Semiclassical study of collision-induced predissociation: Comparison of the Landau-Zener model with the method of analytic continuation

Semiclassical calculations are carried out by two methods for the problem of collision-induced predissociation of electronically excited I₂. The first method is that of surface-hopping with the Landau-Zener model. The second method is similar to surface-hopping, except that analytic continuation of the adiabatic potential energy surfaces replaces the Landau-Zener model. Results of the calculations by the two methods compare favorably with each other and with experiment. The possible advantages of the second method are discussed.Camille and Henry Dreyfus Teacher-Scholar, Alfred P. Sloan Research Fellow.     

Selective initiation of nonconjugated dienes containing electron donor–electron acceptor systems. II. Polymerization studies of vinyl ether–β-nitrostyrenes

The monomer series, o-, m-, and p-(2-vinyloxyethoxy)-β-nitrostyrenes, was studied. All three monomers were selectively polymerized through the electron-donating vinyloxy group via cationic initiation. The linear polymers from the meta and para isomers containing the electron-accepting nitrovinyl group were readily crosslinked via anionic initiation. The polymer derived from the ortho isomer was not crosslinked by this mechanism, an observation in accord with results previously reported from these laboratories in which it was shown that all o-substituted-β-nitrostyrenes having ortho substituents larger than fluorine exhibited a sterically inhibited propagation step. The meta and para isomers of this series were selectively polymerized through the electron-accepting nitrovinyl group via anionic initiation. Because of the fact that the resulting polymers were soluble only in highly polar solvents, subsequent crosslinking of these polymers via cationic initiation could not be accomplished. However, these polymers showed strong tendencies to undergo crosslinking upon long exposure to air. Because of the sterically induced ortho effect referred to above, no significant polymerization occurred in the case of the ortho isomer of this series via anionic initiation. However, it was shown in this case that initiation via the anion was rapid, and that the slow step was propagation.     

Searching of chemical structure data bases with parallel computer hardware

The use of two types of parallel computer hardware for increasing the efficiency of processing in chemical structure data bases is discussed. The distributed array processor can be used for the clustering of 2-D chemical structure data bases by using the Jarvis—Patrick clustering method and for the ranking of output in an experimental system for substructure searching in the 3-D macromolecules in the Protein Data Bank. The Inmos transputer can be used in the construction of PC-based systems for 2-D substructure searching and in the identification of the maximal substructures common to pairs of 3-D molecules.     

Electrochemical and spectroscopic characterization of surface sol-gel processes

(3-Mercaptopropyl)trimethoxysilane (MTS) forms a unique film on a platinum substrate by self-assembly and sol-gel cross-linking. The gelating and drying states of the self-assembled MTS sol-gel films were probed by use of electrochemical and spectroscopic methods. The thiol moiety was the only active group within the sol-gel network. Gold nanoparticles were employed to detect the availability of the thiol group and their interaction further indicated the physicochemical states of the sol-gel inner structure. It was found that the thiol groups in the open porous MTS aerogel matrix were accessible to the gold nanoparticles while thiol groups in the compact MTS xerogel network were not accessible to the gold nanoparticles. The characteristics of the sol-gel matrix change with time because of its own irreversible gelating and drying process. The present work provides direct evidence of gold nanoparticle binding with thiol groups within the sol-gel structures and explains the different permeability of "aerogel" and "xerogel" films of MTS on the basis of electrochemical and spectroscopic results. Two endogenous species, hydrogen peroxide and ascorbic acid, were used to test the permeability of the self-assembled sol-gel film in different states. The MTS xerogel film on the platinum electrode was extremely selective against ascorbic acid while maintaining high sensitivity to hydrogen peroxide in contrast to the relatively high permeability of ascorbic acid in the MTS aerogel film. This study showed the potential of the MTS sol-gel film as a nanoporous material in biosensor development.     

Computation of the physio-chemical properties and data mining of large molecular collections

Very large data sets of molecules screened against a broad range of targets have become available due to the advent of combinatorial chemistry. This information has led to the realization that ADME (absorption, distribution, metabolism, and excretion) and toxicity issues are important to consider prior to library synthesis. Furthermore, these large data sets provide a unique and important source of information regarding what types of molecular shapes may interact with specific receptor or target classes. Thus, the requirement for rapid and accurate data mining tools became paramount. To address these issues Pharmacopeia, Inc. formed a computational research group, The Center for Informatics and Drug Discovery (CIDD).* In this review we cover the work done by this group to address both in silico ADME modeling and data mining issues faced by Pharmacopeia because of the availability of a large and diverse collection (over 6 million discrete compounds) of drug-like molecules. In particular, in the data mining arena we discuss rapid docking tools and how we employ them, and we describe a novel data mining tool based on a ID representation of a molecule followed by a molecular sequence alignment step. For the ADME area we discuss the development and application of absorption, blood-brain barrier (BBB) and solubility models. Finally, we summarize the impact the tools and approaches might have on the drug discovery process.     

Recombinant cell bioassay systems for the detection and relative quantitation of halogenated dioxins and related chemicals

Proper epidemiological, risk assessment and exposure analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related halogenated aromatic hydrocarbons (HAHs) requires accurate measurements of these chemicals both in the species of interest and in various exposure matrices (i.e. biological, environmental, food and feed). High-resolution instrumental analysis techniques are established for these chemicals, however, these procedures are very costly and time-consuming and as such, they are impractical for large scale sampling studies (i.e. for epidemiological studies and assessment of areas with widespread contamination). Accordingly, numerous bioanalytical methods have been developed for the detection of these chemicals in extracts from a variety of matrices, the majority of which take advantage of the ability of these chemicals to activate the aromatic hydrocarbon receptor (AhR) and the AhR signal transduction pathway. Here we review the currently available in vitro AhR-based cell bioassay systems with a focus on recent recombinant reporter gene cell lines that have been developed for detection and relative quantitation of TCDD and related HAHs. Comparison of the relative sensitivities of the various cell bioassays and examples of their use in screening and analysis of environmental, biological, and food and feed samples are presented. Currently available experimental results and validation studies demonstrate the utility of these cell bioassay systems to provide a relatively rapid, accurate, and cost effective screening approach for the detection of TCDD and related HAHs in a variety of environmental, biological, food and feed samples. The availability of these cell bioassay systems will not only facilitate the large scale sampling studies needed for accurate assessment of contamination and exposure to these environmental chemicals, but they provide avenues for the identification of novel classes of TCDD-like chemicals.     

Phytochemicals from Echinacea and Hypericum: A Direct Synthesis of Isoligularone

Reaction of trienes with α,β-unsaturated aldehydes produces bicyclic products via a tandem Diels-Alder/ene reaction. The adduct from tiglic aldehyde was converted into isoligularone by conversion to a furan followed by benzylic oxidation.     

17O NMR studies of electronic and steric interactions of substituted quinoxaline-2(1H),3(4H)-diones

¹⁷O nmr studies, at natural abundance, of substituted quinoxaline-2(1H),3(4H)-diones demonstrate that the ¹⁷O chemical shift data can provide new insights into steric and electronic interactions due to long range substituent effects on the aromatic ring. The role of considerable “keto” character and torsion angle deformation of the diamide group in solution is emphasized.     

Development and validation of routine analysis methods for the determination of essential, nonessential, and toxic minor and trace elements in cereal and cereal flour samples by inductively coupled plasma-atomic emission spectrometry

Various digestion procedures were carefully investigated and accurately evaluated with respect to their effect on the analysis of cereals and cereal flours. Multielement methods were selected and well developed for the determination of essential (Cr, Cu, Fe, Mg, Mn, and Zn), nonessential (Ag, Al, Ba, Bi, In, and Ga), and toxic (Cd and Pb) minor and trace elements by inductively coupled plasma-atomic emission spectrometry. Only Ag could be determined, either with aqueous standard or standard addition calibration methods, while the standard addition methods were more accurate for the determination of other elements. The recoveries were mostly within the range of 84.1-113% for the expected values of all analytes with respect to certified reference material NIST SRM 1586a (rice flour). The results proved that, for cereals and cereal flours, the use of H2O2 for wet digestion and HNO3 for dry ashing were not necessary. Linear regression analysis and Student's paired t-test were applied to evaluate the significant differences between different procedures and type of samples.     

Dynamics of self-assembled chaining in magnetorheological fluids

The aggregation dynamics of paramagnetic spherical particles embedded in a viscous fluid is investigated via numerical simulations using a fully coupled three-dimensional model. Particles experience simultaneously Brownian motion, dipolar magnetic attraction, and multibody hydrodynamic interactions. When the dipole strength characterizing the ratio of magnetic attraction to random diffusion exceeds a critical value, particles join together forming supraparticle structures. As time evolves, particle/chain and chain/ chain interactions lead to a continuous increase of the cluster size. The mean length of particle chains has a power-law dependence with respect to time, as predicted by the theory of diffusion-limited aggregation. Both the exponent and the characteristic time scale agree very well with the experimental results of Promislow et al.