Assessing how well a modeling protocol captures a structure-activity landscape

We introduce the notion of structure-activity landscape index (SALI) curves as a way to assess a model and a modeling protocol, applied to structure-activity relationships. We start from our earlier work [ J. Chem. Inf. Model., 2008, 48, 646-658], where we show how to study a structure-activity relationship pairwise, based on the notion of "activity cliffs"-pairs of molecules that are structurally similar but have large differences in activity. There, we also introduced the SALI parameter, which allows one to identify cliffs easily, and which allows one to represent a structure-activity relationship as a graph. This graph orders every pair of molecules by their activity. Here, we introduce the new idea of a SALI curve, which tallies how many of these orderings a model is able to predict. Empirically, testing these SALI curves against a variety of models, ranging over two-dimensional quantitative structure-activity relationship (2D-QSAR), three-dimensional quantitative structure-activity relationship (3D-QSAR), and structure-based design models, the utility of a model seems to correspond to characteristics of these curves. In particular, the integral of these curves, denoted as SCI and being a number ranging from -1.0 to 1.0, approaches a value of 1.0 for two literature models, which are both known to be prospectively useful.     

Changing dynamical complexity with time delay in coupled fiber laser oscillators

We investigate the complexity of the dynamics of two mutually coupled systems with internal delays and vary the coupling delay over 4 orders of magnitude. Karhunen-Loève decomposition of spatiotemporal representations of fiber laser intensity data is performed to examine the eigenvalue spectrum and significant orthogonal modes. We compute the Shannon information from the eigenvalue spectra to quantify the dynamical complexity. A reduction in complexity occurs for short coupling delays while a logarithmic growth is observed as the coupling delay is increased.     

A radical mediated approach to the stereoselective formal total synthesis of (+)-Sch 642305

A formal total synthesis of (+)-Sch-642305 is described. The synthesis, which commenced from a simple chiral synthon (5S)-5-(hydroxymethyl)dihydrofuran-2(3H)-one, employed, as a key step, a radical mediated opening of a chiral epoxy alcohol intermediate with Cp₂Ti(III)Cl following an efficient method developed by us earlier. The resultant intermediate radical was intramolecularly trapped by the electron deficient double bond present in the molecule to give rise to its highly functionalized six-membered carbocyclic ring in stereoselective manner.     

Polymer-mediated spatial organization of nanoparticles in dense melts: Transferability and an effective one-component approach

We study two problems in the framework of the integral equation theory of polymer-mediated spatial organization of nanoparticles in dense melts motivated by multiscale simulation and many body physics issues. How nonspherical nanoparticle shape modifies polymer-induced interactions under dilute nanoparticle conditions is investigated over a range of primary particle sizes and interfacial cohesion strengths. Nonuniversal consequences of nonspherical shape are found for the pair-correlation function on local scales and some qualitative differences on larger scales due primarily to intraparticle connectivity constraints. For a large enough nanoparticle site diameter, the potentials of mean force (PMF) for all shapes studied (sphere, rod, disk, compact tetrahedral cluster) exhibit linear scaling with the size ratio of nanoparticle to polymer monomer site diameter and quite good "transferability." The ability of a simple effective one-component approach, based on the dilute nanoparticle PMF as an effective pair-decomposable potential, to describe interparticle structure at nonzero volume fractions is also studied. Although not generally quantitatively accurate due to neglect of many body correlation effects, especially at high nanoparticle loadings and near contact separations, the simple approach captures rather well many aspects of the real space structure. The errors incurred depend systematically on whether interfacial cohesion strength results in contact aggregation, steric stabilization, or bridging. For the filler collective static structure factor, many body effects are weakest for local cage scale correlations and grow significantly at smaller wavevectors under depletion or bridging conditions.     

Doubly Bridged Dinuclear Cadmium(II)azido Schiff Base Complexes: Synthesis, X-Ray Structure and Luminescence Properties of [Cd(L)(N3)]2(Y)2 [L = Schiff Bases, Y = ClO4 −, PF6 −]

Three new Schiff bases, -(bis(pyridin-2-yl)alkylidene)butane-1,4-diamine [(py)(R)C=N-(CH)N=C(R)(py), L: py = pyridine; R = H, -(bis(pyridin-2-yl)formylidene)butane-1,4-diamine (bpfd); R = Me, -(bis(pyridin-2-yl)methylidene)butane-1,4-diamine (bpmd); R = C, -(bis(pyridin-2-yl)bezylidene)butane-1,4-diamine (bpbd)] were prepared and used to synthesize six dinuclear cadmium(II)azido complexes of type [Cd(L)(N)](Y) [L = bpfd, Y = ClO (1a); L = bpfd, Y = PF (1b); L = bpmd, Y = ClO (2a); L = bpmd, Y = PF (2b); L = bpbd, Y = ClO (3a); and L = bpbd, Y = PF (3b)]. Two representative members of the series, 3a and 3b, have been characterized by single crystal X-ray diffraction measurements. Structural study reveals that each cadmium center in both dinuclear compounds is located in a distorted octahedral coordination environment surrounded by six nitrogen atoms—four (N1, N2, N3, N4) from tetradentate ligand, and the fifth and sixth positions occupied by nitrogen atoms (N5, N5^*) of doubly end-on bridging azides. The complexes display intraligand ¹ fluorescence and intraligand ³ phosphorescence in glassy solutions (MeOH at 77 K).     

The Blue Obelisk-interoperability in chemical informatics

The Blue Obelisk Movement (http://www.blueobelisk.org/) is the name used by a diverse Internet group promoting reusable chemistry via open source software development, consistent and complimentary chemoinformatics research, open data, and open standards. We outline recent examples of cooperation in the Blue Obelisk group: a shared dictionary of algorithms and implementations in chemoinformatics algorithms drawing from our various software projects; a shared repository of chemoinformatics data including elemental properties, atomic radii, isotopes, atom typing rules, and so forth; and Web services for the platform-independent use of chemoinformatics programs.     

Dynamics of end-to-end loop formation for an isolated chain in viscoelastic fluid

We theoretically investigate the looping dynamics of a linear chain immersed in a viscoelastic fluid. The dynamics of the chain is governed by a Rouse model with a fractional memory kernel recently proposed by Weber et al. [S.C. Weber, J.A. Theriot, A.J. Spakowitz, Phys. Rev. E 82 (2010) 011913]. Using the Wilemski–Fixman [G. Wilemski, M. Fixman, J. Chem. Phys. 60 (1974) 866] formalism we calculate the looping time for a chain in a viscoelastic fluid where the mean square displacement of the center of mass of the chain scales as t^1/2$t^{1/2}$. We observe that the looping time is faster for the chain in a viscoelastic fluid than for a Rouse chain in a Newtonian fluid up to a chain length and above this chain length the trend is reversed. Also no stable scaling of the looping time with the length of the chain seems to exist for the chain in a viscoelastic fluid.