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. The use of CSP in the prediction of likely cocrystal stoichiometry was also explored, demonstrating multiple possible approaches. Crystallographic disorder emerged as an important theme throughout the test as both a challenge for analysis and a major achievement where two groups blindly predicted the existence of disorder for the first time. Additionally, large-scale comparisons of the sets of predicted crystal structures also showed that some methods yield sets that largely contain the same crystal structures.

The seventh blind test of crystal structure prediction (CSP) methods substantially increased the level of complexity of the target compounds relative to the previous tests organized by the Cambridge Crystallographic Data Centre. In this work, the performance of density-functional methods is assessed using numerical atomic orbitals and the exchange-hole dipole moment dispersion correction (XDM) for the energy-ranking phase of the seventh blind test. Overall, excellent performance was seen for the two rigid molecules (XXVII, XXVIII) and for the organic salt (XXXIII). However, for the agrochemical (XXXI) and pharmaceutical (XXXII) targets, the experimental polymorphs were ranked fairly high in energy amongst the provided candidate structures and inclusion of thermal free-energy corrections from the lattice vibrations was found to be essential for compound XXXI. Based on these results, it is proposed that the importance of vibrational free-energy corrections increases with the number of rotatable bonds.

The landscapes of observed and predicted three-dimensional crystal packing arrangements of small-molecule drug candidates can be complex. The possible appearance of a more thermodynamically stable solid form during drug development has led to the digital workflow of informatics-based risk assessments, named a Solid Form Health Check. Herein, we describe the use of a combined approach consisting of experiments, informatics together with energetic calculations in analysis of four competing polymorphs of PF-06282999, a myeloperoxidase (MPO) inhibitor with conformational flexibility and multiple plausible hydrogen bond networks. This combined approach offered a comprehensive understanding of the solid form structure, properties, and performance, ensuring robust solid form derisking and selection.

Predicting the experimentally accessible crystal structures of a molecular material is one of the fundamental challenges of solid-state science.Since 1999 the Crystal Structure Prediction (CSP) blind tests, organised by the Cambridge Crystallographic Data Centre (CCDC), have provided an unbiased assessment of state-of-the-art methods from CSP, with subsequent publications capturing the developments made over the years and providing readers with an overview of the methodologies available and in-development.To date, 7 blind tests have been carried out with the most recent ending in June 2022.In this talk we will present the major developments and remaining challenges facing CSP methods as evidenced by the outcomes of the 7th blind test, and explore the structural-energetic insights gained from analysis and graphical visualisation of crystal structure landscapes submitted.

An analysis of the geometries of interaction between C6H5-C aromatic rings and between substituted rings (of the form C6H4-XC where X is a non-carbon substituent, and C is a carbon substituent) and pyridine rings, extracted from the Cambridge Structural Database, has shown that when ring centroid-centroid separations are less than 6 angstrom there is a high degree of similarity in the geometries of interactions, though with variation in the proportions of parallel ring orientations with respect to T-shaped geometries. Using a scripted version of the Aromatics Analyzer tool (of Mercury), data sets of structures containing only C6H5-C aromatic rings were analyzed to obtain the number of C6H5-C aromatic rings and the number of strong ring-ring interactions. These data were combined with simple molecular descriptors such as molecular weight, shortest molecular dimension, and fraction aromaticity of the molecule to examine whether molecular characteristics influenced the number of strong aromatic interactions observed in the solid state. Results of the analysis suggest that the molecular weight, shape, and aromaticity of a molecule do vary with the number of strong aromatic interactions, in intuitive ways.

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTProfessor Roger Davey: Master of All Crystal TradesAurora J. Cruz-Cabeza*Aurora J. Cruz-Cabeza*Email: [email protected]More by Aurora J. Cruz-Cabezahttps://orcid.org/0000-0002-0957-4823, Ghazala Sadiq*Ghazala Sadiq*Email: [email protected]More by Ghazala Sadiq, Thomas Vetter*Thomas Vetter*Email: [email protected]More by Thomas Vetter, and Simon Black*Simon Black*Email: [email protected]More by Simon Blackhttps://orcid.org/0000-0003-3147-376XCite this: Cryst. Growth Des. 2022, 22, 6, 3565–3574Publication Date (Web):May 9, 2022Publication History Published online9 May 2022Published inissue 1 June 2022https://pubs.acs.org/doi/10.1021/acs.cgd.2c00411https://doi.org/10.1021/acs.cgd.2c00411editorialACS PublicationsCopyright © Published 2022 by American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views1913Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (7 MB) Get e-AlertscloseSUBJECTS:Crystal structure,Crystallization,Crystals,Kinetics,Nucleation Get e-Alerts

Analysis of the molecular and structural features of the GSK crystal structure database and Cambridge Structural Database leads to improved reliability in hydrogen bond propensity models for pharmaceutical polymorphs.

Suzanna Ward and Ghazala Sadiq introduce the CrystEngComm themed issue on the Cambridge Structural Database – a wealth of knowledge gained from a million structures.

