Two-dimensional similarity between forms I and II of cytenamide, a carbamazepine analogue

Cytenamide form I (R (3) over bar) undergoes a solid-state transformation upon heating to form II (P (1) over bar), with the structures exhibiting the same two-dimensional similarity that exists between the R (3) over bar and P (1) over bar forms of carbamazepine.

Discovery of three polymorphs of 7-fluoroisatin reveals challenges in using computational crystal structure prediction as a complement to experimental screening

A combined computational and experimental polymorph search was undertaken to establish the crystal forms of 7-fluoroisatin, a simple molecule with no reported crystal structures, to evaluate the value of crystal structure prediction studies as an aid to solid form discovery. Three polymorphs were found in a manual crystallisation screen, as well as two solvates. Form I ( P2(1)/c, Z0 1), found from the majority of solvent evaporation experiments, corresponded to the most stable form in the computational search of Z0 1 structures. Form III ( P21/ a, Z0 2) is probably a metastable form, which was only found concomitantly with form I, and has the same dimeric R2 2( 8) hydrogen bonding motif as form I and the majority of the computed low energy structures. However, the most thermodynamically stable polymorph, form II ( P1 , Z0 2), has an expanded four molecule R 4 4( 18) hydrogen bonding motif, which could not have been found within the routine computational study. The computed relative energies of the three forms are not in accord with experimental results. Thus, the experimental finding of three crystalline polymorphs of 7- fluoroisatin illustrates the many challenges for computational screening to be a tool for the experimental crystal engineer, in contrast to the results for an analogous investigation of 5- fluoroisatin.

Solvent influences on metastable polymorph lifetimes: real-time interconversions using energy dispersive X-ray diffractometry

Solvent influences on the crystallization of polymorph and hydrate forms of the nootropic drug piracetam (2-oxo-pyrrolidineacetamide) were investigated from water, methanol, 2-propanol, isobutanol, and nitromethane. Crystal growth profiles of piracetam polymorphs were constructed using time-resolved diffraction snapshots collected for each solvent system. Measurements were performed by in situ energy dispersive X-ray diffraction recorded in Station 16.4 at the synchrotron radiation source (SRS) at Daresbury Laboratory, CCLRC UK. Crystallizations from methanol, 2-propanol, isobutanol, and nitromethane progressed in a similar fashion with the initial formation of form I which then converted relatively quickly to form II with form III being generated upon further cooling. However, considerable differences were observed for the polymorphs lifetime and both the rate and temperature of conversion using the different solvents. The thermodynamically unstable form I was kinetically favored in isobutanol and nitromethane where traces of this polymorph were observed below 10 degrees C. In contrast, the transformation of form II and subsequent growth of form III were inhibited in 2-propanol and nitromethane solutions. Aqueous solutions produced hydrate forms of piracetam which are different from the reported monohydrate; this crystallization evolved through successive generation of transient structures which transformed upon exchange of intramolecular water between the liquid and crystalline phases. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:1069-1078, 2007.

Conformational polymorphism of the molecular complex of 3-fluorobenzoic acid with 4-acetylpyridine

Two polymorphs of the molecular complex formed between 3-fluorobenzoic acid with 4-acetylpyridine are described and found to be based upon the same dimeric supramolecular construct. The conformational freedom around the hydrogen bond results in a 180 degrees rotation about this intermolecular link, distinguishing the polymorphs and affecting the packing of the dimeric units. The two polymorphs are fully characterised by single crystal X-ray and neutron diffraction and quantum mechanical calculations. There is evidence of structured crystal growth defects in both polymorphic crystals via observation of diffuse scattering and a disorder model for the average structure of Form I, which can be interpreted as a mixing of the two dimer conformations. The similarity of energy of the distinct dimeric units, supporting their likely co-existence, has been verified by periodic quantum chemical calculations.

Essence and properties

The distinction between the essence of an object and its properties has been obscured in contemporary discussion of essentialism. Locke held that the properties of an object are exclusively those features that ‘flow’ from its essence. Here he follows the Aristotelian theory, leaving aside Locke’s own scepticism about the knowability of essence. I defend the need to distinguish sharply between essence and properties, arguing that essence must be given by form and that properties flow from form. I give a precise definition of what the term of art ‘flow’ amounts to, and apply the distinction to various kinds of taxonomic issues.

