Zilong
Wu
a,
Wenbo
Fang
a,
Chenyu
Wu
b,
Nathaniel
Corrigan
a,
Tong
Zhang
a,
Sihao
Xu
a and
Cyrille
Boyer
*a
aCluster for Advanced Macromolecular Design and Australian Centre for NanoMedicine, School of Chemical Engineering, The University of New South Wales, Sydney, NSW 2052, Australia. E-mail: cboyer@unsw.edu.au
bQingdao Institute for Theoretical and Computational Sciences, Institute of Frontier and Interdisciplinary Science, Shandong University, Qingdao 266237, Shandong, P. R. China
First published on 1st September 2022
We report an aqueous and near-infrared (NIR) light mediated photoinduced reversible addition–fragmentation chain transfer (photo-RAFT) polymerization system using tetrasulfonated zinc phthalocyanine (ZnPcS4−) as a photocatalyst. Owing to the high catalytic efficiency and excellent oxygen tolerance of this system, well-controlled polyacrylamides, polyacrylates, and polymethacrylates were synthesized at fast rates without requiring deoxygenation. Notably, NIR wavelengths possess enhanced light penetration through non-transparent barriers compared to UV and visible light, allowing high polymerization rates through barriers. Using 6.0 mm pig skin as a barrier, the polymerization rate was only reduced from 0.36 to 0.21 h−1, indicating potential for biomedical applications. Furthermore, longer wavelengths (higher λ) can be considered an ideal light source for dispersion photopolymerization, especially for the synthesis of large diameter (d) nanoparticles, as light scattering is proportional to d6/λ4. Therefore, this aqueous photo-RAFT system was applied to photoinduced polymerization-induced self-assembly (photo-PISA), enabling the synthesis of polymeric nanoparticles with various morphologies, including spheres, worms, and vesicles. Taking advantage of high penetration and reduced light scattering of NIR wavelengths, we demonstrate the first syntheses of polymeric nanoparticles with consistent morphologies through thick barriers.
Meanwhile, using aqueous media instead of organic solvents for polymerizations provides economic and environmental benefits, further increasing these systems for bio-applications.50,61–64 However, long-wavelength-mediated aqueous photo-RDRP systems have seldom been reported,17,20,51 due to the typically low solubility of NIR absorbing catalysts in aqueous media. In 2020, Qiao and co-workers developed an aqueous visible- and NIR-mediated photoinduced electron/energy transfer reversible addition–fragmentation chain transfer (PET-RAFT) polymerization process catalyzed by a self-assembled carboxylated porphyrin photocatalyst.51 However, this system suffers from low polymerization rates under NIR irradiation and provided only low monomer conversions without deoxygenation. Recently, the groups of Pan and Pang reported the successful utilization of upconversion nanoparticles as heterogeneous photocatalysts to induce photoinduced atom-transfer radical polymerizations (photo-ATRP) under NIR laser light in aqueous media.17,20 Nevertheless, prior deoxygenation and high-intensity light sources were required in these systems to achieve appreciable monomer conversions.
In this study, aqueous photo-RAFT systems catalyzed by tetrasulfonated zinc phthalocyanine (ZnPcS4−) under NIR light irradiation (λmax = 730 nm) were successfully developed. ZnPcS4− has been used widely as a photosensitizer in photodynamic therapy (PDT) owing to its absorption of extended wavelengths and excellent solubility in water,65–70 however, this is the first example of ZnPcS4− as a PC to mediate photopolymerization. These aqueous systems exhibited excellent oxygen tolerance, providing high polymerization rates and polymers with narrow molecular weight distributions (MWDs). Taking advantage of the enhanced penetration of NIR light, photopolymerizations were performed with non-transparent barriers between the light source and the reaction vessel, resulting in high polymerization rates (0.21–0.34 hour−1) and well-defined polymers (dispersity (Đ) < 1.15). Although photopolymerization through barriers has been demonstrated in previous NIR light mediated RDRP systems,21–23,44–46,51 this is the first aqueous system which displays fast polymerization in the presence of thick barriers and does not require deoxygenation. Aqueous media and excellent oxygen tolerance facilitate the potential application of this NIR system in materials engineering and biomedicine.50,61–64
In addition, the developed polymerization systems are highly suited for aqueous polymerization-induced self-assembly (PISA) as they do not require deoxygenation, which simplifies the synthetic procedure. More importantly, long wavelength (λ) NIR light is an ideal energy source to perform photoinitiated polymerization-induced self-assembly (photo-PISA),71–82 especially for synthesizing large (d) nanoparticles, as light scattering is directly proportional to d6/λ4.83–87 Reduced scattering diminishes light intensity gradients in the reaction media, promoting light penetration in colloidal dispersions, which can favor the production of polymeric nanoparticles with more well-defined morphologies. Photo-RAFT mediated aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) was conducted using a poly(ethylene glycol) (PEG) functionalized RAFT agent as the first stabilizing block. As a result, nanoparticles with various morphologies, including spheres, worms, and vesicles, were successfully synthesized by simply changing the targeted degree of polymerization (DP). Furthermore, polymeric nanoparticles with consistent morphologies were synthesized via photo-PISA through a biological barrier (6.0 mm thick pig skin). To our knowledge, this is the first example of polymeric nanoparticle synthesis through thick barriers using NIR light. Like the barrier-free photo-PISA, we observed a similar evolution of nanoparticle morphologies, i.e., from spheres to vesicles, when a biological barrier was introduced. The successful synthesis of large vesicles (∼200 nm diameter) through thick barriers indicated the high efficiency of this system.
