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The role of charge transfer in the photophysics of dithiophene-based (NIADs) fluorescent markers for amyloid-β detection

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Abstract

Detection of amyloid-β (Aβ) aggregates in the brain is essential for an early diagnosis and for tracing the evolution of Alzheimer’s disease. Positron emission tomography is the most commonly used technique for Aβ detection, but fluorescence imaging is a promising alternative. For their in vivo application, fluorescent Aβ markers should emit in the near-infrared region and present strong binding affinities for Aβ aggregates. The dithiophene-based NIAD-4 dye and its derivatives NIAD-11 and NIAD-16 are within the most interesting Aβ markers as they fulfill these two criteria. In this contribution, the photophysical properties of these compounds as well as their binding to amyloid-β fibrils have been studied with a combination of computational techniques (TDDFT and MS-CASPT2 calculations, AIMD simulations and fit-induced docking calculations). Modifications on the NIAD-4 skeleton have little effects on the ground and excited state properties of the dye as well as on the feasibility of the most probable non-radiative deactivation pathways. However, they tune the absorption and emission wavelengths and affect significantly the blood–brain barrier (BBB) permeability and binding site preference toward Aβ fibrils. A red-shifting of the emission wavelength is achieved by enlarging the π-system in NIAD-11 and by increasing the charge transfer in NIAD-16, the effect of the former being significantly larger in gas phase. However, the larger solvatochromic effect observed for NIAD-16 leads to similar emission wavelengths in water solution for the two dyes. Overall, the variation of the charge transfer extent of the transition seems to be more appropriate at least in this case, since it has a smaller effect on the BBB permeability and binding site preference of the new dye with respect to the original NIAD-4.

