First-Principles Models of Polymorphism of Pharmaceuticals: Maximizing the Accuracy-to-Cost Ratio

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F24%3A43929344" target="_blank" >RIV/60461373:22340/24:43929344 - isvavai.cz</a>

Result on the web

<a href="https://pubs.acs.org/doi/10.1021/acs.jctc.4c00099#" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jctc.4c00099#</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jctc.4c00099" target="_blank" >10.1021/acs.jctc.4c00099</a>

Result language

angličtina

Original language name

First-Principles Models of Polymorphism of Pharmaceuticals: Maximizing the Accuracy-to-Cost Ratio

Original language description

Accuracy and sophistication of in silico models of structure, internal dynamics, and cohesion of molecular materials at finite temperatures increase over time. Applicability limits of ab initio polymorph ranking that would be feasible at reasonable costs currently represent crystals of moderately sized molecules (less than 20 nonhydrogen atoms) and simple unit cells (containing rather only one symmetry-irreducible molecule). Extending the applicability range of the underlying first-principles methods to larger systems with a real-life significance, and enabling to perform such computations in a high-throughput regime represent additional challenges to be tackled in computational chemistry. This work presents a novel composite method that combines the computational efficiency of density-functional tight-binding (DFTB) methods with the accuracy of density-functional theory (DFT). Being rooted in the quasi-harmonic approximation, it uses a cheap method to perform all of the costly scans of how static and dynamic characteristics of the crystal vary with respect to its volume. Such data are subsequently corrected to agree with a higher-level model, which must be evaluated only at a single volume of the crystal. It thus enables predictions of structural, cohesive, and thermodynamic properties of complex molecular materials, such as pharmaceuticals or organic semiconductors, at a fraction of the original computational cost. As the composite model retains the solid physical background, it suffers from a minimum accuracy deterioration compared to the full treatment with the costly approach. The novel methodology is demonstrated to provide consistent results for the structural and thermodynamic properties of real-life molecular crystals and their polymorph ranking. © 2024 The Authors. Published by American Chemical Society.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10403 - Physical chemistry

Project

<a href="/en/project/GM23-05476M" target="_blank" >GM23-05476M: Making ab initio modelling possible for disordered molecular semi-conductive materials</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Chemical Theory and Computation

ISSN

1549-9618

e-ISSN

1549-9626

Volume of the periodical

20

Issue of the periodical within the volume

7

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

2858-2870

UT code for WoS article

001192353500001

EID of the result in the Scopus database

2-s2.0-85188988978