Fluolab【Angew.Chem.】吉林大学安泽胜联合天津师范大学李春举|15毫米猪皮都挡不住！全新超分子近红外光催化剂实现高效、耐氧水相精准聚合
文章标题：Supramolecular Near‐Infrared Photocatalysts for Efficient and Oxygen‐Tolerant Aqueous RAFT Polymerization
通讯作者：Chunju Li, Zesheng An
文章概要
引言
光控可逆失活自由基聚合技术凭借其温和的反应条件以及优异的时空可控性，已经成为精准合成先进功能聚合物的强大工具。然而，目前大多数光控聚合系统仍然高度依赖紫外光或可见光，这极大限制了它们在生物医学领域的广泛应用，因为这些波段的光线无法穿透深层生物组织。相比之下，近红外光由于波长较长，具有更强的组织穿透能力和极佳的生物相容性，因而备受研究人员关注。在近红外光诱导的电子/能量转移可逆addition-fragmentation链转移聚合（PET-RAFT）中，核心挑战在于开发出能同时兼顾高聚合速率、分子量精准控制以及高耐氧性的催化剂。目前常见的近红外光催化剂如卟啉和酞菁等，由于具有大共轭结构，在水相介质中极易发生聚集，导致催化效率严重降低。虽然通过复杂的化学修饰可以改善其水溶性，但往往面临步骤繁琐、产率低等问题。为此，研究团队提出了一种完全不同的思路，试图利用简便的超分子主客体识别机制，在水相中构筑高度分散的超分子近红外光催化剂，以攻克催化剂聚集、催化效率低以及对氧气敏感的行业瓶颈。
(a) Schematic formation of a supramolecular NIR photocatalyst. Using a suitable macrocyclic host ensures that the photocatalyst forms a host–guest complex in aqueous solution, rather than aggregates. (b) NIR photocontrolled RAFT polymerization in aqueous media using such a supramolecular photocatalyst; chemical structures of the ZnPcS4− photocatalyst, macrocyclic host molecules, and monomers used in this study.
主要实验及结论
研究人员选用具有可调空腔大小和阳离子功能化的联苯撑三芳烃大环分子（WQP3） 作为超分子主机，与带有负电荷的近红外光催化剂水溶性酞菁锌（ZnPcS4-）进行构筑。光谱测试、质谱分析以及高精度分子动力学模拟共同证实，WQP3与ZnPcS4-通过协同的疏水作用、π-π堆积和强静电吸引力，在水中自组装形成了高度稳定的一比一化学计量比主客体复合物。这种超分子包合物的形成成功将酞菁锌分子从聚集态中解放出来，使其Q带吸收峰显著红移并大幅增强了解离状态下的光物理活性。
Characterization of the host–guest complexation between WQP3 and ZnPcS4−. (a) UV–visible absorption spectroscopy monitoring of WQP3 titration into a 10 µM ZnPcS4− solution. (b) Plots of absorbance at 684 nm versus WQP3/ZnPcS4− molar ratio. (c) Fluorescence spectroscopy monitoring of ZnPcS4− titration into a 10 µM WQP3 solution (_λ_ex = 335 nm slit width: 5 nm, 5 nm). (d) Nonlinear least-square analysis to determine the association constant (Ka). (e) ESI-MS spectrum recorded for the WQP3–ZnPcS4− complex. (f) Optimized molecular geometry indicated by GaMD simulation.
1H NMR spectroscopy (500 MHz, 25°C, DMSO-d6, number of scans: 128) studies of the titration of WQP3 into ZnPcS4− (0.40 mM). (a) Evolution of ZnPcS4− spectra on increasing the WQP3/ZnPcS4− molar ratio. (b) ZnPcS4− chemical structure with labeled protons. (c) Plot of the change in chemical shift (Δδ) for the ZnPcS4− proton b (the most upfield split) versus WQP3/ZnPcS4− molar ratio. (Under the NMR measurement concentration, ZnPcS4− undergoes strong aggregation in D2O. This results in a drastic reduction in proton relaxation times, which prevents observation of the proton signals. In contrast, DMSO-d6 can more effectively disrupt the π–π stacking interaction).
