Microenvironment-switchable singlet oxygen generation by axially-coordinated hydrophilic ruthenium phthalocyanine dendrimers

Article abstract of DOI:10.1039/c0cp01015d

A series of new metallodendrimers built around a ruthenium phthalocyanine core has been prepared. Employing a convergent synthetic strategy, pyridine-containing ligands were prepared and then assembled onto the ruthenium phthalocyanine through axial ligand coordination. The growing shell of oligoethylene glycol chains surrounding the lipophilic core allows solubilisation in water. Photophysical studies show that all the metallodendrimers are strongly phosphorescent and the deactivation pathway of their triplet state depends on the medium in which the compounds are dissolved. On one hand, quenching of the triplet state by the dendritic shell is observed and found to be substantially enhanced in aqueous media. On the other, the dendrimer shields the phthalocyanine from oxygen. This notwithstanding, the phthalocyanines are able to generate singlet oxygen in less polar environments such as in CHCl₃ or THF solution, while in water the generation of singlet oxygen is almost completely switched off. the Owner Societies 2011.

Full text of DOI:10.1039/c0cp01015d

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PAPER
Microenvironment-switchable singlet oxygen generation by
axially-coordinated hydrophilic ruthenium phthalocyanine dendrimersw
Uwe Hahn,a Francesca Setaro,a Xavier Ragas,b Angus Gray-Weale,c Santi Nonell*b
and Tomas Torres*a
Received 28th June 2010, Accepted 19th November 2010
DOI: 10.1039/c0cp01015d
A series of new metallodendrimers built around a ruthenium phthalocyanine core has been
prepared. Employing a convergent synthetic strategy, pyridine-containing ligands were prepared
and then assembled onto the ruthenium phthalocyanine through axial ligand coordination.
The growing shell of oligoethylene glycol chains surrounding the lipophilic core allows
solubilisation in water. Photophysical studies show that all the metallodendrimers are strongly
phosphorescent and the deactivation pathway of their triplet state depends on the medium in
which the compounds are dissolved. On one hand, quenching of the triplet state by the dendritic
shell is observed and found to be substantially enhanced in aqueous media. On the other,
the dendrimer shields the phthalocyanine from oxygen. This notwithstanding, the phthalocyanines
are able to generate singlet oxygen in less polar environments such as in CHCl3 or THF solution,
while in water the generation of singlet oxygen is almost completely switched off.
Phthalocyanines and their metalloderivatives are two-
Introduction
dimensional 18 p-electron aromatic porphyrin synthetic
Since the first report in 1978 by Vogtle et al.,1 a plethora
of dendrimers has been described in the literature.2 The
analogues.8 One of the outstanding characteristics of this kind
¨
of dye molecules is their exceptionally high absorption in the
tremendous advances in the preparation and modification of
visible region of the UV/vis spectrum from 630 to 750 nm.
these branched structures have allowed dendrimers in recent
This so-called Q-band makes them valuable in different fields
of science and technology.9 However, phthalocyanines have
years to move on from academic research and to enter the
market in a variety of applications.3 Generally, the use of
another interesting feature: the generation of singlet oxygen.
dendrimers is closely related to their precisely controlled size
Metallophthalocyanines are being studied as photosensitizers
and symmetry.1,4 Within their regularly branched architecture
for the treatment of cancer by photodynamic therapy, which
selected chemical units can be introduced in predetermined
takes advantage of the interaction between light and a photo-
sensitizing agent to selectively kill cancer cells.10 The growing
sites, namely in the core, within the branching units or at the
surface.1,4 Consequently, the size and more importantly the
popularity of this therapeutic method can be attributed to the
properties of the macromolecule can be tailored. The steadily
high selectivity of destruction of diseased tissues and tumors
growing interest in dendrimer structures is based on their
through the localized generation of cytotoxic singlet oxygen
potential for molecular design, which offers numerous
while surrounding healthy cells remain unaffected. Among
others, phthalocyanines comprising zinc,11 silicon,12 or ruthenium
possibilities, particularly in the field of biomedicine, e.g. as
markers for magnetic resonance imaging (MRI),5 as gene
as the metal in the central cavity have been found to exhibit
transfection agents,3c,6 or for the treatment of cancer.7
the PDT effect.13 Ruthenium phthalocyanines have the added
advantage that they are strongly phosphorescent,14 providing
a
´
´
´
Departamento de Quımica Organica, Universidad Autonoma de
Madrid (UAM), Madrid, Spain. E-mail: tomas.torres@uam.es;
Fax: +34 91497 3966; Tel: +34 91497 4151
a convenient means for assessing the mechanistic details of
singlet oxygen production in microheterogeneous environments,
e.g., cells.15
b
´
´
Grup d’Enginyeria Molecular, Institut Quımic de Sarria,
Universitat Ramon Llull, Barcelona, Spain.
E-mail: santi.nonell@iqs.url.edu; Fax: +34 932 056 266;
Tel: +34 932 672 000
The phthalocyanine macrocycle has also been part of
dendritic structures.16 In most cases this porphyrin analogue
is embedded in a dendritic environment thereby aiming at
creating a hydrophilic surface.11a,17 In this context, dendritic
modification of phthalocyanines is possible by two distinct
methods, being (i) the functionalization of the phthalocyanine
outer rim or (ii) via axial ligand coordination. Hydrophilic
c School of Chemistry, Monash University, Clayton 3800, Victoria,
Australia
w Electronic supplementary information (ESI) available: 1H NMR
spectra of dendritic pyridine ligands 5–7 and RuP1–3; phosphorescence
spectra at 1140 nm of RuP1–3; singlet oxygen luminescence at 1270 nm of
RuP1–3 in CHCl3, THF and D2O. See DOI: 10.1039/c0cp01015d
c
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systems described in the literature deal for instance with
a charged surface consisting of carboxylate moieties of
oligoethylene-terminated Fre
´
chet-type dendrimer shells
provides a straightforward means to switch their ability to
produce singlet oxygen on and off between non-polar and
polar environments. Theoretical calculations have been
conducted to support the isolation phenomenon of the
centre by the dendritic environment, thus demonstrating that
aggregation is effectively prevented upon dendritic encapsulation
at least for the highest generation specimens.
