fibrils or the formation of intermediate oligomeric structures. However, the molecular bases at the initial stage of the anchoring and stabilization of the hIAPP in a hydroperoxidized membrane are not yet well understood. To shed some light on this matter, in this contribution, three bilayer models were modeled: neutral (POPC), anionic (POPS), and oxidized (POPCOOH), and full atom Molecular Dynamics (MD) simulations were performed. Our results show that the POPCOOH bilayer increases the helicity in hIAPP when compared to POPC or POPS bilayer. The modification in the secondary structure covers the residues of the so-called amyloidogenic core of the hIAPP. Overall, the hydroperoxidation of the neutral lipids modifies both the anchoring and the stabilization of the peptide hIAPP by reducing the random conformations of the peptide and increasing of hydrogen bond population with the hydroperoxidized lipids.

Exploration of the chemical space and its three historical regimes.

Chemical research unveils the structure of chemical space, spanned by all chemical species, as documented in more than 200 y of scientific literature, now available in electronic databases. Very little is known, however, about the large-scale patterns of this exploration. Here we show, by analyzing millions of reactions stored in the Reaxys database, that chemists have reported new compounds in an exponential fashion from 1800 to 2015 with a stable 4.4% annual growth rate, in the long run neither affected by World Wars nor affected by the introduction of new theories. Contrary to general belief, synthesis has been the means to provide new compounds since the early 19th century, well before Wöhler's synthesis of urea. The exploration of chemical space has followed three statistically distinguishable regimes. The first one included uncertain year-to-year output of organic and inorganic compounds and ended about 1860, when structural theory gave way to a century of more regular and guided production, the organic regime. The current organometallic regime is the most regular one. Analyzing the details of the synthesis process, we found that chemists have had preferences in the selection of substrates and we identified the workings of such a selection. Regarding reaction products, the discovery of new compounds has been dominated by very few elemental compositions. We anticipate that the present work serves as a starting point for more sophisticated and detailed studies of the history of chemistry.

How frequently do clusters occur in hierarchical clustering analysis? A graph theoretical approach to studying ties in proximity.

BACKGROUND: Hierarchical cluster analysis (HCA) is a widely used classificatory technique in many areas of scientific knowledge. Applications usually yield a dendrogram from an HCA run over a given data set, using a grouping algorithm and a similarity measure. However, even when such parameters are fixed, ties in proximity (i.e. two equidistant clusters from a third one) may produce several different dendrograms, having different possible clustering patterns (different classifications). This situation is usually disregarded and conclusions are based on a single result, leading to questions concerning the permanence of clusters in all the resulting dendrograms; this happens, for example, when using HCA for grouping molecular descriptors to select that less similar ones in QSAR studies. RESULTS: Representing dendrograms in graph theoretical terms allowed us to introduce four measures of cluster frequency in a canonical way, and use them to calculate cluster frequencies over the set of all possible dendrograms, taking all ties in proximity into account. A toy example of well separated clusters was used, as well as a set of 1666 molecular descriptors calculated for a group of molecules having hepatotoxic activity to show how our functions may be used for studying the effect of ties in HCA analysis. Such functions were not restricted to the tie case; the possibility of using them to derive cluster stability measurements on arbitrary sets of dendrograms having the same leaves is discussed, e.g. dendrograms from variations of HCA parameters. It was found that ties occurred frequently, some yielding tens of thousands of dendrograms, even for small data sets. CONCLUSIONS: Our approach was able to detect trends in clustering patterns by offering a simple way of measuring their frequency, which is often very low. This would imply, that inferences and models based on descriptor classifications (e.g. QSAR) are likely to be biased, thereby requiring an assessment of their reliability. Moreover, any classification of molecular descriptors is likely to be far from unique. Our results highlight the need for evaluating the effect of ties on clustering patterns before classification results can be used accurately.Graphical abstractFour cluster contrast functions identifying statistically sound clusters within dendrograms considering ties in proximity.

Lemont B. Kier: a bibliometric exploration of his scientific production and its use.

We thought an appropriate way to celebrate the seminal contribution of Kier is to explore his influence on science, looking for the impact of his research through the citation of his scientific production. From a bibliometric approach the impact of Kier's work is addressed as an individual within a community. Reviewing data from his curriculum vitae, as well as from the ISI Web of Knowledge (ISI), his role within the scientific community is established and the way his scientific results circulate is studied. His curriculum vitae is explored emphasising the approaches he used in his research activities and the social ties with other actors of the community. The circulation of Kier's publications in the ISI is studied as a means for spreading and installing his discourse within the community. The citation patterns found not only show the usage of Kier's scientific results, but also open the possibility to identify some characteristics of this discursive community, such as a common vocabulary and common research goals. The results show an interdisciplinary research work that consolidates a scientific community on the topic of drug discovery.

Three dissimilarity measures to contrast dendrograms.

We discussed three dissimilarity measures between dendrograms defined over the same set, they are triples, partition, and cluster indices. All of them decompose the dendrograms into subsets. In the case of triples and partition indices, these subsets correspond to binary partitions containing some clusters, while in the cluster index, a novel dissimilarity method introduced in this paper, the subsets are exclusively clusters. In chemical applications, the dendrograms gather clusters that contain similarity information of the data set under study. Thereby, the cluster index is the most suitable dissimilarity measure between dendrograms resulting from chemical investigation. An application example of the three measures is shown to remark upon the advantages of the cluster index over the other two methods in similarity studies. Finally, the cluster index is used to measure the differences between five dendrograms obtained when applying five common hierarchical clustering algorithms on a database of 1000 molecules.

Topological study of the periodic system.

We carried out a topological study of the Space of Chemical Elements, SCE, based on a clustering analysis of 72 elements, each one defined by a vector of 31 properties. We looked for neighborhoods, boundaries, and other topological properties of the SCE. Among the results one sees the well-known patterns of the Periodic Table and relationships such as the Singularity Principle and the Diagonal Relationship, but there appears also a robustness property of some of the better-known families of elements. Alkaline metals and Noble Gases are sets whose neighborhoods have no other elements besides themselves, whereas the topological boundary of the set of metals is formed by semimetallic elements.