PET-RAFT systems were first tested in the presence of ZnPcS4− as PC. As PET-RAFT polymerization can be carried out under two different quenching pathways, namely an oxidative quenching pathway (OQP, Scheme 2A)43,46,48 and a reductive quenching pathway (RQP, Scheme 2B).39,40 We decided to investigate the efficiency of each pathway in the presence of ZnPcS4− under inert atmosphere. Under the OQP, a modest monomer conversion was noted (9% after 10 hours; Table 1, #1), whereas, under the RQP in the presence of triethanolamine (TEOA), a higher monomer conversion was observed (20% after 3 hours; Table 1, #2). In the absence of ZnPcS4−, both OQP and RQP systems exhibited no monomer conversion (Table 1, #3 and 4). As expected, PET-RAFT polymerization via OQP was completely inert without deoxygenation (Table 1, #5), as radical species were quenched by dissolved oxygen. However, surprisingly in the case of RQP in the presence of air, the monomer conversion reached 65% in 3 hours (Table 1, #6). To confirm this surprising result in the presence of TEOA and air, we performed polymerization kinetics with and without deoxygenation. A much higher apparent propagation rate (kpapp) (0.36 hour−1versus 0.08; ESI, Fig. S2†) was determined when the polymerization was conducted without deoxygenation, which suggests a new reaction pathway in the presence of TEOA and oxygen. Control experiments without deoxygenation demonstrated the need for the presence of ZnPcS4− (Table 1, #7), TEOA (Table 1, #5), and light (Table 1, #8), as negligible monomer conversions were observed in the absence of either species or light irradiation. Furthermore, in the presence of ZnPcS4−, TEOA, and oxygen, the control experiment without RAFT agent displayed a modest monomer conversion (18% after 10 hours), suggesting that initiating species can be formed in the absence of RAFT agent (Table 1, #9). This is in contrast to PET-RAFT polymerization via RQP (i.e., in the presence of ZnPcS4− and TEOA after deoxygenation) where we did not observe monomer conversion in the absence of RAFT agent (Table 1, #10). In the presence of oxygen, photopolymerization displays a different pathway (Table 1, #6 and 9) from PET-RAFT process (Table 1, #2 and 10). Regardless of the conditions employed, PDMA was successfully synthesized in a controlled manner (Table 1, #1, 2, and 6; ESI, Table S1 and Fig. S3†), as indicated by the excellent agreement between theoretical (Mn,theo) and experimental (Mn,GPC) molecular weights, and low dispersity (Đ) determined by gel permeation chromatography (GPC).
