Postsynthetic Functionalization of Zr4+ Immobilized Core-shell

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Postsynthetic Functionalization of Zr Immobilized Core-shell Structured Magnetic Covalent Organic Frameworks for Selective Enrichment of Phosphopeptides Chao hong Gao, Jing Bai, Yan Ting He, Qiong Zheng, Wen De Ma, Zhi Xian Lei, Mingyue Zhang, Jie Wu, FengFu Fu, and Zian Lin ACS Appl. Mater. Interfaces, Just Accepted Manuscript • DOI: 10.1021/acsami.9b03330 • Publication Date (Web): 20 Mar 2019 Downloaded from http://pubs.acs.org on March 20, 2019

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Postsynthetic Functionalization of Zr4+ Immobilized Core-shell Structured Magnetic Covalent Organic Frameworks for Selective Enrichment of Phosphopeptides Chaohong Gao, Jing Bai, Yanting He, Qiong Zheng, Wende Ma, Zhixian Lei, Mingyue Zhang, Jie Wu, Fengfu Fu, and Zian Lin* Ministry of Education Key Laboratory of Analytical Science for Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350116, China ABSTRACT: Chemical modification of covalent organic frameworks (COFs) is indispensable for integrating functionalities of greater complexity and accessing advanced COF materials suitable for more potential applications. Reported here is a novel strategy for fabricating controllable core-shell structured Zr4+ immobilized magnetic covalent organic frameworks (MCNC@COF@Zr4+) composed of a high-magnetic-response magnetic colloid nanocrystal cluster (MCNC) core and Zr4+ ion functionalized two-dimensional COFs as the shell by sequential postsynthetic functionalization, and for the first time, the application of the MCNC@COF@Zr4+ composites for efficient and selective enrichment of phosphopeptides. The as-prepared MCNC@COF@Zr4+ composites possess regular porosity with large surface areas, high Zr4+ loading amount, strong magnetic responsiveness, and good thermal/chemical stability, which can serve as an ideal adsorbent for selective enrichment of phosphopeptides and simultaneous size exclusion of biomacromolecules like proteins. The high detection sensitivity (10 fmol) together with the excellent recovery of phosphopeptides is also obtained. These outstanding features suggest that the MCNC@COF@Zr4+ composites have great benefit for the pretreatment prior to mass spectrometry (MS) analysis of phosphopeptides. In addition, the performance of the developed approach in selective enrichment of phosphopeptides from the tryptic digests of defatted milk and directly specific capture of endogenous phosphopeptides from human serum gives powerful proofs for its high selectivity and effectiveness in identifying the low-abundance phosphopeptides from complicated biological samples. This study not only provides a strategy for versatile functionalization of magnetic COFs, but also opens a new avenue in their use in phosphoproteome analysis. KEYWORDS: magnetic covalent organic frameworks, postsynthetic functionalization, enrichment, phosphopeptide, immobilized metal

INTRODUCTION Covalent organic frameworks (COFs) are an emerging class of porous crystalline polymers originated from the precise integration of organic building blocks into periodic structures by virtue of covalent bonds.1,2 The unique features of high and regular porosity, large surface areas, tunable

pore size and excellent structural stability make COFs excellent candidates for a variety of applications in gas storage,3,4 optoelectronics,5,6 catalysis7,8 and sensing.9,10 In particular, twodimensional (2D) and three-dimensional (3D) COFs comprising extended π-conjugated systems and well-defined nanosized internal cavities are

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promising class of separation media for sample pretreatment and stationary phase in chromatog-

Figure 1. Representation of the strategy for preparing Zr4+ immobilized magnetic covalent organic frameworks through sequential postsynthetic modifications.

raphy.11-17 Despite the great progress in the exploration of topology and synthetic reactions have been made over the past decade, construction of functional COFs is still a rather difficult task because it has to meet the requirements for crystallinity and functionality simultaneously.1 Against this backdrop, there has been significant interest very recently in the functionalization of COFs to predetermine their properties and provide structurally and chemically precise platforms for extending the applicability. Currently, there are two prevailing functionalization strategies to design the COF materials tailored for specific properties.18 One strategy is pre-synthesis by functionalizing the molecular building blocks.17,19-21 For example,

