Xiyang
Zhang‡
a,
Chaobin
Pang‡
a,
Xiaolu
Wang
a,
Shuyan
Zhang
a,
Lei
Zhang
*a,
Wei
Ji
a,
Ling
Huang
a,
Yantong
Li
b and
Su
Jing
*a
aSchool of Chemistry and Molecular Engineering, Nanjing Tech University, 30 South Puzhu Road, Nanjing 211816, Jiangsu, China. E-mail: ias_lzhang@njtech.edu.cn; sjing@njtech.edu.cn
b2011 college, Nanjing Tech University, 30 South Puzhu Road, Nanjing 211816, Jiangsu, China
First published on 25th July 2024
The iron-based Fenton chemistry has been used as the radical initiator in reversible addition–fragmentation chain-transfer (RAFT) polymerization. However, its practical application in polymeric materials science has been restricted due to the unmodified nature of inorganic iron and its non-functional properties. To address this, we introduce a strategy termed ferrocene-directed photo-Fenton RAFT polymerization, abbreviated as Fc-PF-RAFT, which combines visible light-controlled ferrocene-based Fenton chemistry as the initiator with the upgradation of RAFT polymerization, enabling the exploration of polymers with unique properties and structures. For demonstration, we employed ferrocenyl compounds Fc1–Fc3 in the Fc-PF-RAFT polymerization of N,N-dimethylacrylamide (DMA) in an open aqueous system. The ferrocene-directed photo-Fenton reaction facilitated the generation of dual radicals Fc-COO˙ and ˙OH, initiating well-controlled RAFT polymers with distinct end-group functionalization types: Fc-, OH-, and carboxylic acid group derived from the RAFT agent. By adjusting the role of Fc-ended functionalization in polymer evolution, we fine-tuned self-assembled morphologies, ranging from simple spherical micelles to crosslinked clusters. Notably, the selenium (Se)-containing Fc3-end group polymer underwent self-assembly driven by Se⋯N noncovalent interactions, along with phenyl and cyclopentadienyl π–π interactions, leading to the formation of hierarchical structures. As Fc3-ended functionalization increased, the driving force for self-assembly transitioned from noncovalent interactions to crystallization, as evidenced by the growth from a polymeric DMA-based corona to an Fc3-based core. This study demonstrates the impact of incorporating ferrocene into the Fenton reaction for radical generation, thereby enhancing the versatility and effectiveness of RAFT polymerization. The resulting Fc-PF-RAFT technique provides a transformative platform for the creation of advanced materials with tailored properties and structures.
The Fenton-RAFT polymerization strategy, introduced by Qiao et al. in 2017,19 utilizes highly reactive hydroxyl radicals (˙OH) generated from the traditional Fenton reaction of free Fe2+ ions and hydrogen peroxide (H2O2) as the initiator. The approach involves an automated/programmable polymerization method that utilizes sequenced reagent injections, operates under benign reaction conditions (room temperature, aqueous solvent, air tolerance), and is compatible with a range of monomers for constructing polymers.20–22 A survey of the literature reveals that most Fenton-RAFT polymerization studies rely on free metal ions, e.g., Fe2+, as the Fenton reagent, which presents challenges in the purification and isolation of Fe2+/Fe3+ ions and limitations in chemically modifying inorganic salts to fabricate higher-order assembly structures. To address these challenges, our research introduces organometallic compounds, specifically focusing on ferrocenyl derivatives as proof of concept, to provide additional functions beyond inducing polymerization while minimizing energy requirements and reducing the occurrence of side reactions in the formation of self-assembled hierarchical structures. Our ultimate goal is to develop a general organometallic-dominant photo-RAFT polymerization approach for creating functional materials with tailored properties.
