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Decisions about “What” and Decisions about “How”
Published in Malcolm Cook, Jan Noyes, Yvonne Masakowski, Decision Making in Complex Environments, 2007
Research into decision making has traditionally focused on how people – as individuals – choose among alternatives and specifically about how they go about finding the best alternative or making the “right” decisions. This is most clearly expressed in the three assumptions that characterise the rational decision maker, the homo economicus (Lee, 1971). The first assumption is that a rational decision maker is completely informed, which means that s/he knows what all the possible alternatives are and what the outcome of any action will be. This presumably includes both short-term and long-term outcomes. The second assumption is that a rational decision maker is infinitely sensitive; hence s/he is able to notice even the slightest difference between alternatives and use this to discriminate among them. One consequence of this assumption is that two alternatives never can be identical, as they will always differ in some way. The third assumption is that the decision maker is rational, which implies that alternatives can be put into a weak ordering and that choices are made so as to maximise something. The weak ordering means that if for three alternatives A, B, and C, the decision maker prefers A over B, and B over C, then the decision maker must also prefer A over C. This in turn requires that there is a common dimension, which can be either simple or composite, by which all alternatives can be rated. This common dimension also enables the decision maker to identify the alternative that has the highest value, hence to maximise his or her decision outcome.
The use of residual dipolar couplings for conformational analysis of non-steroidal anti-inflammatory drugs dissolved in weakly ordering media
Published in Liquid Crystals, 2018
Maria Enrica Di Pietro, Giorgio Celebre, Rosachiara Antonia Salvino, Christie Aroulanda, Denis Merlet, Giuseppina De Luca
In Equation (1), μ0 is the vacuum permeability, γi and γj are the gyromagnetic constants of the two nuclei and h is the Plank constant. The symbol < > indicates the statistical average over all the orientations sampled by the internuclear vector. In a normal solution, the solute tumbles isotropically and, as a result, the time average of the angular term is 0, leading to null dipolar couplings. A different situation occurs if a solute is dissolved in an aligning medium: the orienting environment imposes a certain anisotropy on the solute motion, making some orientations slightly more favourite than others; then, the angular term is no longer 0 and a ‘residual’ dipolar coupling is observed in the NMR spectrum. For flexible compounds, an additional averaging process must be considered: that due to internal torsions. On the NMR timescale, torsional internal motions interconverting the possible conformers are indeed rapid enough to give averaged observables. The upper bar in Equation (1) indicates exactly this average of the RDCs on internuclear intramolecular distances and angles and provides the key to grasp the information concerning the spatial arrangement of atoms in the molecule; consequently, it allows, in principle, to investigate the structural and conformational complete distribution of a flexible solute directly in solution. In practice, despite the extremely informative content of these parameters, the effective application of RDCs to the conformational problem presents some difficulties in the extraction as well as in the interpretation of experimental data. To describe the conformational distribution of a highly flexible solute, a large number of independent experimental parameters are necessary, and since the magnitude of the observed RDCs directly depends on the degree of solute’s orientational order induced by the solvent, the choice of using strong or weak ordering media is fundamental in order to collect an experimental data set as large as possible. Being drug molecules typically highly substituted, unsymmetrical and very flexible compounds, the use of weakly ordering solvents is an appropriate choice. The weakly ordering chiral liquid crystal made of PBLG dissolved in helicogenic organic co-solvents [34–42] has been the medium chosen to treat all the NSAID molecules here reported. However, although the spectra in this phase generally retain first-order features, the extraction of a large set of couplings is not always trivial and could require performing several multidimensional NMR experiments on the different nuclei in the molecule. Moreover, due to the flexibility inherent to the selected molecules, the interpretation of these average values of RDCs is complicated by the intrinsic interdependence existing between orientational order and conformational distribution that has to be addressed by adequate theoretical models [9,19–23].