On-demand acid-gated fluorescence switch-on in photo-generated nanospheres

Article abstract of DOI:10.1039/d0cc01557a

Herein, we introduce a fast, additive-free, ambient temperature photochemical approach - utilising the novel Diels-Alder cycloaddition of a photo-activeortho-methylbenzaldehyde (oMBA) with a terminal alkyne - for preparing functional acid-sensitive proflu

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DOI: 10.1039/D0CC01557A
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On-Demand Acid-Gated Fluorescence Switch-On in Photo-
Generated Nanospheres
a
a b
a
c
a
Jordan P. Hooker, Florian Feist, Laura Delafresnaye, Federica Cavalli, Leonie Barner* and
Christopher Barner-Kowollik*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Herein, we introduce a fast, additive-free, ambient temperature temperatures, radical reactions, additives, extended reaction
photochemical approach
utilising the novel Diels-Alder times and restricted functionality certainly become
cycloaddition of a photo-active ortho-methylbenzaldehyde (oMBA) limiting.
with an asymmetric alkyne – for preparing functional acid-sensitive Importantly, new synthetic methods for polymer particle
–
–
6,16,17
profluorescent nano-/micro-spheres in one step. Never previously synthesis with advantages over classical methods have
reported, the possibility of applying such a reaction in the context developed into powerful tools in both research and industry.
of particle synthesis provides new possibilities for particle design, Some important examples include polymerisation-induced self-
where multi-step reactivity can be gated into distinct steps. First, a assembly (PISA) – utilising the power of modern reversible-
photochemically-gated particle formation step yields a material deactivation radical polymerisation techniques – and the
possessing a reactive, spring-loaded intermediate at every cross- extensive development of particle synthesis via thiol-ene step-
linking point. A second, on-demand step to initiate fluorescence growth polymerisation into functional particles with complex
1
8-24
generation subsequently imparts the novel properties of the backbone structures.
chemical transformation to the material itself. The synthesised Synthetic photochemistry is key developmental strategy,
particles are narrow-disperse with an average diameter ranging and a powerful enabling technology for the construction of
from 170 – 380 nm.
advanced (macro)-molecular architectures. One recently
reviewed aspect of this is its ability to achieve precise
spatiotemporal control over a chemical reaction, potentially
Polymer particles are an important and ubiquitous class of
materials possessing an array of characteristics attracting wide-
ranging application and continuous development.
25
opening the door to a plethora of applications. Indeed,
1
-6
Such
although light has been extensively employed for the
fabrication of sophisticated materials, the use of modern
synthetic photo-reactions in particle synthesis has largely
remained unexplored. Particularly noting the difficulty of
translating new chemistries to particle synthesis, we have
recently highlighted the potential of utilising such reactions by
developing a new platform for particle synthesis. Specifically,
we reported how well-defined polymers functionalised with
photo-active moieties (tetrazole or oMBA) were rapidly cross-
linked into functional microspheres at ambient temperature
under UV (λ = 320 nm) or visible (λ = 415 nm) irradiation without
applications include toners, chromatography, instrument
calibration, photonic crystals, coatings and composite
7-10
materials.
More specifically, fluorescent nano- and
microspheres have been developed as powerful biochemical
and medicinal tools, for instance in in vivo imaging, for drug
delivery, biological tracers and flow cytometry.1
such broad application obviously necessitates control over the
properties of these particles. Considering this, traditional
methods of particle synthesis – often requiring elevated
1-15
However,
2
6,27
the need for stabilisers, bases or initiators.
Further, control
a.Centre for Materials Science, School of Chemistry and Physics, Institute for Future
Environments, Queensland University of Technology (QUT), 2 George Street, QLD
over the concentration, solvent combination and irradiation
intensity led to a broad and tunabe size range (0.2 – 5 μm).
Importantly, the novel properties of the resulting moieties were
translated to the particles, for instance to prepare inherently
fluorescent particles, multi-functional particles with useful
acrylate and hydroxyl groups for further functionalisation, and
even a novel visible-light [4+4] cycloaddition facilitating a single
polymer system.
4
000, Brisbane, Australia. Email: christopher.barnerkowollik@qut.edu.au;
leonie.barner@qut.edu.au
Max Planck Institute for Polymer Research, Ackermannweg 10, Mainz 55128,
Germany.
