Does DMSO affect the conformational changes of drug molecules in supercritical CO2 Media?

Journal of Molecular Liquids(2023)

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摘要
This work investigated the effect of DMSO-d6 on the conformation of lidocaine and fenamates. Using lidocaine as a model compound, the study investigated the influence of DMSO-d6 on the conformational preferences of fenamates, which have similar fragment structures to the molecule. The NOESY spectra of mefenamic, flufenamic and tolfenamic acid were compared in a mixture of scCO2 + DMSO-d6 at the same state parameters as lidocaine (45 degrees C and 9 MPa). The two-position exchange model was used to calculate the proportions of fenamate conformer groups in scCO2 + DMSO-d6. The addition of DMSO-d6 did not significantly alter the conformation of mefenamic acid, and the ratio of conformers was determined to be 75.3 / 24.7, which is very close to the previously measured in pure scCO2. The results showed that the addition of DMSO-d6 did not significantly alter the conformation of lidocaine and mefenamic acid. This suggests that adding 2 %, DMSO-d6 can be used to evaluate the structure of poorly soluble drug compounds using the NOESY method in supercritical carbon dioxide. The findings of this study are encouraging.
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关键词
supercritical co2 media,dmso,drug molecules,conformational changes
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