[Supporting Information] 3D Porous Crystalline Polyimide Covalent Organic Frameworks for Drug Delivery Qianrong Fang,, Junhua Wang, Shuang Gu, Robert B. Kaspar, Zhongbin Zhuang, Jie Zheng, Hongxia Guo,, Shilun Qiu,*, and Yushan Yan*, State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, Jilin University, Changchun 130012, P. R. China Department of Chemical and Biomolecular Engineering, Center for Catalytic Science and Technology, University of Delaware, Newark, DE 19716, USA College of Material Science and Engineering, Beijing University of Technology, Beijing 100124, P. R. China Contents: Section 1. Materials and Characterization Section 2. Figures S1 S39 Section 3. Tables S1 S8 Section 4. References S1
Section 1. Materials and Characterization All starting materials and solvents, unless otherwise noted, were obtained from Aldrich Chemical Co. and used without purification. All products were isolated and handled under nitrogen using either glovebox or Schlenk line techniques. 1,3,5,7-tetraaminoadamantane (TAA) was synthesized by the method of literatures. 1-3 1 H NMR spectra were recorded on an AV400 NMR spectrometer. 13 C NMR spectra were recorded on an AVIII 500 MHz solid-state NMR spectrometer. FT-IR spectra were recorded on a Thermo Nicolet Nexus 470 spectrometer equipped with a MCT-A (mercury cadmium telluride) detector with 5 mg samples. TGA was carried out under nitrogen on a TGA/DSC 1 thermal analyzer from METTLER TOLEDO. PXRD data were collected on a Philips X Pert powder diffractometer using a Cu Kα source (λ = 1.5418 Å) over the range of 2θ = 2.0 40.0 with a step size of 0.02 and 2 s per step. The sorption isotherm for N 2 was measured by using a Micromeritics ASAP 2020 analyzer with ultra-highpurity N 2 (99.999% purity). To estimate pore size distributions for PI-COFs, nonlocal density functional theory (NLDFT) was applied to analyze the N 2 isotherm on the basis of the model of N 2 @77K on carbon with slit pores and the method of non-negative regularization. UV-VIS spectra were measured on a Lambda 20 spectrophotometer. The SEM images were obtained on JEOL JSM7400F microscope, operating at an acceleration voltage of 3-10 kev and current of 10 µa. (1) Synthesis of PI-COF-4 A Pyrex tube measuring o.d. i.d. = 10 8 mm 2 was charged with PMDA (43.6 mg, 0.2 mmol) and TAA (19.6 mg, 0.1 mmol) in a mixed solution of NMP (0.2 ml), mesitylene (1.0 ml), and isoquinoline (0.02 ml). The tube was flash frozen at 77 K (LN 2 bath), evacuated to an internal pressure of 0.15 mmhg and flame sealed. Upon sealing the length of the tube was reduced to ca. 13 cm. The reaction mixture was heated at 160 C for 5 days to afford a brown precipitate which was isolated by filtration over a medium glass frit and washed with anhydrous tetrahydrofuran (THF, 20.0 ml). The product was immersed in anhydrous THF (20.0 ml) for 8 h, during which the activation solvent was decanted and S2
freshly replenished four times. The solvent was removed under vacuum at 85 C to afford PI-COF-4 as a brown powder (51.3 mg, 86%). Anal. Calcd for C 15 H 8 N 2 O 4 : C, 64.29; H, 2.88; N, 10.00. Found: C, 63.78; H, 2.80; N, 10.86. (2) Synthesis of PI-COF-5 Similar to PI-COF-4, PMDA (43.6 mg, 0.2 mmol) was treated with TAPM (38.1 mg, 0.1 mmol) in a mixed solution of NMP (0.2 ml), mesitylene (1.0 ml), and isoquinoline (0.02 ml). The tube was flash frozen at 77 K (LN 2 bath), evacuated to an internal pressure of 0.15 mmhg, and flame sealed. Upon sealing the length of the tube was reduced to ca. 13 cm. The reaction mixture was heated at 160 C for 5 days to afford a brown precipitate which was isolated by filtration over a medium glass frit and washed with anhydrous THF (20.0 ml). The product was immersed in anhydrous THF (20.0 ml) for 8 h, during which the activation solvent was decanted and freshly replenished four times. The solvent was removed under vacuum at 85 C to afford PI-COF-5 as a brown powder (63.3 mg, 81%). Anal. Calcd for C 45 H 20 N 4 O 8 : C, 72.58; H, 2.71; N, 7.52. Found: C, 73.10; H, 2.77; N, 7.88. (3) Drug loading and release The drug was loaded by immersing solvent-free samples in IBU hexane solution of a certain concentration. A typical procedure for loading IBU in PI-COF-4 or PI-COF-5 was as follows: 250 mg of PI- COF was suspended in 10 ml of 0.1 M IBU hexane solution under stirring for 2 h while preventing evaporation of hexane by covering with a cap. The drug-loaded sample was separated from solution by vacuum filtration, washed with hexane, and dried at room temperature. A typical procedure for releasing IBU from PI-COF-4 or PI-COF-5 was as follows: the drug-loaded PI-COF (100 mg) was placed in a vial and dipped in 2 ml of simulated body fluid (SBF, ph = 7.4, standard buffer solution from Fisher Chemical) at 37 C. At predetermined time intervals, the dissolution medium was replaced with 2 ml of fresh SBF and the withdrawn medium was used to determine the drug concentration. The IBU S3
concentration was analyzed by UV-VIS spectrophotometry with the help of a calibration curve. The release study was continued until no IBU was detectable in the withdrawn SBF. In addition, the procedure for loading and release captopril or caffeine was similar to those for IBU. S4
Section 2. Figures S1 S39 Figure S1. Size of TAA and TAPM measured from center of molecule to nitrogen atoms of amine groups. Figure S2. Size of bis-imide links measured from the tetrahedral centers. S5
Figure S3. SEM image of PI-COF-4. Figure S4. SEM image of PI-COF-5. S6
Figure S5. FT-IR spectra of PI-COF-4 (a, black), TAA (b, red), and PMDA (c, blue). Figure S6. FT-IR spectra of PI-COF-5 (a, black), TAPM (b, red), and PMDA (c, blue). S7
Figure S7. Solid-state 13 C NMR spectra of PI-COF-4 (a, black) and -5 (b, red). Asterisks (*) indicate peaks arising from spinning side bands. Figure S8. TGA of PI-COF-4. S8
Figure S9. TGA of PI-COF-5. Figure S10. IR of PI-COF-4 based on different time: (a) one day, (b) three days, and (c) five days. S9
Figure S11. IR of PI-COF-5 based on different time: (a) one day, (b) three days, and (c) five days. Figure S12. PXRD of PI-COF-4 based on different time: (a) one day, (b) three days, and (c) five days. S10
Figure S13. PXRD of PI-COF-5 based on different time: (a) one day, (b) three days, and (c) five days. Figure S14. Calculated PXRD pattern of PI-COF-4 based on the non-interpenetrated diamond net. S11
Figure S15. Calculated PXRD pattern of PI-COF-4 based on the 2-fold interpenetrated diamond net. Figure S16. Calculated PXRD pattern of PI-COF-4 based on the 3-fold interpenetrated diamond net. S12
Figure S17. Comparison of PXRD patterns for PI-COF-4: experimental (a, black) as well as calculated from the non- (b, green), 2-fold (c, red) or 3-fold (d, blue) interpenetrated diamond nets. Figure S18. Calculated PXRD pattern of PI-COF-5 based on the non-interpenetrated diamond net. S13
Figure S19. Calculated PXRD pattern of PI-COF-5 based on the 2-fold interpenetrated diamond net. Figure S20. Calculated PXRD pattern of PI-COF-5 based on the 3-fold interpenetrated diamond net. S14
Figure S21. Calculated PXRD pattern of PI-COF-5 based on the 4-fold interpenetrated diamond net. Figure S22. Comparison of PXRD patterns for PI-COF-5: experimental (a, black) as well as calculated from the non- (b, green), 2-fold (c, red), 3-fold (d, blue) or 4-fold (e, pink) interpenetrated diamond nets. S15
Figure S23. BET plot of PI-COF-4 calculated from N 2 adsorption isotherm at 77 K. Figure S24. BET plot of PI-COF-5 calculated from N 2 adsorption isotherm at 77 K. S16
Figure S25. Pore size distribution histogram of PI-COF-4 calculated from N 2 adsorption isotherm at 77 K. Figure S26. Pore size distribution histogram of PI-COF-5 calculated from N 2 adsorption isotherm at 77 K. S17
Figure S27. PXRD of PI-COF-4 (a, black) and IBU-loaded PI-COF-4 (b, red). Figure S28. PXRD of PI-COF-5 (a, black) and IBU-loaded PI-COF-5 (b, red). S18
Figure S29. SEM image of IBU-loaded PI-COF-4. Figure S30. SEM image of IBU-loaded PI-COF-5. S19
Figure S31. N 2 sorption isotherms of PI-COF-4 (a, red) and IBU-loaded PI-COF-4 (b, blue). Figure S32. BET plot of IBU-loaded PI-COF-4 calculated from N 2 adsorption isotherm at 77 K. S20
Figure S33. N 2 sorption isotherms of PI-COF-5 (a, red) and IBU-loaded PI-COF-5 (b, blue). Figure S34. BET plot of IBU-loaded PI-COF-5 calculated from N 2 adsorption isotherm at 77 K. S21
Figure S35. TGA of IBU. Figure S36. TGA of IBU-loaded PI-COF-4. S22
Figure S37. TGA of IBU-loaded PI-COF-5. Figure S38. Release profile of captopril-loaded 3D PI-COFs. Inset: the structure of captopril. C, black; H, gray; O, red; N, blue, S, yellow. S23
Figure S39. Release profile of caffeine-loaded 3D PI-COFs. Inset: the structure of caffeine. C, black; H, gray; O, red; N, blue. S24
Section 3. Tables S1 S8 Table S1. Unit cell parameters and fractional atomic coordinates for PI-COF-4 based on the noninterpenetrated diamond net. Space group I4 1 /amd (No. 141) Calculated unit cell a = b = 20.49 Å, c = 32.20 Å, α = β = γ = 90º Measured unit cell a = b = 20.41 Å, c = 32.16 Å, α = β = γ = 90º Pawley refinement R p = 4.58%; wr p = 7.95% atom x y z C1 0.34725 0.69668 0.30103 C2 0.29431 0.71639 0.27374 C3 0.43739 0.75000 0.34595 C4 0.43894 0.81106 0.37500 C5 0.50000 0.75000 0.43041 C6 0.25000 0.82007 0.25000 O1 0.36384 0.64018 0.30584 N1 0.37790 0.75000 0.31869 H1 0.44049 0.85710 0.35712 H2 0.50000 0.73286 0.46313 H3 0.25000 0.87287 0.25000 S25
Table S2. Unit cell parameters and fractional atomic coordinates for PI-COF-4 based on the 2-fold interpenetrated diamond net. Space group P4 2 /n (No. 86) Calculated unit cell a = b = 15.42 Å, c = 14.06 Å, α = β = γ = 90º atom x y z C1-0.05937 0.05937 0.56351 C2 0.00000 0.11616 0.50000 C3-0.12274 0.12274 0.72002 C4-0.18705 0.18705 0.74753 C5-0.17552 0.17551 0.58744 C6-0.22029 0.22029 0.66397 C7-0.21541 0.21541 0.83702 C8 0.00000 0.00000 0.62523 O1-0.08047 0.08047 0.77660 O2-0.18870 0.18870 0.50324 N1-0.11641 0.11641 0.62229 H1-0.03889 0.15910 0.45319 H2 0.03889 0.15910 0.54681 H3-0.18939 0.18939 0.90252 H4-0.45828 0.45828 1.17075 S26
Table S3. Unit cell parameters and fractional atomic coordinates for PI-COF-4 based on the 3-fold interpenetrated diamond net. Space group I4 1 /amd (No. 141) Calculated unit cell a = b = 22.62 Å, c = 8.64 Å, α = β = γ = 90º atom x y z C1 0.71743 0.75000 0.61634 C2 0.68941 0.75000 0.75770 C3 0.67088 0.75000 0.50105 C4 0.62636 0.75000 0.72537 C5 0.77919 0.75000 0.60246 C6 0.44139 0.25000 0.52258 C7 0.50000 0.25000 0.42809 C8 0.44372 0.19372 0.62500 O1 0.68015 0.75000 0.36217 O2 0.58919 0.75000 0.82657 N1 0.61529 0.75000 0.56783 H1 0.69885 1.25000 0.99124 H2 0.50000 0.75000 0.05167 H3 0.44112 0.84510 0.45300 S27
Table S4. Unit cell parameters and fractional atomic coordinates for PI-COF-5 based on the noninterpenetrated diamond net. Space group I4 1 /amd (No. 141) Calculated unit cell a = b = 27.93 Å, c = 49.31 Å, α = β = γ = 90º atom x y z C1 0.31944 0.71086 0.28462 C2 0.28195 0.72535 0.26589 C3 0.43898 0.79300 0.34453 C4 0.40199 0.79310 0.32548 C5 0.38176 0.75000 0.31566 C6 0.45672 0.75000 0.35545 C7 0.25000 0.80140 0.25000 C8 0.50000 0.75000 0.37500 O1 0.32867 0.66921 0.28959 N1 0.34236 0.75000 0.29592 H1 0.45404 0.82707 0.35058 H2 0.39070 0.82781 0.31868 H3 0.59014 0.50000 0.50000 S28
Table S5. Unit cell parameters and fractional atomic coordinates for PI-COF-5 based on the 2-fold interpenetrated diamond net. Space group P4 2 /n (No. 86) Calculated unit cell a = b = 20.39 Å, c = 23.09 Å, α = β = γ = 90º atom x y z C1-0.11883 0.11929 0.61777 C2-0.20115 0.13555 0.69825 C3-0.23121 0.18978 0.72948 C4-0.15944 0.22551 0.66116 C5-0.20490 0.24653 0.70608 C6-0.27744 0.19081 0.77441 C7 1.12220 0.94940 0.61865 C8 1.04253 0.95708 0.54014 C9 1.08453 0.98701 0.58063 C10 1.07642 0.85070 0.57795 C11 1.03870 0.88824 0.53991 C12 1.00000 1.00000 0.50000 O1-0.21262 0.07777 0.70721 O2-0.12702 0.26241 0.63107 N1-0.15796 0.15827 0.65719 H1-0.29776 0.14284 0.79232 H2 1.15601 0.97520 0.65069 H3 1.08752 1.04281 0.58211 H4 1.07242 0.79497 0.57637 H5 1.00417 0.86313 0.50804 S29
Table S6. Unit cell parameters and fractional atomic coordinates for PI-COF-5 based on the 3-fold interpenetrated diamond net. Space group I4 1 /amd (No. 141) Calculated unit cell a = b = 35.39 Å, c = 7.84 Å, α = β = γ = 90º atom x y z C1 0.72332 0.75000 0.62365 C2 0.71226 0.75000 0.79207 C3 0.68887 0.75000 0.52394 C4 0.67110 0.75000 0.79118 C5 0.76145 0.75000 0.57425 C6 0.53977 0.75000 0.46093 C7 0.61730 0.75000 0.57233 C8 0.60765 0.75000 0.39821 C9 0.57033 0.75000 0.34514 C10 0.58684 0.75000 0.69005 C11 0.54895 0.75000 0.63571 C12 0.50000 0.75000 0.37500 O1 0.68879 0.75000 0.36880 O2 0.65198 0.75000 0.92020 N1 0.65700 0.75000 0.62669 H1 0.50000 0.48004 1.30830 H2 0.50000 0.62198 1.45291 H3 0.50000 0.68490 1.54119 H4 0.50000 0.72175 1.01600 H5 0.50000 0.65879 0.92424 S30
Table S7. Unit cell parameters and fractional atomic coordinates for PI-COF-5 based on the 4-fold interpenetrated diamond net. Space group P4/n (No. 85) Calculated unit cell a = b = 20.57 Å, c = 11.43 Å, α = β = γ = 90º Measured unit cell a = b = 20.63 Å, c = 11.50 Å, α = β = γ = 90º Pawley refinement R p = 6.83%; wr p = 9.62% atom x y z C1 0.47571 0.44200 0.55616 C2 0.52064 0.43984 0.46410 C3 0.55155 0.38515 0.40597 C4 0.54406 0.49556 0.41002 C5 0.63302 0.36942 0.23675 C6 0.62965 0.30142 0.24008 C7 0.66682 0.26372 0.16367 C8 0.70824 0.29296 0.08099 C9 0.71205 0.36119 0.07924 C10 0.67483 0.39883 0.15563 C11 0.91081 1.02527 1.31895 C12 0.75000 0.25000 0.00000 O1 0.95703 1.17188 1.43028 O2 0.88153 0.98856 1.25392 N1 0.59416 0.40820 0.31546 H1 0.45787 0.39496 0.59794 H2 0.59630 0.27631 0.30568 H3 0.66387 0.20843 0.16769 H4 0.74590 0.38655 0.01478 H5 0.67870 0.45406 0.15157 S31
Table S8. Parameters of drug loading and release amount in 3D PI-COFs. material drug loading capacity (wt%) PI-COF-4 PI-COF-5 release capacity (%) ibuprofen 24 95 captopril 23 91 caffeine 28 96 ibuprofen 20 95 captopril 18 90 caffeine 23 95 S32
Section 4. References (1) Newkome, G. R.; Nayak, A.; Behera, R. K.; Moorefield, C. N.; Baker, G. R. J. Org. Chem. 1992, 57, 358. (2) Senchyk, G. A.; Lysenko, A. B.; Boldog, I.; Rusanov, E. B.; Chernega, A. N.; Krautscheid, H.; Domasevitch, K. V. Dalton Trans. 2012, 41, 8675. (3) Fang, Q. R.; Gu, S.; Zheng, J.; Zhuang, Z. B.; Qiu, S. L.; Yan, Y. S. Angew. Chem., Int. Ed. 2014, 53, 2878. S33