Fre
´
chet-18 or Newkome-type,19 or with terminal oligoethylene
chains.20 The latter approach of assembling the dendritic units
in the axial positions, which is applicable in the case of
e.g., silicon or ruthenium metal centres, has been exploited
to a lesser degree. Nonetheless, this strategy is particularly
appealing as such ligands can be incorporated in the last step
of the synthetic methodology. Furthermore, in the case of
ruthenium phthalocyanines in which the ligand is bound in a
non-covalent manner to the central metal atom, high yields
are usually obtained while assembling the final dendritic
structures.
Results and discussion
Synthesis
Under the use of the convergent methodology for the
construction of dendrimers, branched pyridine-containing
ligands have been prepared. Accordingly, first to third
Here, we report the high yield synthesis of a new series of
monodisperse and well-defined ruthenium phthalocyanine-
based dendrimers RuP1–3 (Chart 1) obtained through
orthogonal coordination of pyridine-containing ligands, with
the largest dendrimers being readily soluble in aqueous
solution. The photophysics and singlet oxygen generation
ability of encapsulated photoactive phthalocyanine core
moieties have been investigated in organic and aqueous
media. The results lead to the surprising finding that
Frechet-type dendrons with terminal oligoethylene glycol
´
chains have been obtained via the well-established protocol
as reported in the literature.20,21 The first generation inter-
mediate 1 bearing a benzylic alcohol function at the focal point
was then coupled to a 3,5-disubstituted pyridine derivative
using two different strategies. Initial attempts were based
thereby on the transformation of the diacid into the
corresponding diacid dichloride under the use of thionyl
chloride and a catalytic amount of dimethylformamide and
subsequent reaction with 1 to give diester 5 in 68% yield
after purification by chromatography. On the contrary,
the engineering of
a
ruthenium phthalocyanine with
N-(3-dimethylaminopropyl)-N0-ethylcarbodiimide
(EDCI)
hydrochloride-mediated esterification with pyridine diacid 4
in the presence of dimethylaminopyridine (DMAP) in dichloro-
methane resulted in the formation of target structure 5 in a
significant higher yield of 85% (Scheme 1). The latter reaction
conditions have then been applied to the conjugation of
pyridine diacid 4 with the oligoethylene glycol-modified higher
generation dendritic wedges 2 and 3 (Scheme 1). The two
diesters of second, 6 and third generation, 7 have been
obtained in high to moderate yields of 83 and 51%,
respectively, and similar to the smallest pyridine-containing
ligand as colourless highly viscous oils.
On the other hand, ruthenium phthalocyanine 9 was
synthesized following a modified protocol as described by
Hanack et al. Accordingly, formation of the ruthenium phthalo-
cyanine was accomplished by reaction of 1,3-diiminoisoindoline
(8) in 2-ethoxyethanol (EE) and in the presence of
ruthenium(III) chloride and a catalytic amount of diaza(1,3)-
bicyclo[5.4.0]undecane (DBU) as base.22 The crude product
obtained after workup was then heated to 100 1C for 4 hours
in benzonitrile to yield ruthenium phthalocyanine 9 with two
Scheme 1 Preparation of dendritic pyridine ligands 5–7 with terminal
oligoethylene glycol chains (light spheres represent the polyarylether
branching units, darker spheres represent triethylene glycol mono-
methyl ether end groups). Reagents and conditions: (i) EDCI–HCl,
DMAP, CH2Cl2, rt, 1 d (5; 6: 2 d; 7: 4 d).
Chart 1
c
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unaffected upon changing the solvent from CDCl3 to deuter-
ated THF. As expected, the 13C NMR spectra of the series of
dendrimers showed analogous shifts for the corresponding
carbon atoms.
Absorption spectra
The absorption spectra of the series of RuP1–3 dendrimers are
depicted in Fig. 1. For comparison purposes, a simple model
phthalocyanine RuPy consisting of two pyridine moieties
orthogonally coordinated to the ruthenium centre has been
included. The spectra have been recorded in THF (Fig. 1a)
and CHCl3 (Fig. 1b) as examples of common organic solvents,
and in neat water (Fig. 1c).
Scheme 2 Preparation of dendritic RuP1–3. Reagents and conditions:
(i) RuCl3ꢀ3H2O, DBU, EE, 140 1C, 24 h; (ii) PhCN, 100 1C, 5 h;
(iii) THF, 60 1C, 7 h (RuP1; RuP2: 10 h; RuP3: 24 h).
In general, these spectra show many features archetypical of
aggregation phenomena in these dyes: broad Q bands and with
lower absorption coefficients than the typical monomer
phthalocyanines. While phthalocyanine molecules have indeed
a high tendency to aggregate, thereby showing coplanar
association under formation of dimers, trimers, and higher
oligomers, respectively,24 the introduction of bulky peripheral
substituents or axial ligands should effectively prevent this
phenomenon. Indeed, the defined signal patterns as observed
for the NMR spectra of all samples and the lack of concen-
tration effects on the spectra rule out such putative formation
of aggregated species. However, the appearance of broad
Q-bands for the whole series of phthalocyanines regardless
of the polarity of the solvent appears to be a particular
intrinsic phenomenon apparent in bis-pyridyl-coordinated
ruthenium phthalocyanines. This is in line with findings
that have been observed before for similar orthogonally
axial benzonitrile ligands (Scheme 2) after purification by
chromatography. In the final step, as a result of the weaker
association constant of the benzonitrile moieties to the ruthenium
metal centre, replacement by the dendritic pyridine-based
ligands was feasible. Consequently, simple heating at 60 1C
in tetrahydrofuran for several hours gave the monodisperse
dendrimers RuP1–3 in excellent yields of 89 to 93%
(Scheme 2). It is important to notice that reaction times
required to ensure complete orthogonal complexation were
longer due to the higher steric demand of the ligands to allow
the pyridine subunit to access the ruthenium centre. All target
dendrimers RuP1–3 could be easily separated from the slight
excess of the corresponding pyridine ligands by size exclusion
chromatography and were obtained as intense blue coloured
highly viscous compounds.
Structural characterization
Due to the presence of the oligoethylene glycol chains at the
surface of the ruthenium phthalocyanine macromolecules, all
structures are very soluble in common organic solvents such as
CH2Cl2, CHCl3 or THF, thus facilitating spectroscopic
characterization by NMR, UV/Vis, and MS techniques.
Furthermore, the largest dendrimers RuP2 and RuP3, i.e.
the entities of second and third generation, are soluble in neat
water, while RuP1 can still be solubilized if small amounts of
organic solvents are added. The increasing amount of hydro-
philic surface moieties creates an amphiphilic environment in
which the hydrophobic core is shielded by the oligoethylene
glycol termini. Elucidation of all structures was easily possible
as all signals of the various parts of the dendrimers appear in
specific regions and do thus assist the assignments of sets of
signals (see ESIw). Additionally, it proved advantageous to
incorporate the highly symmetric peripherally unsubstituted
phthalocyanine centrepiece whose signals were located as two
sets of signals at 9.1 and 7.8 ppm, respectively.
The protons of the 3,5-disubstituted pyridine moieties
coordinated in the axial positions are significantly shifted
while being affected by the phthalocyanine ring current and
can be found as signals at 7.2 and 3.1 ppm, respectively. This is
in good agreement with similar systems described in the
literature.23 Concerning the signals of the branches the inner
protons are slightly upfield shifted in contrast to the outer
protons which hardly notice the influence of the ring current of
the phthalocyanine subunit. Likewise, proton shifts remain
Fig. 1 UV/Vis spectra of RuPy (-ꢀ-), RuP1 (ꢀ ꢀ ꢀꢀ ꢀ ꢀ), RuP2 (——) and
RuP3 (---) in (a) THF and (b) CHCl3; (c) UV/Vis spectra of RuP2
(——) and RuP3 (---) in H2O.
c
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constructed species,23 including dendrimers with thiophene-
derived ligands in axial positions.23a
the same radius of gyration: r = 0.03 sꢁ3 26b
, which is
2.2 nmꢁ3 for the lipophilic groups. RBT normally takes into
account interactions through the Flory–Huggins parameters,
but here we neglect this for brevity (w = 0). Our results are not
sensitive to any of these choices or approximations.
However, other spectral variations are apparent upon closer
inspection of Fig. 1. First, an increasing contribution of the
dendrimers is observed around 280 nm on passing from RuP1
to RuP3. Additionally, small changes in the absorption
coefficients can be spotted throughout the UV/Vis spectral
range. In THF, the Q-band maxima for all compounds under
study are identical and can be found at lmax = 630 nm.
Nonetheless, intensities are increasing upon going from RuPy
to RuP3 and are at least two-fold with respect to the model
compound RuPy. Likewise, in CHCl3 a similar trend of higher
absorption coefficients for the dendrimers has been observed.
However, it is interesting to note that coordination with the
fractal pyridine ligands in this solvent provokes a bathochromic
shift of B10 nm, thus giving rise to Q-bands centered at
lmax = 638 nm for all dendrimers. These findings cannot be
attributed to changes in phthalocyanine/solvent interactions,
but to an increasing intramolecular interaction between the
phthalocyanine core and the dendrimer part of the series of
fractal structures, similar to that described for related
fullerodendrimers.25 Finally, the intensity ratio of the two Q
bands (590 and 638 nm) decreases when the solvent polarity is
increased. At present we cannot ascertain whether this stems
from the interaction between the phthalocyanine core and the
dendrimers or from the interaction between the phthalocyanine
and the pyridyl ligands.
Our estimate of the maximum permitted density of
lipophilic monomers is 2.2 nmꢁ3. Fig. 2 shows the density
profiles for metallodendrimers of all three generations. For
RuP2 and RuP3 the density of lipophilic groups is 1 nmꢁ3 or
more over a considerable range. For two metal centres to
approach each other closely, either their dendron groups
would have to overlap, or they would have to move out of
the way. In either case, the density of lipophilic groups would
approach this maximum density. This would have a large
entropy cost. The use of the random close packed density as
a maximum here is conservative: we have neglected the effects
of regular branching, which is likely to further constrain the
distribution of lipophilic groups. We feel that this calculation
is useful evidence that the metal centres cannot aggregate,
being surrounded by a lipophilic shell, but experimental
confirmation is clearly desirable.
Phosphorescence
All dendrimers show strong triplet phthalocyanine
phosphorescence at 1140 nm as depicted in Fig. 3. It has been
previously reported for similar compounds that the dendritic
wedges are able to partially shield the photoactive core from
molecular oxygen, increasing the triplet lifetime upon increasing
the dendrimer complexity.25,29 Interestingly, a different trend
is observed for RuP1–3. The phosphorescence decays are
monoexponential in CHCl3 and THF, with lifetimes tT
ranging from 1 to 1.5 ms. A clear trend, i.e. a negative dendritic
effect, can be noticed on passing from RuP1 to RuP3, i.e., tT
decreased upon increasing the dendrimer complexity. This
confirms that the electron-rich dialkoxyphenyl moieties of
Theoretical calculations
In line with the idea of structurally not aggregated and thus
independent phthalocyanine chromophores are results
obtained by theoretical calculations. Random Branching
Theory (RBT) constructs a model solution structure for a
branched polymer by random assembly from units that may
be oligomers or larger clusters. It has been shown to describe
accurately the structures of a variety of synthetic and natural,
regular and randomly branched polymers.26,27 Remarkably,
the assembly of a model structure based on random branching
provides a good model of the density distributions of
dendrimers,26b though perhaps this is understandable now
that we know that monomers of the outermost generation
are often distributed through the dendrimer. Here we do not
seek to construct a detailed picture of the distribution of
different groups within the metallodendrimers. Rather, we
use RBT to estimate the thickness of the dendrimer distribution
around the metal centre.
We estimate that the dendron’s groups may approach no
closer than 0.4 nm to the metal centre, and that the dendrons
are attached to the metal complex no more than 1 nm from the
ruthenium atom. The monomers in the dendron are of the AB2
type, and we assume that in the fluctuating solution structure a
monomer’s B group has a Gaussian distribution about its A
group, with a width of s = 0.24 nm. The distribution of mass
in the oligoethylene glycol chains is also assumed to be
Gaussian, with a width estimated at s = 0.35 nm. This led
us to assume that the chain can completely reorient over
three bonds. The maximum number density permitted for
monomers is the random close packed density of spheres with
Fig. 2 Random Branching Theory estimates of the distributions of
lipophilic groups (solid lines), and polyether chains (dashed), about
the ruthenium atom at r = 0. For the lipophiles, the density integrates
to the number of aromatic rings. For the polyethers, the density
integrates to the number of oligomers. Our estimate of the maximum
achievable density monomers is 2.2 nmꢁ3 in these units. Density at less
than r = 0.4 nm is an artefact of the mean-field approximation.
c
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the three compounds (see ESIw). The complex decays suggest a
distribution equilibrium between conformers, the decay
kinetics likely reflecting the outcome of the interactions
between the dialkoxy groups and the phthalocyanine core,
the rest of the dendrimer, and the solvent. The outcome of
these complex ternary interactions differs among the three
compounds. Compared to those in organic solvents, the
lifetimes are substantially shorter in aqueous media, which is
consistent with a more extensive interaction as already
observed in the absorption spectra. It is worth noting that
this process reflects a dynamic quenching of the triplet excited
state, as only the triplet lifetime, and not the signals’ intensity,
is modified.
Generation of singlet oxygen
Photoirradiation of organic dyes often leads to the formation
of singlet oxygen (molecular oxygen in its electronically
excited state O2(a1Dg)) through energy transfer from a
photoexcited dye to molecular oxygen.30 The efficiency of this
process is determined, among others, by the ability of oxygen
to trap the dye’s metastable electronically excited states. As
such, singlet oxygen is an ideal probe for studying the effects
of the dendrimer on the phthalocyanine photophysics,
particularly the extent to which the dendrimer shields the
phthalocyanine from its surroundings. These processes are
best studied by time-resolved near-IR phosphorescence
spectroscopy.31,32
Fig. 3 Time-resolved near-IR phosphorescence measurements at
1140 nm for (A) RuP1, (B) RuP2, and (C) RuP3 in THF, under
(a) argon-saturated atmosphere, (b) air-saturated atmosphere, and
(c) oxygen-saturated atmosphere. Insets: oxygen concentration
dependence of the rate constant for triplet decay, kT. Oxygen
concentrations have been calculated from published solubility data
after correcting for the oxygen partial pressure above the solutions.28
The quenching rate constant kq has been derived from the slope of the
linear fit of the equation kT = 1/tT + kq [O2] to the data points, where
tT is the triplet lifetime in argon-saturated solutions.
Notwithstanding the shielding effect exerted by the
dendrimers, the phthalocyanine phosphorescence can be
quenched by oxygen. The increasing complexity of the
dendrimer core is reflected in the values of the quenching rate
constants (kq, cf. Table 1), which decrease concomitantly,
as already observed by other authors with similar
compounds.25,29,33 In all cases the quenching rate constants
are slightly below the diffusional limit while oxygen quenching
is diffusional for RuPy.23b,34 In addition, formation of singlet
oxygen O2(a1Dg) is unequivocally demonstrated by its
emission at 1270 nm (see ESIw). Basically, as observed in
Table 1, the singlet oxygen quantum yields (FD) are not
affected by the oligoethylene glycol chains. However, the
situation in organic solvents is different than that in D2O,
the dendrimer branches interact with the phthalocyanine
providing an additional deactivation pathway for the excited
states. The rate constants for this process (kD) can be
calculated as kD = 1/tT ꢁ 1/tT(0), where tT(0) = 12 ms is
the triplet lifetime of a ruthenium phthalocyanine axially
coordinated with two pyridyl units.23a–c The values are
collected in Table 1. The decays are more complex in aqueous
media, RuP2 showing the longest phosphorescence lifetime of
Table 1 Photochemical properties of RuP1–3
Compound
Solvent
tTa/ms
kDb/sꢁ1
kqc/Mꢁ1 sꢁ1
FO
t
Df/ms
d
FD
e
2
T
RuP1
RuP1
RuP1g
CHCl3
THF
D2O
1.51 ꢂ 0.01
1.43 ꢂ 0.01
0.80 (0.54)
0.21 (0.46)
1.43 ꢂ 0.01
1.38 ꢂ 0.01
0.75 (0.79)
0.29 (0.21)
1.26 ꢂ 0.01
0.93 ꢂ 0.01
0.30
5.8 ꢃ 105
6.2 ꢃ 105
1.8 ꢃ 106
6.1 ꢃ 105
6.4 ꢃ 105
1.5 ꢃ 106
7.1 ꢃ 105
9.9 ꢃ 105
3.3 ꢃ 106
8.1 ꢃ 108
1.1 ꢃ 109
5.3 ꢃ 108
7.3 ꢃ 108
8.1 ꢃ 108
3.8 ꢃ 108
6.1 ꢃ 108
7.2 ꢃ 108
1.5 ꢃ 108
0.60 ꢂ 0.05
0.60 ꢂ 0.05
0.005 ꢂ 0.003
0.68
0.67
0.02
200 ꢂ 2
20.5 ꢂ 0.5
65.2 ꢂ 0.5
RuP2
RuP2
RuP2
CHCl3
THF
D2O
0.57 ꢂ 0.05
0.60 ꢂ 0.05
0.010 ꢂ 0.005
0.58
0.61
0.05
190 ꢂ 2
20.1 ꢂ 0.5
58.8 ꢂ 0.5
RuP3
RuP3
RuP3
CHCl3
THF
D2O
0.53 ꢂ 0.05
0.50 ꢂ 0.05
0.006 ꢂ 0.003
0.56
0.44
0.04
166 ꢂ 2
20.1 ꢂ 0.5
52.1 ꢂ 0.5
a
b
Lifetime of 1140 nm posphorescence in argon-saturated solutions. Relative amplitudes in parentheses. Rate constant for dendrimer-mediated
c
triplet decay. Rate constant for triplet quenching by oxygen. Error bar 10%. Singlet oxygen quantum yield in air-saturated solutions.
