The adsorption of drugs on nanoplastics has severe biological impact.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
28 10 2024
Historique:
received: 20 06 2024
accepted: 08 10 2024
medline: 29 10 2024
pubmed: 29 10 2024
entrez: 29 10 2024
Statut: epublish

Résumé

Micro- and nanoplastics can interact with various biologically active compounds forming aggregates of which the effects have yet to be understood. To this end, it is vital to characterize these aggregates of key compounds and micro- and nanoplastics. In this study, we examined the adsorption of the antibiotic tetracycline on four different nanoplastics, made of polyethylene (PE), polypropylene (PP), polystyrene (PS), and nylon 6,6 (N66) through chemical computation. Two separate approaches were employed to generate relevant conformations of the tetracycline-plastic complexes. In the first approach, we folded the plastic particle from individual polymer chains in the presence of the drug through multiple separate simulated annealing setups. In the second, more biased, approach, the neat plastic was pre-folded through simulated annealing, and the drug was placed at its surface in multiple orientations. The former approach was clearly superior to the other, obtaining lower energy conformations even with the antibiotic buried inside the plastic particle. Quantum chemical calculations on the structures revealed that the adsorption energies show a trend of decreasing affinity to the drug in the order of N66> PS> PP> PE. In vitro experiments on tetracycline-sensitive cell lines demonstrated that, in qualitative agreement with the calculations, the biological activity of tetracycline drops significantly in the presence of PS particles. Preliminary molecular dynamics simulations on two selected aggregates with each plastic served as first stability test of the aggregates under influence of temperature and in water. We found that all the selected cases persisted in water indicating that the aggregates may be stable also in more realistic environments. In summary, our data show that the interaction of micro- and nanoplastics with drugs can alter drug absorption, facilitate drug transport to new locations, and increase local antibiotic concentrations, potentially attenuating antibiotic effect and at the same time promoting antibiotic resistance.

Identifiants

pubmed: 39468142
doi: 10.1038/s41598-024-75785-4
pii: 10.1038/s41598-024-75785-4
doi:

Substances chimiques

Tetracycline F8VB5M810T
Anti-Bacterial Agents 0
Microplastics 0
Polystyrenes 0
Polypropylenes 0
Polymers 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

25853

Subventions

Organisme : European Research Council
ID : 951513
Pays : International
Organisme : Fundação de Amparo à Pesquisa do Estado de São Paulo
ID : #2020/10246-0
Organisme : Deutsche Forschungsgemeinschaft
ID : 511713970
Organisme : Bundesministerium für Klimaschutz, Umwelt, Energie, Mobilität, Innovation und Technologie
ID : microONE
Organisme : Austrian Science Fund
ID : P26011
Organisme : National Research, Development and Innovation Office
ID : OTKA-FK 138823
Organisme : Nemzeti Kutatási, Fejlesztési és Innovaciós Alap
ID : ÚNKP-22-5

Informations de copyright

© 2024. The Author(s).