Qian et al.17 showed a pre-synthesis strategy to construct chiral COFs and an in situ growth approach to fabricate chiral COF-bound capillary columns for chiral gas chromatography, in which 1,3,5-triformylphloroglucinol (Tp) was first modified with chiral (+)-diacetyl-L-tartaric anhydride ((+)-Ac-L-Ta) to form the chiral functionalized monomer CTp and further condensed with other building blocks to form chiral COFs. Such strategy intrinsically guarantees the homogeneous dispersion of chiral functionalities with the highest content.22 However, the scope of functional groups within the pores of the COFs is rather limited because not all functional groups are compatible with or stable to the conditions for the COF synthesis.23


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As an alternative, the post-synthesis strategy by modification at the preformed framework itself has attracted great concern and been developed rapidly in recent years.12, 23-26 Lu et al.12 proposed an attractive strategy for fabricating a 3D carboxy-functionalized COF through postsynthetic modi

Figure 2. SEM and TEM images of (A, C) MCNCs and (B, D) MCNC@COF (the inset of Figure 2D shows mono MCNC@COF); (E) FT-IR spectra of the MCNC, MCNC@COF, SA-MCNC@COF, PAMCNC@COF and MCNC@COF@Zr4+; (F) TGA profiles of the (MCNC, MCNC@COF, SAMCNC@COF and PA-MCNC@COF; (G) N2 sorption isotherm profiles of the COF (red), MCNC@COF (blue), SA-MCNC@COF (green) and MCNC@COF@Zr4+ (black); (H) Pore size distribution profiles of the corresponding products (colors display the same material as indicated in (G)) fication of hydroxyl-functionalized COF, which was applied as an adsorbent for selective extraction of lanthanide ions. Sulfur derivatives were also modified on a newly designed vinyl functionalized mesoporous COFs via thiol-ene “click” reaction and further applied to the efficient removal of mercury from aqueous solutions and the air.23 The post-synthesis strategy can offer incorporation of “on demand” desired functionality on the surface of the COF backbone, together with reducing the influence of the modified sites and harsh reaction conditions on the COF crystallinity. However, the introduction of functional groups in COFs remains a challenge due to the lack of modifiable reactive groups in almost all COFs reported to date. Different from zeolites,27 mesoporous

organosilicas,28 and metal-organic frameworks,29 where the postsynthetic modification is commonly adopted, the functionalization of COFs is a great challenge. Due to its pivotal role in regulating a number of biological process and its involvement in a variety of diseases, reversible protein phosphorylation has attracted a large number of research interest.30 Mass spectrometry (MS) has become the most powerful tool for identifying protein/peptide phosphorylation based on its high sensitivity and rapid sequence mapping. However, inevitable challenges including low stoichiometry, poor ionization efficiency, and signal suppression by high-abundance non-phosphorylated peptides have greatly limited its direct use in the analysis of phosphopeptides. The selective enrichment of



phosphopeptides prior to MS analysis is thus an essential step for in-depth phosphoproteome study.31,32 At present, diverse approaches including immunoprecipitation,33 chemical 34 modification, metal oxide affinity 35 chromatography (MOAC), and immobilized metal affinity chromatography (IMAC),36 have been explored for phosphopeptide enrichment. Despite great successes have been achieved, development of novel porous nanomaterialsbased absorbents tailored for highly efficient and selective enrichment of phosphopeptides is highly desirable. Herein, we present a novel strategy for fabrication of Zr4+ immobilized magnetic COFs through sequential postsynthetic modifications of a hydroxyl-functionalized magnetic COFs (Figure 1), in which the high-magnetic-response magnetic colloid nanocrystalclusters (MCNCs) were used as the core and 2D COFs after aldimine condensation of 1, 3, 5-tri (4formylbiphenyl) benzene (TfPb) and 3, 3’dihydroxybenzidine (DHBD) were used as the shell (Step Ⅰ, denoted MCNC@COF). Then, the three-step sequential functionalization involving the conversion of hydroxyl groups to carboxyl groups via ring opening reaction in the presence of succinic anhydride (SA) (Step Ⅱ, denoted SAMCNC@COF), the introduction of pamidronic acid (PA) to obtain the desired phosphoate groups (Step Ⅲ, denoted PA-MCNC@COF), and the final formation of Zr4+ immobilized magnetic COF composites through Zr4+-phosphate coordination (Step Ⅳ, denoted 4+ MCNC@COF@Zr ) were performed. To the best of our knowledge, this is the first example on functionalized magnetic COFs for phosphopeptide enrichment. The obtained MCNC@COF@Zr4+ composites showed regular porosity, high surface areas, narrow mesopore size distribution, strong magnetic responsiveness, good crystallinity and thermal/chemical stability. More importantly, the magnetic COFs displayed high Zr4+ loading amount, which exhibited excellent adsorption capacity and high selectivity for phosphopeptides. In addition, the feasibility of the MCNC@COF@Zr4+ composites for realsample applications was also discussed in this work.

