Abstract
Mitochondria metabolism is an emergent target for the development of novel anticancer agents. It is amply recognized that strategies that allow for modulation of mitochondrial function in specific cell populations need to be developed for the therapeutic potential of mitochondria-targeting agents to become a reality in the clinic. In this work, we report dipolar and quadrupolar quinolizinium and benzimidazolium cations that show mitochondria targeting ability and localized light-induced mitochondria damage in live animal cells. Some of the dyes induce a very efficient disruption of mitochondrial potential and subsequent cell death under two-photon excitation in the Near-infrared (NIR) opening up possible applications of azonia/azolium aromatic heterocycles as precision photosensitizers. The dipolar compounds could be excited in the NIR due to a high two-photon brightness while exhibiting emission in the red part of the visible spectra (600–700 nm). Interaction with the mitochondria leads to an unexpected blue-shift of the emission of the far-red emitting compounds, which we assign to emission from the locally excited state. Interaction and possibly aggregation at the mitochondria prevents access to the intramolecular charge transfer state responsible for far-red emission.
Highlights
Mitochondria metabolism is an emergent target for the development of novel anticancer agents
Compounds based on quinolizinium (Q) and benzimidazolium (B) cations have been designed for selective in vivo labelling of subcellular organelles and controlled mitochondria damage
Using simple/double Knoevenagel condensations, eight compounds were obtained with spectroscopic purity and good yields for which the upconverted emission properties and the performance as labels in live animal cells is here discussed for the first time
Summary
Mitochondria metabolism is an emergent target for the development of novel anticancer agents. Some of the dyes induce a very efficient disruption of mitochondrial potential and subsequent cell death under two-photon excitation in the Near-infrared (NIR) opening up possible applications of azonia/azolium aromatic heterocycles as precision photosensitizers. The quadratic dependence of the twophoton absorption (TPA) probability on the light intensity confines the process to a highly localized focal volume reducing the off-target photodamage While nanomaterials such as gold clusters, semiconductor quantum dots and graphene quantum dots have been reported to have very high TPA cross-sections[10,11,12,13], the development of nonlinear molecular materials continues to be of high relevance due to the more favourable cellular uptake kinetics and distribution[14]. Some of the compounds show an efficient light-induced mitochondria damage upon two-photon excitation in the NIR opening possible applications of azonia/azolium aromatic heterocycles as precision photosensitizers. Examples of that are the interaction of dyes with DNA increasing their quantum yields in the nucleus, and aggregation or hindered rotation increasing the quantum yield at the mitochondria[32,44]
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