4 research outputs found
Two Notions Of Safety
Timothy Williamson (1992, 224–5) and Ernest Sosa (1996) have ar- gued that knowledge requires one to be safe from error. Something is said to be safe from happening iff it does not happen at “close” worlds. I expand here on a puzzle noted by John Hawthorne (2004, 56n) that suggests the need for two notions of closeness. Counterfac- tual closeness is a matter of what could in fact have happened, given the specific circumstances at hand. The notion is involved in the semantics for counterfactuals and is the one epistemologists have typically assumed. Normalized closeness is rather a matter of what could typically have happened, that is, what would go on in a class of normal alternatives to actuality, irrespectively of whether or not they could have happened in the circumstances at hand
“<i>In-Silico</i> Seeding”: Isostructurality and Pseudoisostructurality in a Family of Aspirin Derivatives
Novel crystal packings of the aspirin
molecule and 17 molecules
that are related to aspirin by substitution are studied using a computational
approach. The packings are created by taking a crystal structure for
which the crystal packing and molecular geometry have been determined
experimentally and replacing the native molecule with a different
one. The resulting crystal structures are optimized using molecular
mechanics, followed by a quantum mechanical method based on density
functional theory and including a correction for dispersive interactions.
There are 21 known, experimental, crystal structures for the molecules
considered, some of which are polymorphic. For any given molecule,
the lowest, calculated lattice energy is always found to be that of
a crystal structure which corresponds to experiment. For the three
polymorphic molecules, the second lowest lattice energy is also found
to correspond to an experimental structure. The agreement between
the observation of a particular packing and its low rank in the list
of possible packings is evidence of the accuracy of the method for
calculating the lattice energy. Further analysis of the results shows
patterns reflecting the underlying supramolecular constructs that
are common to the different packings of these molecules. This leads
to some speculation as to the possibilities of finding new polymorphs
for some of these molecules
Chrysomela goettingensis
Crystal structure prediction methods have been used to
explore
the potential energy landscape for crystals of a melatonin agonist
(MA). All known experimental polymorphs were found in the search for
crystal packing alternatives with a single molecule in the asymmetric
unit, and the predicted order of stability agrees with experiment.
The crystal structure corresponding to the global minimum has not
been observed experimentally, but analysis of the crystal structures
of similar molecules in the Cambridge Structural Database (CSD) indicates
that the packing motif present in the predicted structure is also
found in nature. To date it has not been experimentally possible to
crystallize the most stable polymorph of the biologically active <i>R</i>-enantiomer, whereas the <i>S</i>-enantiomer
readily crystallizes in the stable form. Analysis of the results shows
that this polymorph has an uncommon packing motif which is found just
once among the 12 lowest energy predicted structures but is seen in
two crystal structures of MA-like molecules whose structures are stored
in the CSD. On the basis of the calculations and comparisons with
experimental crystal structures, suggestions are made as to possible
routes for crystallizing the, as yet unknown, polymorph of MA, which
corresponds to the predicted structure with the lowest lattice energy
Crystal Structure Prediction of a Flexible Molecule of Pharmaceutical Interest with Unusual Polymorphic Behavior
Crystal structure prediction methods have been used to
explore
the potential energy landscape for crystals of a melatonin agonist
(MA). All known experimental polymorphs were found in the search for
crystal packing alternatives with a single molecule in the asymmetric
unit, and the predicted order of stability agrees with experiment.
The crystal structure corresponding to the global minimum has not
been observed experimentally, but analysis of the crystal structures
of similar molecules in the Cambridge Structural Database (CSD) indicates
that the packing motif present in the predicted structure is also
found in nature. To date it has not been experimentally possible to
crystallize the most stable polymorph of the biologically active <i>R</i>-enantiomer, whereas the <i>S</i>-enantiomer
readily crystallizes in the stable form. Analysis of the results shows
that this polymorph has an uncommon packing motif which is found just
once among the 12 lowest energy predicted structures but is seen in
two crystal structures of MA-like molecules whose structures are stored
in the CSD. On the basis of the calculations and comparisons with
experimental crystal structures, suggestions are made as to possible
routes for crystallizing the, as yet unknown, polymorph of MA, which
corresponds to the predicted structure with the lowest lattice energy