Computation screening for incorrectly determined cocrystal structures

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11320%2F25%3A10508337" target="_blank" >RIV/00216208:11320/25:10508337 - isvavai.cz</a>

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=XtC4oGTl4-" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=XtC4oGTl4-</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1107/S205252062500068X" target="_blank" >10.1107/S205252062500068X</a>

Result language

angličtina

Original language name

Computation screening for incorrectly determined cocrystal structures

Original language description

Pharmaceutical solid forms, like salts and cocrystals, play a crucial role in drug formulation. Despite differing mainly by a single hydrogen atom, the regulatory requirements set by the US Food and Drug Administration for these forms vary significantly. We previously developed a DFT-based computational method to distinguish salts from cocrystals. This method, validated on 95 structures, performed well for systems where hydrogen bonds were longer than 2.613 (16) angstrom. Here, benefits of the rSCAN functional over the PBE functional are discussed. We expand the dataset to 404 cocrystal models. Analysis confirms that 301 of these forms are indeed cocrystals. Additionally, 87 salt-cocrystal continuum forms are identified and 16 cocrystals are classified as possible salts. These 16 problematic structures are further investigated and for seven of them, single crystals were grown and their structure determined using single-crystal X-ray diffraction. Among the phases exhibiting salt-like behaviour, five of them are identified as salts. In some cases, rSCAN alone gives unreliable results for strong hydrogen bonds, but these discrepancies are often corrected using better-renormalized or hybrid functionals (i.e. r2SCAN, PBE0 and PBE50). For future calculations, we recommend using the r2SCAN functional for salt-cocrystal differentiation, as it provides reliable results for O-H center dot center dot center dot N bonds longer than 2.554 (5) angstrom. The r2SCAN functional offers a good balance between accuracy and computational efficiency for systems with longer O-H center dot center dot center dot N bonds.

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

10302 - Condensed matter physics (including formerly solid state physics, supercond.)

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

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

Name of the periodical

Acta Crystallographica. Section B: Structural Science, Crystal Engineering and Materials

ISSN

2052-5206

e-ISSN

2052-5206

Volume of the periodical

81

Issue of the periodical within the volume

2

Country of publishing house

GB - UNITED KINGDOM

Number of pages

9

Pages from-to

208-216

UT code for WoS article

001467038700006

EID of the result in the Scopus database

2-s2.0-105002703780