scholarly journals Minimizing Polymorphic Risk Through Cooperative Computational and Experimental Exploration

2020 ◽  
Author(s):  
Christopher R. Taylor ◽  
Matthew T. Mulvee ◽  
Domonkos S. Perenyi ◽  
Michael R. Probert ◽  
Graeme Day ◽  
...  
Keyword(s):  
Crystal Structure ◽  
High Pressure ◽  
Structure Prediction ◽  
Experimental Approach ◽  
Significant Risk ◽  
Free Energy Calculations ◽  
Crystal Structure Prediction ◽  
Crystal Forms ◽  
Wide Range ◽  
Solid Form

<div> <p>We combine state-of-the-art computational crystal structure prediction (CSP) techniques with a wide range of experimental crystallization methods to understand and explore crystal structure in pharmaceuticals and minimize the risk of unanticipated late-appearing polymorphs. Initially, we demonstrate the power of CSP to rationalize the difficulty in obtaining polymorphs of the well-known pharmaceutical isoniazid and show that CSP provides the structure of the recently discovered, but unsolved, Form III of this drug despite there being only a single known form for almost 70 years. More dramatically, our blind CSP study predicts a significant risk of polymorphism for the related iproniazid. Employing a wide variety of experimental techniques, including high-pressure experiments, we experimentally obtained the first three known non-solvated crystal forms of iproniazid, all of which were successfully predicted in the CSP procedure. We demonstrate the power of CSP methods and free energy calculations to rationalize the observed elusiveness of the third form of iproniazid, the success of high-pressure experiments in obtaining it, and the ability of our synergistic computational-experimental approach to “de-risk” solid form landscapes.</p> </div>

scholarly journals Minimizing Polymorphic Risk Through Cooperative Computational and Experimental Exploration

2020 ◽  
Author(s):  
Christopher R. Taylor ◽  
Matthew T. Mulvee ◽  
Domonkos S. Perenyi ◽  
Michael R. Probert ◽  
Graeme Day ◽  
...  
Keyword(s):  
Crystal Structure ◽  
High Pressure ◽  
Structure Prediction ◽  
Experimental Approach ◽  
Significant Risk ◽  
Free Energy Calculations ◽  
Crystal Structure Prediction ◽  
Crystal Forms ◽  
Wide Range ◽  
Solid Form

<div> <p>We combine state-of-the-art computational crystal structure prediction (CSP) techniques with a wide range of experimental crystallization methods to understand and explore crystal structure in pharmaceuticals and minimize the risk of unanticipated late-appearing polymorphs. Initially, we demonstrate the power of CSP to rationalize the difficulty in obtaining polymorphs of the well-known pharmaceutical isoniazid and show that CSP provides the structure of the recently discovered, but unsolved, Form III of this drug despite there being only a single known form for almost 70 years. More dramatically, our blind CSP study predicts a significant risk of polymorphism for the related iproniazid. Employing a wide variety of experimental techniques, including high-pressure experiments, we experimentally obtained the first three known non-solvated crystal forms of iproniazid, all of which were successfully predicted in the CSP procedure. We demonstrate the power of CSP methods and free energy calculations to rationalize the observed elusiveness of the third form of iproniazid, the success of high-pressure experiments in obtaining it, and the ability of our synergistic computational-experimental approach to “de-risk” solid form landscapes.</p> </div>

scholarly journals New high-pressure phases of Fe7N3 and Fe7C3 stable at Earth's core conditions: evidences for carbon–nitrogen isomorphism in Fe-compounds

RSC Advances ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 3577-3581 ◽  
Author(s):  
Nursultan Sagatov ◽  
Pavel N. Gavryushkin ◽  
Talgat M. Inerbaev ◽  
Konstantin D. Litasov
Keyword(s):  
Crystal Structure ◽  
High Pressure ◽  
Ab Initio ◽  
Structure Prediction ◽  
Harmonic Approximation ◽  
Crystal Structure Prediction ◽  
Earth’S Core ◽  
Earth's Core ◽  
Core Conditions

We carried out ab initio calculations on the crystal structure prediction and determination of P–T diagrams within the quasi-harmonic approximation for Fe7N3 and Fe7C3.