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EXPERIMENTAL SECTION Synthesis of Core-shell Structured MCNC@COF@Zr4+ Composites. The MCNCs were synthesized by a solvothermal reaction. The subsequent coating with COF shell was carried out in a THF via template-controlled precipitation polymerization. There are three sequential postsynthetic modification steps to produce MCNC@COF@Zr4+ composite nanospheres. The first step included the conversion of the phenolic hydroxyl groups to carboxyl groups in presence of succinic anhydride (SA) via ring opening reaction to yield SA-MCNC@COF. The second step consisted of the conversion of these surface carboxyl groups to phosphoate groups in the presence of pamidronic acid (PA) to afford the desired phosphoate functionalized PA- MCNC@COF. The third step involved the chelation between Zr4+ and the phosphoate group of PA, Zr4+ ions were immobilized on the PA-MCNC@COF by incubation in an aqueous solution of ZrOCl2 (see Supporting Information for the detailed procedures). RESULTS AND DISCUSSION Preparation and Characterization of the MCNC@COF@Zr4+ Composite. Hydroxyl functionalities are ideal for postsythetic modifications because of their easy derivatizable feature under mild reaction conditions. DHBD as one of the building blocks was selected for COF construction. Meanwhile, TfPb with expanded πconjugated planar structure contains three aldehyde groups and can be used as another building block for COF synthesis. As a result, the core-shell structured MCNC@COF composites containing rich hydroxyl functionalities could be synthesized by Schiff base condensation reaction in the presence of THF. Representative SEM images of the MCNCs and MCNC@COF composites showed their size and shape. The smooth spherical shape of MCNCs with monodispersed size of ~250 nm was obtained (Figure 2A). In contrast, the MCNC@COF composites showed a rough surface (Figure 2B). Compared with the MCNCs (Figure 2C), a rough shell with the thickness of 30 nm was clearly observed in TEM (Figure 2D and its inset).


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Moreover, the thickness of the COF shell could be tailored by adjusting the total contents of the MCNCs and two building blocks (Figure S1), which varied from 10 nm to 100 nm. In this case, the MCNC@COF composites with the thickness of 30 nm were adopted for the further studies mainly considering its morphology, monodispersity and adsorption performance. To immobilize Zr4+ ions, the MCNC@COF composites were sequentially reacted with SA and PA, and finally incubated with ZrOCl2 solution. The obtained MCNC@COF@Zr4+ composites were further analyzed by TEM (Figure S2), which indicated that the similar core-shell structure and rough COF shells were well retained during the sequential postsynthetic modifications. The Fourier transform infrared (FT-IR) spectra (Figure 2E)) of the serial products all exhibited the same absorption bands at 584 cm-1 ascribed to Fe-O-Fe vibration. In comparison with the monomers of TfPb and DHBD (Figure S3), the spectrum of the MCNC@COF composites revealed the disappearance of C=O stretching vibration along with the emerging C=N stretch at 1617 cm-1, confirming the successful condensation reaction of the COF. In contrast to the MCNC@COF composites, the SA-MCNC@COF composites displayed the adsorption band of –OH at 3401 cm-1 along with the strong adsorption bands at 1685 and 1050 cm-1 that assigned to the C-O stretching vibration of carboxylates formed after surface modification, implying the successful grafting of SA. The spectrum of the PAMCNC@COF composites showed the new vibration bands at 1250 cm-1 and 1560 cm-1, which were assigned to the stretching of P=O of phosphate group and the stretching of C-N of secondary amine after the introduction of PA. To further prove the successful modifications, the zeta potential (Figure S4) was performed for the serial products. The zeta potential of the MCNC@COF composites was about -3.45 mV in water. After reacting with SA, the zeta potential of the SA-MCNC@COF composites was changed into -7.90 mV. The grafted PA had a slight drop on the zeta potential of the SAMCNC@COF composites (-5.91 mV). After chelation between Zr4+ and the phosphoate group of PA, the zeta potential was changed from -5.91