Scheme 2 Proposed mechanism of photo-RAFT polymerization catalyzed by ZnPcS4−via three pathways.a Note: a(A) PET-RAFT polymerization via an oxidative quenching pathway (OQP) and (B) a reductive quenching pathway (RQP). (C) Photo-RAFT polymerization via an oxygen-mediated photoinitiation (O-PI) system. Values indicate the Gibbs free energy change (ΔG) of electron transfer reactions in three pathways calculated by DFT (coordinates and energies of PC, RAFT agent, TEOA, and O2 were shown in ESI†). |
# | RAFT agent | PC | Deoxygenation | Reducing agent | Time (hour) | α (%) | k p app (hour−1) | M n,theo (g mol−1) | M n,GPC (g mol−1) | Đ |
---|---|---|---|---|---|---|---|---|---|---|
a Notes: Reactions were performed at room temperature under NIR light (λmax = 730 nm; I = 60 mW cm−2) in water at [DMA]/[water] = 50 (v/v). A fixed reaction stoichiometry of [DMA]:[CTCPA]:[TEOA]:[ZnPcS4−] = 200:1:4:0.01 (50 ppm ZnPcS4− relative to monomer) was used. b Theoretical molecular weight was calculated using the following equation: Mn,theo = [M]0/[RAFT agent]0 × MWM × α + MWRAFT agent, where [M]0, [RAFT agent]0, MWM, α, and MWRAFT agent correspond to initial monomer concentration, initial RAFT agent concentration, molar mass of monomer, monomer conversion determined by 1H NMR, and molar mass of RAFT agent, respectively. c Molecular weight and dispersity (Đ) were determined by GPC analysis (DMAC as eluent) calibrated using PMMA standards. d Reaction was placed in the dark. | ||||||||||
1 | CTCPA | ZnPcS4− | Yes | — | 10 | 9 | 0.01 | 2100 | 2600 | 1.16 |
2 | CTCPA | ZnPcS4− | Yes | TEOA | 3 | 20 | 0.08 | 4300 | 4900 | 1.12 |
3 | CTCPA | — | Yes | — | 10 | 0 | — | — | — | — |
4 | CTCPA | — | Yes | TEOA | 10 | 0 | — | — | — | — |
5 | CTCPA | ZnPcS4− | No | — | 0 | 0 | — | — | — | — |
6 | CTCPA | ZnPcS4− | No | TEOA | 3 | 65 | 0.36 | 13200 | 13000 | 1.09 |
7 | CTCPA | — | No | TEOA | 10 | 0 | — | — | — | — |
8d | CTCPA | ZnPcS4− | No | TEOA | 10 | 0 | — | — | — | — |
9 | — | ZnPcS4− | No | TEOA | 10 | 18 | — | — | 260700 | 2.62 |
10 | — | ZnPcS4− | Yes | TEOA | 10 | 0 | — | — | — | — |
To further investigate the photopolymerization mechanism in the presence of TEOA without deoxygenation, we performed a model reaction in water containing ZnPcS4−, TEOA, and air under light irradiation. 1H NMR spectroscopy was employed to monitor the formation of new species. Interestingly, with increasing irradiation time, we observed the emergence of a new signal at ∼10.3 ppm via1H NMR (Fig. 1C, #2; ESI, Fig. S4B†), which was attributed to the formation of hydrogen peroxide (H2O2). The addition of commercial H2O2 in the reaction medium was carried out resulting in an increased intensity of this signal (ESI, Fig. S4C†), confirming the formation of H2O2. Notably, a faster generation of H2O2 was observed in the presence of a higher concentration of TEOA (Fig. 1C, #3; ESI, Fig. S5†), indicating the crucial role of TEOA in H2O2 formation. In a following experiment, RAFT agent and monomer were added, the signal at 10.3 ppm was also detected (Fig. 1C, #4; ESI, Fig. S6†), showing that RAFT agent or monomer does not interfere with the formation of H2O2. Having established the formation of H2O2, we turned our attention to its role in the initiation of this polymerization. Previous publications examining zinc phthalocyanines for photodynamic therapy demonstrated their capability to photosensitize (hydro)peroxides to generate initiating species under light irradiation (ESI, Fig. S7A†).88,89 To determine if H2O2 can be activated by ZnPcS4−, a small quantity of commercial H2O2 (24.3 mM) was added to the reaction mixture consisting of ZnPcS4−, DMA, and CTCPA in water. Under NIR light exposure, we observed 68% monomer conversion after 2 hours (ESI, Fig. S7B,† green line), which indicated that H2O2 was successfully activated by this system. In the absence of light or ZnPcS4−, no polymerization was observed (ESI, Fig. S7B,† red points).