Références

Carpenter, E. J., Anderson, S. J., Harvey, G. R., Miklas, H. P. & Peck, B. B. Polystyrene spherules in coastal waters. Science 178, 749–750 (1972).
pubmed: 4628343 doi: 10.1126/science.178.4062.749
Thompson, R. C. Lost at sea: Where is all the plastic?. Science 304, 838 (2004).
pubmed: 15131299 doi: 10.1126/science.1094559
Cole, M., Lindeque, P., Halsband, C. & Galloway, T. S. Microplastics as contaminants in the marine environment: A review. Mar. Pollut. Bull. 62, 2588–2597 (2011).
pubmed: 22001295 doi: 10.1016/j.marpolbul.2011.09.025
Gall, S. & Thompson, R. The impact of debris on marine life. Mar. Pollut. Bull. 92, 170–179 (2015).
pubmed: 25680883 doi: 10.1016/j.marpolbul.2014.12.041
Gruber, E. S. et al. To waste or not to waste: Questioning potential health risks of micro-and nanoplastics with a focus on their ingestion and potential carcinogenicity. Exposure Health. 1–19 (2022).
Wayman, C. & Niemann, H. The fate of plastic in the ocean environment—A minireview. Environ. Sci. Process. Impacts 23, 198–212 (2021).
pubmed: 33475108 doi: 10.1039/D0EM00446D
Marsden, P. et al. Microplastics in Drinking Water (World Health Organization, 2019).
Schwabl, P. et al. Detection of various microplastics in human stool: A prospective case series. Ann. Internal Med. 171, 453–457 (2019).
doi: 10.7326/M19-0618
Leslie, H. A. et al. Discovery and quantification of plastic particle pollution in human blood. Environ. Int. 163, 107199 (2022).
pubmed: 35367073 doi: 10.1016/j.envint.2022.107199
Kopatz, V. et al. Micro-and nanoplastics breach the blood-brain barrier (bbb): Biomolecular corona’s role revealed. Nanomaterials 13, 1404 (2023).
pubmed: 37110989 pmcid: 10141840 doi: 10.3390/nano13081404
Shan, S., Zhang, Y., Zhao, H., Zeng, T. & Zhao, X. Polystyrene nanoplastics penetrate across the blood-brain barrier and induce activation of microglia in the brain of mice. Chemosphere 298, 134261 (2022).
pubmed: 35302003 doi: 10.1016/j.chemosphere.2022.134261
Meng, X. et al. Effects of nano-and microplastics on kidney: Physicochemical properties, bioaccumulation, oxidative stress and immunoreaction. Chemosphere 288, 132631 (2022).
pubmed: 34688716 doi: 10.1016/j.chemosphere.2021.132631
Horvatits, T. et al. Microplastics detected in cirrhotic liver tissue. EBioMedicine. 82 (2022).
Montano, L. et al. Raman microspectroscopy evidence of microplastics in human semen. Sci. Total Environ. 901, 165922 (2023).
pubmed: 37532047 doi: 10.1016/j.scitotenv.2023.165922
Triebskorn, R. et al. Relevance of nano-and microplastics for freshwater ecosystems: A critical review. TrAC Trends Analyt. Chem. 110, 375–392 (2019).
doi: 10.1016/j.trac.2018.11.023
Laskar, N. & Kumar, U. Plastics and microplastics: A threat to environment. Environ. Technol. Innovat. 14, 100352 (2019).
doi: 10.1016/j.eti.2019.100352
Thompson, R. C. Microplastics in the marine environment: Sources, consequences and solutions. Mar. Anthropogenic Litter. 185–200 (2015).
Yu, Q. et al. Distribution, abundance and risks of microplastics in the environment. Chemosphere 249, 126059 (2020).
pubmed: 32062205 doi: 10.1016/j.chemosphere.2020.126059
Brun, N. R. et al. Polystyrene nanoplastics disrupt glucose metabolism and cortisol levels with a possible link to behavioural changes in larval zebrafish. Commun. Biol. 2, 382 (2019).
pubmed: 31646185 pmcid: 6802380 doi: 10.1038/s42003-019-0629-6
Kihara, S. et al. Soft and hard interactions between polystyrene nanoplastics and human serum albumin protein corona. Bioconjugate Chem. 30, 1067–1076 (2019).
doi: 10.1021/acs.bioconjchem.9b00015
Gopinath, P. M. et al. Assessment on interactive prospectives of nanoplastics with plasma proteins and the toxicological impacts of virgin, coronated and environmentally released-nanoplastics. Sci. Rep. 9, 8860 (2019).
