No abstract

A collaborative workshop was held in May 1999 at the Cambridge Crystallographic Data Centre to test how well currently available methods of crystal structure prediction perform when given only the atomic connectivity for an organic compound. A blind test was conducted on a selection of four compounds and a wide range of methodologies representing, the principal computer programs currently available were used. There were 11 participants who were allowed to propose at most three structures for each compound. No program gave consistently reliable results. However, seven proposed structures were close to an experimental one and were classified as "correct". One compound occurred in two polymorphs, but only one form was predicted correctly among the calculated structures. The basic problem with lattice energy based methods of crystal structure prediction is that many structures are found within a few kJ mol(-1) of the global minimum. The fine detail of the force-field methodology and parametrization influences the energy ranking within each method. Nevertheless, present methods may be useful in providing a set of structures as possible polymorphs for a given molecular structure.

Electrostatic potentials and Mulliken net atomic charges were calculated from STO-3G, 6-31G, and 6-31G* * SCF-MO wavefunctions for hydrogen fluoride, water, ammonia, methane, acetylene, ethylene, carbon dioxide, formaldehyde, methanol, formamide, formic acid, acetonitrile, diborane, and carbonate ion. In each case optimized net atomic charges (potential-derived charges) were also obtained by fitting the electrostatic potentials calculated directly from the wavefunctions in a shell enveloping the molecules outside of their van der Waals surfaces. The electrostatic potentials calculated from the potential-derived charge distributions were then compared with the defined quantum mechanical electrostatic potentials and with the electrostatic potentials of the Mulliken charge distributions.

The first collaborative workshop on crystal structure prediction (CSP1999) has been followed by a second workshop (CSP2001) held at the Cambridge Crystallographic Data Centre. The 17 participants were given only the chemical diagram for three organic molecules and were invited to test their prediction programs within a range of named common space groups. Several different computer programs were used, using the methodology wherein a molecular model is used to construct theoretical crystal structures in given space groups, and prediction is usually based on the minimum calculated lattice energy. A maximum of three predictions were allowed per molecule. The results showed two correct predictions for the first molecule, four for the second molecule and none for the third molecule (which had torsional flexibility). The correct structure was often present in the sorted low-energy lists from the participants but at a ranking position greater than three. The use of non-indexed powder diffraction data was investigated in a secondary test, after completion of the ab initio submissions. Although no one method can be said to be completely reliable, this workshop gives an objective measure of the success and failure of current methodologies.

Recognition of the clinical features of rumination syndrome in children and adolescents is essential; the diagnosis is often delayed and associated with morbidity. Extensive diagnostic testing is unnecessary. Early behavioral therapy is advocated, and patient outcomes are generally favorable.

The previously described least-squares derivation of nonbonded potential parameters from crystalline aromatic hydrocarbons was extended to include nonaromatic hydrocarbons. Further evidence was obtained that no specially large energy effects are present in the aromatic crystal structures with their π-electron systems. A better separation of the nonbonded energy into C···C, C···H, and H···H components was obtained when the observational equations for the aromatic and nonaromatic structures were combined. The potentials obtained from the combined observational equations gave better fits to the nonaromatics than to the aromatics. Evidence is presented favoring an H–C–H angle of less than 106° in crystalline n-pentane and n-hexane. The parallel packing of molecular chains in the n-hexane crystal and the nonparallel packing in the n-pentane crystal were reproduced by a steepest descent minimization of the lattice energy using the observed lattice constants.

No abstract

Dexamethasone, 2 mg every 6 hours for 4 doses, was given to 4 hypothyroid patients receiving treatment with synthetic thyroxine (T4) and to 8 untreated hyperthyroid patients with Graves' disease, and serum concentrations of thyroid hormones were measured by radioimmunoassays. Serum concentration of 3,3'5'-triiodothyronine (reverse T3, rT3) increased appreciably within 8 hours after the first dose of dexamethasone, was maximum at 24-32 hours after beginning dexamethasone, and remained elevated for about 24 hours after discontinuing the steroid. The mean baseline serum rT3 was 58 ng/per 100 ml in treated hypothyroid patients and 119 ng per 100 ml in patients with Graves' disease; the corresponding maximal post-dexamethasone serum rT3 values were 87 and 170 serum concentration of 3,3',5-triiodothyronine (T3) decreased. The decrease in serum T3 was significant at about 24 hours after beginning dexamethasone and was maximal at about 30 hours in both groups of cases under study. The decrease in serum T3 persisted in treated hypothyroid cases for about 24-48 hours and in Graves' disease cases as long as studied, at least 5 days after discontinuing hexamethasone. The changes in serum rT3 and T3 could not be attributed to the effect of dexamethasone on serum protein binding of the iodothyronines because the dialyzable fractions of rT3 and T3 following steroid administration were not different from those before it. Serum T4 did not change appreciably in treated hypothyroid cases, but decreased in Graves' disease cases from a mean baseline value of 23.5 mug per 100 ml to 18.4 mug per 100 ml 3 days after beginning dexamethasone. In addition, 3 hyperthyroid cases were studied before, during, and after administration of dexamethasone, 2 mg every 6 h for 5 days. Serum rT3 increased again as noted above and the increase persisted until about 24 hours after the last dose of the steroid. Serum T3 decreased considerably and remained decreased as long as studied, at least 4 days after discontinuing the steroid. Serum T4 decreased appreciably in 2 of the 3 cases studied. The data suggest that 1) conversion of T4 to T3 and to rT3 may occur via two distinct pathways in the metabolism of T4; 2) the changes in serum rT3 and T3 observed in our study may be due in part at least to a steroid-induced 'shift' in the metabolism of T4 whereby conversion of T4 to T3 is diminished and that to rT3 is enhanced; 3) in addition to the effect on peripheral metabolism of T4, steroids appear to reduce the circulating thyroid hormones in Graves' disease by another mechanism, probably by reduction in thyroid secretion.