e
d
f
Fraction of phthalocyanine triplet excited states deactivated by oxygen in air-saturated solutions. Error bar 5%. Singlet oxygen lifetime in
g
air-saturated solutions. RuP1 was dissolved in a 0.3 : 99.7 THF : D2O mixture.
c
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where the FD values are roughly two orders of magnitude
smaller. In addition, the FD values of RuP2 and RuP3
increased ca. five-fold upon solvent saturation with oxygen.
shell. In organic solvents, the triplet lifetimes decrease
following the trend RuP1 > RuP2 > RuP3 while the trend
is more complex in aqueous media. The dendrimer does not
isolate the phthalocyanine from oxygen though a noticeable
shielding effect can be observed. Notwithstanding, singlet
oxygen is readily produced in organic solvents, the quantum
yields decreasing by two orders of magnitude in D2O due to
the short lifetime of the triplet state and of the oxygen
quenching rate constants in this solvent. The results disclose
the surprising finding that the engineering of a ruthenium
D2O
These results can be rationalized in the light of eqn (1):
kq½O2ꢄ
FD ¼ FTSD ꢃ
ð1Þ
1
tT
þ kq½O2ꢄ
where FT is the quantum yield for triplet state formation, SD is
the efficiency of energy transfer from the triplet phthalocyanine,
and the quotient yields the fraction of triplets trapped by
oxygen at a given oxygen concentration.31 Thus, trapping of
the phthalocyanine triplets is quantitative in THF for all
compounds, despite their differences in tT and kq (Table 1).
In D2O, the simultaneous decrease of tT, kq and [O2] leads to
1/tT c kq[O2] and the FD values increase proportionally to the
oxygen concentration. In sum, our results reveal a previously
unnoticed opposite effect of the dendritic ligands on the triplet
lifetime of the core macrocycle. On one hand, the dendrimer
shields the phthalocyanine from oxygen, leading to lower
kq values. On the other, the dendrimer interacts with the
phthalocyanine, perturbing its electronic structure, and
quenching its excited states. This effect is strongly solvent
dependent. The combination of structural and solvent effects
has dramatic consequences for the compounds’ ability to
photosensitise the production of singlet oxygen, which can
be almost switched on and off by changing the environment of
the compounds.
phthalocyanine with oligoethylene-terminated Frechet-type
´
dendrimer shells provides a straightforward means to switch
their ability to produce singlet oxygen on and off between
non-polar and polar environments.
Based on these results, the design of further hydrophilic
phthalocyanine dendrimers is currently underway in our labs.
In these attempts, the nature of the centrepiece as well as the
dendritic surrounding will be subject to modification.
Experimental
Materials and methods
Reagents and solvents were purchased as reagent grade and
used without further purification. The synthesis of dendritic
oligoethylene-terminated branches 1–3 has been accomplished
according to literature procedures.20,21 All reactions were
performed in standard glassware under an inert argon atmosphere.
Column chromatography: silica gel 60 (230–400 mesh,
0.040–0.063 mm) from E. Merck. TLC: glass sheets coated
with silica gel 60 F254 from E. Merck; visualization by UV
light. UV/Vis spectra were measured on a Perkin Elmer
Lambda 19 spectrophotometer. NMR spectra were recorded
on Bruker AM 300 (300 MHz) instruments with solvent signal
as reference (Hpc: phthalocyanine protons, Hpy: pyridine
protons, Har: aromatic protons, HPhCN: benzonitrile protons).
Matrix-assisted laser desorption ionization time-of-flight
(MALDI-TOF) mass spectra were obtained in the positive
ion mode from a Applied Biosystem 4700 instrument or a
Bruker Ultraflex III TOFTOF both equipped with a Nd:YAG
laser operating at 355 nm.
With regards to the singlet oxygen lifetime (tD)values, the
results in CHCl3 and D2O indicate that 1O2 is partially
quenched by the dendrimer cage, as deduced from the lower
lifetime values relative to those in neat solvents (240 ms in
CHCl3, 68 ms in D2O, and 20 ms in THF)35 and by the clear
trend observed on passing from RuP1 to RuP3. A similar effect
was observed by Nierengarten et al. in fullerodendrimers.29
Conclusions
Here, we report the convergent synthesis of a new series of
monodisperse ruthenium phthalocyanine-based dendrimers
obtained through axial coordination of pyridine-containing
ligands. All dendrimers comprising triethylene glycol
monomethyl ether end groups show excellent solubility in
common organic solvents. In addition, owing to the increasing
shell of such hydrophilic moieties, the largest dendrimers
are readily soluble in aqueous solution. The encapsulated
photoactive phthalocyanine core moieties have been investigated
by means of photophysics exhibiting a rather broad Q-band
centred at 638 nm. Theoretical calculations have been
conducted to support the idea of suppression of aggregation
as exerted by the dendritic environment. These calculations are
based on conservative estimates of the number of monomers
that can occupy a given volume, and an argument based
on the entropic cost of this random close packing. Further
calculations including the effects of solvent would be useful, as
would experimental tests of our theoretical predictions. All
phthalocyanines are strongly phosphorescent and the triplet
lifetimes are shorter than for the model compound RuPy,
revealing interactions of the phthalocyanine with its dendrimer
Synthesis
Compound 9. DBU (0.5 mL) was added dropwise to a
preheated (140 1C) mixture of 1,3-diiminoisoindoline (8,
250 mg, 1.72 mmol) and RuCl3ꢀ3H2O (113 mg, 0.43 mmol)
in EE (7 mL) under argon. The resulting intense blue coloured
solution was kept at 140 1C for 18 h. After cooling to room
temperature, the solution is poured onto water and the
forming precipitate filtered. The remaining solid is dried at
120 1C for several hours and then transferred into a 100 mL
one-neck flask. Benzonitrile (10 mL) was added and the
solution heated to 100 1C for 5 h. The residual benzonitrile
was eliminated by distillation and the crude mixture purified
by gradient column chromatography on silica gel (CH2Cl2) to
give 9 (118.9 mg, 34%) as intense blue coloured solid which
was collected as first fraction. 1H NMR (300 MHz,
CDCl3): d = 9.30 (m, 8H, Hpc), 7.98 (m, 8H, Hpc), 6.84
c
3390 Phys. Chem. Chem. Phys., 2011, 13, 3385–3393
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(t, J = 8 Hz, 2H, HPhCN), 6.51 (t, J = 8 Hz, 4H, HPhCN), 5.52
(d, J = 8 Hz, 4H, HPhCN).
3.68–3.73 (m, 32H, CH2), 3.60–3.67 (m, 64H, CH2),
3.49–3.54 (m, 32H, CH2), 3.34 (s, 48H, CH3) ppm.
13C NMR (300 MHz, CDCl3): d = 164.3, 160.1, 154.4,
139.1, 138.4, 137.5, 126.1, 107. 5, 106.5, 106.2, 102.0, 101.7,
101.2, 72.0, 70.9, 70.7, 70.6, 70.2, 70.1, 69.7, 67.6, 67.4, 59.1
ppm. MALDI-TOF-MS (dithranol + NaI): m/z (%) calcd.
for C217H314NO80: 4216.8 [M + H]+; found: 4238.1 (100)
[M + Na]+, 4216.2 (4) [M + H]+.
General procedure for the preparation of 5 to 7. EDCI
(2.2 equiv.) was added to a stirred solution of 3,5-pyridinedi-
carboxylic acid (4, 1 equiv.), the dendritic benzylic alcohol of
the respective generation (2.05 equiv.), DMAP (0.2 equiv.) in
CH2Cl2 at 0 1C. After 1 h, the mixture was allowed to slowly
warm to rt and then stirred at this temperature for several days
(5: 1 d, 6: 2 d and 7: 4 d). The arising solid was filtered off, the
solvent evaporated, and the crude product purified as outlined
in the following text.
General procedure for the preparation of RuPy and RuP1–3.
A solution of pyridine or the appropriate dendritic pyridine-
containing ligand (2.1 equiv.) and 9 (1 equiv.) in THF was
heated to 60 1C for a certain time (RuPy: 1 h; RuP1: 7 h; RuP2:
10 h; RuP3: 24 h). The solvent was evaporated to dryness and
the crude mixture purified as outlined in the following text.
Compound 5. Prepared from 1 (615.0 mg, 1.42 mmol) and 4
(115.9 mg, 0.69 mmol). Gradient column chromatography
on silica gel (CH2Cl2 to CH2Cl2/MeOH 15 : 1) and gel
permeation chromatography (Biorad, Biobeads SX-1, CH2Cl2)
yielded 5 (410.0 mg, 85%) as a colourless highly viscous oil.
1H NMR (300 MHz, CDCl3): d = 9.37 (d, J = 2 Hz, 2H,
Compound RuPy. Prepared from pyridine (4.1 mL,
51.3 mmol) and 9 (20.0 mg, 24.4 mmol) in THF (4 mL). Column
chromatography (SiO2, CH2Cl2) yielded RuPy (14.6 mg, 78%)
H
py), 8.88 (t, J = 2 Hz, 1H, Hpy), 6.58 (d, J = 2 Hz, 4H, Har),
1
as a deep blue solid. H NMR (300 MHz, CDCl3): d = 9.12
6.47 (t, J = 2 Hz, 2H, Har), 5.31 (s, 4H, CO2CH2), 4.10
(t, J = 5 Hz, 8H, CH2), 3.83 (t, J = 5 Hz, 8H, CH2), 3.69–3.73
(m, 8H, CH2), 3.61–3.68 (m, 16H, CH2), 3.51–3.55 (m, 8H,
CH2), 3.35 (s, 12H, CH3) ppm. 13C NMR (300 MHz, CDCl3):
d = 164.0, 160.0, 154.2, 138.0, 137.2, 125.8, 106.9, 101.4, 71.8,
70.6, 70.5, 70.4, 69.5, 67.4, 67.1, 58.8 ppm. MALDI-TOF-MS
(dithranol + NaI): m/z (%) calcd. for C49H74NO20: 996.5
[M + H]+; found: 1018.5 (100) [M + Na]+, 996.5 (28)
[M + H]+.
(br m, 8H, Hpc), 7.88 (br m, 8H, Hpc), 6.02 (tt, J = 6 Hz,
J = 2 Hz, 2H, Hpy), 5.23 (t, J = 6 Hz, 4H, Hpy), 3.08 (dd,
J = 6 Hz, J = 2 Hz, 4H, Hpy) ppm.