Ferrocenyl compounds have been demonstrated to effectively generate ˙OH through photo-promoted Fenton chemistry.23 Leveraging the reversible redox properties of the ferrocene unit, our group has been dedicated to incorporating ferrocenyl compounds into nanocomposites for photo-Fenton-based therapy of tumors.24–26 Notably, organometallic ferrocene has been identified as a rigid template for self-assembly into ordered structures, as demonstrated in the pioneering work by Manners and co-workers.27–30 Moreover, poly(ferrocenyldimethylsilane) was shown to undergo living crystallization-driven self-assembly,31 leading to the formation of cylindrical supermicelles. The above work served as inspiration for the rational design of ferrocenyl compounds as promising candidates for photo-RAFT polymerization and subsequent self-assembly to achieve hierarchical structures. The design offers manifold advantages stemming from the benefits of synergistic controlled polymerization and morphology regulation, which have been challenging to achieve through conventional RAFT polymerization methods. As shown in Scheme 1 and S1,† we explored ferrocene derivatives with distinct structural modifications, including ferrocenylcarboxylic acid (Fc1), ferrocenylseleno propane carboxylic acid (Fc2), and ferrocenylseleno benzyl carboxylic acid (Fc3). The UV–visible absorption spectra of Fc1–Fc3 demonstrated a notable capability for efficient absorption of visible light (Fig. S1†). Upon irradiation with blue light and in the presence of H2O2, these ferrocenylcarboxylic derivatives facilitated the generation of FcCOO˙ and ˙OH radicals (Fig. 1 and S2†). This initiated a well-controlled RAFT polymerization of the N,N-dimethylacrylamide (DMA) monomer in an aqueous environment. The process led to the synthesis of polymers with three distinct end-group functionalizations: a carboxylic acid end-group from the RAFT agent, a hydroxyl end-group resulting from HO˙—commonly seen in iron Fenton-RAFT polymerization—and, more importantly, an Fc-end group, unique to polymerization initiated exclusively by our Fc-PF-RAFT strategy. The introduction of selenium (Se)-containing Fc2 and Fc3 compounds into the system further enriched the functionalities of the Fc-end polymers and facilitated their self-assembly process, resulting in the formation of hierarchical architectures. The aqueous Fc-PF-RAFT approach described in this study offers significant potential for the fabrication of polymer architectures featuring robust ferrocene-end group functionalization.
To assess the controllable chain-end livingness of our synthetic polymers, we evaluated the chain extension process utilizing PDMA with DP values of 50 (PDMA50) and 100 (PDMA100) as macro-RAFT agents. Given the symmetrical nature of the RAFT agent, the trithiocarbonate (TTC) group should be embedded at the mid-chain position of the resulting PDMA polymers. GPC chromatogram displayed a clear shift toward higher molecular-weight species (Fig. 1C), indicating successful chain extension. Specially, the symmetrical peak shape and minimal tailing toward lower molecular–weight species suggested high chain-end fidelity or vitality of the synthesized PDMA, enabling facile formation of multiblock copolymer structures. These results demonstrate the effectiveness of the chain extension process and highlight the potential for creating complex polymer architectures with chain-end functionality.
MALDI-TOF spectral analysis was further employed to demonstrate the structural fidelity of the synthesized RAFT polymers, revealing a multimodal peak series for PDMA100 (Fig. 1D and Fig. S4†) representing predictable polymer structures ranging from 2000 to 8000 Da. In the magnified mass spectrum of PDMA100, the main peaks labeled with “●” were assigned to PDMA products containing two hydroxyl end groups directly initiated by ˙OH. These peaks were observed with adjacent main peaks separated by the exact mass of the DMA repeating unit (99.13 g mol−1). The peak series labeled with “★” corresponded to PDMA products containing two ferrocenyl ester groups, confirming the end-group functionalization by the ferrocene unit. Additionally, some subpeaks labeled with “▲” corresponded to PDMA products with two carboxylic acid end groups derived from the bis-TTC RAFT agent. Further subpeaks (labeled “■”) corresponded to Na+ complexes of the “▲” PDMA products. Notably, all products retained the thiocarbonylthio moiety, indicating the high livingness of the polymer chains, which was consistent with the results obtained from the chain extension experiments shown in Fig. 1C. The content of Fc1-end PDMA in the three types of end-functionalized polymers was estimated by a quantitative analysis of iron performed using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). The approximately 4.8% content demonstrated the presence of Fc1-end group functionalized polymers.
