Supporting Information

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1 Supporting Information Intrinsic Hydrophobicity versus Intraguest Interactions in Hydrophobically Driven Molecular Recognition in Water Roshan W. Gunasekara and Yan Zhao* Department of Chemistry, Iowa State University, Ames, Iowa , USA Table of Contents General Method...2 Scheme S1...3 Scheme S2...3 Scheme S3...3 Syntheses...4 Synthesis of MINPs DLS Measurements Figure 1S Figure 2S Figure 3S Figure 4S Figure 5S Figure 6S Figure 7S Figure 8S Figure 9S Figure 10S Figure 11S Figure 12S Figure 13S S1

2 Figure 14S Figure 15S Figure 16S Figure 17S Figure 18S Figure 19S Figure 20S Figure 21S Figure 22S Figure 23S H and 13 C NMR spectra General Method All reagents and solvents were of ACS-certified grade or higher, and were used as received from commercial suppliers. Routine 1 H and 13 C NMR spectra were recorded on a Bruker DRX-400, on a Bruker AV II 600, or on a Varian VXR-400 spectrometer. ESI-MS mass was recorded on Shimadzu LCMS-2010 mass spectrometer. ITC was performed using a MicroCal VP-ITC Microcalorimeter with rigin 7 software and VPViewer2000 (GE Healthcare, Northampton, MA). Fluorescence spectra were recorded at ambient temperature on a Varian Cary Eclipse Fluorescence spectrophotometer. S2

3 Scheme S1 Scheme S2 Scheme S3 S3

4 Syntheses Synthesis of compounds 1, 1,2 2, 1 3, 1 10, 3 and 11 4 were previously reported. Compound 12. 2,5-Dimethoxyaniline 10 (0.20 g, 1.31 mmol) and triethylamine (0.54 ml, 3.90 mmol) were dissolved in THF (5.00 ml) at 0 C. Triphosgene (0.129 g, 0.44 mmol) in THF (4 ml) was added dropwise to the reaction mixture. The reaction mixture was then allowed to warm to room temperature. After 2 h, methyl L-ornithine dihydrochloride 11 (0.141 g, 0.65 mmol) and triethylamine (0.27 ml, 1.94 mmol) were added and the reaction mixture was stirred at 65 C for 12 h. The reaction was monitored with TLC and the hot mixture was filtered. The crude product was precipitated at room temperature and recrystallized from 1:2 ethyl acetate/dichloromethane to obtain a white powder (0.29 g, 90%). 1 H NMR (600 MHz, DMS-d6, δ): 8.17 (s, 1H), 7.91 (s, 1H), 7.80 (d, J = 3.1 Hz, 1H), 7.76 (d, J = 3.1 Hz, 1H), 7.41 (d, J = 7.7 Hz, 1H), 7.00 (t, J = 5.6 Hz, 1H), 6.85 (dd, J = 12.4, 8.9 Hz, 2H), 6.41 (ddd, J = 15.1, 8.9, 3.1 Hz, 2H), 4.22 (td, 1H), 3.76 (s, 6H), 1.73 (m, 1H), 1.60 (dt, 1H), 1.47 (m, 2H). 13 C NMR (150 MHz, DMS-d6, δ): 173.8, 155.6, 155.2, 153.7, 142.0, 142.0, 130.9, 130.5, 111.8, 111.7, 105.4, 105.2, 105.2, 104.9, 56.7, 56.7, 55.7, 55.6, 52.7, 52.3, 45.8, 45.7, 29.6, 26.6.ESI-MS (m/z): [M+H] + cacld for C24H33N48, ; found, ; [M+Na] + cacld for C24H32N4Na8, ; found, Compound 4. A solution of compound 12 (0.20 g, mmol) in 2 M lithium hydroxide (1.98 ml, 3.96 mmol) and methanol (4 ml) was stirred at room temperature for 4 h. The organic solvent was removed by rotary evaporation. After a dilute HCl solution (0.05 M, 10 ml) was added to the mixture, the precipitate formed was collected by suction filtration, washed with cold water, and dried in vacuo to get a white powder (193 mg, 99%). To obtain the sodium salt of this compound, 1 Awino, J. K.; Zhao, Y. J. Am. Chem. Soc. 2013, 135, Gunasekara, R.W.; Zhao, Y. J. Am. Chem. Soc. 2017, 139, Wang, G. T; Zhao, X.; Li, Z.T. Tetrahedron 2011, 67, Ptchelintsev, Dmitri S.; Hu, Hong; Menon, Gopinathan K.; Schmalenberg, Kristine; Lyga, John W. 2010, US S4