Compound RuP1. Prepared from 5 (63.7 mg, 64.0 mmol) and
9 (25.0 mg, 30.5 mmol) in THF (20 mL). Gel permeation
chromatography (Biorad, Biobeads SX-1, CH2Cl2) yielded
RuP1 (68.4 mg, 93%) as a deep blue solid. UV/Vis (CHCl3):
l/nm (e/dm3 molꢁ1 cmꢁ1) = 314 (96 340), 450 (10 990),
1
590 (sh, 31 878), 638 (59 060); H NMR (300 MHz, CDCl3):
Compound 6. Prepared from 2 (600.0 mg, 619 mmol) and 4
(50.5 mg, 302 mmol). Gradient column chromatography
on silica gel (CH2Cl2 to CH2Cl2/MeOH 15 : 1) and gel
permeation chromatography (Biorad, Biobeads SX-1,
CH2Cl2) yielded 6 (521.0 mg, 83%) as a colourless highly
d = 9.06 (br m, 8H, Hpc), 7.82 (br m, 8H, Hpc), 7.17 (t, J = 2 Hz,
2H, Hpy), 6.52 (t, J = 2 Hz, 4H, Har), 6.21 (d, J = 2 Hz, 8H,
Har), 4.62 (s, 8H, CO2CH2), 4.06 (t, J = 5 Hz, 16H, CH2), 3.88
(t, J = 5 Hz, 16H, CH2), 3.72–3.77 (m, 16H, CH2), 3.62–3.70
(m, 32H, CH2), 3.50–3.55 (m, 16H, CH2), 3.35 (s, 24H, CH3),
3.08 (d, J = 2 Hz, 4H, Hpy) ppm. 13C NMR (300 MHz,
CDCl3): d = 161.0, 160.2, 154.5, 143.9, 140.6, 136.4, 134.8,
128.3, 125.1, 121.7, 107.6, 101.9, 72.1, 71.0, 70.8, 70.7, 69.9,
67.7, 67.6, 59.2 ppm. MALDI-TOF-MS (DCTB): m/z (%)
1
viscous oil. H NMR (300 MHz, CDCl3): d = 9.38 (br s, 2H,
H
py), 8.91 (br s, 1H, Hpy), 6.65 (d, J = 2 Hz, 4H, Har), 6.57
(m, 10H, Har), 6.43 (t, J = 2 Hz, 4H, Har), 5.33 (s, 4H,
CO2CH2), 4.95 (s, 8H, CH2), 4.10 (t, J = 5 Hz, 16H, CH2),
3.83 (t, J = 5 Hz, 16H, CH2), 3.69–3.74 (m, 16H, CH2),
3.62–3.68 (m, 32H, CH2), 3.51–3.55 (m, 16H, CH2), 3.36
(s, 24H, CH3) ppm. 13C NMR (300 MHz, CDCl3):
d = 164.2, 160.7, 154.3, 138.9, 138.2, 137.4, 107.3, 106.0,
102.0, 101.1, 71.9, 70.8, 70.6, 70.5, 70.0, 69.6, 67.5, 67.3, 58.9
ppm. MALDI-TOF-MS (dithranol + NaI): m/z (%) calcd.
for C105H154NO40: 2070.1 [M + H]+; found: 2092.1 (100)
[M + Na]+, 2070.1 (28) [M + H]+.
calcd. for C130H162N10O40Ru: 2605.0 [M]+ꢅ; found: 2604.9
+
(15) [M]+ꢅ, 1609.5 [M ꢁ 1 ligand] (32).
ꢅ
Compound RuP2. Prepared from 6 (120.0 mg, 58.0 mmol)
and 9 (22.6 mg, 27.6 mmol) in THF (20 mL). Gel permeation
chromatography (Biorad, Biobeads SX-1, CH2Cl2) yielded
RuP2 (118.1 mg, 90%) as a deep blue viscous oil. UV/Vis
(CHCl3): l/nm (e/dm3 molꢁ1 cmꢁ1) = 284 (70 940), 313
(100 420), 450 (9540), 590 (31 960), 638 (61 350); 1H NMR
(300 MHz, CDCl3): d = 9.10 (br m, 8H, Hpc), 7.75 (br m, 8H,
Hpc), 7.18 (t, J = 2 Hz, 2H, Hpy), 6.60 (m, 20H, Har), 6.43
(t, J = 2 Hz, 8H, Har), 6.30 (d, J = 2 Hz, 8H, Har), 4.90
(s, 16H, CH2), 4.64 (s, 8H, CO2CH2), 4.07 (t, J = 5 Hz, 32H,
CH2), 3.79 (t, J = 5 Hz, 32H, CH2), 3.67–3.71 (m, 32H, CH2),
3.60–3.66 (m, 64H, CH2), 3.49–3.53 (m, 32H, CH2), 3.34
(s, 48H, CH3), 3.10 (d, J = 2 Hz, 2H, Hpy) ppm. 13C NMR
(300 MHz, CDCl3): d = 160.9, 160.2, 160.1, 154.4, 143.8,
140.6, 139.1, 136.5, 134.8, 128.2, 125.1, 121.6, 107.7,
106.2, 102.3, 101.3, 72.0, 70.9, 70.7, 70.6, 70.1, 69.7, 67.6,
59.1 ppm. MALDI-TOF-MS (DCTB): m/z (%) calcd. for
Compound 7. Prepared from 3 (200.0 mg, 98 mmol) and 4
(8.0 mg, 48 mmol). Gradient column chromatography on silica
gel (ethyl acetate/acetone 1 : 1 to 1 : 3 to CHCl3/acetone 1 : 1
to 1 : 10) and gel permeation chromatography (Biorad,
Biobeads SX-1, CH2Cl2) yielded 7 (103.5 mg, 51%) as a
colourless highly viscous oil. 1H NMR (300 MHz, CDCl3):
d = 9.36 (d, J = 2 Hz, 2H, Hpy), 8.91 (t, J = 2 Hz, 1H, Hpy),
6.68 (d, J = 2 Hz, 4H, Har), 6.65 (d, J = 2 Hz, 8H, Har),
6.60 (t, J = 2 Hz, 2H, Har), 6.56 (d, J = 2 Hz, 16H, Har), 6.52
(t, J = 2 Hz, 4H, Har), 6.43 (t, J = 2 Hz, 8H, Har), 5.33 (s, 4H,
CO2CH2), 4.96 (s, 8H, CH2), 4.93 (s, 16H, CH2), 4.09
(t, J = 5 Hz, 32H, CH2), 3.81 (t, J = 5 Hz, 32H, CH2),
c
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C242H322N10O80Ru: 4750.1 [M]+ꢅ; found: 4752.4 (2) [M]+
,
ꢅ
Acknowledgements
2683.0 [M ꢁ 1 ligand]+ (100).