Use of in situ FT-Raman spectroscopy to study the kinetics of the transformation of carbamazepine polymorphs

The solid-state transformation of carbamazepine from form III to form I was examined by Fourier Transform Raman spectroscopy. Using a novel environmental chamber, the isothermal conversion was monitored in situ at 130◦C, 138◦C, 140◦C and 150◦C. The rate of transformation was monitored by taking the relative intensities of peaks arising from two C H bending modes; this approach minimised errors due to thermal artefacts and variations in power intensities or scattering efficiencies from the samples in which crystal habit changed from a characteristic prism morphology (form III) to whiskers (form I). The solid-state transformation at the different temperatures was fitted to various solid-state kinetic models of which four gave good fits, thus indicating the complexity of the process which is known to occur via a solid–gas–solid mechanism. Arrhenius plots from the kinetic models yielded activation energies from 344 kJ mol−1 to 368 kJ mol−1 for the transformation. The study demonstrates the value of a rapid in situ analysis of drug polymorphic type which can be of value for at-line in-process control.

Introduction and the problems of weather interpretation

Numerical forecasts of the atmosphere based on the fundamental dynamical and thermodynamical equations have now been carried for almost 30 years. The very first models which were used were drastic simplifications of the governing equations and permitting only the prediction of the geostrophic wind in the middle of the troposphere based on the conservation of absolute vorticity. Since then we have seen a remarkable development in models predicting the large-scale synoptic flow. Verification carried out at NMC Washington indicates an improvement of about 40% in 24h forecasts for the 500mb geopotential since the end of the 1950’s. The most advanced models of today use the equations of motion in their more original form (i.e. primitive equations) which are better suited to predicting the atmosphere at low latitudes as well as small scale systems. The model which we have developed at the Centre, for instance, will be able to predict weather systems from a scale of 500-1000 km and a vertical extension of a few hundred millibars up to global weather systems extending through the whole depth of the atmosphere. With a grid resolution of 1.5 and 15 vertical levels and covering the whole globe it is possible to describe rather accurately the thermodynamical processes associated with cyclone development. It is further possible to incorporate sub-grid-scale processes such as radiation, exchange of sensible heat, release of latent heat etc. in order to predict the development of new weather systems and the decay of old ones. Later in this introduction I will exemplify this by showing some results of forecasts by the Centre’s model.

The counter-propagating Rossby-wave perspective on baroclinic instability. I: Mathematical basis

It is shown that Bretherton's view of baroclinic instability as the interaction of two counter-propagating Rossby waves (CRWs) can be extended to a general zonal flow and to a general dynamical system based on material conservation of potential vorticity (PV). The two CRWs have zero tilt with both altitude and latitude and are constructed from a pair of growing and decaying normal modes. One CRW has generally large amplitude in regions of positive meridional PV gradient and propagates westwards relative to the flow in such regions. Conversely, the other CRW has large amplitude in regions of negative PV gradient and propagates eastward relative to the zonal flow there. Two methods of construction are described. In the first, more heuristic, method a ‘home-base’ is chosen for each CRW and the other CRW is defined to have zero PV there. Consideration of the PV equation at the two home-bases gives ‘CRW equations’ quantifying the evolution of the amplitudes and phases of both CRWs. They involve only three coefficients describing the mutual interaction of the waves and their self-propagation speeds. These coefficients relate to PV anomalies formed by meridional fluid displacements and the wind induced by these anomalies at the home-bases. In the second method, the CRWs are defined by orthogonality constraints with respect to wave activity and energy growth, avoiding the subjective choice of home-bases. Using these constraints, the same form of CRW equations are obtained from global integrals of the PV equation, but the three coefficients are global integrals that are not so readily described by ‘PV-thinking’ arguments. Each CRW could not continue to exist alone, but together they can describe the time development of any flow whose initial conditions can be described by the pair of growing and decaying normal modes, including the possibility of a super-modal growth rate for a short period. A phase-locking configuration (and normal-mode growth) is possible only if the PV gradient takes opposite signs and the mean zonal wind and the PV gradient are positively correlated in the two distinct regions where the wave activity of each CRW is concentrated. These are easily interpreted local versions of the integral conditions for instability given by Charney and Stern and by Fjørtoft.

