Ratiometric Imaging Detection of Amyloid-β Fibrils by a Dual-Emissive Tris-Heteroleptic Ruthenium Complex.

Area of Science:

• Coordination Chemistry
• Biophysical Chemistry
• Materials Science

Background:

• Amyloid-beta (Aβ) aggregation is implicated in neurodegenerative diseases.
• Development of sensitive and specific probes for Aβ detection is crucial.
• Ruthenium(II) complexes offer unique photophysical properties for sensing applications.

Purpose of the Study:

• To design and synthesize novel dual fluorescent/phosphorescent ruthenium(II) complexes for Aβ sensing.
• To evaluate the efficacy of these complexes in ratiometric emissive and imaging detection of Aβ aggregation and fibrils.
• To investigate the interaction mechanisms between the complexes and Aβ species.

Main Methods:

• Synthesis of tris-heteroleptic mononuclear Ru(II) complexes [Ru(phen)(dppz)(L)](PF6)2.
• Ratiometric emissive detection of Aβ40 and Aβ42 aggregation over time.
• Ratiometric imaging detection of Aβ40 and Aβ42 fibrils.
• Molecular docking and computational calculations to elucidate binding interactions.

Main Results:

• Complex 2 demonstrated ratiometric emissive detection of Aβ aggregation, with a new phosphorescence band enhancing over time while fluorescence remained stable.
• Complex 2 exhibited enhanced ratiometric photoluminescence for Aβ40 aggregation compared to Aβ42.
• Ratiometric imaging revealed brighter phosphorescence signals from Aβ40 and Aβ42 fibrils using complex 2.
• Molecular docking indicated strong interactions between complex 2 and Aβ40 fibrils via π/π, π/C-H, and π/H interactions.

Conclusions:

• The designed Ru(II) complexes, particularly complex 2, are effective dual probes for ratiometric sensing of Aβ aggregation and fibrils.
• Complex 2 shows potential for distinguishing between Aβ40 and Aβ42 aggregation states.
• The findings provide insights into the development of advanced luminescent probes for neurodegenerative disease diagnostics.