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References

  1. Querfurth HW, Laferla FM (2010) N Engl J Med 362:329–344

    Article  CAS  Google Scholar 

  2. LaFerla FM, Green KN (2012) Cold Spring Harb Perspect Med 2:1–13

    Article  Google Scholar 

  3. Petkova AT, Yau W-M, Tycko R (2006) Biochemistry 45:498–512

    Article  CAS  Google Scholar 

  4. Lu J-X, Qiang W, Yau W-M et al (2013) Cell 154:1257–1268

    Article  CAS  Google Scholar 

  5. Tycko R (2011) Annu Rev Phys Chem 62:279–299

    Article  CAS  Google Scholar 

  6. Lührs T, Ritter C, Adrian M et al (2005) Proc Natl Acad Sci USA 102:17342–17347

    Article  Google Scholar 

  7. Ntziachristos V (2006) Annu Rev 8:1–33

    CAS  Google Scholar 

  8. Staderini M, Martín MA, Bolognesi ML, Menéndez JC (2015) Chem Soc Rev 44:1807–1819

    Article  CAS  Google Scholar 

  9. Nesterov EE, Skoch J, Hyman BT et al (2005) Angew Chem Int Ed 44:5452–5456

    Article  CAS  Google Scholar 

  10. Peccati F, Hernando J, Blancafort L et al (2015) Phys Chem Chem Phys 17:19718–19725

    Article  CAS  Google Scholar 

  11. Raymond SB, Skoch J, Hills ID et al (2008) Eur J Nucl Med Mol Imaging 35:93–98

    Article  Google Scholar 

  12. Frisch MJ, Trucks GW, Schlegel HB et al (2009) Gaussian 09. Gaussian Inc, Wallingford, CT

  13. Yanai T, Tew DP, Handy NC (2008) Chem Phys Lett 393:51–57

    Article  Google Scholar 

  14. Ditchfield R, Hehre WJ, Pople JA (1971) J Chem Phys 54:724–728

    Article  CAS  Google Scholar 

  15. Adamo C, Jacquemin D (2013) Chem Soc Rev 42:845–856

    Article  CAS  Google Scholar 

  16. Peccati F, Wiśniewska M, Solans-Monfort X, Sodupe M (2016) Phys Chem Chem Phys 18:11634–11643

    Article  CAS  Google Scholar 

  17. Marenich AV, Cramer CJ, Truhlar DG (2009) J Phys Chem B 113:6378–6396

    Article  CAS  Google Scholar 

  18. Scalmani G, Frisch MJ, Mennucci B et al (2006) J Chem Phys 124:094107

    Article  Google Scholar 

  19. Le Bahers T, Adamo C, Ciofini I (2011) J Chem Theory Comput 7:2498–2506

    Article  Google Scholar 

  20. Ciofini I, Le Bahers T, Adamo C et al (2012) J Phys Chem C 116:11946–11955

    Article  CAS  Google Scholar 

  21. Peach MJG, Williamson MJ, Tozer DJ (2011) J Chem Theory Comput 7:3578–3585

    Article  CAS  Google Scholar 

  22. Aquilante F, Pedersen TB, Veryazov V, Lindh R (2013) Wiley Interdiscip Rev Comput Mol Sci 3:143–149

    Article  CAS  Google Scholar 

  23. Pou-Amérigo R, Merchán M, Nebot-Gil I et al (1995) Theor Chim Acta 92:149–181

    Article  Google Scholar 

  24. Ghigo G, Roos BO, Malmqvist PÅ (2004) Chem Phys Lett 396:142–149

    Article  CAS  Google Scholar 

  25. Huix-Rotllant M, Filatov M, Gozem S et al (2013) J Chem Theory Comput 9:3917–3932

    Article  CAS  Google Scholar 

  26. VandeVondele J, Krack M, Mohamed F et al (2005) Comput Phys Commun 167:103–128

    Article  CAS  Google Scholar 

  27. Perdew J, Burke K, Ernzerhof M (1996) Phys Rev Lett 77:3865–3868

    Article  CAS  Google Scholar 

  28. Grimme S (2006) J Comput Chem 27:1787–1799

    Article  CAS  Google Scholar 

  29. Hartwigsen C, Goedecker S, Hutter J (1998) Phys Rev B 58:3641–3662

    Article  CAS  Google Scholar 

  30. Goedecker S, Teter M, Hutter J (1996) Phys Rev B 54:1703–1710

    Article  CAS  Google Scholar 

  31. VandeVondele J, Hutter J (2007) J Chem Phys 127:114105

    Article  Google Scholar 

  32. Madadkar-Sobhani A, Guallar V (2013) Nucleic Acids Res. doi:10.1093/nar/gkt454

    Google Scholar 

  33. Clark DE, Pickett SD (2000) Drug Discov Today 5:49–58

    Article  CAS  Google Scholar 

  34. www.molinspiration.com

  35. Abraham MH, Takács-Novák K, Mitchell RC (1997) J Pharm Sci 86:310–315

    Article  CAS  Google Scholar 

  36. Nadal-Ferret M, Gelabert R, Moreno M, Lluch JM (2013) J Chem Theory Comput 9:1731–1742

    Article  CAS  Google Scholar 

  37. Sanchez-Garcia E, Doerr M, Thiel W (2009) J Comput Chem 31:1603–1612

    Google Scholar 

  38. Imhof P (2012) J Chem Theory Comput 8:4828–4836

    Article  CAS  Google Scholar 

  39. Isborn CM, Götz AW, Clark MA et al (2012) J Chem Theory Comput 8:5092–5106

    Article  CAS  Google Scholar 

  40. De Mitri N, Monti S, Prampolini G, Barone V (2013) J Chem Theory Comput 9:4507–4516

    Article  Google Scholar 

  41. Stsiapura VI, Maskevich A, Kuzmitsky V et al (2008) J Phys Chem B 112:15893–15902

    Article  CAS  Google Scholar 

  42. Beljonne D, Shuai Z, Pourtois G, Bredas JL (2001) J Phys Chem A 105:3899–3907

    Article  CAS  Google Scholar 

  43. Molnar F, Ben-Nun M, Martínez TJ, Schulten K (2000) J Mol Struct 506:169–178

    Article  CAS  Google Scholar 

  44. Valsson O, Filippi C (2010) J Chem Theory Comput 6:1275–1292

    Article  CAS  Google Scholar 

  45. Levine BG, Ko C, Quenneville J, MartÍnez TJ (2006) Mol Phys 104:1039–1051

    Article  CAS  Google Scholar 

  46. Tycko R, Wickner RB (2013) Acc Chem Res 46:1487–1496

    Article  CAS  Google Scholar 

  47. Borrelli KW, Vitalis A, Alcantara R, Guallar V (2005) J Chem Theory Comput 1:1304–1311

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge financial support from MINECO (projects CTQ2014-59544-P) and the Generalitat de Catalunya (projects and 2014SGR-482). MS acknowledges the Generalitat de Catalunya for the 2011 ICREA Academia award and XSM for a Professor Agregat Serra Húnter position.

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Authors and Affiliations

  1. Departament de Química, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain

    Francesca Peccati, Xavier Solans-Monfort & Mariona Sodupe

Authors
  1. Francesca Peccati
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  2. Xavier Solans-Monfort
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  3. Mariona Sodupe
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Corresponding authors

Correspondence to Xavier Solans-Monfort or Mariona Sodupe.

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Published as part of the special collection of articles “Charge Transfer Modeling in Chemistry”.

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Peccati, F., Solans-Monfort, X. & Sodupe, M. The role of charge transfer in the photophysics of dithiophene-based (NIADs) fluorescent markers for amyloid-β detection. Theor Chem Acc 135, 184 (2016). https://doi.org/10.1007/s00214-016-1934-5

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  • DOI: https://doi.org/10.1007/s00214-016-1934-5

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