The above NMR and MALDI analyses confirmed that, following Fc-PF-RAFT polymerization, ferrocene was not present in its free form; instead, it was functionalized onto the polymer end groups. To further investigate the initiation mechanism of Fc-PF-RAFT polymerization, spin-trapping EPR experiments were further conducted on our systems using 5,5′-dimethyl-1-pyrrololine-N-oxide (DMPO) as the trapping agent. As depicted in Fig. 1E, when H2O2 under irradiation was analyzed by itself with DMPO, it produced a characteristic EPR signal for the DMPO-˙OH adduct. The intensity ratio of 1:
2
:
2
:
1 (Fig. 1E, blue line), refers to the relative intensities of the peaks in the EPR spectrum, which is typical for the DMPO-˙OH adduct in an iron-based Fenton system.32 The Fc1 + H2O2 photo-Fenton system resulted in a more complex EPR signal (Fig. 1E, grey line). The intensity ratio of 1
:
2
:
1
:
2
:
1
:
2
:
1 suggests a different interaction or possibly multiple radical species being trapped by DMPO. The oxidation of Fc1 with H2O2 involves an intramolecular electron transfer mechanism, resulting in the formation of ferrocenyl radicals.33,34 Additionally, O–H hydrogen atom transfer of a carboxylic acid can yield a carboxyl radical.35 The presence of different radical species or interactions in ferrocene-directed photo-Fenton initiation alters the resultant EPR spectrum compared to when H2O2 was used alone. Based on these findings, we propose that in the current photo-Fenton reaction, the oxidized Fc1, in combination with H2O2 under light irradiation, may undergo an intramolecular process, generating both FcCOO˙ and ˙OH radicals. When the RAFT reagent was introduced, only DMPO-˙OH signal peaks were observed in the Fc1 + H2O2 + bis-TTC system, with a typical intensity ratio of 1
:
2
:
2
:
1 (Fig. 1E, yellow line), indicating that FcCOO˙ radicals were likely consumed in reaction with bis-TTC. However, in the absence of the RAFT agent, the Fc1 + H2O2 + DMA system (Fig. 1E, red line) did not exhibit characteristic peaks analogous to those of the Fc1 + H2O2 system (Fig. 1E, blue line), suggesting that the FcCOO˙ and ˙OH radicals are likely acting as initiators to start a radical polymerization reaction with the DMA monomer. When these radicals reacted with the DMA monomer, they can transfer their own radical nature to the monomer, creating a carbon-centered radical.36 This radical could then propagate the polymerization process by reacting with other monomer molecules, forming polymer chains. Mass spectrometry analysis further demonstrated that both FcCOO˙ and ˙OH radicals undergo radical addition to DMA monomer independently of RAFT reagents, subsequently leading to the formation of polymeric DMA (Fig. 1F–H and Fig. S5–S7†).
These results above shed light on the Fc-PF-RAFT mechanism, as illustrated in Fig. 2: (i) Fc1 induced the generation of FcCOO˙ and ˙OH radicals through a photo-Fenton reaction, thereby initiating the polymerization process. (ii) The dual radicals subsequently react with DMA monomer or bis-TTC RAFT agent, forming carbon-centered radicals crucial for essential chain growth. (iii) The activation of the RAFT agent or DMA by dual radicals distinguishes Fc-PF-RAFT polymerization from traditional methods. In contrast to ferrocene-induced radical polymerization in the absence of a RAFT reagent (Fig. S3†), the Fc-PF-RAFT strategy effectively mitigated the occurrence of uncontrollable radical chain growth polymerization.