5 the above acid was mixed with saturated sodium bicarbonate (0.3 ml) and methanol (4 ml). The reaction mixture was stirred for 5 h. After the solvents were removed by rotary evaporation, the residue was dissolved in methanol (4 ml). The solution was filtered and then concentrated by rotary evaporation to give the sodium salt as a white powder. 1 H NMR (400 MHz, MeH-d4, δ): 8.26 (s, 1H), 7.42 (dd, J = 7.3, 3.0 Hz, 2H), 6.53 (d, J = 8.9 Hz, 2H), 6.17 (dd, J = 8.9, 3.0 Hz, 2H), 3.92 (dd, 1H), 3.52 (d, J = 2.1 Hz, 6H), 3.43 (d, J = 1.4 Hz, 6H), 2.95 (q, 2H), 1.40 (dp, 4H). 13 C NMR (150 MHz, DMS-d6, δ): 173.4, 155.2, 154.8, 153.3, 153.3, 141.6, 141.6, 130.5, 130.1, 111.4, 111.3, 105.0, 104.8, 104.8, 104.5, 97.5, 56.3, 56.3, 55.3, 55.2, 51.9, 39.9, 39.8, 39.7, 39.6, 39.5, 39.4, 39.3, 39.2, 39.2, 39.1, 38.6, 29.2, ESI-MS (m/z): [M+Na] + cacld for C23H30N48Na, ; found, Compound 13. A suspension of 4-methyl-2-nitroanisole (6.0 g, 35.8 mmol) in absolute ethanol (20 ml) was deoxygenated and then hydrogenated in the presence of reduced Pd/C (20%, 0.35 g) under 550 psi of H2 at room temperature for 22 h. The catalyst was removed by filtration through a layer of celite. The filtrate was concentrated by rotary evaporation to give yellow oil. (4.8 g, 99%) 1 H NMR (400 MHz, CDCl3, δ): 6.69 (s, 1H), 6.54 (d, 2H), 3.83 (s, 3H), 2.23 (s, 3H). 13 C NMR (100 MHz, CDCl3, δ): 145.3, 135.8, 130.5, 118.7, 116.0, 110.5, 55.6, ESI-MS (m/z): [M+H] + cacld for C8H12N, ; found, Compound 14. Compound 13 (0.20 g, 1.46 mmol) and triethylamine (0.61 ml, 4.38 mmol) were dissolved in THF (5.00 ml) at 0 C. Triphosgene (0.144 g, 0.49 mmol) in THF (5.00 ml) was added to the reaction dropwise to the reaction mixture. The reaction mixture was then allowed to warm to room temperature. After 2.5 h, methyl L-ornithine dihydrochloride 11 (0.159 g, mmol) and triethylamine (0.34 ml, 2.44 mmol) were added and the reaction mixture was stirred at 65 C for 12 h. The reaction was monitored with TLC and the hot mixture was filtered. The S5

