Biomedical subjects

P Verwer

Publications and source records attributed to P Verwer.

5 recordsLinked to original sources

PubMed2005

Epitaxial 2D nucleation of the stable polymorphic form of the steroid 7alphaMNa on the metastable form: implications for Ostwald's rule of stages.

This paper presents in situ observations of the epitaxial nucleation and growth of the stable polymorph of a steroid, 7alphaMna, on a specific face of the metastable form at low supersaturation, using optical microscopy and in situ Raman spectroscopy. The presence of the metastable polymorph is essential for the nucleation and growth of the stable one. The order of the metastable zones of the stable and metastable polymorphs is reversed for the epitaxial growth process as compared to the case of 3D nucleation. The rate of transformation of the metastable polymorph to the stable one can be controlled by the supersaturation.

Acetone↗

PubMed2005

A third blind test of crystal structure prediction.

Following the interest generated by two previous blind tests of crystal structure prediction (CSP1999 and CSP2001), a third such collaborative project (CSP2004) was hosted by the Cambridge Crystallographic Data Centre. A range of methodologies used in searching for and ranking the likelihood of predicted crystal structures is represented amongst the 18 participating research groups, although most are based on the global minimization of the lattice energy. Initially the participants were given molecular diagrams of three molecules and asked to submit three predictions for the most likely crystal structure of each. Unlike earlier blind tests, no restriction was placed on the possible space group of the target crystal structures. Furthermore, Z' = 2 structures were allowed. Part-way through the test, a partial structure report was discovered for one of the molecules, which could no longer be considered a blind test. Hence, a second molecule from the same category (small, rigid with common atom types) was offered to the participants as a replacement. Success rates within the three submitted predictions were lower than in the previous tests - there was only one successful prediction for any of the three ;blind' molecules. For the ;simplest' rigid molecule, this lack of success is partly due to the observed structure crystallizing with two molecules in the asymmetric unit. As in the 2001 blind test, there was no success in predicting the structure of the flexible molecule. The results highlight the necessity for better energy models, capable of simultaneously describing conformational and packing energies with high accuracy. There is also a need for improvements in search procedures for crystals with more than one independent molecule, as well as for molecules with conformational flexibility. These are necessary requirements for the prediction of possible thermodynamically favoured polymorphs. Which of these are actually realised is also influenced by as yet insufficiently understood processes of nucleation and crystal growth.

Algorithms↗

PubMed2005

Method for the computational comparison of crystal structures.

A new method for assessing the similarity of crystal structures is described. A similarity measure is important in classification and clustering problems in which the crystal structures are the source of information. Classification is particularly important for the understanding of properties of crystals, while clustering can be used as a data reduction step in polymorph prediction. The method described uses a radial distribution function that combines atomic coordinates with partial atomic charges. The descriptor is validated using experimental data from a classification study of clathrate structures of cephalosporins and data from a polymorph prediction run. In both cases, excellent results were obtained.

Journal Article↗

PubMed2000

A test of crystal structure prediction of small organic molecules.

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.

Journal Article↗

PubMedDate not supplied

Comparative spectra analysis (CoSA): spectra as three-dimensional molecular descriptors for the prediction of biological activities.

A novel 3D QSAR approach, comparative spectra analysis (CoSA), in which molecular spectra are used as three-dimensional molecular descriptors for the prediction of biological activities, is presented and discussed. To this purpose, experimentally determined 1H NMR, mass, and IR spectra, as well as simulated IR and 13C NMR spectra, for a set of 45 diverse progestagens are converted by a program, SpecMat, into matrixes, which are subsequently employed in a multivariate regression analysis (PLS). The results are compared with those resulting from a comparative molecular field analysis (CoMFA). When used individually, spectral descriptors yield better correlations and predictions than molecular field descriptors. A combination of spectral descriptors with other descriptors, either spectral or molecular field in nature, leads in most cases to models that are statistically superior to the ones obtained by their corresponding individual spectral or molecular field descriptors.

Magnetic Resonance Spectroscopy↗