Intrigued by the formation of H2O2, we decided to investigate the mechanism in detail. First, a series of control experiments were carried out to confirm the role of ZnPcS4−, oxygen and light in the production of H2O2. After deoxygenation, no formation of H2O2 was detected after 3 hours in the presence of ZnPcS4− and TEOA under NIR light irradiation (ESI, Fig. S4E†). Without deoxygenation, similar results were obtained in the absence of ZnPcS4− or light (ESI, Fig. S4D and F†). As reported in previous publications,90,91 H2O2 can be generated from reactive oxygen species (ROS), such as singlet oxygen (1O2) or superoxide (O2˙−). Under light irradiation and in the presence of excited ZnPcS4− (3PC*), oxygen (O2) can be transformed into singlet oxygen (1O2) by triplet–triplet annihilation (TTA; Scheme 2C).92,93 To confirm the formation of 1O2, we performed model experiments in the absence of TEOA and RAFT agents but in the presence of ZnPcS4− and 9,10-dimethylanthracene (9,10-DMA) as 1O2 quencher94 (Fig. 1A, #1; ESI, Scheme S1A†) using water and DMF as the solvent. DMF was used to increase the solubility of 9,10-DMA and replace the monomer in our system. Under irradiation, we observed a decrease of 9,10-DMA signals between 330 and 420 nm (Fig. 1A, #2) due to the formation of endoperoxide (ESI, Scheme S1A†), confirming the generation of 1O2. According to previous reports,95–97 we hypothesized that 1O2 can react with TEOA to yield superoxide (O2˙−) (Scheme 2C, O-PI-I). To confirm this assumption, we performed model reactions where different concentrations of TEOA were gradually added, and we measured the consumption of 9,10-DMA. Interestingly, with an increasing concentration of TEOA, we noted a significantly slower disappearance of the characteristic peaks of 9,10-DMA (at ∼379 nm), suggesting that 1O2 was quenched by TEOA (Fig. 1A, #3 and 4; ESI, Fig. S8†). To confirm that O2˙− was generated from the electron transfer between TEOA and 1O2 (Scheme 2C, O-PI-I), quenching experiments of O2˙− in the presence of nitrotetrazolium blue chloride (NBT) were performed (Fig. 1B, #1). Indeed, NBT reacts with O2˙− (ESI, Scheme S1B†) to yield monoformazan (MF; λmax at ∼525 nm) and diformazan (DF; λmax at ∼740 nm).98 In the absence of TEOA, no absorptions of characteristic MF and DF signals were observed, indicating the absence of O2˙− formation (Fig. 1B, #2). In contrast, two characteristic signals of MF and DF appeared when TEOA was added to the mixture, suggesting O2˙− generation (Fig. 1B, #3). Additionally, a faster increase in absorption of MF and DF was observed when a higher ratio of TEOA was added (Fig. 1B #4; ESI, Fig. S9†), indicating a more efficient generation of O2˙− in this condition which is in accord with the literature.98 Subsequently, the protonation of O2˙− (Scheme 2C, proton transfer) results in the formation of hydroperoxyl radical (HO2˙),99,100 which is regarded as a precursor of H2O2.90,91 The accumulation of H2O2 was confirmed by the presence of a signal at 10.3 ppm determined by 1H NMR analysis (Fig. 1C; ESI, Fig. S5 and S6†).
In addition to experimental evidence, a series of density-functional theory (DFT) calculations were performed to calculate the Gibbs free energy change (ΔG) for the three different reaction pathways (Scheme 2). The reaction step possessing a lower value of ΔG indicates a more favorable electron transfer. ΔG values of each reaction involved with electron transfer are listed in Scheme 2. In this work, PET-RAFT polymerization via RQP is more favorable than OQP, showing lower values of ΔG (11.1 kcal mol−1 for RQP-I and 7.0 kcal mol−1 for RQP-II versus OQP-I = 17.5 kcal mol−1). This is in agreement with the faster polymerization rate measured in PET-RAFT polymerization via RQP than OQP (0.08 hour−1versus 0.01 hour−1 in ESI, Fig. S2†). Furthermore, ΔG of the electron transfer from TEOA to 1O2 in O-PI pathway was calculated as −16.1 kcal mol−1, which is significantly more favorable than the activation steps both in OQP and RQP. This computational result confirms our experimental observation that O-PI displays significantly faster polymerization (ESI, Fig. S2†) than OQP and RQP.
Subsequently, the concentration of PC in this system was optimized (ESI, Fig. S11 and Table S3†). As expected, photopolymerization with 50 ppm ZnPcS4− showed a faster apparent propagation rate (0.36 hour−1; ESI, Fig. S11, green line; Table S3,† #2) than 20 ppm (0.24 hour−1; ESI, Fig. S11, red line; Table S3,† #1). This result can be explained by the faster production of 1O2 at a higher concentration of ZnPcS4−, which favors H2O2 generation and photoinitiation. However, as ZnPcS4− concentration increased further to 100 ppm, the kpapp slightly decreased from 0.36 to 0.33 hour−1 (ESI, Fig. S11, blue line; Table S3,† #3), which can be attributed to limiting light penetration in the system due to the absorption of ZnPcS4−.
To demonstrate the versatility of this PC to activate different RAFT agents, three other RAFT agents, including 4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid (CDTPA), 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT), and 2-(butylthiocarbonothioylthio)propanoic acid (BTPA) (Scheme 1B), were tested in this aqueous system using a relatively high monomer concentration (50 v% (49 wt%)) in water, to enable the solubilization of these RAFT agents. Compared to BTPA-mediated photopolymerization (ESI, Fig. S12, red line; Table S4,† #4), CDTPA and DDMAT (ESI, Fig. S12, orange and blue lines; Table S4,† #2 and 3) displayed faster polymerization rates and better control. This can be attributed to favorable activation of the tertiary R group of CDTPA and DDMAT than the secondary R group of BTPA.43,101,102 Moreover, owing to the better water-solubility of CTCPA than CDTPA and DDMAT, a faster polymerization rate and narrower MWD of synthesized PDMA were also observed in the presence of CTCPA (ESI, Fig. S12A, green line; Table S4,† #1). In summary, the optimal polymerization condition was established using CTCPA as the RAFT agent with [TEOA]:[CTCPA] = 4:1 in the presence of 50 ppm ZnPcS4−.
Temporal control of this aqueous photo-RAFT polymerization was demonstrated (Fig. 2A) by no monomer conversion when the light was turned OFF. Polymerization resumed when the reaction was placed under light irradiation with little change in kpapp (kpappbefore = 0.38 hour−1versus kpappafter = 0.40 hour−1). In the dark condition, H2O2 was not activated by ZnPcS4−, and as a consequence, did not form radicals to initiate the photopolymerization. An excellent agreement between Mn,theo and Mn,GPC and a decreasing Đ from 1.2 to 1.1 were observed during the polymerization (Fig. 2B). Moreover, the MWDs of synthesized PDMA shifted toward higher molecular weight with increasing irradiation time (Fig. 2C), confirming the controlled character of this aqueous photo-RAFT polymerization. To confirm the maintenance of trithiocarbonate at the end of the polymerization, PDMA was successfully chain extended by adding fresh DMA, leading to clear shifts of MWDs of PDMA-b-PDMA (Fig. 2D). Similar results were obtained when poly(oligo(ethylene glycol)methyl ether methacrylate) (POEGMA) was chain extended in the presence of DMA to yield POEGMA-b-PDMA block copolymers (ESI, Fig. S13†). Similar to photopolymerizations performed after deoxygenation (ESI, Fig. S14B†), the high end group fidelity of polymers synthesized in the presence of oxygen was also confirmed by 1H NMR spectroscopy (ESI, Fig. S14A†). Signals at 5.1 ppm attributed to the CH adjacent to the trithiocarbonate on the R-group side remained in a similar ratio to the CH3 protons from the n-butyl Z-group under both deoxygenated and non-deoxygenated conditions. Subsequently, the degrees of polymerization (DPs) varied from 100 to 800 (ESI, Table S5 and Fig. S15†), resulting in the preparation of PDMA with narrow and symmetric MWDs (Đ < 1.2). To investigate the versatility of this system toward various monomers, we decided to expand the family and type of water-soluble monomers (ESI, Table S6 and Fig. S16†). In the presence of ZnPcS4−, TEOA and CTCPA, N,N-diethylacrylamide (DEA), 2-hydroxyethyl acrylate (HEA), oligo(ethylene glycol)methyl ether acrylate (OEGA, Mn = 300 g mol−1), and oligo(ethylene glycol)methyl ether methacrylate (OEGMA, Mn = 480 g mol−1) were successfully polymerized in a controlled manner (Đ < 1.35) under NIR light irradiation without requiring prior deoxygenation.
