Triplet–Triplet Annihilation Upconversion Is Impeded in Liposomes that Prevent Sensitizer and Annihilator Co-Confinement

TL;DR

This study shows that TTA-UC efficiency is reduced in liposomes when sensitizers and annihilators are not properly co-localized in the membrane.

Contribution

The work demonstrates the importance of co-localization for Dexter energy transfer in membrane-constrained TTA-UC systems.

Findings

TTA-UC was efficient in solution but not observed in liposomes.

Molecular dynamics simulations revealed poor co-orientation of sensitizer and annihilator in the membrane.

DPA and Ru complex occupied different regions of the membrane, limiting energy transfer.

Abstract

Triplet–triplet annihilation upconversion (TTA-UC)
implemented
in liposomes may be a promising tool in drug delivery and sensing.
Indeed, we recently demonstrated that colocalization of lipophilic
reagents to the membrane hydrophobic core improves the TTA-UC efficiency
in liposomes compared to solution. Here, we examined if the counter
is true, i.e., we evaluate if TTA-UC is inhibited when the sensitizer
and annihilator occupy different regions within a single leaflet of
a liposome membrane. To test this hypothesis, we used a Ru­(II) complex,
with tridentate ligand 2,6-di­(quinolin-8-yl)­pyridyl) (bqp) [Ru­(bqp)­(bpq-oct)]2+(Ru-bqp-oct) where oct is a C8 alkyl chain appended to facilitate
integration into the liposome, as a sensitizer and diphenylanthracene
(DPA) as an annihilator. TTA-UC from this pair was evaluated and compared
in solution and liposomal nanovesicles. This Ru­(II)-bqp complex was
selected for its exceptionally long-lived emission and high triplet
quantum yield, due to its expanded N-Ru-N bite angles. In solution,
TTA-UC was efficient with a quantum yield of 3.11%, but in liposomes,
no anti-Stokes shifted emission was observed even with an increased
concentration of sensitizer and annihilator in the membrane. Molecular
dynamics simulations were used to understand this effect and confirmed
poor co-orientation of sensitizer and annihilator in the membrane
was responsible for lack of TTA-UC in the membrane. DPA was determined
to orient at the hydrophobic core, while the cationic Ru complex is
embedded shallowly at the membrane interface, the closest approach
of donor and acceptor in the membrane was determined as 0.7 nm. This
work highlights the critical importance of colocalization of sensitizers
and annihilators, even within a single membrane leaflet to facilitate
Dexter energy transfer through collision in membrane-constrained TTA-UC
systems and the value of MD simulations in system design.

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