Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Sci Rep. 2024 Nov 5;14(1):26757. doi: 10.1038/s41598-024-78415-1.

Possibilities and limitations of computer assisted chiral HPLC method 
development for ozanimod on polysaccharide based chiral stationary phases.

Ferencz E(#)(1), Szabó ZI(#)(1)(2), Zöldhegyi A(3), Dombi G(4)(5), Molnár 
G(4)(5), Dobó M(4)(5), Varga E(1), Molnár I(3), Tóth G(6)(7).

Author information:
(1)George Emil Palade University of Medicine, Pharmacy, Science, and Technology 
of Targu Mures, Târgu Mureş, Romania.
(2)Sz-imfidum Ltd, Lunga, 525401, Romania.
(3)Molnár-Institute for Applied Chromatography, Berlin, Germany.
(4)Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes E. u. 
9, Budapest, 1092, Hungary.
(5)Center for Pharmacology and Drug Research & Development, Semmelweis 
University, Budapest, Hungary.
(6)Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes E. u. 
9, Budapest, 1092, Hungary. toth.gergo@semmelweis.hu.
(7)Center for Pharmacology and Drug Research & Development, Semmelweis 
University, Budapest, Hungary. toth.gergo@semmelweis.hu.
(#)Contributed equally

In this study, a direct HPLC method was developed to determine the enantiomeric 
purity of the immunomodulatory drug, ozanimod. A systematic method development 
process was followed, incorporating risk assessment, identification of critical 
analytical procedure parameters, initial screening of stationary phases, and 
software-assisted optimization of method parameters. Eight different 
polysaccharide-based chiral columns were selected to assess chiral separation of 
enantiomers under polar organic elution mode. The most promising results were 
obtained using a methanol:2-propanol mixture on the amylose-based Chiralpak AD 
column. Following this, systematic modeling was conducted using DryLab software 
to optimize method conditions, including isocratic eluent composition, 
temperature, and flow rate. Baseline separation was achieved within fifteen 
minutes using the optimized parameters: Chiralpak AD column thermostated at 
10 °C, and a mobile phase of methanol:2-propanol: diethylamine, 70:30:0.1 (v/v/v 
%), delivered at a flow rate of 0.8 mL/min. The developed method was validated 
according to current guidelines and in silico robustness testing was conducted 
to determine tolerance limits for critical separation parameters and their 
impact on enantioresolution. Our findings demonstrate the utility of DryLab, 
typically employed for reversed-phase achiral separations, in optimizing chiral 
methods even in polar organic mode. Limitations of the selected approach the 
development of chiral separation methods are also highlighted.

© 2024. The Author(s).

DOI: 10.1038/s41598-024-78415-1
PMCID: PMC11538454
PMID: 39500751 [Indexed for MEDLINE]

Conflict of interest statement: Imre Molnár is the founder, while Arnold 
Zöldhegyi is employed by Molnár-Institute for Applied Chromatography, the 
developer of the DryLab software. All other authors declare no competing 
financial interests or personal relationships that could have appeared to 
influence the work reported in this paper.


2. Phys Chem Chem Phys. 2024 Nov 4. doi: 10.1039/d4cp03926b. Online ahead of
print.

Insights into the chirality-dependent recognition of Danshensu Bingpian Zhi 
stereoisomers with PPAR(γ).

Zhao J(1), Zhao Y(1), Zhang S(1), Zhang L(1), Yang Z(1).

Author information:
(1)MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed 
Matter, School of Physics, Xi'an Jiaotong University, Xi'an 710049, China. 
yzws-123@xjtu.edu.cn.

