Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Quantum chemical and molecular dynamics modelling of hydroxylated polybrominated diphenyl ethers
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
Number of Authors: 32017 (English)In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 19, no 41, p. 28263-28274Article in journal (Refereed) Published
Abstract [en]

A series of 19 hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been studied using density functional theory (DFT) and molecular dynamics simulations with the purpose of investigating eventual correlations between their physicochemical properties and toxic action. Dissociation constants (pK(a)), solvation free energies and octanol-water partition coefficients (logP) have been computed. Additionally, metadynamics simulations of OH-PBDEs passing through a lipid bilayer have been carried out for four OH-PBDE species. No correlations between computed pKa values and toxicity data have been found. Medium correlations were found between partition coefficients and the ability of OH-PBDEs to alter membrane potential in cell cultures, which is attributed to higher uptake of molecules with larger log P parameters. It was also demonstrated that in lipid bilayers, OH-PBDE molecules differ in their orientational distributions and can adopt different conformations which can affect the uptake of these molecules and influence the pathways of their toxic action.

Place, publisher, year, edition, pages
2017. Vol. 19, no 41, p. 28263-28274
National Category
Chemical Sciences
Research subject
Physical Chemistry
Identifiers
URN: urn:nbn:se:su:diva-148826DOI: 10.1039/c7cp03471gISI: 000413778800039PubMedID: 29028067OAI: oai:DiVA.org:su-148826DiVA, id: diva2:1156735
Available from: 2017-11-14 Created: 2017-11-14 Last updated: 2019-02-11Bibliographically approved
In thesis
1. Modeling of biomembranes: from computational toxicology to simulations of neurodegenerative diseases
Open this publication in new window or tab >>Modeling of biomembranes: from computational toxicology to simulations of neurodegenerative diseases
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

It was known from the middle of the last century that a cell-membrane is a lipid bilayer. Since that time a large number of experimental studies has been done in order to see how a certain molecule can penetrate through a membrane. Due to the complexity of laboratory experiments computational chemistry became a convenient tool for investigations involving this process. In a real life a compound has to pass through several membranes of different chemical composition before reaching the actual target. Such a diversity in constitution gives a various selectivity to cell-membranes: some molecules will penetrate through them and others will not. That is why the development and a choice of suitable models for lipid bilayers are important steps in such a research. In this thesis new all-atomistic models for polyunsaturated phospholipids in cis conformations have been derived and added to the SLipids force field. After a successful force field validation, the new lipid models were used in molecular dynamics and well-tempered metadynamics simulations of several problems, such as toxicity of hydroxylated polybrominated diphenyl ethers (OH-PBDE), behavior of cholesterol in various membranes, an aggregation of amyloid-β (Aβ) peptides. The significance of the presence of lipid unsaturation has been demonstrated by all computations. 2’-OH-BDE68 (ortho) showed the affinity to saturated lipid bilayer, but had more conformational variations in the center of the unsaturated membrane. Cholesterol did not exhibit the preference to polynsaturated lipid bilayers from free energy calculations, but the diversity in orientations of this molecule, depending on its locations was observed. The behavior of Aβ peptides was dependent on membrane saturation as well. The insertion of Aβ peptides was detected in lipid bilayers containing higher amounts of polyunsaturated phospholipids, while in systems with more saturated membranes amyloids aggregated on membrane surfaces. Moreover, a comparison of simulations for quadro- and mono-component lipid bilayers showed that the membrane built of 18:0-22:6 PC can serve as a good model for the ’healthy’ tissue of a human brain. Also the lipid bilayer built of 14:0-14:0 PC exhibited similar features as the quadro-lipid membrane representing the brain tissue affected by Alzheimer’s disease. Good agreement of some computational results with available experimental findings demonstrated the applicability of computer simulations to real life problems.

Place, publisher, year, edition, pages
Stockholm: Department of Materials and Environmental Chemistry, Stockholm University, 2019. p. 90
Keywords
biomembranes, lipid bilayers, Alzheimer's disease, Parkinson disease, computational toxicology, passive diffusion, hydroxylated polybrominated diphenyl ethers, omega-3, omega-6, amyloid beta peptide, molecular dynamics simulations, SLipids force field
National Category
Physical Chemistry
Research subject
Physical Chemistry
Identifiers
urn:nbn:se:su:diva-165940 (URN)978-91-7797-584-7 (ISBN)978-91-7797-585-4 (ISBN)
Public defence
2019-03-27, Magnélisalen Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 14:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Submitted. Paper 5: Submitted.

Available from: 2019-03-04 Created: 2019-02-08 Last updated: 2019-02-25Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Ermilova, InnaStenberg, SamuelLyubartsev, Alexander P.
By organisation
Department of Materials and Environmental Chemistry (MMK)
In the same journal
Physical Chemistry, Chemical Physics - PCCP
Chemical Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 13 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf