Rigid oligoperylenediimide rods: Anion-π slides with photosynthetic activity

Article abstract of DOI:10.1002/anie.200703749

(Chemical Equation Presented) Slide rules: A new class of membrane-active rigid-rod molecules comprising π-acidic, n-semiconducting oligoperylene-diimides is introduced (see picture). They are able to combine passive anion transport across lipid bilayers with photoactive electron transport in the other direction across intact vesicle membranes. Thus, the compounds demonstrate artificial photosynthetic activity.

Full text of DOI:10.1002/anie.200703749

Angewandte
Chemie
DOI: 10.1002/anie.200703749
Membrane Transport
Rigid Oligoperylenediimide Rods: Anion–p Slides with Photosynthetic
Activity**
Alejandro Perez-Velasco, Virginie Gorteau, and Stefan Matile*
To combine ion-channel[1] and photosynthetic activity[2–4]
productively is one of the great challenges of synthetic
multifunctional nanoarchitecture. One expectation is the
ability to compensate the transmembrane electronic imbal-
ance caused by photoinduced active electron transport with
passive anion transport in the other direction. Such electro-
neutral electron–anion antiport should prevent saturation of
the system by membrane polarization.[2] The problem is the
high, but so far elusive, anion selectivity required to avoid
collapse of the entire multifunctional system.[4]
The recent introduction of rigid-rod oligo(p-phenylene)-
N,N-naphthalenediimide (O-NDI) anion–p slides has pro-
vided a newapproach to transmembrane anion transport that
focuses on anion–p interactions[5] for selectivity and multi-ion
hopping.[6] Photosynthetic activity remains, however, inacces-
sible with O-NDI anion–p slides for synthetic reasons.[4,6]
Herein, we introduce the differently colored oligo(p-phenyl-
ene)-N,N-perylenediimide (O-PDI) rods 1 and 2 as anion–p
slides with photosynthetic activity (Figure 1).
solvent; photoinduced charge separation in linear dimers was
less favorable).[7a]
Rigid O-PDI rod 1 was synthesized in 12 steps from
commercially available starting materials, such as perylene
dianhydride and glutamate (Scheme S1 and Figures S1–S3,
Supporting Information). Synthetic procedures and analytical
and spectroscopic data for all newcompounds can be found in
the Supporting Information.[9]
Egg yolk phosphatidylcholine large unilamellar vesicles
(EYPC LUVs) loaded with the pH-sensitive fluorescent
probe 8-hydroxy-1,3,6-pyrenetrisulfonate (HPTS) were used
to evaluate the activity of rigid O-PDI rod 1 as an anion–p
slide.[6,9,10] Vesicles with internal NaBr were diluted with
isoosmolar buffer containing different salts MX, and rod 1
was added (Figure 2). This version of the HPTS assay[6,9] fails
to detect the ability of rod 1 to dissipate the applied
transmembrane NaX and MBr gradients by transmembrane
PDIs are p-acidic n-semiconductors.[7,8] These properties
are compatible with electron transport in one direction and
anion transport by anion–p interactions in the other. The
ideal topology of the PDI chromophore to align with the lipid
tails in one leaflet of a bilayer membrane has been noted
recently.[4] In rigid O-PDI rod 1 (Figure 1), two PDIs are
unbendably placed in line to reach the matching length to
span a lipid bilayer membrane. Anionic triglutamate tails
were added at one end to obtain the water solubility needed
to assure delivery to membrane vesicles, intervesicular trans-
fer, oriented partitioning, and parallel self-assembly. Pyrroli-
dinyl substituents were added to the PDI core because the 1,7-
bis(pyrrolidin-1-yl)-3,4:9,10-perylene-bis(dicarboximide)
chromophore was shown by Wasielewski and co-workers to
have optoelectrical characteristics similar to those of chlor-
ophyll, the green pigment of plants (Figure 1).[7] For instance,
face-to-face dimers of these green PDIs were found to
undergo symmetry-breaking, relatively long-lived photoin-
duced charge separation (lifetime t ꢀ 4 ns, depending on
[*] Dr. A. Perez-Velasco, V. Gorteau, Prof. S. Matile
Department of Organic Chemistry, University of Geneva
1211 Geneva (Switzerland)
Fax: (+41)22-379-3215
E-mail: stefan.matile@chiorg.unige.ch
Homepage: http://www.unige.ch/sciences/chiorg/Matile/Group/
Figure 1. Rigid O-PDI rods 1 and 2 with anion transport and photo-
synthetic activity. a) Passive anion efflux is thought to occur by anion–
p interactions on the p-acidic PDI surfaces. b) Active, photoinduced
electron influx with frontier orbital energy levels of external ethyl-
enediaminetetraacetic acid (EDTA) donors, internal [Co(bpy)3]3+
(bpy=2,2’-bipyridine) acceptors, and PDIs with c) two pyrrolidinyl and
d) two phenoxy core substituents (from refs. [3] and [7]).
