Toward a molecular understanding of the detection of amyloid proteins with flexible conjugated oligothiophenes
2014 (English)In: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 118, no 42, 9820-9827 p.Article in journal (Refereed) Published
Molecular and electronic structures and optical absorption properties of oligothiophenes used for spectral assignment of amyloid deposits have been investigated for a family of probes known as luminescent conjugated oligothiophenes (LCOs). Theoretical absorption spectra have been determined using conformational averaging, combining classical molecular dynamics (MD) simulations with quantum mechanical/molecular mechanics (QM/MM) time-dependent density functional theory (TD-DFT) spectrum calculations. Theoretical absorption spectra are in excellent agreement with experiments, showing average errors below 5 nm for absorption maxima. To couple observed properties to molecular structures, a measure of planarity is defined, revealing a strong correlation between the transition wavelength of the first and dominating electronically excited state and dihedral rotations. It is shown that from this correlation, predictions can be made of the absorption properties of probes based only on information from MD trajectories. We show experimentally that red shifts observed in the excitation maxima of LCOs when bound to amyloid protein aggregates are also evident in absorption spectra. We predict that these red shifts are due to conformational restriction of the LCO in a protein binding pocket, causing a planarization of the conjugated backbone. On the basis of our studies of planarity, it is shown that such shifts are both possible and realistic.
Place, publisher, year, edition, pages
American Chemical Society (ACS), 2014. Vol. 118, no 42, 9820-9827 p.
UV/vis absorption spectra, density functional theory, QM/MM, molecular dynamics
Theoretical Chemistry Organic Chemistry
IdentifiersURN: urn:nbn:se:liu:diva-109095DOI: 10.1021/jp506797jISI: 000343741100004OAI: oai:DiVA.org:liu-109095DiVA: diva2:737011
At the time for thesis presentation publication was in status: Manuscript
Funding agencies: We acknowledge financial support from the Swedish Research Council (Grant No. 621-2010-5014) as well as a grant for computing time at the National Supercomputer Centre (NSC), Sweden. M.L. thanks the Swedish e-Science Research Center (SeRC) for financial support. Our work is supported by the Swedish Foundation for Strategic Research (K.P.R.N., R.A.S.). K.P.R.N. is financed by an ERC Starting Independent Researcher Grant (Project: MUMID) from the European Research Council. R.A.S. is enrolled in the doctoral program Forum Scientum. M.L. is grateful to Linkoping University for a guest professorship. Parts of this work were supported by the LUPAS project supported by the EU FP7 program.2014-08-112014-08-072016-10-06Bibliographically approved