1,720,964 research outputs found
Exploring bonding interactions of biochemical relevance in silicon, platinum(II) and iron(III) positively charged species
Full text linkElements playing a biological role that are present in nature or in synthetic drugs, such as silicon, platinum(II) and iron(III) usually appear coordinated to ligands in more or less composite molecular architectures. This notion is particularly true when a metal ion is placed in the active center of an enzyme or otherwise integrated into simple biomolecules and proteins. Whereas multifaceted factors affect a charged (metal) centre in a biological environment, the gas-phase provides an interesting medium for elucidating intrinsic interactions between metal ions and biological targets. The idea underlying this doctoral thesis is to highlight how state of the art techniques combining mass spectrometry, IR spectroscopy and computational chemistry can be applied to the study of ionic complexes in an isolated state. In a first section the reactivity behavior of gaseous complexes from the (CH3)3Si+ addition to acetylene has been fully explored by FT-ICR mass spectrometry and ab initio calculations. In this way the C5H11Si+ potential energy surface has been elucidated and the computational results nicely account for the experimental evidence showing an isomerization process from a primarily formed complex (a β-silyl-substituted vinyl cation acquiring an asymmetric cyclic geometry) to CH2=C(CH3)-Si(CH3)2+ silyl cation. The computational methods tested in dealing with the C5H11Si+ ion problem have been further applied to more challenging systems. In a second and third section a comprehensive investigation of the structural features of the key intermediates which are formed from cisplatin by replacement of chloro ligands by water or methionine is described. Here the experimental approach has involved vibrational spectroscopy carried out with a recently designed and assembled apparatus. The NH/OH stretching region has been found highly structurally diagnostic in the aqua complexes where hydrogen bonding interactions are crucial in determining relative conformer stability. The infrared characterization of the monofunctional adducts of platinum(II) drugs with methionine has led to identify distinct modes of interaction with cisplatin and transplatin derived species. In fact, the preferred ligand atom (S or N) seems to be depending on the specific isomer (cis- or trans-) that is reacting with the metal. Cisplatin and transplatin derived species have been sampled both experimentally and computationally, taking into account relativistic effects in the heavy metal. In a fourth task the binding properties of azole ligands toward ferric heme have been examined. Starting from simple ligands such as pyridine, 1-methylimidazole and 1H-1,2,4-triazole, the focus was then directed to imidazole- and triazole-based antifungal drugs. These drugs are known to act as inhibitors of CYP51enzyme, through binding to the heme prosthetic group. Relative binding energies were determined experimentally by energy variable collision induced dissociation experiments performed on the selected ionic complexes and evaluated theoretically by Car-Parrinello molecular dynamics calculations. To this end, theoretical investigations were carried out during a training period spent at the “Parc Cientific de Barcelona”, under the supervision of Research Professor Carme Rovira. Imidazole-based drugs consistently display higher dissociation energies when compared to triazole-based drugs
Beta-secretase: quantitative structure-activity relationships (3-D QSARs) and evaluation of predictive ability
No full textVibrational signatures of the naked aqua complexes from platinum(II) anticancer drugs
No full textA computational and vibrational spectroscopic study of the aqua complexes obtained by hydrolysis of cis-and trans-diamminedichloroplatinum(II) is reported. Electrospray ionization has allowed cis-and trans-[PtCl(NH 3)2(H2O)]+ species to be obtained as free ions in the gas phase where they were sampled by infrared multiple photon dissociation (IRMPD) spectroscopy in the NH/OH stretching frequency range (3200-3800 cm-1). The experimental features have been assigned by comparison with the linear IR spectra calculated for the optimized structures, revealing vibrational signatures characteristic of the two isomers. © 2013 American Chemical Society
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Isomeric C5H11Si+ Ions from the Trimethylsilylation of Acetylene: an Experimental and Theoretical Study
No full textThe gas phase offers a unique medium to conduct the electrophilic addition reaction of (CH3)3Si+ (trimethylsilylium ion) to acetylene. However, this deceptively simple reaction displays a remarkable dependence on the gas phase pressure, revealing the interplay of competitive pathways. In FT-ICR mass spectrometry at ca 10-8 mbar, the nascent (CH3)3Si+-acetylene complex undergoes a rearrangement process yielding the CH2=C(CH3)-Si(CH3)2+ ion. This structure has been assigned on the basis of the ion-molecule reactivity displayed by the sampled C5H11Si+ adducts, matching the one of the model ion obtained from 2-(trimethylsilyl)propene. Whereas the absolute values of kinetic rate constants could not discriminate between isomeric species, the branching ratios for competitive addition-elimination channels in the reaction with i-C3H7OH and t-C4H9OCH3 were found to be diagnostic of different structures. The pathways leading from the (CH3)3Si+-acetylene complex primarily formed to the candidate C5H11Si+ isomers have been investigated by ab initio quantum chemical calculations at CCSD(T)/6-311++G(2d,2p)//B3LYP/6-31G(d,p) level. The energy profiles show that the path to the CH2=C(CH3)-Si(CH3)2+ isomer is associated to the lowest activation energy barrier, below the reactants energy level. The energy released in the (CH3)3Si+-acetylene association process, remaining stored in the complex formed at low pressure, thus allows the isomerization to a species holding the positive charge on electropositive silicon. Interestingly, the most stable of the conceivable isomers, (E)-(CH3)-CH=CH-Si(CH3)2+, is not accessed because of an activation energy barrier protruding above the reactants energy level. The combined information of ion-molecule reactivity and ab initio calculations of potential isomers and rearrangement pathways has thus afforded a comprehensive view of the (CH3)3Si+ addition reaction to acetylene under various pressure regimes
Binding of azole drugs to heme: a combined MS/MS and computational approach
No full textThe binding properties of azole drugs toward ferric heme have been examined, focusing on well known antifungal drugs bearing imidazole and triazole heteroaromatic rings. These drugs are known to act as inhibitors of the Candida albicans P450 sterol 14a-demethylase enzyme, through binding to the heme prosthetic group. Absolute binding energies have been determined experimentally by energy variable collision induced dissociation experiments performed on the selected ionic complexes and evaluated theoretically using density functional theory, within the Car–Parrinello Molecular Dynamics method. The two series display some agreement in the relative binding energies data. These findings suggest that the combined ab initio and mass spectrometric approach may prove fruitful in assaying complexes
between a prosthetic group and an array of ligands of potential pharmacological activity. It is shown that the axial interaction of the imidazole-based drugs with iron(III) is somewhat stronger than that of the triazole-based drugs. This general observation fails if specific interactions remote from the metal center come into play. For example, a hydrogen bond interaction is established in the ferric heme complex with fluconazole, a drug of the triazole family owning a hydroxyl group prone to interact with the carbonyl oxygen of a propionyl group on the periphery of protoporphyrin IX. However, the relatively uniform values for both the experimental and theoretically calculated binding energies underline the important role played by the prosthetic group environment in tuning the heme interaction with biological and xenobiotic molecules and ultimately in modulating enzyme activity
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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