Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography
Samo za registrovane korisnike
2022
Autori
Šegan, SandraJevtić, Ivana
Tosti, Tomislav
Penjišević, Jelena
Šukalović, Vladimir
Kostić Rajačić, Slađana
Milojković-Opsenica, Dušanka
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Lipophilicity and ionization constant of sixteen fentanyl analogues were investigated by reversed-phase thin-layer chromatography (RP-TLC). Fourteen compounds have nitrogen containing groups at C-3 position of the piperidine ring and two compounds are 3-carbomethoxy derivatives of fentanyl. Among them, five are diastereomeric cis/trans couples and six novel trans diastereomers. In addition, the lipophilicity and ionization constant of fentanyl were also determined by the same method, as a reference. The physicochemical property, lipophilicity, expressed as retention indices RM0, b, and C0, as well as PC1, was determined and correlated with in silico values. Ionization constants were determined on the basis of the relationships between analyte's retention expressed as RF and mobile phase pH. Calculated structural descriptors together with the retention indices, were subjected to the principal component analysis – PCA and hierarchical cluster analysis – HCA, in order to provide basic ins...ights into the similarities among the studied compounds. The blood – brain barrier (BBB) permeation was investigated in the function of experimentally obtained values of lipophilicity, polar surface area and molecular weight. In general, results of the present research corroborate well with previously determined antinociceptive activities of the investigated compounds, pointing out that besides the cis/trans isomerism, another set of important parameters should be taken into account when designing new derivatives of C-3 substituted fentanyl, especially lipophilicity, voluminosity and HBD/A character of the substituents. Accordingly, RP-TLC can be considered as a valuable asset in the ligand-based drug design.
Ključne reči:
Chemometric analysis / Fentanyl / Ionization constants / Lipophilicity / Reverse-phased thin-layer chromatographyIzvor:
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 2022, 1211, 123481-Izdavač:
- Elsevier
Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200026 (Univerzitet u Beogradu, Institut za hemiju, tehnologiju i metalurgiju - IHTM) (RS-200026)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200168 (Univerzitet u Beogradu, Hemijski fakultet) (RS-200168)
DOI: 10.1016/j.jchromb.2022.123481
ISSN: 1570-0232; 1873-376X
PubMed: 36209674
WoS: 000876754500006
Scopus: 2-s2.0-85139291628
Institucija/grupa
IHTMTY - JOUR AU - Šegan, Sandra AU - Jevtić, Ivana AU - Tosti, Tomislav AU - Penjišević, Jelena AU - Šukalović, Vladimir AU - Kostić Rajačić, Slađana AU - Milojković-Opsenica, Dušanka PY - 2022 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/5413 AB - Lipophilicity and ionization constant of sixteen fentanyl analogues were investigated by reversed-phase thin-layer chromatography (RP-TLC). Fourteen compounds have nitrogen containing groups at C-3 position of the piperidine ring and two compounds are 3-carbomethoxy derivatives of fentanyl. Among them, five are diastereomeric cis/trans couples and six novel trans diastereomers. In addition, the lipophilicity and ionization constant of fentanyl were also determined by the same method, as a reference. The physicochemical property, lipophilicity, expressed as retention indices RM0, b, and C0, as well as PC1, was determined and correlated with in silico values. Ionization constants were determined on the basis of the relationships between analyte's retention expressed as RF and mobile phase pH. Calculated structural descriptors together with the retention indices, were subjected to the principal component analysis – PCA and hierarchical cluster analysis – HCA, in order to provide basic insights into the similarities among the studied compounds. The blood – brain barrier (BBB) permeation was investigated in the function of experimentally obtained values of lipophilicity, polar surface area and molecular weight. In general, results of the present research corroborate well with previously determined antinociceptive activities of the investigated compounds, pointing out that besides the cis/trans isomerism, another set of important parameters should be taken into account when designing new derivatives of C-3 substituted fentanyl, especially lipophilicity, voluminosity and HBD/A character of the substituents. Accordingly, RP-TLC can be considered as a valuable asset in the ligand-based drug design. PB - Elsevier T2 - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences T1 - Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography VL - 1211 SP - 123481 DO - 10.1016/j.jchromb.2022.123481 ER -
@article{ author = "Šegan, Sandra and Jevtić, Ivana and Tosti, Tomislav and Penjišević, Jelena and Šukalović, Vladimir and Kostić Rajačić, Slađana and Milojković-Opsenica, Dušanka", year = "2022", abstract = "Lipophilicity and ionization constant of sixteen fentanyl analogues were investigated by reversed-phase thin-layer chromatography (RP-TLC). Fourteen compounds have nitrogen containing groups at C-3 position of the piperidine ring and two compounds are 3-carbomethoxy derivatives of fentanyl. Among them, five are diastereomeric cis/trans couples and six novel trans diastereomers. In addition, the lipophilicity and ionization constant of fentanyl were also determined by the same method, as a reference. The physicochemical property, lipophilicity, expressed as retention indices RM0, b, and C0, as well as PC1, was determined and correlated with in silico values. Ionization constants were determined on the basis of the relationships between analyte's retention expressed as RF and mobile phase pH. Calculated structural descriptors together with the retention indices, were subjected to the principal component analysis – PCA and hierarchical cluster analysis – HCA, in order to provide basic insights into the similarities among the studied compounds. The blood – brain barrier (BBB) permeation was investigated in the function of experimentally obtained values of lipophilicity, polar surface area and molecular weight. In general, results of the present research corroborate well with previously determined antinociceptive activities of the investigated compounds, pointing out that besides the cis/trans isomerism, another set of important parameters should be taken into account when designing new derivatives of C-3 substituted fentanyl, especially lipophilicity, voluminosity and HBD/A character of the substituents. Accordingly, RP-TLC can be considered as a valuable asset in the ligand-based drug design.", publisher = "Elsevier", journal = "Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences", title = "Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography", volume = "1211", pages = "123481", doi = "10.1016/j.jchromb.2022.123481" }
Šegan, S., Jevtić, I., Tosti, T., Penjišević, J., Šukalović, V., Kostić Rajačić, S.,& Milojković-Opsenica, D.. (2022). Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography. in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences Elsevier., 1211, 123481. https://doi.org/10.1016/j.jchromb.2022.123481
Šegan S, Jevtić I, Tosti T, Penjišević J, Šukalović V, Kostić Rajačić S, Milojković-Opsenica D. Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography. in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. 2022;1211:123481. doi:10.1016/j.jchromb.2022.123481 .
Šegan, Sandra, Jevtić, Ivana, Tosti, Tomislav, Penjišević, Jelena, Šukalović, Vladimir, Kostić Rajačić, Slađana, Milojković-Opsenica, Dušanka, "Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography" in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 1211 (2022):123481, https://doi.org/10.1016/j.jchromb.2022.123481 . .