Solid-state vibrational circular dichroism for pharmaceutical applications: Polymorphs and cocrystal of sofosbuvir

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378271%3A_____%2F24%3A00586380" target="_blank" >RIV/68378271:_____/24:00586380 - isvavai.cz</a>

Alternative codes found

RIV/61388963:_____/24:00586380 RIV/60461373:22340/24:43929565

Result on the web

<a href="https://doi.org/10.1016/j.saa.2024.124478" target="_blank" >https://doi.org/10.1016/j.saa.2024.124478</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.saa.2024.124478" target="_blank" >10.1016/j.saa.2024.124478</a>

Result language

angličtina

Original language name

Solid-state vibrational circular dichroism for pharmaceutical applications: Polymorphs and cocrystal of sofosbuvir

Original language description

X-ray diffraction is a commonly used technique in the pharmaceutical industry for the determination of the atomic and molecular structure of crystals. However, it is costly, sometimes time-consuming, and it requires a considerable degree of expertise. Vibrational circular dichroism (VCD) spectroscopy resolves these limitations, while also exhibiting substantial sensitivity to subtle modifications in the conformation and molecular packaging in the solid state. This study showcases VCD's ability to differentiate between various crystal structures of the same molecule (polymorphs, cocrystals). We examined the most effective approach for producing high-quality spectra and unveiled the intricate link between structure and spectrum via quantum-chemical computations. We rigorously assessed, using alanine as a model compound, multiple experimental conditions on the resulting VCD spectra, with the aim of proposing an optimal and efficient procedure. The proposed approach, which yields reliable, reproducible, and artifact-free results with maximal signal-to-noise ratio, was then validated using a set comprising of three amino acids (serine, alanine, tyrosine), one hydroxy acid (tartaric acid), and a monosaccharide (ribose) to mimic active pharmaceutical components. Finally, the optimized approach was applied to distinguish three polymorphs of the antiviral drug sofosbuvir and its cocrystal with piperazine. Our results indicate that solid-state VCD is a prompt, cost-effective, and easy-to-use technique to identify crystal structures, demonstrating potential for application in pharmaceuticals. We also adapted the cluster and transfer approach to calculate the spectral properties of molecules in a periodic crystal environment. Our findings demonstrate that this approach reliably produces solid-state VCD spectra of model compounds. Although for large molecules with many atoms per unit cell, such as sofosbuvir, this approach has to be simplified and provides only a qualitative match, spectral calculations, and energy analysis helped us to decipher the observed differences in the experimental spectra of sofosbuvir.

Czech name

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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

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

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

Name of the periodical

Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy

ISSN

1386-1425

e-ISSN

1873-3557

Volume of the periodical

318

Issue of the periodical within the volume

October

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

124478

UT code for WoS article

001245236500001

EID of the result in the Scopus database

2-s2.0-85193828447