Sensitivity of feature-based analysis methods of storm tracks to the form of background field removal

For the tracking of extrema associated with weather systems to be applied to a broad range of fields it is necessary to remove a background field that represents the slowly varying, large spatial scales. The sensitivity of the tracking analysis to the form of background field removed is explored for the Northern Hemisphere winter storm tracks for three contrasting fields from an integration of the U. K. Met Office's (UKMO) Hadley Centre Climate Model (HadAM3). Several methods are explored for the removal of a background field from the simple subtraction of the climatology, to the more sophisticated removal of the planetary scales. Two temporal filters are also considered in the form of a 2-6-day Lanczos filter and a 20-day high-pass Fourier filter. The analysis indicates that the simple subtraction of the climatology tends to change the nature of the systems to the extent that there is a redistribution of the systems relative to the climatological background resulting in very similar statistical distributions for both positive and negative anomalies. The optimal planetary wave filter removes total wavenumbers less than or equal to a number in the range 5-7, resulting in distributions more easily related to particular types of weather system. For the temporal filters the 2-6-day bandpass filter is found to have a detrimental impact on the individual weather systems, resulting in the storm tracks having a weak waveguide type of behavior. The 20-day high-pass temporal filter is less aggressive than the 2-6-day filter and produces results falling between those of the climatological and 2-6-day filters.

Determining the effect of asymmetric data on the variogram. I. Underlying asymmetry

Matheron's usual variogram estimator can result in unreliable variograms when data are strongly asymmetric or skewed. Asymmetry in a distribution can arise from a long tail of values in the underlying process or from outliers that belong to another population that contaminate the primary process. This paper examines the effects of underlying asymmetry on the variogram and on the accuracy of prediction, and the second one examines the effects arising from outliers. Standard geostatistical texts suggest ways of dealing with underlying asymmetry; however, this is based on informed intuition rather than detailed investigation. To determine whether the methods generally used to deal with underlying asymmetry are appropriate, the effects of different coefficients of skewness on the shape of the experimental variogram and on the model parameters were investigated. Simulated annealing was used to create normally distributed random fields of different size from variograms with different nugget:sill ratios. These data were then modified to give different degrees of asymmetry and the experimental variogram was computed in each case. The effects of standard data transformations on the form of the variogram were also investigated. Cross-validation was used to assess quantitatively the performance of the different variogram models for kriging. The results showed that the shape of the variogram was affected by the degree of asymmetry, and that the effect increased as the size of data set decreased. Transformations of the data were more effective in reducing the skewness coefficient in the larger sets of data. Cross-validation confirmed that variogram models from transformed data were more suitable for kriging than were those from the raw asymmetric data. The results of this study have implications for the 'standard best practice' in dealing with asymmetry in data for geostatistical analyses. (C) 2007 Elsevier Ltd. All rights reserved.

The cumulus-capped boundary layer. I: Modelling transports in the cloud layer

Scalar-flux budgets have been obtained from large-eddy simulations (LESs) of the cumulus-capped boundary layer. Parametrizations of the terms in the budgets are discussed, and two parametrizations for the transport term in the cloud layer are proposed. It is shown that these lead to two models for scalar transports by shallow cumulus convection. One is equivalent to the subsidence detrainment form of convective tendencies obtained from mass-flux parametrizations of cumulus convection. The second is a flux-gradient relationship that is similar in form to the non-local parametrizations of turbulent transports in the dry-convective boundary layer. Using the fluxes of liquid-water potential temperature and total water content from the LES, it is shown that both models are reasonable diagnostic relations between fluxes and the vertical gradients of the mean fields. The LESs used in this study are for steady-state convection and it is possible to treat the fluxes of conserved thermodynamic variables as independent, and ignore the effects of condensation. It is argued that a parametrization of cumulus transports in a model of the cumulus-capped boundary layer should also include an explicit representation of condensation. A simple parametrization of the liquid-water flux in terms of conserved variables is also derived.