Using crystallography to search for nucleation pathways: α and β polymorphs of p-aminobenzoic acid.

Objective: To evaluate the influence of physician attire on patient perceptions including their trust, satisfaction and confidence. Methodology: This cross-sectional observational study was carried out in the Gynecology and Obstetrics department of Al Sadiq SSH and Quaid e Azam International Hospital, Rawalpindi, Pakistan from January 2017 to April 2017. Results: Of the 450 patients or caretakers who were approached, 336 responded to the questionnaire, with 280 complete responses used in subsequent analyses. The mean age of using self-administered questionnaires respondents was 41.9 years and 40.3% were male. Regardless of a doctor's gender, the white coat with formal dress was judged to be the most appropriate style of dress, followed by surgical scrubs with white coat. Conclusion: Attire is one of the important factors that inspires patients trust and confidence in physicians. Shirt and tie with white coat or scrubs remains the patient's preferred attire for physicians compared to short sleeved shirt and no tie.

Objective: To determine prevalence of post natal depression (PND) in our part of the world and correlate risks with obstetric and demographic variables. Methodology: This observational cross sectional study was conducted at Quaid-e-Azam International Hospital Islamabad and AI-Sadiq-SSH Rawalpindi, Pakistan, from March to May 2014. Women delivering in QIH or SSH and those attending for their baby's vaccination at 4 to 12 weeks post partum were included; those having previous psychiatric illness were excluded. Data were collected by interviewing them. PND symptoms were defined when subjects had Edinburgh Postnatal Depression Scale score of 10 or higher. Variables included were age, education, family setup, parity, baby's sex, and emotional response. Results: Out of 380 women, PND was seen in 88 (23%) women. Social support showed a decrease in risk by 20%. Elderly and professional women and those showing negative response were at a higher risk 38.46 % and (39%). Conclusion: Post natal depression is a common occurrence. Social support from a joint family system plays a significant role in reducing risk of PND.

The crystallization of alpha-p-aminobenzoic acid (pABA) from mixed solutions in ethanol (EtOH) and nitromethane (NMe) is reported. From solutions with compositions >60 wt % NMe, the known alpha-polymorph of pABA appears. In contrast, crystals prepared from mixed solvent with <60 wt % NMe reveal the presence of a previously unknown NMe solvate, which crystallizes concomitantly with the alpha-form. The crystal structure of this new form has been determined and is compared with the previously known structure of the alpha-polymorph. The crystal structure of the NMe solvate has similar synthonic interactions with respect to alpha-pABA, in particular, the OH center dot center dot center dot O H-bonded dimers and the NH center dot center dot center dot O H-bonds between the pABA molecules. However, the pi-pi stacking interactions between the phenyl ring groups are found to be much more offset and do not form a continuous chain through the structure, as found in alpha-pABA. The synthonic interactions in the NMe solvate structure are generally weaker than those found in alpha-pABA, and the lattice energy is calculated to be significantly lower, suggesting the solvate structure is metastable with respect to alpha-pABA. The impact of NMe on the morphology of alpha-pABA crystals, together with molecular modelling results suggest that this solvent is able to disrupt the pi-pi stacking interactions that dominate growth along the needle (b-axis) direction of alpha-pABA, and are intimately linked to the ultimate formation of the solvate.

Effects of three polymers, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and copolymer of vinylpyrrolidone/vinyl acetate (PVP-VA), on the dissolution behavior of the cocrystals of flufenamic acid with theophylline (FFA-TP CO) and nicotinamide (FFA-NIC CO) were investigated at multiple length scales. At the molecular level, the interactions of crystal surfaces with a polymer were analyzed by observing etching pattern changes using atomic force microscopy. At the macroscopic scale, dissolution rates of particular faces of a single crystal were determined by measurement of the physical retreat velocities of the faces using optical light microscopy. In the bulk experiments, the FFA concentration in a dissolution medium in the absence or presence of a polymer was measured under both sink and nonsink conditions. It has been found that the dissolution mechanisms of FFA-TP CO are controlled by the defect sites of the crystal surface and by precipitation of the parent drug FFA as individual crystals in the bulk fluid. In contrast, the dissolution mechanisms of FFA-NIC CO are controlled by surface layer removal and by a surface precipitation mechanism, where the parent drug FFA precipitates directly onto the surface of the dissolving cocrystals. Through controlling the dissolution environment by predissolving a polymer, PVP or PVP-VA, which can interact with the crystal surface to alter its dissolution properties, improved solubility, and dissolution rates of FFA-TP CO and FFA-NIC CO have been demonstrated.

Introduction: Depression in pregnancy has adverse health outcomes for mothers and children. The aim of this study was to determine prevalence of Post partum depression PPD in our part of the world; correlate the risk with obstetric and demographic variables including family support, emotional response towards pregnancy and level of education of couple. Introduction: Depression in pregnancy has adverse health outcomes for mothers and children. The aim of this study was to determine prevalence of Post partum depression PPD in our part of the world; correlate the risk with obstetric and demographic variables including family support, emotional response towards pregnancy and level of education of couple.