Peroxisome proliferator-activated receptor γ (PPARγ), a nuclear receptor 
involved in metabolic processes, inflammation, and energy balance, represents a 
promising therapeutic target for cardiovascular diseases. Danshensu Bingpian Zhi 
(DBZ), a chiral compound derived from traditional Chinese medicine, exhibits 
potential as a PPARγ agonist. Using an ensemble-based docking approach, 
molecular dynamics (MD) simulations, and the molecular mechanics generalized 
born surface area (MM/GBSA) methods, we explored the binding modes and 
energetics of DBZ stereoisomers with the PPARγ ligand-binding domain (LBD). The 
results indicated that the right-handed stereoisomer (DBZR) binds like a full 
agonist, while the left-handed stereoisomer (DBZS) binds as a partial agonist 
with stronger binding energies (ΔGbind), indicating a robust interaction with 
PPARγ. Both the stereoisomers stabilize the β-sheet region of PPARγ-LBD, 
potentially protecting Ser245 from phosphorylation by Cdk5, a process implicated 
in atherosclerosis. Principal component analysis (PCA) and dynamic 
cross-correlation matrices (DCCM) revealed the complex structural dynamics 
within the Ω loop, β-sheet, and AF-2 region of PPARγ-LBD upon ligand binding, 
which may contribute to the unique binding mode and efficacy of DBZS. These 
findings provide insights into the molecular recognition of PPARγ-LBD by DBZ 
stereoisomers and their impact on the conformational dynamics of PPARγ, 
highlighting the therapeutic potential of DBZ and the significance of chirality 
in drug design.

DOI: 10.1039/d4cp03926b
PMID: 39495487


3. Anal Chim Acta. 2024 Nov 22;1330:343290. doi: 10.1016/j.aca.2024.343290. Epub 
2024 Sep 30.

Chiral sensing of glucose by surface-enhanced Raman spectroscopy.

Lee D(1), Pang Y(2).

Author information:
(1)Department of Chemistry, Gwangju Institute of Science and Technology, 123 
Cheomdangwagi-ro, Buk-gu, Gwangju, 61005, Republic of Korea.
(2)Department of Chemistry, Gwangju Institute of Science and Technology, 123 
Cheomdangwagi-ro, Buk-gu, Gwangju, 61005, Republic of Korea. Electronic address: 
ypang@gist.ac.kr.

BACKGROUND: Chiral-selective molecular interactions are considered crucial in 
numerous physiological processes. Chiral-selective analytical methods of 
biomolecules with sufficient sensitivity are of great interest in numerous 
applications. Several surface-enhanced Raman scattering (SERS)-based methods 
have recently been reported for chiral sensing of biomolecules. However, the 
lack of molecular-level understanding of SERS spectral changes of reporter and 
analyte molecules may mislead the development of chiral detection methods.
RESULTS: We report the chiral sensing of glucose (Glu) by SERS of L- and 
D-phenylalanine (Phe) with colloidal gold nanoparticles (AuNPs) synthesized by 
borohydride ions. The Phe SERS showed drastic spectral changes only when Glu of 
the same chirality as Phe was added, which also showed strong dependence on Glu 
concentration. The increase of δ(COO-) and decrease of νs(COO-) modes in Phe 
SERS, exclusively observed with the chiral-selective bimolecular interactions of 
chirally matching Glu, are understood as modified surface adsorption geometry of 
the carboxylate group. Quantitative spectral analysis for the Glu concentration 
of a specific chirality showed the detection limit down to 2 × 10-9 - 2 × 10-7 M 
levels depending on the existence of the opposite enantiomer of Glu.
SIGNIFICANCE: In this study, we demonstrated that the Phe SERS on AuNPs can be 
utilized in the chiral sensing of Glu molecules with quantitative concentration 
analysis. The bimolecular interactions of surface-adsorbed Phe and chirally 
matching Glu are suggested for the chiral recognition of Phe SERS. These results 
imply that a molecule-level understanding is indispensable for developing 
SERS-based chiral sensing methods.

Copyright © 2024 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.aca.2024.343290
PMID: 39489971 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest The authors 
declare that they have no known competing financial interests or personal 
relationships that could have appeared to influence the work reported in this 
paper.


4. Precis Chem. 2024 Apr 23;2(5):208-220. doi: 10.1021/prechem.4c00008.
eCollection  2024 May 27.

Catalytic Asymmetric Diastereodivergent Synthesis of 2-Alkenylindoles Bearing 
both Axial and Central Chirality.

Yang S(1), Huang JB(2), Wang DH(3), Wang NY(1), Chen YY(1), Ke XY(2), Chen H(1), 
Ni SF(2), Zhang YC(1), Shi F(1)(4).

Author information:
(1)Research Center of Chiral Functional Heterocycles, School of Chemistry and 
Materials Science, Jiangsu Normal University, Xuzhou 221116, China.
(2)Department of Chemistry, Key Laboratory for Preparation and Application of 
Ordered Structural Materials of Guangdong Province, Shantou University, Shantou 
515063, China.
(3)Department of Otolaryngology, Xuzhou First People's Hospital, Affiliated 
Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou 221002, China.
(4)School of Petrochemical Engineering, Changzhou University, Changzhou 213164, 
China.