To emphasize the enhanced penetration of NIR light through non-transparent barriers compared to visible light (400–700 nm), the light intensity of various wavelengths (violet light, λmax = 405 nm; green light, λmax = 530 nm; NIR light λmax = 730 nm) were measured before and after passing through barriers with different thicknesses (Fig. 3A). Through 3.0 mm pig skin, the light intensity (I) of violet light decreased to 0.2% of the initial value (I0). While green light was less attenuated than violet light, the light intensity still dropped to only 1.7% of the original I0 value after passing through 3.0 mm pig skin. In contrast to the limited light penetration of these shorter wavelengths, 730 nm light was able to penetrate through the barriers in appreciable quantities, with 30.7% and 14.7% of the initial light passing through 3.0 and 6.0 mm pig skin, respectively.
To compare the photopolymerization performance between the visible light mediated system and the NIR light mediated system through barriers, zinc meso-tetra(N-methyl-4-pyridyl) porphine tetrachloride (ZnTMPyP; Fig. S20†) was employed as a model PC owing to its water solubility and broad absorption in visible regions50 (ESI, Table S8 and Fig. S21†). Under violet (λmax = 405 nm) and green (λmax = 530 nm) light irradiation and in the absence of barriers, photo-RAFT polymerization catalyzed by ZnTMPyP displayed significantly fast polymerization rates (Fig. 3B and C, 6.30 h−1 under violet light and 0.93 h−1 under green light), which is much faster than NIR light system (0.36 h−1) under similar light intensities (Iviolet = 45 mW cm−2; Igreen = 72 mW cm−2; INIR = 60 mW cm−2). However, in the presence of 3.0 mm pig skin as the barrier, polymerization under violet light showed no monomer conversion after 3 hours (Fig. 3B). Meanwhile, a very long induction period (2 hours) and a slow polymerization rate (0.07 h−1) were noted when green light was employed (Fig. 3C). In contrast to violet and green light systems, photo-RAFT mediated by NIR light under NIR showed a slight decrease in kpapp from 0.36 to 0.27 h−1 (Fig. 3D) when a 3 mm pig skin was introduced.
In this work, PEG113-CDTPA macromolecular RAFT agent was used as the first stabilizing block, and the chains were extended in the presence of hydroxypropyl methacrylate (HPMA) as the core-forming monomer in this aqueous photo-RAFT dispersion polymerization (Scheme 1B and Fig. 4A). Optimization experiments with various ratios of TEOA (ESI, Table S9†) were conducted using a 20 wt% solids content of HPMA in water with 1 mL reaction volume in a 2 mL glass vial under NIR light irradiation without prior deoxygenation. Interestingly, in contrast to homogenous polymerization showing good efficiency at [TEOA]:[CTCPA] = 2 (ESI, Table S2,† #2: 53% monomer conversion in 3 hours), a limited monomer conversion (8% monomer conversion in 24 hours) was observed in dispersion photopolymerization using this ratio (ESI, Table S9† #2). This was attributed to the lower monomer content used in dispersion polymerization in contrast to homogenous polymerization (20 wt% versus 50 v% (49 wt%)). As [TEOA]:[PEG113-CDTPA] increased further to 4:1, monomer conversion reached 99% in 24 hours as indicated by 1H NMR spectroscopy (ESI, Fig. S22†). GPC analysis confirmed successful chain extension of PEG113-CDTPA and the preparation of narrow molecular weight diblock copolymers (ESI, Fig. S23†).