[**] We thank D. Jeannerat, A. Pinto, and S. Grass for NMR spectroscopy
measurements, P. Perrottet and the group of F. Gülaçar for mass
spectometry measurements, and the Swiss NSF for financial
support.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Communications
tions and differed clearly from the results with the more p-
acidic O-NDIs (Figures S8–S10, Supporting Information).[9]
The photosynthetic activity of the anionic O-PDI p slide 1
in the neutral EYPC LUVs was determined with the “Hurst
assay”.[3] In this assay, intravesicular photoreduction of [Co-
(bpy)3]3+ is detected as a change in absorption around 320 nm
(Figure 3a); EDTA is used as an external hole acceptor
Figure 2. Anion transport activity of O-PDI 1. Change in HPTS
emission I during addition of 1 (1.5 mm) to EYPC LUVsꢁHPTS in MX
(100 mm); a) M=Na, X varied (50 mm for Na2SO4), b) X=Br, M
varied, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES,
10 mm), pH 7.0.
cation (M = Na) or anion (X = Br) exchange (antiport),
because both processes do not cause a change in intra-
vesicular pH. However, the assay becomes exceptionally
informative as soon as rod 1 can transport intravesicular Na+
or BrÀ but fails to transport extravesicular M+ or XÀ in the
other direction. The applied NaX and MBr gradients can in
this case be partially relieved only by either H+/Na+ or OHÀ/
BrÀ antiport. The resulting formal H+ or OHÀ pumping into
vesicles is then detectable by HPTS as an intravesicular
decrease or increase in pH. This pumping assay is attractive
because it works only in intact vesicles and with highly
selective ionophores.
Figure 3. Photosynthetic activity of a,b) O-PDI 1 and c) 2. a) Differ-
ential absorption spectra of EYPC LUVsꢁ[Co(bpy)3]3+ with externally
added EDTA and 1, which show increasing change at 320 nm after 10,
20, 30, 40, and 50 min of irradiation (Xe lamp, cutoff at 580 (1) or
480 nm (2)). b) Photoreduction of [Co(bpy)3]3+ after 15 min of irradi-
&
ation as a function of concentration of 1 in the absence ( ) and
presence (”) of carbonylcyanide 4-(trifluoromethoxy)phenylhydrazone
(FCCP; 5 mm), detected as change in absorption at 320 nm as
illustrated in (a). c) The same for 2, but without FCCP.
According to this assay, the response to the addition of O-
(Figure 1). The dark reduction of [Co(bpy)3]3+ with EDTA is
unfavorable. Successful photoreduction thus converts pho-
tonic energy into chemical energy.
PDI 1 to EYPC LUVs exposed to opposing BrÀ/NO3
À
gradients was indeed a strong increase of intravesicular pH
(Figure 2a). Similar increases of intravesicular pH were found
According to the Hurst assay, O-PDI rod 1 exhibited
significant photosynthetic activity (Figure 3a and b). The Hill
plot revealed a Hill coefficient n = 8.7 Æ 2.6, which indicates
unusually high cooperativity. This finding demonstrated that
self-assembly is essential for photosynthetic activity, that is,
the existence of a supramolecular function.[10,11] It further
revealed that the self-assembly of the active structure is
endergonic. As with all n > 1 systems, all nonspecific struc-
tural and photophysical studies will thus fail to report on the
active structure.[10–13]
The Hill plots for the photosynthetic activity of O-PDI
rod 1 measured in the presence and absence of FCCP were
nearly superimposable (Figure 3b). This insensitivity toward
the proton carrier FCCP demonstrated that photosynthesis by
O-PDI rod 1 is electroneutral.[2,3,10] This finding supported the
constructive combination of active electron influx with
passive anion efflux, that is, the constructive combination of
ion transport and photosynthetic activity by the electron–
anion antiport.
Advanced O-PDI rod 2 was synthesized next in 15 steps
(Figure 1; Scheme S2 and Figures S4–S6, Supporting
Information). Compared to O-PDI rod 1, the green 1,7-
bis(pyrrolidin-1-yl)-3,4:9,10-perylene-bis(dicarboximide)
chromophore in the inner leaflet of the bilayer membrane is
replaced by a red 1,7-bis(3,5-di-tert-butylphenoxy)-3,4:9,10-
perylenebis(dicarboximide) chromophore with two phenoxy
rather than two pyrrolidinyl substituents in the core. The
activity and selectivity of O-PDI rod 2 to transport anions
with external SO42À, ClO4À, and even ClÀ instead of NO3
À
(Figure 2a), and with internal ClÀ instead of BrÀ (Figure S7,
Supporting Information). The application of cation gradients
did not cause similar changes in intervesicular pH (Fig-
ure 2b). These findings revealed that rod 1 transports anions
rather than cations, with a preference for OHÀ over SO4
,
2À
NO3À, ClO4À, and ClÀ. They further demonstrated that rod 1
transports anions across intact vesicle membranes and firmly
excluded the occurrence of less specific transport mechanisms
as well as lysis.