6 crude product was precipitated at room temperature and recrystallized from 1:2 ethyl acetate/dichloromethane to obtain a white powder (0.30 g, 89 %). 1 H NMR (400 MHz, DMS-d6, δ): 7.98 (s, 1H), 7.80 (d, J = 2.1 Hz, 1H), 7.50 (s, 1H), 7.08 (d, J = 7.0 Hz, 1H), 6.73 (d, J = 8.2 Hz, 1H), 6.57 (dd, J = 8.1, 2.2 Hz, 1H), 4.06 (d, J = 5.4 Hz, 2H), 3.91 (m, 1H), 3.68 (s, 3H), 3.07 (d, J = 4.1 Hz, 6H), 2.41 (s, 3H), 2.09 (s, 3H), 2.02 (dd, J = 12.4, 5.7 Hz, 1H), 1.68 (t, J = 4.9 Hz, 2H), 1.46 (m, 1H). 13 C NMR (100 MHz, DMS-d6, δ): 173.9, 155.5, 155.2, 145.7, 129.6, 129.5, 129.3, 121.8, 121.5, 119.4, 119.1, 119.1, 110.9, 110.8, 56.2, 52.7, 52.3, 49.1, 41.3, 39.8, 39.0, 29.6, 26.6, ESI-MS (m/z): [M+H] + cacld for C24H33N46, ; found, Compound 5. A solution of compound 14 (0.20 g, mmol) in 2 M lithium hydroxide (2.12 ml, 4.24 mmol) and methanol (4.5 ml) was stirred at room temperature for 4 h. The organic solvent was removed by rotary evaporation. After a dilute HCl solution (0.05 M, 10 ml) was added to the mixture, the precipitate formed was collected by suction filtration, washed with cold water, and dried in vacuo to get a white powder (193 mg, 99%). To obtain the sodium salt of this compound, the above acid was mixed with saturated sodium bicarbonate (0.3 ml) and methanol (4 ml). The reaction mixture was stirred for 5 h. After the solvents were removed by rotary evaporation, the residue was dissolved in methanol (4 ml). The solution was filtered and then concentrated by rotary evaporation to give the sodium salt as a white powder. 1 H NMR (600 MHz, D2, δ): 8.45 (s, 1H), 7.49 (m, 1H), 7.32 (m, 1H), (m, 4H), 4.13 (d, J = 7.1 Hz, 1H), 3.79 (s, 6H), 2.24 (s, 6H), 1.85 (m, 1H), (m, 3H). 13 C NMR (150 MHz, DMS-d6, δ): 175.0, 166.3, 155.1, 154.8, 154.8, 145.6, 145.6, 145.2, 129.8, 129.4, 129.0, 128.9, 121.2, 120.8, 120.7, 119.2, 118.7, 110.5, 110.4, 55.8, 55.7, 54.4, 40.9, 40.1, 39.9, 39.7, 39.5, 39.4, 39.3, 39.2, 39.1, 38.9, 31.5, 26.3, ESI-MS (m/z): [M+H] + cacld for C23H31N46, ; found, S6

7 Compound 15. A suspension of 1,4-dimethyl-2-nitrobenzene (2.0 g, 13.2 mmol) in absolute ethanol (10 ml) was deoxygenated and then hydrogenated in the presence of reduced Pd/C (20%, 0.2 g) under 550 psi of H2 at room temperature for 16 h. The catalyst was removed by filtration through a layer of celite. The filtrate was concentrated by rotary evaporation to give yellow oil (1.58 g, 99%). 1 H NMR (600 MHz, CDCl3, δ): 6.93 (d, J = 7.4 Hz, 1H), 6.53 (d, 2H), 2.25 (s, 3H), 2.11 (m, 3H). 13 C NMR (150 MHz, CDCl3, δ): 144.1, 136.7, 130.3, 119.6, 119.5, 115.9, 21.1, ESI-MS (m/z): [M+H] + cacld for C8H12N, ; found, Compound 16. 2,5-Dimethylaniline 15 (0.20 g, 1.65 mmol) and triethylamine (0.69 ml, 4.95 mmol) were dissolved in THF (6.00 ml) at 0 C. Triphosgene (0.163 g, 0.55 mmol) in THF (5 ml) was added to the reaction dropwise to the reaction mixture. The reaction mixture was then allowed to warm to room temperature. After 2.5 h, methyl L-ornithine dihydrochloride 11 (0.179 g, mmol) and triethylamine (0.34 ml, 2.44 mmol) were added and the reaction mixture was stirred at 65 C for 12 h. The reaction was monitored with TLC and the hot mixture was filtered. The crude product was precipitated at room temperature and recrystallized from 1:2 ethyl acetate/dichloromethane to obtain a white powder (0.33 g, 92 %). 1 H NMR (600 MHz, DMS-d6, δ): 8.52 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 17.8 Hz, 1H), 7.53 (m, 1H), 7.18 (m, 2H), 6.96 (dd, J = 19.2, 11.6 Hz, 2H), 6.66 (d, J = 7.5 Hz, 1H), 6.56 (dt, J = 10.9, 5.9 Hz, 1H), 4.30 (dt, 1H), 3.54 (m, 1H), 3.12 (m, 2H), 2.48 (s, 3H ), 2.27 (s, 3H), 2.19 (s, 3H), 2.10 (s, 3H), 2.03 (s, 3H), 1.82 (m, 1H), (m, 4H). 13 C NMR (100 MHz, DMS-d6, δ): 173.9, 155.9, 138.4, 136.3, 135.3, 130.8, 130.3, 130.2, 130.0, 129.8, 129.6, 123.3, 123.0, 121.5, 57.0, 40.4, 39.2, 29.7, 29.4, 25.9, 21.4, 20.7, 17.9, ESI-MS (m/z): [M+H] + cacld for C24H33N44, ; found, Compound 6. A solution of compound 15 (0.20 g, mmol) in 2 M lithium hydroxide (2.27 ml, 4.54 mmol) and methanol (4.5 ml) was stirred at room temperature for 4 h. The organic S7

8 solvent was removed by rotary evaporation. After a dilute HCl solution (0.05 M, 10 ml) was added to the mixture, the precipitate formed was collected by suction filtration, washed with cold water, and dried in vacuo to get a white powder (192 mg, 99%). To obtain the sodium salt of this compound, the above acid was mixed with saturated sodium bicarbonate (0.3 ml) and methanol (4 ml). The reaction mixture was stirred for 5 h. After the solvents were removed by rotary evaporation, the residue was dissolved in methanol (4 ml). The solution was filtered and then concentrated by rotary evaporation to give the sodium salt as a white powder. 1 H NMR (400 MHz, MeH-d4, δ): 8.45 (s, 1H), 7.17 (d, J = 8.0 Hz, 4H), 7.04 (d, J = 8.0 Hz, 2H), 4.11 (d, 2H), 2.28 (s, 6H), 2.19 (s, 6H), (m, 4H). 13 C NMR (150 MHz, DMS-d6, δ): 174.9, 155.5, 155.0, 154.9, 138.5, 138.4, 134.6, 134.5, 129.6, 123.8, 123.7, 122.1, 121.9, 121.3, 121.2, 79.2, 40.1, 39.9, 39.7, 39.5, 39.3, 39.1, 38.9, 31.5, 26.2, 21.0, 17.8, ESI-MS (m/z): [M+H] + cacld for C23H31N44, ; found, Compound 17. Methyl L-ornithine dihydrochloride 11 (0.24 g, 1.1 mmol), 2,4-dinitrobenzoic acid (0.48 g, 2.29 mmol), (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BP, 1.01 g, 2.3 mmol), 1-hydroxybenzotriazole hydrate (HBt, g, 2.3 mmol), and N,N-diisopropylethyl-amine (DIPEA, 1.59 ml, 9.16 mmol) were dissolved in N,Ndimethylformamide (6 ml). The reaction mixture was stirred for 2 h in a microwave reactor at 65 C (150 W), cooled down to room temperature, and poured into a dilute HCl aqueous solution (0.05 M, 18 ml). The precipitate formed was collected by suction filtration, washed with water, dried in air, and purified by column chromatography over silica gel with 5:1 dichloromethane/methanol as the eluent to give an off-white powder (0.47 g, 80%). 1 H NMR (600 MHz, DMS-d6, δ): 9.42 (s, 1H), 8.97 (t, J = 5.7 Hz, 1H), 8.77 (dd, J = 12.9, 2.2 Hz, 2H), 8.62 (ddd, J = 17.8, 8.4, 2.3 Hz, 2H), 7.88 (dd, J = 8.4, 2.2 Hz, 2H), 4.52 (m, 5.1 Hz, 1H), 3.71 (s, 3H), S8