ꢅ
Financial support for work by the MEC, Spain (CTQ2008-
00418/BQU and CONSOLIDER-INGENIO 2010 CDS
2007-00010), and CAM (MADRISOLAR-2, S2009/PPQ/
1533) is gratefully acknowledged. U.H. thanks the MEC
Compound RuP3. Prepared from 7 (95.0 mg, 22.5 mmol) and
9 (8.8 mg, 10.7 mmol) in THF (20 mL). Gel permeation
chromatography (Biorad, Biobeads SX-1, CH2Cl2) yielded
RuP3 (86.6 mg, 89%) as a deep blue viscous oil. UV/Vis
(CHCl3): l/nm (e/dm3 molꢁ1 cmꢁ1) = 283 (102 870), 314
(96 470), 450 (9040), 590 (29 130), 638 (58 690); 1H NMR
(300 MHz, CDCl3): d = 9.14 (br m, 8H, Hpc), 7.76 (br m,
8H, Hpc), 7.10 (t, J = 2 Hz, 2H, Hpy), 6.72 (d, J = 2 Hz, 16H,
Har), 6.63 (t, J = 2 Hz, 4H, Har), 6.52 (m, 40H, Har), 6.40
(t, J = 2 Hz, 16H, Har), 6.35 (d, J = 2 Hz, 8H, Har), 4.92
(s, 16H, CH2), 4.98 (s, 32H, CH2), 4.62 (s, 8H, CO2CH2), 4.04
(t, J = 5 Hz, 64H, CH2), 3.78 (t, J = 5 Hz, 64H, CH2),
3.66–3.71 (m, 64H, CH2), 3.59–3.65 (m, 128H, CH2),
3.47–3.53 (m, 64H, CH2), 3.34 (s, 96H, CH3), 3.16
(d, J = 2 Hz, 4H, Hpy) ppm. 13C NMR (300 MHz, CDCl3):
d = 160.9, 160.20, 160.16, 154.3, 151.6, 143.9, 140.6, 139.2,
139.1, 136.6, 135.9, 135.8, 128.4, 125.6, 125.0, 121.7, 107.8,
106.6, 106.2, 102.0, 101.7, 101.2, 72.0, 70.9, 70.7, 70.6, 70.1,
69.7, 68.1, 67.6, 59.1 ppm. MALDI-TOF-MS (DCTB): m/z
(%) calcd. for C466H642N10O160Ru: 9040.2 [M]+ꢅ; found:
(Spain) for a ‘‘Ramon y Cajal’’ research contract.
´
Notes and references
1 E. Buhleier, W. Wehner and F. Vogtle, Synthesis, 1978, 2,
¨
155.
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and Dendrons, Wiley-VCH, Weinheim, 2001; (b) Dendrimers and
other Dendritic Polymers, ed. J. M. J. Fre
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John Wiley & Sons, Chichester, 2001; (c) F. Vo
and N. Werner, Dendrimer Chemistry, WILEY-VCH, Weinheim,
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3 See for example: (a) www.dendritech.com; (b) www.starpharma.
com; (c) www.qiagen.com; (d) www.perstorp.com.
4 (a) Topics in Current Chemistry, Dendrimers V, ed. C. A. Schalley
chet and D. A. Tomalia,
gtle, G. Richardt
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and F. Vogtle, Springer, Heidelberg, 2003, vol. 228, and previous
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Phosphorescence of O2 and RuP1–3 were detected by means
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detail elsewhere.32 Briefly, a diode-pumped pulsed Nd:Yag
laser (FTSS355-Q, Crystal Laser, Berlin, Germany) working
at 10 kHz repetition rate at 532 nm (12 mW, 1.2 mJ per pulse)
was used for excitation. A 1064 nm rugate notch filter
(Edmund Optics, UK) was placed at the exit port of the laser
to remove any residual component of its fundamental emission
in the near-IR region. The luminescence exiting from the side
of the sample was filtered by a cold mirror (CVI Melles Griot,
USA) to remove any scattered laser radiation, and focused on
the entrance slit of a Science Tech 9055 dual grating mono-
chromator. A near-IR sensitive photomultiplier tube assembly
(H9170-45, Hamamatsu Photonics Hamamatsu City, Japan)
was used as a detector at the exit port of the monochromator.
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lifetime values. The O2(a1Dg) quantum yields (FD) were
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signals to those of optically-matched solutions of the
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reference photosensitizers 5,10,15,20-tetraphenylporphine
= 0.62 in benzene,36 assumed to hold in THF;
TPP
(TPP; FD
FD
= 0.50 in CHCl3)37 and 5,10,15,20-tetrakis(4-sulfonato-
TPP
G. Zheng, in The Porphyrin Handbook, ed. K. M. Kadish,
K. M. Smith and R. Guillard, Academic Press, San Diego, 2003,
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TPPS, D2O
phenyl)porphine (TPPS, FD
= 0.64).36 Measurements
were carried out in standard 1 ꢃ 1 cm quartz fluorescence
cuvettes at 295 K. The concentration of the phthalocyanines
was in the range 1–5 mM. The concentration of oxygen in the
solutions was changed by gentle bubbling with solvent-
saturated argon or oxygen for at least 30 min.
c
3392 Phys. Chem. Chem. Phys., 2011, 13, 3385–3393
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15 A. Jime
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