4 research outputs found
Use of Crystal Structure Informatics for Defining the Conformational Space Needed for Predicting Crystal Structures of Pharmaceutical Molecules
Determining
the range of conformations that a flexible pharmaceutical-like
molecule could plausibly adopt in a crystal structure is a key to
successful crystal structure prediction (CSP) studies. We aim to use
conformational information from the crystal structures in the Cambridge
Structural Database (CSD) to facilitate this task. The conformations
produced by the CSD Conformer Generator are reduced in number by considering
the underlying rotamer distributions, an analysis of changes in molecular
shape, and a minimal number of molecular <i>ab initio</i> calculations. This method is tested for five pharmaceutical-like
molecules where an extensive CSP study has already been performed.
The CSD informatics-derived set of crystal structure searches generates
almost all the low-energy crystal structures previously found, including
all experimental structures. The workflow effectively combines information
on individual torsion angles and then eliminates the combinations
that are too high in energy to be found in the solid state, reducing
the resources needed to cover the solid-state conformational space
of a molecule. This provides insights into how the low-energy solid-state
and isolated-molecule conformations are related to the properties
of the individual flexible torsion angles
Density functional theory predictions of the mechanical properties of crystalline materials
The mechanical properties of crystalline materials are crucial knowledge for their screening, design, and exploitation. Density functional theory (DFT), remains one of the most effective computational tools for quantitatively predicting and rationalising the mechanical response of these materials. DFT predictions have been shown to quantitatively correlate to a number of experimental techniques, such as nanoindentation,
high-pressure X-ray crystallography, impedance spectroscopy, and spectroscopic ellipsometry. Not only can bulk mechanical properties be derived from DFT calculations, this computational methodology allows for a full understanding of the elastic anisotropy in complex crystalline systems. Here we introduce the concepts behind DFT, and highlight a number of case studies and methodologies for predicting the elastic constants of materials that span ice, biomolecular crystals, polymer crystals, and metal–organic frameworks
(MOFs). Key parameters that should be considered for theorists are discussed, including exchange– correlation functionals and dispersion corrections. The broad range of software packages and post-analysis tools are also brought to the attention of current and future DFT users. It is envisioned that the accuracy of DFT predictions of elastic constants will continue to improve with advances in high-performance computing power, as well as the incorporation of many-body interactions with quasi-harmonic approximations to overcome the negative effects of calculations carried out at absolute zero
Quantitative Prediction of Optical Absorption in Molecular Solids from an Optimally Tuned Screened Range-Separated Hybrid Functional
We show that fundamental
gaps and optical spectra of molecular
solids can be predicted quantitatively and nonempirically within the
framework of time-dependent density functional theory (TDDFT) using
the recently developed optimally tuned screened range-separated hybrid
(OT-SRSH) functional approach. In this scheme, the electronic structure
of the gas-phase molecule is determined by optimal tuning of the range-separation
parameter in a range-separated hybrid functional. Screening and polarization
in the solid state are taken into account by adding long-range dielectric
screening to the functional form, with the modified functional used
to perform self-consistent periodic-boundary calculations for the
crystalline solid. We provide a comprehensive benchmark for the accuracy
of our approach by considering the X23 set of molecular solids and
comparing results obtained from TDDFT with those obtained from many-body
perturbation theory in the GW-BSE approximation. We additionally compare
results obtained from dielectric screening computed within the random-phase
approximation to those obtained from the computationally more efficient
many-body dispersion approach and find that this influences the fundamental
gap but has little effect on the optical spectra. Our approach is
therefore robust and can be used for studies of molecular solids that
are typically beyond the reach of computationally more intensive methods
A piezoelectric ionic cocrystal of glycine and sulfamic acid
Cocrystallization of two or more molecular compounds can dramatically change the physicochemical properties of a functional molecule without the need for chemical modification. For example, coformers can enhance the mechanical stability, processability, and solubility of pharmaceutical compounds to enable better medicines. Here, we demonstrate that amino acid cocrystals can enhance functional electromechanical properties in simple, sustainable materials as exemplified by glycine and sulfamic acid. These coformers crystallize independently in centrosymmetric space groups when they are grown as single-component crystals but form a noncentrosymmetric, electromechanically active ionic cocrystal when they are crystallized together. The piezoelectricity of the cocrystal is characterized using techniques tailored to overcome the challenges associated with measuring the electromechanical properties of soft (organic) crystals. The piezoelectric tensor of the cocrystal is mapped using density functional theory (DFT) computer models, and the predicted single-crystal longitudinal response of 2 pC/N is verified using second-harmonic generation (SHG) and piezoresponse force microscopy (PFM). The experimental measurements are facilitated by polycrystalline film growth that allows for macroscopic and nanoscale quantification of the longitudinal out-of-plane response, which is in the range exploited in piezoelectric technologies made from quartz, aluminum nitride, and zinc oxide. The large-area polycrystalline film retains a damped response of ≥0.2 pC/N, indicating the potential for application of such inexpensive and eco-friendly amino acid–based cocrystal coatings in, for example, autonomous ambient-powered devices in edge computing