Crystal structure prediction of ReN2 under high pressure

2019 ◽  
Vol 94 (11) ◽  
pp. 1711-1716
Author(s):  
H. Y. Wang ◽  
P. Yan ◽  
L. Xu ◽  
D. W. Zhou ◽  
D. Li
Keyword(s):  
Crystal Structure ◽  
High Pressure ◽  
Structure Prediction ◽  
Crystal Structure Prediction

scholarly journals Crystal structures of two furazidin polymorphs revealed by a joint effort of crystal structure prediction and NMR crystallography

2020 ◽  
Vol 76 (3) ◽  
pp. 322-335 ◽  
Author(s):  
Marta K. Dudek ◽  
Piotr Paluch ◽  
Edyta Pindelska
Keyword(s):  
Crystal Structure ◽  
Crystal Structures ◽  
Structure Determination ◽  
Structure Prediction ◽  
Structural Features ◽  
Crystal Structure Determination ◽  
Crystal Structure Prediction ◽  
Crystal Forms ◽  
Space Groups ◽  
Nmr Crystallography

This work presents the crystal structure determination of two elusive polymorphs of furazidin, an antibacterial agent, employing a combination of crystal structure prediction (CSP) calculations and an NMR crystallography approach. Two previously uncharacterized neat crystal forms, one of which has two symmetry-independent molecules (form I), whereas the other one is a Z′ = 1 polymorph (form II), crystallize in P21/c and P 1 space groups, respectively, and both are built by different conformers, displaying different intermolecular interactions. It is demonstrated that the usage of either CSP or NMR crystallography alone is insufficient to successfully elucidate the above-mentioned crystal structures, especially in the case of the Z′ = 2 polymorph. In addition, cases of serendipitous agreement in terms of 1H or 13C NMR data obtained for the CSP-generated crystal structures different from the ones observed in the laboratory (false-positive matches) are analyzed and described. While for the majority of analyzed crystal structures the obtained agreement with the NMR experiment is indicative of some structural features in common with the experimental structure, the mentioned serendipity observed in exceptional cases points to the necessity of caution when using an NMR crystallography approach in crystal structure determination.

scholarly journals Insight from energy surfaces: structure prediction by lattice energy exploration

2014 ◽  
Vol 70 (a1) ◽  
pp. C28-C28
Author(s):  
Graeme Day
Keyword(s):  
Crystal Structure ◽  
Structure Prediction ◽  
Crystal Packing ◽  
Lattice Energy ◽  
Organic Crystals ◽  
Crystal Structure Prediction ◽  
Stability Order ◽  
The Stability ◽  
Solid Form ◽  
Energy Surfaces

A long-standing challenge for the application of computational chemistry in the field of crystallography is the prediction of crystal packing, given no more than the chemical bonding of the molecules being crystallised. Recent years have seen significant progress towards reliable crystal structure prediction methods, even for traditionally challenging systems involving flexible molecules and multi-component solids [1]. These methods are based on global searches of the lattice energy surface: a search is performed to locate all possible packing arrangements, and these structures are ranked by their calculated energy [2]. One aim of this lecture is to provide an overview of advances in methods for crystal structure prediction, focussing on molecular organic crystals, and highlighting strategies that are being explored to extend the reach of these methods to more complex systems. A second aim is to discuss the range applications of crystal structure prediction calculations, which have traditionally included solid form screening, particularly of pharmaceutically active molecules, and structure determination. As energy models become more reliable at correctly ranking the stability order of putative structures, and the timescale required for structure searching decreases, crystal structure prediction has the potential for the discovery of novel molecular materials with targeted properties. Prospects for computer-guided discovery of materials will be discussed.

scholarly journals Unbiased crystal structure prediction of NiSi under high pressure

2015 ◽  
Vol 48 (3) ◽  
pp. 906-908 ◽  
Author(s):  
Pavel N. Gavryushkin ◽  
Zakhar I. Popov ◽  
Konstantin D. Litasov ◽  
Alex Gavryushkin
Keyword(s):  
Crystal Structure ◽  
High Pressure ◽  
Structure Prediction ◽  
Type Structure ◽  
Stable Phase ◽  
Stable Form ◽  
Model Structure ◽  
Crystal Structure Prediction ◽  
Cscl Type ◽  
Pressure Phase

On the basis of an unbiased structure prediction, it is shown that the stable form of NiSi under pressures of 100 and 200 GPa is thePmmnstructure. Furthermore, a new stable phase has been discovered: the deformed tetragonal CsCl-type structure witha= 2.174 Å andc= 2.69 Å at 400 GPa. Specifically, the sequence of high-pressure phase transitions is the following: thePmmnstructure below 213 GPa, the tetragonal CsCl type in the range 213–522 GPa, and cubic CsCl higher than 522 GPa. As the CsCl-type structure is considered as the model structure of the FeSi compound at the conditions of the Earth's core, this result implies restrictions on the Fe–Ni isomorphic miscibility in FeSi.

Crystal structure prediction of uranium hydrides at high pressure: A new hydrogen-rich phase

2018 ◽  
Vol 382 (40) ◽  
pp. 2959-2964 ◽  
Author(s):  
Xiaohui Wang ◽  
Menglei Li ◽  
Fawei Zheng ◽  
Ping Zhang
Keyword(s):  
Crystal Structure ◽  
High Pressure ◽  
Structure Prediction ◽  
Crystal Structure Prediction ◽  
Rich Phase
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