mV to +6.84 mV due to the high Zr4+ loading amount. Energy dispersive X-ray (EDX) spectra (Figure S5) were also measured to confirm that Fe, C, N, O, P and Zr were the six main elements of the core-shell composites (Table S1), demonstrating that the obtained MCNC@COF@Zr4+ composites were made up of the target components. Thermogravimetric analysis (TGA) revealed the thermal stability and mass ratios of different components (Figure 2F). For the MCNC@COF@Zr4+ composites, they were very stable under 350 ℃ , indicating its excellent thermal stability. In addition, the MCNC@COF composites had the almost weight loss of 27.31 wt% over 850 ℃ in comparison with the MCNCs, indicating that the COF shell was high yielding. Meanwhile, the TGA analysis of the SA-MCNC@COF and PA-MCNC@COF composites showed the weight loss up to 31.06 % and 34.91 % at 850 ℃ compared with the MCNCs, which were attributed to the sequential postsynthetic modifications of SA and PA. Furthermore, the chemical stability of the MCNC@COF@Zr4+ composites was further examined and the results (Figure S6) showed that all the products exhibited similar diffraction peaks in XRD patterns, suggesting their good crystallinity. The Brunauer-Emmett-Teller (BET) surface area was investigated by measuring N2 sorption isotherms at 77K (Figure 2G). All of the composites displayed typical Ⅳ sorption isotherm profiles that were belonged to mesoporous characteristic. Table S2 listed the pore structure of the corresponding composites including the specific surface area, pore volume and pore size. Distinctly, as the steps of postsynthetic modifications increased, the BET surface area, pore volume and pore size of the resultant composites dropped. The corresponding BET surface area and pore volume were calculated to be 49.15 m2 g-1 and 0.13 cm3 g-1 for MCNC@COF@Zr4+, respectively. The pore size distributions of the corresponding composites were calculated by the Barrett–Joyner–Halenda (BJH) model, and the obtained MCNC@COF@Zr4+ composites had the pore size predominated from 2.7 to 3.3 nm (Figure 2H). The crystalline structure and phase purity of the obtained products were determined by XRD



analysis. Wide-angle XRD patterns (Figure S7A) for the MCNCs and the subsequent MCNC@COF composites exhibited the same 7 peaks, which matched well with those from the JCPDS card (65-3107) for magnetite, confirming that all the products were crystalline nature and maintained high crystallinity after coating. Moreover, compared to the bulk COF, all the products (Figure S7B) displayed an intense peak at around 2.5°, indicating that they had stable crystalline stacking model. In addition, the MCNC@COF@Zr4+ composites possessed good superparamagnetic property (Figure S8), which was estimated to be 42.4 emu g-1, just a little drop compared with the MCNCs (58.0 emu g-1). Owing to the high magnetic-response (the inset of Figure S8), the MCNC@COF@Zr4+ composites could be separated from the brown suspension in only 1 min and selectivity of the MCNC@COF@Zr4+ composites were mainly attributed to its regular mesoporous structure with high surface area, and the strong affinity interaction between Zr4+ ions and phosphoate groups of model compounds. Adsorption Performance and Application. The performance of the MCNC@COF@Zr4+ composites for selective enrichment of phosphate group-related molecules was evaluated. Herein, two different groups of representative compounds, including adenosine triphosphate (ATP) and adenosine (A), phosphopeptide (TRG[pY]GTSTRK, pY1) and nonphosphopeptide (TRGYGTSTRK, nY1) with and without phosphate group, were chosen as model compounds. As shown in Figure S9, the saturated adsorption capacity (Qmax, mg g-1) of the MCNC@COF@Zr4+ composites for ATP was estimated to be 58.50 mg g-1, much higher than that of A (~4.5 mg g-1). Similarly, the MCNC@COF@Zr4+ composites also exhibited much higher adsorption capacity for pY1 than nY1, where their corresponding Qmax was estimated to be 46.48 mg g-1 and 5.1 mg g-1 , respectively. Apparently, its high adsorption and selectivity were mainly attributed to its regular mesoporousstructure with high surface area, and the strong affinity interaction between Zr4+ ions and phosphoate groups of model compounds.In addition, the reusability of the MCNC@COF@Zr4+ composites for