Subsequently, the kinetics study of ZnPcS4− mediated photo-RAFT dispersion polymerization of HPMA were investigated at a reaction stoichiometry of [HPMA]:[PEG113-CDTPA]:[TEOA]:[ZnPcS4−] = 350:1:4:0.02 at 20 wt% solids content. As expected, photo-RAFT dispersion polymerization was successfully catalyzed by ZnPcS4− without requiring prior deoxygenation under 730 nm light irradiation, although a short inhibition period of 1 hour was observed (Fig. 4A). As reported previously,49,50,64 we noted two different regimes: a low kpapp (0.072 hour−1) at the starting of the dispersion polymerization (Fig. 4B, 0–4 h), followed by an acceleration of kpapp (1.003 hour−1) which was attributed to the formation of nanoparticles (micellization). To confirm this assumption, transmission electron microscopy (TEM) was performed at different time points (t = 5, 6, and 7 hours). At t = 5 hours, the early stage of the micellization was confirmed by the presence of spherical nanoparticles with ∼20 nm diameter and short worms (Fig. 4E). As the photopolymerization continued, the morphologies of nanoparticles evolved from a mixture of spheres and worms to worms and vesicles (Fig. 4F). At the final point of the kinetics (92% monomer conversion at t = 7 hours), pure vesicles with ∼250 nm diameter were observed (Fig. 4G). This evolution in morphology was supported by the apparent change from a transparent solution to a cloudy (milky) solution (Fig. 4E–G, photos at right bottom). In addition, the size distribution of these particles increased with higher monomer conversions, as indicated by dynamic light scattering (DLS) analyses (ESI, Table S10 and Fig. S24†). Moreover, this aqueous dispersion polymerization was performed in a controlled manner, as indicated by the analysis of the diblock copolymers by GPC (Fig. 4C and D). We observed a good agreement between Mn,GPC and Mn,theo and relatively low MWD (Đ < 1.4). Concerning Đ, a decrease was observed first from 1.27 to 1.14 before the micellization (Fig. 4C), which can be attributed to the photoactivation of PEG113-CDTPA macroRAFT agent to PEG113-b-PHPMA with increasing irradiation time as indicated by GPC analyses (Fig. 4D: 0, 2, 4, and 5 hours). After that, Đ increased gradually from 1.14 to 1.36 in the phase of dispersion polymerization (Fig. 4C, last three red triangle points). In addition, a clear shift of MWDs towards higher molecular weight with increasing reaction time was observed (Fig. 4D) in this photo-PISA system, indicating the living characters of synthesized polymers.
The evolution of the morphology was also studied at 10 and 15 wt% solids concentration by varying DPs from 100 to 400. A phase diagram was plotted, reflecting the morphologies of these nanoparticles versus various DPs and solids content (Fig. 6A). At 10 wt% solids content, although the morphologies of synthesized PEG113-b-PHPMA did not show any transformation with increasing DPs, we observed an apparent increase of spherical nanoparticle sizes from ∼25 nm at 100 DP to ∼56 nm at 400 DP (Fig. 6B, bottom row). In contrast to 10 wt%, the change in morphology at 15 wt% solids concentration was similar to 20 wt%, evolving from S/W to V with increasing DPs. On the other hand, there are size differences of synthesized nanoparticles between 15 wt% (Fig. 6B, top row) and 20 wt% (Fig. 5C), which can be easily observed in TEM and DLS analyses (ESI, Table S13 and Fig. S28†). For an example of 400 DP, the diameter of synthesized vesicles at 15 wt% was ∼200 nm, while at 20 wt% solids concentration, the size was ∼400 nm. Overall, a phase diagram was successfully plotted in this photo-PISA system (Fig. 6A), facilitating the nanoparticle synthesis with specific morphologies and sizes under NIR light irradiation. Furthermore, PEG113-b-PHPMA copolymers forming the nanoparticles displayed narrow MWDs (ESI, Fig. S26 and S27†) and a good correlation between Mn,GPC and Mn,theo (ESI, Tables S11 and S12†).
Fig. 6 (A) Phase diagram of photo-PISA synthesized by ZnPcS4− mediated dispersion photopolymerization of HPMA. Polymerizations were conducted under the irradiation of 730 nm light (I = 60 mW cm−2) for 24 hours without prior deoxygenation in water at fixed reaction stoichiometries of [PEG113-CDTPA]:[TEOA]:[ZnPcS4−] 1:4:0.02. (B) TEM images of synthesized polymeric nanoparticles at 10 and 15 wt% solids content (note: TEM images at 20 wt% were presented in Fig. 5C). |
Footnote |
† Electronic supplementary information (ESI) available: UV-vis spectrum of zinc tetrasulfonated phthalocyanine (ZnPcS4−), kinetics of photopolymerization, 1H NMR spectra of polymers, molecular weight distributions determined by GPC, DLS derived intensity-based size distributions of polymeric nanoparticles prepared by PISA (Fig. S1–S29, Tables S1–S13), experiments of trapping ROS (Scheme S1), and DFT calculations. See https://doi.org/10.1039/d2sc03952d |
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