TY - JOUR
T1 - What are molecular effects of co-administering vitamin C with artemisinin-type antimalarials? A model mass spectrometry and quantum chemical study
AU - Pashynska, Vlada
AU - Stepanian, Stepan
AU - Gömöry, Ágnes
AU - Adamowicz, Ludwik
N1 - Funding Information:
Authors acknowledge the Program of cooperation between Ukrainian and Hungarian Academies of Sciences for the financial support of visit of the scientists from B. Verkin Institute for Low Temperature Physics and Engineering of the National Academy of Sciences of Ukraine to the Institute of Organic Chemistry of Research Centre for Natural Sciences in Hungary, where the mass spectrometry experiments were carried out. This work was partially supported by the National Academy of Sciences of Ukraine (NASU) (Grant N 0120U100157). An allocation of computer time from UA Research High Performance Computing (HPC) and High Throughput Computing (HTC) at the University of Arizona is gratefully acknowledged. V. Pashynska also thanks Prof. Magda Claeys from the University of Antwerp (Belgium) for the preceding fruitful cooperation in ESI mass spectrometry study of antimalarial drugs intermolecular interactions and for provision of the samples of the artemisinin-type drugs.
Funding Information:
Authors acknowledge the Program of cooperation between Ukrainian and Hungarian Academies of Sciences for the financial support of visit of the scientists from B. Verkin Institute for Low Temperature Physics and Engineering of the National Academy of Sciences of Ukraine to the Institute of Organic Chemistry of Research Centre for Natural Sciences in Hungary, where the mass spectrometry experiments were carried out. This work was partially supported by the National Academy of Sciences of Ukraine (NASU) (Grant N 0120U100157). An allocation of computer time from UA Research High Performance Computing (HPC) and High Throughput Computing (HTC) at the University of Arizona is gratefully acknowledged. V. Pashynska also thanks Prof. Magda Claeys from the University of Antwerp (Belgium) for the preceding fruitful cooperation in ESI mass spectrometry study of antimalarial drugs intermolecular interactions and for provision of the samples of the artemisinin-type drugs.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/5/15
Y1 - 2021/5/15
N2 - In this study the electrospray ionization mass spectrometry (ESI MS) and quantum chemical modeling methods are employed to examine the interactions of molecules of artemisinin-type drugs and of ascorbic acid (ASC). These biologically significant interactions are relevant to antimalarial therapy, in particular, when artemisinin agents are co-administrated with supporting vitamin/antioxidant preparations or could be affiliated with the patient's food. The formation of stable noncovalent complexes of the artemisinin-type drugs (artemisinin, dihydroartemisinin, α-artemether, and β-arteether) with ascorbic acid molecules in a polar solvent, such as methanol, is revealed by the ESI MS probing of binary systems containing an antimalarial drug and ASC in the 1:1 molar ratio. Also, a peak corresponding to noncovalent [ASC•DPPC•Na]+ cationized complexes is identified in the spectrum of the mixture of ASC and dipalmitoylphosphatidylcholine (DPPC, membrane phospholipid) with the 1:5 molar ratio. Next, the ternary system containing dihydroartemisinin (DHAn; the assumed active metabolite of the artemisinin-type drugs in the human organism), ASC, and DPPC in the 1:1:5 molar ratio is examined. The study reveals a competition between the antimalarial agent and ASC for binding with the DPPC molecules. The existence of the competition is supported by the observation of peaks with similar intensities corresponding to the noncovalent DHAn•DPPC and ASC•DPPC complexes in the mass spectra. An evidence for the complexation between the antimalarial drug and ASC is also found in the spectra of triple model systems studied. To elucidate the structural and energetic characteristics of the noncovalent complexes observed in the ESI MS experiments, model ab initio calculations of DHAn and ASC complexes and clusters of the drug molecules with the polar phosphatidylcholine head of DPPC are performed using the DFT/B3LYP/aug-cc-pVDZ approach. The results of the model study show the possibility of the noncovalent complexation and of the modulation of the biological activity of artemisin-type agents and of the ascorbic acid when they are co-administered in the therapy.
AB - In this study the electrospray ionization mass spectrometry (ESI MS) and quantum chemical modeling methods are employed to examine the interactions of molecules of artemisinin-type drugs and of ascorbic acid (ASC). These biologically significant interactions are relevant to antimalarial therapy, in particular, when artemisinin agents are co-administrated with supporting vitamin/antioxidant preparations or could be affiliated with the patient's food. The formation of stable noncovalent complexes of the artemisinin-type drugs (artemisinin, dihydroartemisinin, α-artemether, and β-arteether) with ascorbic acid molecules in a polar solvent, such as methanol, is revealed by the ESI MS probing of binary systems containing an antimalarial drug and ASC in the 1:1 molar ratio. Also, a peak corresponding to noncovalent [ASC•DPPC•Na]+ cationized complexes is identified in the spectrum of the mixture of ASC and dipalmitoylphosphatidylcholine (DPPC, membrane phospholipid) with the 1:5 molar ratio. Next, the ternary system containing dihydroartemisinin (DHAn; the assumed active metabolite of the artemisinin-type drugs in the human organism), ASC, and DPPC in the 1:1:5 molar ratio is examined. The study reveals a competition between the antimalarial agent and ASC for binding with the DPPC molecules. The existence of the competition is supported by the observation of peaks with similar intensities corresponding to the noncovalent DHAn•DPPC and ASC•DPPC complexes in the mass spectra. An evidence for the complexation between the antimalarial drug and ASC is also found in the spectra of triple model systems studied. To elucidate the structural and energetic characteristics of the noncovalent complexes observed in the ESI MS experiments, model ab initio calculations of DHAn and ASC complexes and clusters of the drug molecules with the polar phosphatidylcholine head of DPPC are performed using the DFT/B3LYP/aug-cc-pVDZ approach. The results of the model study show the possibility of the noncovalent complexation and of the modulation of the biological activity of artemisin-type agents and of the ascorbic acid when they are co-administered in the therapy.
KW - Artemisinin-type agents
KW - Ascorbic acid
KW - Competitive binding
KW - DFT/B3LYP/aug-cc-pVDZ calculations
KW - Dipalmitoylphosphatidylcholine
KW - Electrospray ionization mass spectrometry
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U2 - 10.1016/j.molstruc.2021.130039
DO - 10.1016/j.molstruc.2021.130039
M3 - Article
AN - SCOPUS:85100622264
SN - 0022-2860
VL - 1232
JO - Journal of Molecular Structure
JF - Journal of Molecular Structure
M1 - 130039
ER -