Scaffold topologies. 2. Analysis of chemical databases

We have systematically enumerated graph representations of scaffold topologies for up to eight-ring molecules and four-valence atoms, thus providing coverage of the lower portion of the chemical space of small molecules (Pollock et al. J. Chem. Inf. Model., this issue). Here, we examine scaffold topology distributions for several databases: ChemNavigator and PubChem for commercially available chemicals, the Dictionary of Natural Products, a set of 2742 launched drugs, WOMBAT, a database of medicinal chemistry compounds, and two subsets of PubChem, "actives" and DSSTox comprising toxic substances. We also examined a virtual database of exhaustively enumerated small organic molecules, GDB (Fink et al. Angew. Chem., Int. Ed. 2005, 44, 1504-1508), and we contrast the scaffold topology distribution from these collections to the complete coverage of up to eight-ring molecules. For reasons related, perhaps, to synthetic accessibility and complexity, scaffolds exhibiting six rings or more are poorly represented. Among all collections examined, PubChem has the greatest scaffold topological diversity, whereas GDB is the most limited. More than 50% of all entries (13 000 000+ actual and 13 000 000+ virtual compounds) exhibit only eight distinct topologies, one of which is the nonscaffold topology that represents all treelike structures. However, most of the topologies are represented by a single or very small number of examples. Within topologies, we found that three-way scaffold connections (3-nodes) are much more frequent compared to four-way (4-node) connections. Fused rings have a slightly higher frequency in biologically oriented databases. Scaffold topologies can be the first step toward an efficient coarse-grained classification scheme of the molecules found in chemical databases.     

The Design of Leadlike Combinatorial Libraries

The optimization of low-potency leads into drugs is often accompanied by an increase in molecular weight (M(r)) and lipophilicity, as a consequence of affinity enhancement. Hits with affinity at μM levels discovered by screening leadlike libraries allow scope for this optimization process, as shown schematically by the distributions of M(r) for a leadlike library (1), oral drugs (2), and a typical combinatorial chemistry library (3). y=percentage with a particular molecular weight.     

Translocation of radioactivity from substrate to macromycetes in the Crucea (Romania) uranium mining area

The present study follows the extent of translocation radioactivity from the substrates of the Crucea uranium mining area to the macromycetes spontaneously occurred during June–October 2008. To this end, radioactivity measurements (gross α + β and ¹³⁷Cs) on both macromycetes and their substrates were made. The resultants obtained were confirmed by FT-IR spectroscopy, evidencing the presence of characteristic bands around of 910 cm⁻¹, corresponding to the asymmetric stretching vibration of the uranyl unit and to the interaction between the UO₂ ²⁺ ions and the group belonging to various cellular components.     

Ab initio study of exchange coupling for the consistent understanding of the magnetic ordering at room temperature in V[TCNE] x

We report quantum chemical calculations providing the exchange coupling constants of the V[TCNE]₂ model system, describing the amorphous room temperature molecular magnet V[TCNE] _x (TCNE = tetracyanoethylene, x ~ 2). The geometry is optimized for the ideal lattice using density functional theory (DFT) calculations with periodic boundary conditions. Broken-symmetry DFT calculations indicate antiparallel spin alignment resulting in ferrimagnetic ordering, but heavily overestimate the value of the exchange coupling. Better estimates of the exchange coupling parameters between the V(II) ion and the [TCNE]^? anionic radical are obtained by means of multiconfigurational calculations performed on smaller molecular models cut from the optimized crystal lattice. Complete active space self-consistent field and multireference second-order perturbation theory calculations provide the sign and the strength of the nearest-neighbor as well as next-nearest-neighbor interactions along all three crystallographic directions. We are able to explain also intuitively the mechanism for antiferromagnetic spin coupling in terms of the superexchange pathways, discussing the role of the main four types of contributions to superexchange. Moreover, we clarify the influence of the transition metal ion on the strength of the exchange interaction and on the critical temperature for long-range ferrimagnetic ordering.     