Under optimal irradiation time and H2O2 concentration, we verified the controlled nature of the polymerization reaction by studying the relationship between conversion rate and molecular weight. The relationship between ln([M]0/[M]t) and polymerization time followed pseudo-first-order kinetics, with apparent propagation rate constant (kapp) values of 0.09 and 0.22 min−1 at H2O2 concentrations of 50 and 75 mM (Fig. 3C), respectively. These kinetics results indicated that the amount of radical exhibited a quantitative dependence on the photo-Fenton reaction. Fc-PF-RAFT polymerization showed continued monomer conversion, linear growth of molecular weight, and narrow molecular-weight distribution (PDI < 1.5) (Fig. 3D and Fig. S9, 10†), indicative of controlled polymerization. At higher H2O2 concentration (100 mM), as shown in Fig. 3A, complete monomer conversion was achieved in 6 min, suggesting the occurrence of nonpropagative “radical costing” reactions. Thus, further experiments were performed using a ferrocenyl concentration of 1.25 mM and H2O2 concentration of 75 mM. When Fc1 was replaced by Se-containing compounds Fc2 or Fc3, quantitative monomer conversion (90.3%–97.1%), chain-end fidelity, tunable reaction times, and low dispersity (1.01–1.27) were maintained (Table 1). 1H NMR analysis of the obtained products confirmed the major presence of Fc-PDMA-Fc (where Fc = Fc2 or Fc3) and coexisting compounds OH–PDMA–OH and HCOO–PDMA–COOH (Fig. S11 and S12†). The simplicity and ready availability of the experimental apparatus make this approach particularly appealing for future exploration of Fenton-RAFT polymerization.
Fc | DP | Conv.a (%) | Mn,GPCb (Da) | PDI |
---|---|---|---|---|
a Determined by 1H NMR spectroscopy. b Determined by GPC in 0.1 mol L−1 NaNO3 relative to PEG standards. | ||||
Fc1 | 25 | 89.5 | 1588 | 1.21 |
50 | 98.5 | 5566 | 1.23 | |
100 | 95.4 | 8790 | 1.28 | |
Fc2 | 25 | 91.4 | 1428 | 1.01 |
50 | 96.2 | 4540 | 1.22 | |
100 | 95.5 | 6878 | 1.27 | |
Fc3 | 25 | 90.3 | 1300 | 1.22 |
50 | 97.1 | 4554 | 1.19 | |
100 | 94.1 | 9206 | 1.25 |
Transmission electron microscope (TEM) and scanning electron microscope (SEM) were employed to characterize the size and morphology of the assemblies. No discernible morphology was observed for the Fc1-PDMA-Fc1 polymers (DP = 25, 50, 100) after aging, similar to the behavior of free homopolymer PDMA. This lack of observable morphology was attributed to the absence of interaction between the PDMA chain and Fc1. By contrast, stepwise morphological changes were observed after aging when using Se-containing Fc2 as the Fenton reagent (Fig. 4A–C). Specifically, Fc2-PDMA25-Fc2 exhibited spherical micelles with a diameter of approximately 200 nm (Fig. 4A and S13†). EDX mapping confirmed the presence of various elements (C, O, Fe, N, and Se) well distributed over the particles (Fig. 4D and E). Notably, the spherical micelles connected with one another to form clusters. The TEM images revealed a morphological transition induced by longer PDMA chains, progressing from nanospheres (DP = 25) to oval platelets (DP = 50), with a mean length of 761 nm and diameter of 105 nm (Fig. 4B and S14†), and finally to nanorods (DP = 100), with an average length of 324 nm and diameter of 40 nm (Fig. 4C and S15†). This transition was attributed to a kinetic effect, wherein the increased length of the PDMA chain led to lower hydrophilicity and increased folding of chains, resulting in a larger interfacial curvature and subsequent morphological transformation.
Intriguing morphological changes were observed during Fc-PF-RAFT polymerization of the DMA system using Fc3 (containing Se and benzene units), as shown in Fig. 5. Fc3-PDMA25-Fc3 formed spherical micelles, which tended to fuse into nanowires (Fig. 5A and S16†). The SEM images revealed that the mean diameter of Fc3-PDMA25-Fc3 was 165 nm (Fig. S17†). However, when the DP value increased to 50, Fc3-PDMA50-Fc3 formed four-armed microfans characterized by two planar ovals sharing a central axis (Fig. 5B and S18†), with a mean length of 1.29 μm and width of 664 nm (Fig. S19†) and thicker edges than the interior. Moreover, when the DP value increased to 100, Fc3-PDMA100-Fc3 formed multiarmed sea urchin superstructures from hierarchical self-assembly, comprising 11 to 15 nanoflakes (Fig. 5C and S20†). Each flake had a mean length of 7.99 μm and width of approximately 1.54 μm (Fig. S21†). The growth of sea urchin superstructures might have followed stepwise self-assembly directed by π–π stacking of rigid ferrocene and benzene units, where planar oval structures merged to form dimeric structures along two perpendicular directions, aggregating to form the sea urchin superstructure. Additionally, the zeta potentials of the assemblies (Fig. S22†) changed from +14.2 mV for spherical micelles (DP = 25), to −1.2 mV for four-armed microfans (DP = 50), and finally to −10.4 mV for the multiarmed sea urchin superstructure (DP = 100), suggesting electrostatic stability and resistance to aggregation.