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TRG[pY]GTSTRK was also examined and the result (Figure S10) demonstrated that there were nearly 40% loss in adsorption capacity of TRG[pY]GTSTRK after six adsorptionregeneration cycles. The decrease of adsorption capacity was mainly due to the loss of Zr4+ ion caused by the relative strong basic elution buffer. However, the low reusability could be greatly improved if the MCNC@COF@Zr4+ composites were reincubated in 0.2 M ZrOCl2 solution before next cycle. Therefore, reincubation is essential to ensure adsorption continuity. Encouraged by the aforementioned excellent adsorption performance, the selectivity and sensitivity of the MCNC@COF@Zr4+ composites were further studied by selective enrichment and analysis of the phosphopeptides from the tryptic digests of 100 μg mL-1 β-casein. As presented in Figure 3A, only one phosphopeptide with low signal intensity was observed in direct analysis of the tryptic digests without any pretreatment procedure, the obtained mass spectrum was mainly dominated by the peaks of non-phosphopeptides. Figure 3B showed the analysis of the β-casein digests with treatment of the MCNC@COF composites. It was found that no any peaks of phosphopeptides were detected, indicating the ineffectiveness of the MCNC@COF composites. In contrast, after being treatment with the MCNC@COF@Zr4+ composites, three phosphopeptides (β1, β2, β3) possessed both of phosphorylated parts and dephosphorylated counterparts were clearly identified with enhanced signal intensities (Figure 3C). The detailed information of the detected phosphopeptides was summarized in Table S3. The results are coincided well with the aforementioned enrichment performance and much better than the previous work,36 implying the excellent enrichment selectivity of the MCNC@COF@Zr4+ composites. In addition, the limit of detection (LOD) for the β-casein digest after enrichment by the MCNC@COF@Zr4+ composites was also evaluated and the result (Figure S11) demonstrated that the 3 typical phosphopeptides could be unambiguously detected even though the concentration of βcasein was decreased to 0.25 μg mL-1, and the corresponding LOD of β-casein was as low as 10 fmol, lower than the previous reports.37,38


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The applicability of the MCNC@COF@Zr4+ composites was further evaluated by selective enrichment of phosphopeptides from digested mixture of bovine serum albumin (BSA) and βcasein at a molar ratio of 200:1. Direct analysis revealed that the nonphosphopeptides of BSA dominated the mass spectrum (Figure S12A). Evidently, the existence of high abundant nonphosphopeptides seriously suppressed the ionization of low-abundance phosphopeptides. However, 6 peaks corresponding to 3 phosphopeptides with enhanced S/N ratios were distinctly detected after enrichment with the MCNC@COF@Zr4+ composites (Figure S12B), validating again the superior selectivity of the MCNC@COF@Zr4+ composites. Another distinctive character of the MCNC@COF@Zr4+ composites is the sizeexclusion effect because of its unique pore struc ture. Hereto, two proteins with different sizes and molecular weights, including lysozyme and conconvalina A, were mixed with TRG[pY]GTSTRK and used as the models to examine the cutoff mechanism. Figure S13A displayed the baseline separation of

Figure 3. MALDI-TOF mass spectra of the tryptic digests of β-casein: (A) direct analysis; and (B) analysis after enrichment with MCNC@COF composites; and (C) analysis after enrichment with ACS Paragon Plus Environment


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MCNC@COF@Zr4+ composites. MALDI-TOF mass spectra of the tryptic digests of defatted milk: (D) direct analysis, and (E) analysis after enrichment with MCNC@COF@Zr4+ composites; MALDI-TOF mass spectra of diluted human serum: (F) direct analysis, and (G) analysis after enrichment with MCNC@COF@Zr4+ composites. “*” and “#” indicate phosphorylated peptides and their dephosphorylated counterparts, respectively. TRG[pY]GTSTRK and two proteins. After incubation with the MCNC@COF@Zr4+ composites, about 70% of TRG[pY]GTSTRK was captured, but more than 96% of Lyz and Con A were remained in the supernatant (Figure S13B), which was ascribed to the unique mesoporous structure, and therefore the largesize proteins were excludeded from the mesoporous channels. On the contrary, the smallsize phosphopeptide could easily enter into the mesoporous channels and be captured based on the Zr4+-phosphate affinity interaction (Figure S13C). The effectiveness of the MCNC@COF@Zr4+ composites in real complex samples were further verified by selective enrichment of phosphopeptides from the tryptic digests of defatted milk and direct capture of lowabundance endogenous phosphopeptides from 10-fold diluted human serum, respectively. Figure 3D presented the direct analysis of the tryptic digests of diluted defatted milk, where the peaks of nonphosphopeptides predominated the spectrum. After treatment with the 4+ MCNC@COF@Zr composites, 14 phosphopeptide peaks with a clean background were clearly observed (Figure 3E). The detail information on the captured phosphopeptides from the tryptic digests of defatted milk were listed in Table S4. Taking the advantages of high selectivity and size-exclusion effect together, the MCNC@COF@Zr4+ composites were further attempted to directly enrich low-abundance endogenous phosphopeptides from 10-fold diluted human serum. As displayed in Figure 3F, there were no phosphopeptides found in the mass spectrum due to its low abundance and serious suppression by high content of salts, when direct analysis was applied. After the treatment, however, 5 peaks of phosphorylated peptides could be directly detected from human serum (Figure 3G) and the more detailed information were listed in Table S5. The result was well in