The creation of anionic transporters in neutral bilayer
membranes that attract anions rather than cations has rarely
been achieved before. The anion selectivity of 1 excluded
participation from the anionic peptide tail to mediate trans-
port, and thus supported the potential of anion–p interactions
along the p-acidic O-PDI and O-NDI[6] rods as a promising
strategy to transport anions across bilayer membranes.
Indeed, the apparent preference for ClÀ (DGhydr
À
ꢀ 370 kJmolÀ1) over ClO4 (DGhydr ꢀ 230 kJmolÀ1) demon-
strated that the dehydration penalty alone is insufficient to
account for the observed anion selectivity sequence, and thus
confirmed the occurrence of compensatory contributions
from anion binding to the p slide, possibly together with
relatively weak size-exclusion phenomena.[6,10] The results on
ion selectivity in HPTS assays in the presence of an additional
pH gradient, including poor halide discrimination except for
the disfavored FÀ, were in agreement with these interpreta-
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Chem. Soc. Rev. 2006, 35, 1269 – 1286; i) P. A. Gale, Acc. Chem.
across vesicle membranes was similar to that of O-PDI rod 1
(Figures S7–S10, Supporting Information). The apparent
photosynthetic activity of O-PDI rod 2, detectable at
concentrations as lowas 500 n m, was clearly higher than
that of O-PDI rod 1 (Figure 3c). The Hill coefficient,
however, decreased to n = 2.4 Æ 0.5.[13] Competing precipita-
tion at high concentrations (above 5 mm) prevented comple-
tion of the Hill plot with the determination of maximal
activity.
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Photophysical insights from closely related PDI dyads[7]
implied that several possibilities exist to explain the increased
photosynthetic activity of O-PDI 2, which include absorption
at a broader range of visible light, energy transfer, electron
transfer, and prolonged, directional photoinduced charge
separation (Figure 1). However, with structural and photo-
physical studies being meaningless for n > 1 systems (Fig-
ure 3b and c), and other parameters, such as partitioning and
intervesicular transfer, likely to contribute, we concluded that
the origins of the meaningful apparent difference in activity of
rods 1 and 2 cannot be determined at this stage. With the
unknown effective concentrations of n > 1 systems, the
unknown rate-limiting steps recorded in the Hurst assay,
and the lack of comparable positive controls, it is not
meaningful to comment on the absolute photoactivity of
rods 1 and 2.
In summary, we have introduced O-PDIs as a new class of
membrane-active rigid-rod molecules.[14] Their ability to
mediate the passive transport of ions and the active transport
of electrons with light across intact vesicle membranes was
demonstrated unambiguously. Constructive combination of
the two functions in passive/active anion–electron antiport is
indicated with the electroneutrality of photosynthetic activity.
High cooperativity in Hill plots for photosynthetic activity
revealed the occurrence of endergonic self-assembly into
supramolecular active structures. The ability of anionic rods
to selectively attract anions (rather than cations) is considered
as strong evidence for the potential of anion–p interactions to
transport anions across bilayer membranes. The introduced
system produces stimulating questions for experts in the
respective domains and offers an ideal starting point for the
development of refined functional systems.
[8] The nonplanarity of core-substituted PDI chromophores pre-
vents the calculation of quadrupole moments as with the planar
NDIs.[6]
[9] Please see the Supporting Information.
[10] S. Matile, N. Sakai, “The Characterization of Synthetic Ion
Channels and Pores” in Analytical Methods in Supramolecular
Chemistry (Ed.: C. A. Schalley), Wiley-VCH, Weinheim, 2007,
pp. 391–418.
[11] S. Bhosale, S. Matile, Chirality 2006, 18, 849 – 856.
[12] The Hill plot for ion-transport activity exhibited pseudo-linear
behavior at low, nanomolar concentrations (Figure S11,
Supporting Information). This less informative behavior sug-
gested that ion transport is mediated by either 1) monomeric rod
1 or, more likely,[6] 2) an exergonic self-assembly, which would
then further undergo endergonic self-assembly into the unstable
higher-order quaternary structure that is needed for photosyn-
thesis. In any case, different Hill plots confirmed that the
suprastructural requirements for ion transport and photosyn-
thesis are different, with the latter being more demanding.[13]
[13] The experimentally confirmed[7a] stabilization of photoinduced
charge separation in face-to-face p-stacked PDIs could be
considered as one possible explanation for the need of supra-
molecular active structures for photosynthetic activity of 1 and 2.
[14] a) N. Sakai, J. Mareda, S. Matile, Acc. Chem. Res. 2005, 38, 79 –
87; b) R. Bhosale, S. Bhosale, G. Bollot, V. Gorteau, M. D.
Julliard, S. Litvinchuk, J. Mareda, S. Matile, T. Miyatake, F.
Mora, A. Perez-Velasco, N. Sakai, A. L. Sisson, H. Tanaka, D.-H.
Tran, Bull. Chem. Soc. Jpn. 2007, 80, 1044 – 1057.
Received: August 15, 2007
Keywords: p interactions · ion channels · membranes ·
.
photosynthesis · supramolecular chemistry
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