pubmed: 31222081 pmcid: 6586940 doi: 10.1038/s41598-019-45139-6
Wang, S., Liu, M., Wang, J., Huang, J. & Wang, J. Polystyrene nanoplastics cause growth inhibition, morphological damage and physiological disturbance in the marine microalga platymonas helgolandica. Mar. Poll. Bull. 158, 111403 (2020).
doi: 10.1016/j.marpolbul.2020.111403
Machado, M. C., Vimbela, G. V., Silva-Oliveira, T. T., Bose, A. & Tripathi, A. The response of synechococcus sp. pcc 7002 to micro-/nano polyethylene particles-investigation of a key anthropogenic stressor. PloS One. 15, e0232745 (2020).
Prüst, M., Meijer, J. & Westerink, R. H. The plastic brain: Neurotoxicity of micro-and nanoplastics. Part. Fibre Toxicol. 17, 1–16 (2020).
doi: 10.1186/s12989-020-00358-y
Brun, N. R., Beenakker, M. M., Hunting, E. R., Ebert, D. & Vijver, M. G. Brood pouch-mediated polystyrene nanoparticle uptake during daphnia magna embryogenesis. Nanotoxicology 11, 1059–1069 (2017).
pubmed: 29083253 doi: 10.1080/17435390.2017.1391344
Oliveira, Y. M., Vernin, N. S., Zhang, Y., Maginn, E. & Tavares, F. W. Interaction between endocrine disruptors and polyethylene nanoplastic by molecular dynamics simulations. J. Phys. Chem. B. (2024).
D’Angelo, S. & Meccariello, R. Microplastics: A threat for male fertility. Int. J. Environ. Res. Pub. Health 18, 2392 (2021).
doi: 10.3390/ijerph18052392
Fent, K., Weston, A. A. & Caminada, D. Ecotoxicology of human pharmaceutical. Aquat. Toxicol. 76, 122–159 (2006).
pubmed: 16257063 doi: 10.1016/j.aquatox.2005.09.009
Baysal, A. & Saygin, H. Co-occurence of antibiotics and micro (nano) plastics: A systematic review between 2016-2021. J. Environ. Sci. Health Part A. 1–21 (2022).
Yilimulati, M., Wang, L., Ma, X., Yang, C. & Habibul, N. Adsorption of ciprofloxacin to functionalized nano-sized polystyrene plastic: Kinetics, thermochemistry and toxicity. Sci. Total Environ. 750, 142370 (2021).
pubmed: 33182210 doi: 10.1016/j.scitotenv.2020.142370
Liu, P. et al. New insights into the aging behavior of microplastics accelerated by advanced oxidation processes. Environ. Sci. Technol. 53, 3579–3588 (2019).
pubmed: 30829479 doi: 10.1021/acs.est.9b00493
Nath, J., Dror, I. & Berkowitz, B. Effect of nanoplastics on the transport of platinum-based pharmaceuticals in water-saturated natural soil and their effect on a soil microbial community. Environ. Sci. Nano 7, 3178–3188 (2020).
doi: 10.1039/D0EN00651C
Puckowski, A., Cwiek, W., Mioduszewska, K., Stepnowski, P. & Białk-Bielińska, A. Sorption of pharmaceuticals on the surface of microplastics. Chemosphere 263, 127976 (2021).
pubmed: 32835979 doi: 10.1016/j.chemosphere.2020.127976
Berendonk, T. U. et al. Tackling antibiotic resistance: The environmental framework. Nat. Rev. Microbiol. 13, 310–317 (2015).
pubmed: 25817583 doi: 10.1038/nrmicro3439
Stanton, I. C., Murray, A. K., Zhang, L., Snape, J. & Gaze, W. H. Evolution of antibiotic resistance at low antibiotic concentrations including selection below the minimal selective concentration. Commun. Biol. 3, 1–11 (2020).
doi: 10.1038/s42003-020-01176-w
Elder, F. C. et al. Spatiotemporal profiling of antibiotics and resistance genes in a river catchment: Human population as the main driver of antibiotic and antibiotic resistance gene presence in the environment. Water Res. 203, 117533 (2021).
pubmed: 34416649 doi: 10.1016/j.watres.2021.117533
Murray, A. K., Stanton, I., Gaze, W. H. & Snape, J. Dawning of a new era: Environmental risk assessment of antibiotics and their potential to select for antimicrobial resistance. Water Res. 200, 117233 (2021).
pubmed: 34038824 doi: 10.1016/j.watres.2021.117233
