1,721,333 research outputs found
Model-averaging of ab initio spectra for the absolute configuration assignment via vibrational circular dichroism
No full textVibrational absorption and vibrational circular dichroism spectra (VA and VCD) have been recorded for two hybrid isoindolinone-phtalide stereoisomers dissolved in CDCl3. Density-functional calculations have been performed to determine their absolute configuration. A comparison of calculated and measured values has been made using several goodness-of-fit indicators, and also introducing a model-averaging technique, taking into account the variation of calculated spectra with the details of the computational method. The model-averaging technique, preliminarily tested on two VCD spectra already assigned to two diastereomers of tadalafil, gives higher credibility to the ab initio calculations, and should be useful for other molecules with high flexibility and/or more than one stereogenic center
The multi-centre bond index as a measure of aromaticity : is aromaticity a multidimensional concept or not?
Get PDFQuantum chemistry in QSAR : quantum chemical descriptors: use, benefits and drawbacks
No full textThe elucidation of a set of chemical/physical properties modulating the relationship between the chemical structure and the pharmacological activity or other properties is of great interest to the industry. These relationships are known as quantitative structure activity relationships (QSAR) and could be used to predict activities/properties based solely on the chemical structure. In order to obtain adequate relationships, it is necessary to discover and use the particular set of molecular descriptors that adequately describe the activity to be predicted. Therefore, in this research, new informative molecular descriptors are sought. The electron density and its derived characteristics are investigated as molecular descriptors in predicting pharmacological activities/properties, assuming that the quantum chemical molecular descriptors carry important information about the pharmacological activity
Unravelling structural motifs of intrinsically disordered proteins employing Raman optical activity : understanding the basis of neurodegenerative diseases
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
A critical assessment of possible pitfalls in absolute configuration assignment using Vibrational Circular Dichroism
Get PDFVibrational Circular Dichroism (VCD) is no longuer a curious novelty in the field of molecular spectroscopy as VCD spectrometers are commercially available as well as the algorithms to calculate the spectra, which are implemented in various software packages. This makes VCD routinely applicable for the determination of absolute configurations. The VCD technique is gaining interest in mainly pharmaceutical industry and the technique also has been accepted by regulatory agencies (e.g. FDA) as a proof of absolute configuration (AC). Since a misassignment can have serious consequences, it is of vital importance that all assignments are done correctly. Our experience, however, shows that assignemnt can be hindered by serious problems.
First of all, VCD measurements are done in solution, while the calculations are usually performed for a single molecule in vacuum. Intermolecular interactions can cause discrepancies between experimental and theoretical spectra. Inclusion of the solvent in the calculations leads to an improved agreement with the experiments for the case of pulegone and camphor.
The agreement of computed VCD spectra with experimental ones, is known to depend strongly on the extent to which all relevant conformations are included in the calculations. This means that conformational analysis, especially for large flexible molecules, has to be performed very carefully. This is illustrated using dipetidyl peptidases (DPP) inhibitors. It is also demonstrated how manipulation of the synthesis pathway may help skirt these problems.
Finally, the influence of temperature on experimental VCD spectra was studied. First, it was assumed that the interpretation of the experimental spectra would be simplified at lower temperatures due to a decrease in the number of significantly populated conformations. The effect of lowering the temperature is demonstrated for borneol, 3-methylcyclohaxonon and limonene showing that, unfortunately, different effects counterbalance the expected simplification of the spectrum
Machine learning for vibrational circular dichroism : constructing novel and accelerating established applications
No full textAbstract: Determination of the so-called Absolute Configuration (AC) of a chiral compound is an important analytical step in research areas such as medicine and agrochemistry. The AC of a chiral compound can be determined with Vibrational Circular Dichroism (VCD), which measures the difference in absorbance of left and right circularly polarised infrared radiation. VCD spectra exhibit substantial chiral sensitivity and contain an abundance of conformational information. Unfortunately, there are no general empirical rules capable of linking a VCD spectrum to a specific AC or predicting the influence of the conformations on the VCD spectrum. Therefore, in each VCD application one has to rely on expensive (DFT) calculations for the conformers of all possible AC's. In this thesis, the added value of Machine Learning (ML) is explored for the AC determination workflow with VCD. The presented results demonstrate that ML models are capable of directly extracting the AC from the VCD spectrum after training these models on a set of structurally similar compounds. Neural Networks can successfully predict the influence of conformations on the spectrum from their geometries, as long as these conformations correspond to the same AC. Additionally, the potential of linear ML models is tested to determine the composition of terpene mixtures and natural oils
Variations on the Author
Get PDF“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
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