在空气不除氧的开放微孔板体系中，研究团队以丙烯酰胺衍生物为模型单体进行了高通量近红外光控聚合实验。动力学研究表明，相较于单独使用酞菁锌催化剂，超分子催化系统展现出了超过两倍的表观聚合速率常数，不仅在极短时间内实现了近乎定量的单体转化率，而且保持了完美的线性拟合关系。分子量层面的凝胶渗透色谱分析进一步证实，所得到的聚合物具有高度可预测的理论分子量以及极窄的分子量分布，多分散指数低至一点零二。这一高通量合成平台还成功拓宽到了多种具有生物医药前景的单体，并完成了高链端保真度的嵌段聚合物扩链实验，充分验证了该超分子催化剂在水相大体积反应或微量筛选中的广泛适用性。
Kinetic studies for DMA polymerizations obtained using ZnPcS4− and WQP3–ZnPcS4−. (a) Pseudo-first-order plots of ln([M]0/[M]t) versus time. (b) Plots of molecular weight and dispersity versus conversion. (c,d) Corresponding GPC traces recorded for the PDMA homopolymers. Polymerization conditions: [DMA]/[CTPA] = 500, [TEOA] = 0.19 M, [ZnPcS4−] = 0.24 mM (50 ppm relative to monomer), [WQP3] = 0.24 mM, monomer content = 50% v/v, solution volume = 260 µL, air volume = 80 µL, 28°C, NIR light (_λ_max = 738 nm; I = 60 mW cm−2).
为了进一步挖掘该技术在生物医学体内应用中的巨大潜力，研究人员设计了一项极具挑战性的生物屏障穿透聚合实验。他们使用多层离体猪皮组织作为物理阻挡层，对比了不同波长光源的穿透与催化表现。实验结果令人振奋，在整体厚度高达十五毫米的三层猪皮屏障下，传统黄光由于极低的穿透效率导致反应几乎停滞。而近红外光则表现出极其强悍的组织渗透能力，维持了高达百分之十的光透射率，并驱动聚合反应达到了百分之九十的超高转化率。此时得到的聚合物依然具有极窄的分子量分布，直接印证了该系统在深层生物组织内部开展精准大分子合成的切实可行性。
Kinetic studies for the DMA polymerizations conducted under sealed condition (without deoxygenation) and open-to-air condition using WQP3–ZnPcS4−. (a) Pseudo-first-order plots of ln([M]0/[M]t) versus time. (b) Plots of molecular weight and dispersity versus conversion. (c,d) GPC traces recorded for the PDMA homopolymers obtained during the corresponding polymerization process. Polymerization conditions: [DMA]/[CTPA] = 500, [TEOA] = 0.19 M, [ZnPcS4−] = 0.24 mM (50 ppm relative to monomer), [WQP3] = 0.48 mM, monomer content = 50% v/v, solution volume = 170 µL, air volume = 170 µL, 28°C, NIR light (_λ_max = 738 nm; I = 60 mW cm−2).
Photopolymerizations conducted through porcine skin. (a) Schematic illustration of the photocontrolled polymerization conducted through three layers of porcine skin (overall skin thickness = 15 mm) under the irradiation of either NIR light (_I_0 = 80 mW cm−2, _λ_max = 738 nm) or yellow light (_I_0 = 80 mW cm−2, _λ_max = 595 nm). (b) Monomer conversions achieved after 14 h. (c) GPC traces recorded for the PDMA homopolymers obtained after the corresponding polymerization. Polymerization conditions: [DMA] = 50% v/v, [DMA]/[CTPA] = 500, [TEOA] = 0.19 M, [ZnPcS4−] = 0.24 mM (50 ppm relative to DMA), [WQP3] = 0.72 mM, solution volume = 170 µL, head space volume = 170 µL, 28°C.