Penesyan, A., Paulsen, I. T., Kjelleberg, S. & Gillings, M. R. Three faces of biofilms: A microbial lifestyle, a nascent multicellular organism, and an incubator for diversity. NPJ Biofilms Microbiomes. 7, 80 (2021).
pubmed: 34759294 pmcid: 8581019 doi: 10.1038/s41522-021-00251-2
Torresi, E. et al. Diffusion and sorption of organic micropollutants in biofilms with varying thicknesses. Water Res. 123, 388–400 (2017).
pubmed: 28686941 doi: 10.1016/j.watres.2017.06.027
Torresi, E. et al. Biofilm thickness influences biodiversity in nitrifying mbbrs implications on micropollutant removal. Environ. Sci. Technol. 50, 9279–9288 (2016).
pubmed: 27477857 doi: 10.1021/acs.est.6b02007
Sooriyakumar, P. et al. Biofilm formation and its implications on the properties and fate of microplastics in aquatic environments: A review. J. Hazard. Mat. Adv. 6, 100077 (2022).
Arias-Andres, M., Klümper, U., Rojas-Jimenez, K. & Grossart, H.-P. Microplastic pollution increases gene exchange in aquatic ecosystems. Environ. Pollut. 237, 253–261 (2018).
pubmed: 29494919 doi: 10.1016/j.envpol.2018.02.058
Su, Y. et al. Microplastics act as vectors for antibiotic resistance genes in landfill leachate: The enhanced roles of the long-term aging process. Environ. Pollut. 270, 116278 (2021).
pubmed: 33333404 doi: 10.1016/j.envpol.2020.116278
Li, J., Zhang, K. & Zhang, H. Adsorption of antibiotics on microplastics. Environ. Pollut. 237, 460–467 (2018).
pubmed: 29510365 doi: 10.1016/j.envpol.2018.02.050
Xu, B., Liu, F., Brookes, P. C. & Xu, J. Microplastics play a minor role in tetracycline sorption in the presence of dissolved organic matter. Environ. Pollut. 240, 87–94 (2018).
pubmed: 29729573 doi: 10.1016/j.envpol.2018.04.113
Yu, F. et al. Interfacial interaction between diverse microplastics and tetracycline by adsorption in an aqueous solution. Sci. Tot. Environ. 721, 137729 (2020).
doi: 10.1016/j.scitotenv.2020.137729
Zhang, H. et al. Enhanced adsorption of oxytetracycline to weathered microplastic polystyrene: Kinetics, isotherms and influencing factors. Environ. Pollut. 243, 1550–1557 (2018).
pubmed: 30296753 doi: 10.1016/j.envpol.2018.09.122
Zahmatkesh Anbarani, M., Najafpoor, A., Barikbin, B. & Bonyadi, Z. Adsorption of tetracycline on polyvinyl chloride microplastics in aqueous environments. Sci. Rep. 13, 17989 (2023).
pubmed: 37864009 pmcid: 10589219 doi: 10.1038/s41598-023-44288-z
Wang, L., Yang, H., Guo, M., Wang, Z. & Zheng, X. Adsorption of antibiotics on different microplastics (mps): Behavior and mechanism. Sci. Tot. Environ. 863, 161022 (2023).
doi: 10.1016/j.scitotenv.2022.161022
Wang, H. et al. Adsorption of tetracycline and cd (ii) on polystyrene and polyethylene terephthalate microplastics with ultraviolet and hydrogen peroxide aging treatment. Sci. Tot. Environ. 845, 157109 (2022).
doi: 10.1016/j.scitotenv.2022.157109
Hollóczki, O. Evidence for protein misfolding in the presence of nanoplastics. Int. J. Quant. Chem. 121, e26372 (2021).
doi: 10.1002/qua.26372
Holloczki, O. & Gehrke, S. Nanoplastics can change the secondary structure of proteins. Sci. Rep. 9 (2019).
Laughton, C. A study of simulated annealing protocols for use with molecular dynamics in protein structure prediction. Protein Eng. Design Select. 7, 235–241 (1994).
doi: 10.1093/protein/7.2.235
Wille, L. Minimum-energy configurations of atomic clusters: New results obtained by simulated annealing. Chem. Phys. Lett. 133, 405–410 (1987).
doi: 10.1016/0009-2614(87)87091-4
Wilson, S. R., Cui, W., Moskowitz, J. W. & Schmidt, K. E. Conformational analysis of flexible molecules: Location of the global minimum energy conformation by the simulated annealing method. Tetrahedron Lett. 29, 4373–4376 (1988).
doi: 10.1016/S0040-4039(00)80498-0
