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. All of the targets, apart from a single potentially disorderedZ′ = 2 polymorph of the drug candidate, were predicted by at least one submission. Despite many remaining challenges, it is clear that CSP methods are becoming more applicable to a wider range of real systems, including salts, hydrates and larger flexible molecules. The results also highlight the potential for CSP calculations to complement and augment experimental studies of organic solid forms.

The donor/acceptor (D/A) substituted π-conjugated organic molecules possess extremely fast nonlinear optical (NLO) response time that is purely electronic in origin. This makes them promising candidates for optoelectronic applications. In the present study, we utilized four hybrid density functionals (B3LYP, B97-2, PBE0, BMK), Hartree–Fock, and second order Møller–Plesset correlation energy correction, truncated at second-order (MP2) methods with different basis sets to estimate molecular first hyperpolarizability (β) of D/A-substituted benzenes and stilbenes (D=OMe, OH, NMe2, NH2; A=NO2, CN). The results of density functional theory (DFT) calculations are compared to those of MP2 method and to the experimental data. We addressed the following questions: (1) the accurate techniques to compare calculated results to each other and to experiment, (2) the choice of the basis set, (3) the effect of molecular planarity, and (4) the choice of the method. Comparison of the absolute values of hyperpolarizabilities obtained computationally and experimentally is complicated by the ambiguities in conventions and reference values used by different experimental groups. A much more tangible way is to compare the ratios of β’s for two (or more) given molecules of interest that were calculated at the same level of theory and measured at the same laboratory using the same conventions and reference values. Coincidentally, it is the relative hyperpolarizabilities rather than absolute ones that are of importance in the rational molecular design of effective NLO materials. This design includes prediction of the most promising candidates from particular homologous series, which are to be synthesized and used for further investigation. In order to accomplish this goal, semiquantitative level of accuracy is usually sufficient. Augmentation of the basis set with polarization and diffuse functions changes β by 20%; however, further extension of the basis set does not have significant effect. Thus, we recommend 6-31+G* basis set. We also show that the use of planar geometry constraints for the molecules, which can somewhat deviate from planarity in the gas phase, leads to sufficient accuracy (with an error less than 10%) of predicted values. For all the molecules studied, MP2 values are in better agreement with experiment, while DFT hybrid methods overestimate β values. BMK functional gives the best agreement with experiment, with systematic overestimation close to the factor of 1.4. We propose to use the scaled BMK results for prediction of molecular hyperpolarizability at semiquantitative level of accuracy.