The seventh blind test of crystal structure prediction: structure generation methods.

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern.

How many more polymorphs of ROY remain undiscovered.

With 12 crystal forms, 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecabonitrile (a.k.a.

Efficient Screening for Ternary Molecular Ionic Cocrystals Using a Complementary Mechanosynthesis and Computational Structure Prediction Approach.

The discovery of molecular ionic cocrystals (ICCs) of active pharmaceutical ingredients (APIs) widens the opportunities for optimizing the physicochemical properties of APIs whilst facilitating the delivery of multiple therapeutic agents. However, ICCs are often observed serendipitously in crystallization screens and the factors dictating their crystallization are poorly understood. We demonstrate here that mechanochemical ball milling is a versatile technique for the reproducible synthesis of ternary molecular ICCs in less than 30 min of grinding with or without solvent.

Accurate and efficient representation of intramolecular energy in ab initio generation of crystal structures. II. Smoothed intramolecular potentials.

The application of crystal structure prediction (CSP) to industrially relevant molecules requires the handling of increasingly large and flexible compounds. A revised model for the effect of molecular flexibility on the lattice energy that removes the discontinuities and non-differentiabilities present in earlier models (Sugden et al., 2016), with a view to improving the performance of CSP is presented.

Report on the sixth blind test of organic crystal structure prediction methods.

The sixth blind test of organic crystal structure prediction (CSP) methods has been held, with five target systems: a small nearly rigid molecule, a polymorphic former drug candidate, a chloride salt hydrate, a co-crystal and a bulky flexible molecule. This blind test has seen substantial growth in the number of participants, with the broad range of prediction methods giving a unique insight into the state of the art in the field. Significant progress has been seen in treating flexible molecules, usage of hierarchical approaches to ranking structures, the application of density-functional approximations, and the establishment of new workflows and `best practices' for performing CSP calculations.

Efficient Handling of Molecular Flexibility in Ab Initio Generation of Crystal Structures.

A key step in many approaches to crystal structure prediction (CSP) is the initial generation of large numbers of candidate crystal structures via the exploration of the lattice energy surface. By using a relatively simple lattice energy approximation, this global search step aims to identify, in a computationally tractable manner, a limited number of likely candidate structures for further refinement using more detailed models. This paper presents an effective and efficient approach to modeling the effects of molecular flexibility during this initial global search.

Thermal rearrangement mechanisms in icosahedral carboranes and metallocarboranes.

Ab initio MD and potential energy surface sampling has been used to study the rearrangement processes in carboranes and their derivatives. A new mechanism is found, in addition to those previously proposed. The fact that theoretical activation energies are lower than those observed experimentally, and the differing activity of technetium and rhenium complexes, are rationalised by orbital symmetry constraints.