Macromolecular Architectures, Institut für Technische Chemie und
Polymerchemie, Karlsruhe Institute of Technology (KIT), Engesserstr. 18, 76131
Karlsruhe, Germany.
b.
c.
†
Electronic Supplementary Information (ESI) available: Experimental details,
characterisation methods and supplemental data is included
DOI: 10.1039/x0xx00000x
.
See
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DOI: 10.1039/D0CC01557A
1
A
B
Cross-linking
Re-aromatisation
Scheme 1. (A) Preparation of cross-linkable polymers via functionalisation with oMBA 1 and propiolic acid. (B) Synthesis of fluorescent particles from functionalised cross-linkable
polymer precursors P2 and P3.
Of interest due to their unprecedented reactivity and as nucleation begins to generate higher local concentrations of
orthogonality, light-driven reactions of oMBAs and o- photoreactive moieties, which is particularly important in
methylbenzophenones have been extensively developed over stabiliser-free methods of particle synthesis, where the
the past decades, although previously never for use in particle nucleation phase is highly sensitive and adverse events can lead
2
5,28,29
synthesis.
Furthermore, although a select few examples to loss of colloidal stability.
First, a well-defined, low molecular weight poly(styrene-co-
report the reaction of photochemically generated o-
quinodimethanes (oQDM) with electron-deficient alkynes, the chloromethylstyrene) p(St-co-CMS) copolymer P1 was
use of either an asymmetric or terminal alkyne has never been synthesised using nitroxide mediated polymerisation (NMP).
reported. More importantly, the subsequent E1-elimination The percentage of functional monomer (32%) and average
-1
1
(
n
dehydration) of the generated 1,4-dihydronaphthalen-1-ol to molecular weight (M ) (2100 g mol ) were determined by H
the naphthalene was either overlooked or required undesirable NMR and size exclusion chromatography (SEC), respectively
conditions such as elevated temperatures, extended reaction (Fig. S7 – S8, ESI†). These values were calculated to correspond
3
0-35
times in combination with low yields and side products.
Unfortunately, despite significant application potential, these 6, ESI†). Subsequent functionalisation with oMBA (
factors have thus far limited the reaction from realizing any commercially available propiolic acid yielded p(St-co-oMBA) P2
to approximately 5 functional units per polymer chain (Section
3
, ESI†) and
-1
utility in materials synthesis and applications, such as in (2800 g mol , Fig. S10 ESI†) and p(St-co-propiolate) P3 (1600 g
-1
photoinduced macromolecular ligation.
mol , Fig. S12 ESI†), respectively. For copolymer P3, molecular
Herein, we report a method for the synthesis of nano- and weights determined via SEC were found to be shifted to lower
micro-spheres using a novel Diels-Alder cycloaddition involving molecular weights, presumably due to either chemical
the reaction of an oMBA with an asymmetric terminal alkyne, interaction of the attached alkyne with the column material, or
yielding an acid-triggered re-aromatisation to a fluorescent
naphthalene (Scheme 1). Re-aromatisation is achieved via the
generation of a highly sensitive hydroxyl containing 1,4-
dihydronaphthalene moiety at each cross-linking point, which
Table 1 Synthesis of nano- and micro-spheres from functional prepolymers P2 and P3
where C represents the combined polymer concentration (P2 and P3), D represents the
n
upon exposure to acid, subsequently undergoes a rapid E-1
elimination and dehydration to yield a fluorescent naphthalene
moiety. Moreover, the catalytic nature of the re-aromatisation
makes the particles highly sensitive to even very low
concentrations of acid. Importantly, the intermediate is non-
fluorescent and does not absorb light at the employed
wavelength (λ = 365 nm) (Fig. S6, ESI†). The advantages of this
are two-fold: first, a post-synthesis, acid-gated generation of
fluorescence brings novel and interesting properties for use and
application. Second, fluorescent species can absorb photons
during a reaction, which can lead to undesirable side reactions,
reduced reaction rates and less overall control. Thus, this lack
of initial fluorescence ensures that the reaction is not hindered
number average particle diameter, D
Ð represents particle dispersity (D /D
w
represents the weight-average particle diameter,
) and σ represents the standard deviation
w
n
a
a
C
ACN:THF
[%]
D
n
D
w
Ð
σ
-
1
[
mg mL ]
[μm]
[μm]
[D
w
/D
n
]
[μm]
2
3
3
3
100:0
90:10
80:20
70:30
0.172
0.304
0.384
0.236
0.177
0.314
0.409
0.335
1.03
1.03
1.07
1.42
0.02
0.03
0.06
0.09
a
Determined by SEM.