The catalytic asymmetric diastereodivergent synthesis of axially chiral 
2-alkenylindoles was established via chiral phosphoric acid-catalyzed addition 
reactions of C3-unsubstituted 2-alkenylindoles with o-hydroxybenzyl alcohols 
under different reaction conditions. Using this strategy, two series of 
2-alkenylindoles bearing both axial and central chirality were synthesized in a 
diastereodivergent fashion with moderate to high yields and good 
stereoselectivities (up to 99% yield, 95:5 er, >95:5 dr). Moreover, theoretical 
calculations were performed on the key transition states leading to different 
stereoisomers, which provided an in-depth understanding of the origin of the 
observed stereoselectivity and diastereodivergence of the products under 
different reaction conditions. More importantly, these 2-alkenylindoles were 
utilized in asymmetric catalysis as chiral organocatalysts and in medicinal 
chemistry for evaluation of their cytotoxicity, which demonstrated their 
potential applications. This study has not only established the catalytic 
atroposelective synthesis of axially chiral 2-alkenylindoles, but also provided 
an efficient strategy for catalytic asymmetric diastereodivergent construction 
of indole-based scaffolds bearing both axial and central chirality.

© 2024 The Authors. Co-published by University of Science and Technology of 
China and American Chemical Society.

DOI: 10.1021/prechem.4c00008
PMCID: PMC11504580
PMID: 39474410

Conflict of interest statement: The authors declare no competing financial 
interest.


5. Mikrochim Acta. 2024 Oct 28;191(11):704. doi: 10.1007/s00604-024-06788-1.

Preparation of D-NCCDs and its application in fluorescent/colorimetric dual-mode 
discrimination of glutamine enantiomers.

Liao X(#)(1), Lu C(#)(1), Duan Y(1), Ren C(2), Chen H(1).

Author information:
(1)State Key Laboratory of Applied Organic Chemistry, College of Chemistry and 
Chemical Engineering, Lanzhou University, Lanzhou, 730000, People's Republic of 
China.
(2)State Key Laboratory of Applied Organic Chemistry, College of Chemistry and 
Chemical Engineering, Lanzhou University, Lanzhou, 730000, People's Republic of 
China. rencl@lzu.edu.cn.
(#)Contributed equally

A new type of carbon dots (D-NCCDs) was synthesized by 3, 5-diaminobenzoic acid, 
N,N-dimethyl-o-phenylenediamine, and D-cysteine. The morphology and structure of 
D-NCCDs were investigated by transmission electron microscopy (TEM), X-ray 
photoelectron spectroscopy (XPS), and FT-IR spectra, and the chirality was 
characterized by circular dichroism. In the presence of hydrogen peroxide, the 
fluorescence of D-NCCDs at 487 nm (λex = 410 nm) showed great discrimination 
ability towards glutamine enantiomers. The ratio of fluorescence intensity 
(F/F0) to the concentration of D-Gln showed good linearity in the range 
0.5-10 mM, with a detection limits of 0.11 mM. Meanwhile, the color of the 
solution gradually changed from light yellow to yellow-brown. The UV-Vis 
absorption ratio (A/A0) at 410 nm showed good linearity with the concentration 
of D-Gln in the range 0.5 to 20 mM; the detection limit is 7.7 μM. But the 
fluorescence and absorbance of D-NCCDs showed no significant change after the 
addition of L-glutamine. Thus, fluorescence and colorimetry dual-mode 
discrimination of glutamine enantiomers was achieved. The fluorescence 
enantioselectivity of Gln (FL-Gln/FD-Gln) is 1.62, and the colorimetric 
enantioselectivity of Gln (AD-Gln/AL-Gln) is 2.14. The chiral discrimination 
mechanism of D-NCCDs to Gln enantiomers was also investigated systematically. 
This work not only can discriminate glutamine enantiomers with high sensitivity 
and convenience, but also offers a new strategy for preparing new dual mode 
chiral nanoprobes.

© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, 
part of Springer Nature.

DOI: 10.1007/s00604-024-06788-1
PMID: 39467880 [Indexed for MEDLINE]