Wilson, S. R. & Cui, W. Applications of simulated annealing to peptides. Biopolym. Original Res. Biomol. 29, 225–235 (1990).
Hatmal, M. M. & Taha, M. O. Simulated annealing molecular dynamics and ligand-receptor contacts analysis for pharmacophore modeling. Future Med. Chem. 9, 1141–1159 (2017).
pubmed: 28722471 doi: 10.4155/fmc-2017-0061
Hao, G.-F., Xu, W.-F., Yang, S.-G. & Yang, G.-F. Multiple simulated annealing-molecular dynamics (msa-md) for conformational space search of peptide and miniprotein. Sci. Rep. 5, 15568 (2015).
pubmed: 26492886 pmcid: 4616061 doi: 10.1038/srep15568
Jorgensen, W. L. & Tirado-Rives, J. The opls [optimized potentials for liquid simulations] potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin. J. Am. Chem. Society 110, 1657–1666 (1988).
doi: 10.1021/ja00214a001
Jorgensen, W. L., Maxwell, D. S. & Tirado-Rives, J. Development and testing of the opls all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Society 118, 11225–11236 (1996).
doi: 10.1021/ja9621760
Grimme, S., Bannwarth, C. & Shushkov, P. A robust and accurate tight-binding quantum chemical method for structures, vibrational frequencies, and noncovalent interactions of large molecular systems parametrized for all spd-block elements (z = 1–86). J. Chem. Theory Comput. 13, 1989–2009 (2017).
pubmed: 28418654 doi: 10.1021/acs.jctc.7b00118
Bannwarth, C., Ehlert, S. & Grimme, S. Gfn2-xtb-an accurate and broadly parametrized self-consistent tight-binding quantum chemical method with multipole electrostatics and density-dependent dispersion contributions. J. Chem. Theory Comput. 15, 1652–1671 (2019).
pubmed: 30741547 doi: 10.1021/acs.jctc.8b01176
Plimpton, S. Fast parallel algorithms for short-range molecular dynamics. J. Comput. Chem. 4, 1–19 (1995).
Berendsen, H. J. C., Grigera, J. R. & Straatsma, T. P. The missing term in effective pair potentials. J. Phys. Chem. 91, 6269–6271 (1987).
doi: 10.1021/j100308a038
Ryckaert, J.-P., Ciccotti, G. & Berendsen, H. J. Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. J. Comput. Phys. 23, 327–341 (1977).
doi: 10.1016/0021-9991(77)90098-5
Brehm, M. & Kirchner, B. Travis—A free analyzer and visualizer for monte carlo and molecular dynamics trajectories. J. Chem. Inf. Model. 51, 2007–2023 (2011).
pubmed: 21761915 doi: 10.1021/ci200217w
Brehm, M., Weber, H., Thomas, M., Hollóczki, O. & Kirchner, B. Domain analysis in nanostructured liquids: A post-molecular dynamics study at the example of ionic liquids. ChemPhysChem 16, 3271–3277 (2015).
pubmed: 26386251 doi: 10.1002/cphc.201500471
Rodríguez-Hernández, A. G., Muñoz-Tabares, J. A., Aguilar-Guzmán, J. C. & Vazquez-Duhalt, R. A novel and simple method for polyethylene terephthalate (pet) nanoparticle production. Environ. Sci. Nano. 6, 2031–2036 (2019).
doi: 10.1039/C9EN00365G
Schmidt, L. et al. Cebpa-mutated leukemia is sensitive to genetic and pharmacological targeting of the mll1 complex. Leukemia 33, 1608–1619 (2019).
pubmed: 30679799 pmcid: 6612510 doi: 10.1038/s41375-019-0382-3
Skucha, A. et al. Mll-fusion-driven leukemia requires setd2 to safeguard genomic integrity. Nat. Commun. 9, 1983 (2018).
pubmed: 29777171 pmcid: 5959866 doi: 10.1038/s41467-018-04329-y
Zuber, J. et al. An integrated approach to dissecting oncogene addition implicates a myb-coordinated self-renewal program as essential for leukemia maintenance. Genes Develop. 25, 1628–1640 (2011).
pubmed: 21828272 pmcid: 3182026 doi: 10.1101/gad.17269211
Walczyk, D., Bombelli, F. B., Monopoli, M. P., Lynch, I. & Dawson, K. A. What the cell “sees’’ in bionanoscience. J. Am. Chem. Soc. 132, 5761–5768 (2010).
pubmed: 20356039 doi: 10.1021/ja910675v
Lynch, I., Salvati, A. & Dawson, K. A. What does the cell see?. Nat. Nanotechnol. 4, 546–547 (2009).
pubmed: 19734922 doi: 10.1038/nnano.2009.248