Evaluation of the Compatibility of EPDM and IIR I. Specific heat capacity

The thermal effect of mixing of EPDM and IIR was studied by differential scanning calorimetry over the temperature range between 335 and 435 K. O'Neill's method was used for calculating the specific heat capacity with alumina as standard. The greater the butyl rubber content, the lower the heat capacity. The presence of butyl rubber induces a marked thermal instability because of isobutylene units. It is possible that a rearrangement occurs in the molecular sequence, accompanied by secondary reactions involving free radicals. The contribution of each component to the cP of the tested polymeric systems is discussed. Differences between theoretical and experimental specific heat capacities increase as the operation temperature is raised. The relationship between the contributions of the two components to the specific heat capacity values of mixtures can be described by a first order equation, named the law of reciprocal thermal affinity. This aspect can be ascribed to the interaction of various reacting entities, which form certain units with low molar heat capacity. This revised version was published online in July 2006 with corrections to the Cover Date.     

Capillary gas chromatography-mass spectrometry of volatile and semi-volatile compounds of Salvia officinalis

The essential oil and infusion of Salvia officinalis leaves have been widely applied in traditional medicine since ancient times and nowadays subjected to extensive research of their antibacterial, antiviral and cytotoxic properties. This paper shows chemical composition data of S. officinalis leaves essential oil isolated by steam distillation using a Clevenger-type apparatus. Also, the paper presents the chemical content of volatile and semi-volatile compounds of S. officinalis leaves infusion. The volatile and semi-volatile compounds of S. officinalis leaves infusion were isolated by solid-phase extraction (SPE) and liquid-liquid extraction with hexane and dichloromethane. SPE was carried out on 500 mg octadecylsilane (C18) cartridges and elution with dichloromethane. Liquid-liquid extraction was performed with hexane and dichloromethane. The essential oil in dichloromethane and infusion extracts in hexane and dichloromethane were analyzed by gas chromatography coupled with mass spectrometry. The quantitative results obtained by solid-phase extraction and liquid-liquid extraction showed that SPE on C18 performed the highest recovery of the volatile compounds from infusion sample.     

Chemical Composition,Antipathogenic and Cytotoxic Activity of the Essential Oil Extracted from Amorpha fruticosa Fruits

The purpose of this paper was to characterize and investigate the antimicrobial potential of Amorpha fruticosa fruits essential oil (EO). The EO was extracted by hydrodistillation, analyzed by GC-MS, and then evaluated for its interaction with microbial and mammalian cells. The antimicrobial activity was assessed against bacterial and fungal strains, in a planktonic and adherent growth state, using qualitative and quantitative assays. The main components identified in A. fruticosa fruits EO were δ-cadinene, γ-muurolene, and α-muurolene. The Gram-positive strains proved to be more susceptible than Gram-negative bacteria and fungal strains. The EO exhibited good antibiofilm activity, inhibiting the microbial adherence to the inert (96-well plates and Foley catheter section) and cellular substrata. The flow cytometry analysis revealed as one of the possible mechanisms of antimicrobial action the alteration of cell membrane hydrophobicity. The cytotoxicity on the L929 cell line occurred at concentrations higher than 0.3 mg/mL. Taken together, our results demonstrate that A. fruticosa fruits EO contains active compounds with selective inhibitory effect on different microbial strains in planktonic and biofilm growth state, explained at least partially by the interference with microbial membranes due to their hydrophobic character.     

On exchange coupling and bonding in the Gd2@C80 and Gd2@C79N endohedral dimetallo-fullerenes

A series of computational experiments performed with various methods belonging to wave-function and density functional theories approaches the issue of bonding regime and exchange coupling in the title compounds. Gd₂@C₈₀ is computed with a very weak exchange coupling, the sign depending on the method, while Gd₂@C₇₉N has resulted with a strong coupling and ferromagnetic ground state, irrespective of the computational approach. The multi-configuration calculation and broken symmetry estimation are yielding closely coincident coupling constants, of about J ～ 400 cm^?1. No experimental estimation exists, but the ferromagnetic ground state of Gd₂@C₇₉N is confirmed from paramagnetic resonance data. The different behaviour is due to particularities of electron accommodation in the orbital scheme. The exchange effects localised on atom lead to preference for parallel alignment of the electrons placed in the 4f and 5d lanthanide shells, determining also a ferromagnetic inter-centre coupling. The structural insight is completed with a ligand field analysis of the density functional theory results in the context of frozen density embedding. The energy decomposition analysis of bonding effects is also discussed. Finally, with the help of home-made codes (named Xatom+Xsphere), a model for the atom encapsulated in a cage is designed, the exemplified numeric experiments showing relevance for the considered endohedral metallo-fullerene issues.