Biomedical subjects
Publications and source records attributed to Panagiotis G Karamertzanis.
A computational prediction that mixing the synthetic mirror image of progesterone with its natural form would produce a specific racemic crystal structure was validated.
We have performed a variety of high-level electronic structure calculations on two moderately sized organic molecules and found considerable sensitivity of the intramolecular potential energy surface to the method employed. The gas-phase structure of tyrosine-glycine varies qualitatively between B3LYP and MP2 optimizations, producing different close contacts between the tyrosine ring and the glycine moiety. The relative energies of the 2-(acetylamino)benzamide conformations found in its two polymorphs can vary by over 20 kJ mol-1 between MP2 and B3LYP calculations, using the same basis set. It is shown by a novel analysis that the intramolecular equivalent of basis set superposition error competes with the errors in the intramolecular dispersion in causing this sensitivity.
A methodology for the computational prediction of the crystal structures and resolution efficiency for diastereomeric salt pairs is developed by considering the polymorphic system of the diastereomeric salt pair (R)-1-phenylethylammonium (R/S)-2-phenylpropanoate. To alleviate the mathematical complexity of the search for minima in the lattice energy due to the presence of two flexible entities in the asymmetric unit, the range of rigid-body lattice energy global optimizations was guided by a statistical analysis of the Cambridge Structural Database for common ion-pair geometries and ion conformations. A distributed multipole model for the dominant electrostatic interactions and high-level ab initio calculations for the intramolecular energy penalty for conformational distortions are used to quantify the relative stabilities of the p- and n-salt forms. While the ab initio prediction of the known structure of the p-salt as the most stable structure was insensitive to minor changes in the rigid-ion conformations considered, the relative stabilities of the known polymorphs and hypothetical structures of the n-salt were very sensitive. Although this paper provides a significant advance over traditional search algorithms and empirical force fields in determining the structures and relative stabilities of diastereomeric salt pairs, the sensitivity of the computed lattice energies to the fine details of the ion conformations overtaxes current computational models and renders the design of diastereomeric resolution processes by computational chemistry a challenging problem.
A new methodology for the prediction of molecular crystal structures using only the atomic connectivity of the molecule under consideration is presented. The approach is based on the global minimization of the lattice enthalpy of the crystal. The modeling of the electrostatic interactions is accomplished through a set of distributed charges that are optimally and automatically selected and positioned based on results of quantum mechanical calculations. A four-step global optimization algorithm is used for the identification of the local minima of the lattice enthalpy surface. A parallelized implementation of the algorithm permits a much more extensive search of the solution space than has hitherto been possible, allowing the identification of crystal structures in less frequently occurring space groups and with more than one molecule in the asymmetric unit. The algorithm has been applied successfully to the prediction of the crystal structures of 3-aza-bicyclo(3.3.1)nonane-2,4-dione (P2(1)/a, Z' = 1), allopurinol (P2(1)/c, Z' = 1), 1,3,4,6,7,9-hexa-azacycl(3.3.3)azine (Pbca, Z' = 2), and triethylenediamine (P6(3)/m, Z' = 1). In all cases, the experimentally known structure is among the most stable predicted structures, but not necessarily the global minimum.