Auteurs

Leonard Dick (L)

Mulliken Center for Theoretical Chemistry, University of Bonn, Beringstr. 4 6, 53115, Bonn, Germany.
Department of Colloid Chemistry, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476, Potsdam, Germany.

Patrick R Batista (PR)

Mulliken Center for Theoretical Chemistry, University of Bonn, Beringstr. 4 6, 53115, Bonn, Germany.
Institute of Chemistry, University of Campinas, Monteiro Lobato, 270, Cidade Universitária, 13083-862, Campinas, São Paulo, Brazil.

Paul Zaby (P)

Mulliken Center for Theoretical Chemistry, University of Bonn, Beringstr. 4 6, 53115, Bonn, Germany.

Gabriele Manhart (G)

Medical Biochemistry, Department for Biological Sciences and Pathobiology, University of Veterinary Medicine Vienna, 1210, Vienna, Austria.
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.

Verena Kopatz (V)

Department for Experimental and Laboratory Animal Pathology, Medical University of Vienna, Clinical Institute of Pathology, 1090, Vienna, Austria.
Center for Biomarker Research in Medicine (CBmed GmBH), microOne, 8010, Graz, Austria.
Department for Radiation Oncology, Medical University of Vienna, 1210, Vienna, Austria.
Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090, Vienna, Austria.

Lukas Kogler (L)

Center for Biomarker Research in Medicine (CBmed GmBH), microOne, 8010, Graz, Austria.
Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, 1090, Vienna, Austria.
Division of Pharmaceutical Chemistry, University of Vienna, 1090, Vienna, Austria.

Verena Pichler (V)

Center for Biomarker Research in Medicine (CBmed GmBH), microOne, 8010, Graz, Austria.
Division of Pharmaceutical Chemistry, University of Vienna, 1090, Vienna, Austria.

Florian Grebien (F)

Medical Biochemistry, Department for Biological Sciences and Pathobiology, University of Veterinary Medicine Vienna, 1210, Vienna, Austria.
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090, Vienna, Austria.
St. Anna Children's Cancer Research Institute (CCRI), 1090, Vienna, Austria.

Vince Bakos (V)

Department of Chemical Engineering, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111, Budapest, Hungary.

Benedek G Plósz (BG)

Department of Chemical Engineering, University of Bath, Claverton Down, Bath, BA2 7AY, UK.

Nikola Zlatkov Kolev (NZ)

Department of Molecular Biology, Umeå University, Umeå, Sweden.

Lukas Kenner (L)

Department for Experimental and Laboratory Animal Pathology, Medical University of Vienna, Clinical Institute of Pathology, 1090, Vienna, Austria. lukas.kenner@meduniwien.ac.at.
Center for Biomarker Research in Medicine (CBmed GmBH), microOne, 8010, Graz, Austria. lukas.kenner@meduniwien.ac.at.
Comprehensive Cancer Center Vienna, Medical University of Vienna, 1090, Vienna, Austria. lukas.kenner@meduniwien.ac.at.
Christian Doppler Laboratory for Applied Metabolomics, Medical University of Vienna, 1090, Vienna, Austria. lukas.kenner@meduniwien.ac.at.
Unit of Laboratory Animal Pathology, University of Veterinary Medicine Vienna, 1210, Vienna, Austria. lukas.kenner@meduniwien.ac.at.

Barbara Kirchner (B)

Mulliken Center for Theoretical Chemistry, University of Bonn, Beringstr. 4 6, 53115, Bonn, Germany. kirchner@thch.uni-bonn.de.

Oldamur Hollóczki (O)

Department of Physical Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, 4032, Debrecen, Hungary. holloczki.oldamur@science.unideb.hu.

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