The XPS analysis was conducted to investigate the interaction between Fc3 and the PDMA chain. The results revealed a negative shift in the Se 3d peak from 55.7 eV (Fc3) to 55.5 eV (Fc3-PDMA50), along with a positive shift in the N 1s peak from 399.6 eV (Fc1-PDMA50) to 400.1 eV (Fc3-PDMA50). These shifts suggest the presence of a noncovalent Se⋯N bond (Fig. S23†). The four-armed microfan-like assemblies of Fc3-PDMA50-Fc3 (Fig. 5E) were further subjected to treatments adjusted to pH = 2 or with 1% H2O2. As shown in Fig. 5D, acid treatment resulted in obvious porous flakes, likely due to acid protonation of N in PDMA disrupting the noncovalent Se⋯N bond. This caused the positively charged PDMA chains to stretch, hindering PDMA aggregation and ultimately leading to the dissociation of the “cross” assemblies into individual flakes. Alternatively, the addition of H2O2 completely destroyed the original morphology, resulting in amorphous fragments (Fig. 5F). The observed phenomenon was attributed to the oxidation of Se, which disrupted the noncovalent Se⋯N bond, and to the oxidation of neutral hydrophobic ferrocene, which resulted in the formation of cationic hydrophilic ferrocenium. This transformation induced electrostatic repulsion, leading to the disassembly of the π–π stacking in the ferrocene units and ultimately facilitating the release of free PDMA.38,39
Based on the morphological results discussed above, we propose that incorporation of the Fc3 functional group into the end of PDMA is vital for the formation of self-assembled hierarchical structures. The successive morphological evolution observed in Fc3-PDMA-Fc3 agreed with the literature findings that two-dimensional platelets were thermodynamically preferred and low unimer solubility could yield kinetically trapped one-dimensional assemblies.40 As illustrated in Fig. 7, the self-assembly of Fc3-PDMA-Fc3 polymers into hierarchical structures could be attributed to several factors: (1) core–corona structures formed with hydrophobic Fc3 as the core and PDMA chains as hydrophilic stabilizers located on the surface; (2) Se(Fc2/Fc3)⋯N(DMA) noncovalent interactions and parallel offset π–π stacking of the ferrocene (Fc2/Fc3) and phenyl moieties (Fc3) organized the PDMA to form the corona; (3) a high [Fc3]:
[bis-TTC] ratio provided essential nucleation sites for Fc3 crystallization, thereby inducing growth along the longitudinal direction; (4) the decreased hydrophilicity of long PDMA chains led to a large interfacial curvature, which in turn regulated morphological transformation.41
![]() | ||
Fig. 7 Schematic illustration of the self-assembly process of Fc-PF-RAFT polymer chains into hierarchical structures. |
The current study elucidates novel roles for ferrocene in the realm of polymeric materials, showcasing that strategically designed ferrocenyl compounds are pivotal not only for enabling the aqueous Fc-PF-RAFT polymerization to synthesize functional polymers but also for promoting the on-site formation of hierarchical assemblies, thereby enhancing the sustainability of the system. The proposed mechanism, which is thoroughly outlined in this investigation, could provide a robust framework for understanding and harnessing noncovalent interaction-driven homopolymeric self-assembly. This understanding paves the way for the deliberate engineering of hierarchical structures that could lead to advancements in material science and potential applications in various technological fields.
Footnotes |
† Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d4py00517a |
‡ These authors contribute equally. |
This journal is © The Royal Society of Chemistry 2024 |