在深入探究催化增强机制时，研究团队利用荧光探针和电子顺磁共振波谱对关键中间体进行了定量追踪。结果表明，超分子复合物的形成以极快的速度促进了溶液中溶解氧向单线态氧的敏化转化，并在还原剂的存在下将这一过程缩短至短短四十秒。随后，单线态氧进一步诱导生成的羟基自由基捕获速率实现了前所未有的三十五倍加速。这种高效的自由基级联产生机制正是该催化剂展现出超高聚合动力学与卓越耐氧性的根本原因。为了证明该策略的普适性，研究人员还将该超分子主客体构筑策略成功推广到了另一种完全不同的金属游离卟啉催化剂（TCPP）系统中，同样成功实现了催化剂的解聚集并显著提升了近红外光控聚合反应的表现。
Mechanistic analysis of the superior oxygen tolerance and accelerated kinetics conferred when using the WQP3–ZnPcS4− supramolecular photocatalyst compared to ZnPcS4− alone. (a) Proposed NIR photocatalysis-mediated initiation mechanism, with the red color denoting key species for detection. (b) Oxygen consumption measured by an oxygen probe. (c) Spectrophotometric assay for 1O2 formation via ADPA oxidation. (d) Kinetic plots for ADPA oxidation by 1O2. (e) EPR spectra monitoring hydroxyl radical formation via TEMPO trapping. (f) Kinetic plots for hydroxyl radical trapping by TEMPO. Reaction conditions: [TEOA] = 0.19 M, [ZnPcS4−] = 0.24 mM, [WQP3] = 0.48 mM, [ADPA] = 0.33 mM, [TEMPO] = 0.50 mM.
Characterization of host–guest complexation between WQP3 and TCPP. (a) TCPP alone forms aggregates in aqueous solution but the WQP3 macrocyclic host binds with TCPP to form a water-soluble supramolecular complex. (b) 500 MHz 1H NMR spectra recorded at 25°C for WQP3 (0.8 mM), WQP3/TCPP = 1:1 (0.8 mM), TCPP (0.8 mM) (PB buffer/DMSO-d6 = 37:13, 0.2 M) PB buffer prepared in D2O, pH = 7). (c) Spectrophotometric monitoring of WQP3 titration into a TCPP solution ([TCPP] = 10 µM). (d) Plots of absorbance at 421 nm versus WQP3/ZnPcS4− molar ratio.
(a) Reaction scheme for DMA polymerization using WQP3–TCPP or TCPP alone. (b) Pseudo-first-order plots of ln([M]0/[M]t) versus time. (c) Plots of molecular weight and dispersity versus conversion. Polymerization conditions: [DMA] = 30% v/v, [DMA]/[CTPA] = 1000, [TEOA] = 5.82 mM, [TCPP] = 0.29 mM (200 ppm), [WQP3] = 0.58 mM, solution volume = 1.5 mL, argon atmosphere, 20°C, NIR light (_λ_max = 730 nm; I = 120 mW cm−2).
总结及展望
该研究巧妙利用联苯撑三芳烃大环主体的结构多样性，成功开发出一种极具模块化与普适性的超分子近红外光催化剂构筑策略。该方法不仅彻底解决了传统高度共轭催化剂在水相中易聚集、活性低的痼疾，还建立起了一个无需提前除氧、对高浓度氧气展现出极强耐受力的精准水相光聚合反应平台。得益于近红外光优秀的深层组织穿透力以及超分子技术对催化动力学的全方位激活，该体系即使在面对十五毫米厚的活体组织屏障时依然能高效工作。这项成果不仅为大分子精准合成开辟了简便高效的低载量催化新途径，更为未来在生物组织工程、实时细胞疗法监控、先进体内生物材料构筑等前沿医学领域的精准应用奠定了坚实的科学基础。