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Binding modes of drug-albumin complexes investigated by induced CD spectroscopy and TD-DFT calculations
No full textAt the molecular level, the activity of drugs relies on a sequence of biorecognition phenomena, such as the binding to biological macromolecules, which define their pharmacological, toxicological and pharmacokinetic profiles. Physiologically-relevant interactions are usually very stereospecific: the occurrence of high binding affinities for specific stereochemical configurations or conformational arrangements of a drug is a very important research topic in the field of medicinal chemistry. When a drug is bound with high affinity to its target or to a carrier protein, e.g. a serum albumin, the conformational restraint due to the interaction may result in the insurgence of induced circular dichroism (ICD), which can be detected experimentally by spectroscopic analysis: nice examples are given by the ICD spectra of diazepam and ketoprofen complexed with human serum albumin (HSA). [1]
Quantum mechanical (QM) calculations based on time-dependent density functional theory (TD-DFT) can be used to investigate the theoretical ICD spectra of all the possible conformational arrangements of the ligand, and may result very helpful in the identification of possible binding modes. [2] The present communication will report the application of TD-DFT calculations to the investigation of the binding modes of ketoprofen and benzodiazepines to serum albumins: in particular, the stereospecific binding of the M conformation of benzodiazepines to HSA is confirmed, and the peculiar species-dependent ICD spectra observed for the binding of ketoprofen to different serum albumins can be explained by the selection of different mutual arrangements of the phenyl moieties in the binding pockets.
[1] M. Pistolozzi, C. Bertucci, Chirality 20, 552 (2008).
[2] S. Ionescu, I. Matei, C. Tablet, M. Hillebrand, Phys. Chem. Chem. Phys. 15, 11604 (2013)
Non-trivial chiroptical responses (III). Biomolecular recognition: TD-DFT study on drug-albumin binding modes
No full textStereochemical Characterization of Fluorinated 2-Arylpropionic Acids by Enantioselective HPLC Analysis and ECD DetectionStereochemical
No full text
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
Stereochemical characterization of fluorinated 2-arylpropionic acids by enantioselective HPLC analysis and ECD detection
No full textVariations 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
A new scent taget: the enantioenriched (S)-Lioral? Synthesis methodologies, problems and stereochemical characterization
No full textStereochemistry of 2-(6-fluorophenanthren-1-yl)propionic acid unveiled by enantioselective HPLC, ECD spectroscopy, and TD-DFT calculations
No full text1. Introduction
Owing to its peculiarities, fluorine has drawn an increasing attention in the design of new drugs. Among them, fluorinated profens have received particular consideration in reference to the biological activity as successful non-steroidal anti-inflammatory drugs (NSAIDs). In the present communication we report the development of an enantioselective HPLC method for the resolution of racemic 2-(6-fluorophenanthren-1-yl)propionic acid (1),1 and the determination of the absolute configuration (AC) of its enantiomers through electronic circular dichroism (ECD) and time-dependent density functional theory (TD-DFT) computations.
2. Results and Discussion
The column (S,S)-Whelk-O®1 was efficient for the enantioresolution of profen 1. The single enantiomeric fractions were collected and analyzed for determining their enantiomeric excess and ECD spectra. The AC of the enantiomers of 1 was determined by means of ECD theoretical calculations on (S)-1.2 Molecular mechanics conformational analysis and DFT geometry optimization at the B3LYP/TZ2P level isolated the 4 most populated conformers (a, 53.04%; b, 25.70%; c, 19.81%; d, 1.45%). TD-DFT calculations were performed at the B3LYP/TZ2P level and the theoretical ECD spectrum was determined. The ECD spectrum of the second-eluted enantiomer was found to be in excellent agreement with theoretical calculations on (S)-1; therefore, the AC of the first- and second-eluted enantiomers were assessed as (2R)-1 and (2S)-1, respectively.
3. References
[1] Ricci, G., and Ruzziconi, R., J. Org. Chem. 2005, 70, 611-623.
[2] Autschbach, J., Chirality 2009, 21, E116-E152
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