accordance with the previous reports,39,40 firmly confirming that the effectiveness of the MCNC@COF@Zr4+ composites in selective enrichment of phosphopeptides. CONCLUSIONS In summary, we report a new strategy for synthesis of magnetic COF composites through sequential postsynthetic functionalization. The obtained core-shell structured MCNC@COF@Zr4+ composites possessed regular porosity with high surface area, good crystallinity with ordered mesopore, high Zr4+ loading amount, strong magnetic responsiveness, and good thermal/chemical stability. Taking these advantages together, the 4+ MCNC@COF@Zr composites could be applied to the enrichment of phosphopeptides with high adsorption capacity and selectivity. Additionally, the successful applications in selective enrichment of phosphopeptides from the tryptic digests of defatted milk and direct capture of endogenous phosphopeptides from the diluted human serum provide effective proofs for its high selectivity and practicability in identifying the low-abundance phosphopeptides from complicated biological samples. The report not only opens up a general strategy for effectively sequential postsynthetic modifications of magnetic COF composites, but also promotes functionalized magnetic COF materials into an outstanding scaffold for proteomics-related researches. ASSOCIATED CONTENT The Supporting Information is available free of charge via the Internet at http://pubs.acs.org. Materials and methods, synthesis and characterization, Table S1-S5, and Figure S1-S15. AUTHOR INFORMATION Corresponding Author *Corresponding author: Zian Lin; Tel: +86591-22866135; Fax: +86591-22866135


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E-mail: [email protected] (Z.A Lin); Present Addresses Postal address: College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350116, China Notes The authors declare no competing financial interests. ACKNOWLEDGMENT This work was supported by the National Key Research and Development Program of China (2017YFC1600500), the National Natural Science Foundation of China (21675025), the Natural Science Foundation of Fujian Province (2018J01683), and the Program for New Century Excellent Talents in Fujian Province University. REFERENCES (1) Diercks, C. S.; Yaghi, O. M. The Atom, the Molecule, and the Covalent Organic Framework. Science 2017, 355, No. eaal1585. (2) Côté, A. P.; Benin, A. I.; Ockwig, N. W.; O'Keeffe, M.; Matzger, A. J.; Yaghi, O. M. Porous, Crystalline, Covalent Organic Frameworks. Science 2005, 310, 1166-1170. (3) Baldwin, L. A.; Crowe, J. W.; Pyles, D. A.; Mcgrier, P. L. Metalation of a Mesoporous Three-Dimensional Covalent Organic Framework. J. Am. Chem. Soc. 2016, 138, 15134-15137. (4) Doonan, C. J.; Tranchemontagne, D. J.; Glover, T. G.; Hunt, J. R.; Yaghi, O. M. Exceptional Ammonia Uptake by a Covalent Organic Framework. Nat. Chem. 2010, 2, 235238. (5) Du, Y.; Yang, H.; Whiteley, J. M.; Wan, S.; Jin, Y; Lee, S. H.; Zhang, W. Ionic Covalent Organic Frameworks with Spiroborate Linkage. Angew. Chem., Int. Ed. 2016, 55, 1737-1741. (6) Chen, L.; Furukawa, K.; Gao, J.; Nagai, A.; Nakamura, T.; Dong, Y.; Jiang, D. Photoelectric Covalent Organic Frameworks: Converting Open Lattices into Ordered Donor-Acceptor Heterojunctions. J. Am. Chem. Soc. 2014, 136, 9806-9809. (7) Xu, H.; Gao, J.; Jiang, D. Stable, Crystalline, Porous, Covalent Organic Frameworks as a Platform for Chiral Organocatalysts. Nat. Chem. 2015, 7, 905-912.

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TOC

Postsynthetic functionalization of Zr4+ immobilized core-shell structured magnetic COFs for selective enrichment of phosphopeptides based on strong affinity interaction between Zr4+ and phosphopeptides.


Postsynthetic Functionalization of Zr4+ Immobilized Core-shell

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