2
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Fig. 1 Analysis of particles resulting from reactions of P(St-co-photoenol) P2 and P(St-co-propiolate) P3 (A) SEM image of particles from 100:0 ACN:THF; (B) SEM image of particles
from 90:10 ACN:THF; (C) DLS of particles from 90:10 ACN:THF, swollen in THF. Scale bars are 1 μm and 5 μm, respectively.
a decrease in hydrodynamic volume in the SEC solvent measured at ten minute intervals both before and after addition
(
tetrahydrofuran -THF) after functionalisation.
of acid (Fig. 2a). Initially, a small amount of fluorescence was
Given that the rate of particle formation in this case would observed, probably from re-aromatisation during the initial
be expected to correlate with the reactivity of the photo-active reaction. However, in the absence of acid (while still open to
moiety employed as a cross-linker, the high quantum efficiency air), only a negligible increase in fluorescence was observed
of the employed oMBA (P2) facilitates fast reaction times. over the next 3 h, confirming the stability of the non-fluorescent
Particle synthesis reactions were performed with 1:1 mass dihydronaphthalene moiety in the absence of acid. Upon
ratios of P2 and P3 dissolved in varying ratios of acetonitrile subsequent addition of a catalytic amount of p-toluenesulfonic
(
ACN):tetrahydrofuran (THF) (Table 1; Fig. S13, ESI†), without acid, fluorescence increased greater than four-fold over the
need for stabilisers, bases or initiators. Upon irradiation (λmax
next hour, and almost ten-fold over the next 12 h. Given that
65 nm), nucleation began almost instantly, and colloidally nucleation leads to high local concentrations of photo-active
=
3
stable, spherical, narrow-disperse particles could be yielded in moieties, and the aforementioned disadvantages of having
only 2 h as supported by scanning electron microscopy (SEM)
analyses (Fig. 1a and b). Subsequent particle counting showed
n
average diameters (D ) ranging from 170 nm up to 380 nm and
a narrow size dispersity (Đ) from 1.03 – 1.07 for solvent systems
containing up to 20% THF. Dynamic light scattering (DLS)
additionally showed a narrow size-dispersity, although with a
slightly larger D (compared to SEM) due to the swellability of
n
the particles in THF.
Precipitation polymerisation – being a stabiliser-free
method of particle synthesis – necessitates lower loading
concentrations compared to other methods. However, another
strategy for tuning particle size is the addition of a solvent which
solubilises the growing nuclei. Thus, by increasing the ratio of
THF, nucleation is expected to be delayed, with more cross-
linking and aggregation occurring prior to precipitation, leading
to fewer and larger growing nuclei. Although small size
increases are observed in reactions containing up to 20% THF,
increasing to 30% THF lead to a comparatively polydisperse
sample, with particle diameters ranging from below 200 nm and
up to 500 nm (Fig. S13, ESI†). Traditionally, precipitation
polymerisation proceeds via an initial nucleation phase,
followed by a growth phase. In our case, it appears that nuclei
continue to form even after this initial nucleation phase, leading
to polydisperse particles.
Next, the generation of the fluorescent naphthalene adduct
was analysed. The excitation (λmax = 350 nm) and emission (λmax
Fig. 2. Analysis of the fluorescent properties of the particles (A) kinetic analysis of the
fluorescence generation before and after addition of acid, where the black line
represents the fluorescence at 400 nm, before and after addition of acid; (B) particles
after addition of acid, observed under ambient light (left) and under 365 nm light (right).
=
400 nm) spectra of the particles were measured via
fluorescence spectroscopy (Fig. S14, ESI†). In order to explore
the control over the catalytic elimination, fluorescence was
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