9 1.94 (t, 1H), 1.78 (t, 1H), 1.65 (m, 2H). 13 C NMR (100 MHz, DMS-d6, δ): 172.2, 164.6, 164.4, 148.5, 148.3, 147.5, 147.4, 137.9, 137.2, 131.4, 131.2, 128.7, 128.6, 120.2, 120.2, 52.7, 52.6, 39.1, 28.6, ESI-MS (m/z): [M+Na] + cacld for C20H18N612Na, ; found, Compound 7. A solution of compound 17 (0.38 g, 0.71 mmol) in 2 M lithium hydroxide (3.40 ml, 6.8 mmol) and methanol (4 ml) was stirred at room temperature for 4 h. The organic solvent was removed by rotary evaporation. After a dilute HCl solution (0.05 M, 10 ml) was added to the mixture, the precipitate formed was collected by suction filtration, washed with cold water, and dried in vacuo to get a white powder (366 mg, 99%). To obtain the sodium salt of this compound, the above acid was mixed with saturated sodium bicarbonate (0.5 ml) and methanol (5 ml). The mixture was stirred for 5 h. After the solvents were removed by rotary evaporation, the residue was dissolved in methanol (5 ml). The solution was filtered and then concentrated by rotary evaporation to give the sodium salt as a white powder. 1 H NMR (600 MHz, DMS-d6, δ): 8.57 (s, 1H), 8.30 (t, J = 5.7 Hz, 1H), 7.90 (dd, J = 12.9, 2.2 Hz, 2H), 7.90 (ddd, J = 17.8, 8.4, 2.3 Hz, 2H), 7.80 (dd, J = 8.4, 2.2 Hz, 2H), 4.48 (m, 5.1 Hz, 1H), 1.92 (t, 1H), 1.81 (t, 1H), 1.62ii (m, 2H). 13 C NMR (150 MHz, DMS-d6, δ): 171.7, 164.2, 163.9, 148.0, 148.0, 147.8, 147.0, 146.9, 137.4, 136.8, 130.9, 130.7, 128.2, 128.1, 119.7, 119.7, 40.1, 39.9, 39.8, 39.7, 39.5, 39.4, 39.2, 39.2, 39.1, 38.7, 28.1, ESI-MS (m/z): [M+Na] + cacld for C19H16N612Na, ; found, Compound 8. Compound 10 (50 mg, 0.44 mmol) was added to a solution of glutaric anhydride (73 mg, 0.48 mmol) in toluene (4 ml) with constant stirring. The dark colored suspension was heated to reflux for 1 h. The reaction mixture was cooled to room temperature and the precipitate formed was collected by filtration to afford a purple powder (113 mg, 98%). 1 H NMR (400 MHz, MeH-d4, δ): 7.68 (d, J = 3.1 Hz, 1H), 6.89 (d, J = 9.0 Hz, 1H), 6.62 (dd, J = 8.9, 3.1 Hz, 1H), 3.81 (s, 3H), 3.72 (s, 3H), 2.47 (t, J = 7.4 Hz, 2H), 2.38 (t, J = 7.4 Hz, 2H), 1.95 (p, J = 7.4 Hz, S9

10 2H). 13 C NMR (100 MHz, MeH-d4, δ): 172.4, 153.5, 144.1, 127.6, 111.1, 108.4, 55.4, 54.7, 48.0, 47.7, 35.5, 32.7, ESI-MS (m/z): [M+H] + cacld for C13H18 N5, ; found, Compound 9. 4-Aminobutanoic acid (0.030 g, 0.29 mmol) was dissolved in water (1.5 ml) to which sodium bicarbonate (0.048 g, 0.58 mmol) was added. After the mixture was stirred for 2 h, a solution of 2,4-dinitrobenzoic acid (0.068 g, mmol), N-hydroxysuccinimide (0.100 g, 8.70 mmol), and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDCI, g, mmol) in tetrahydrofuran (6 ml) was added. The reaction mixture was stirred for 4 h in a microwave reactor at 55 C (150 W) and extracted with ethyl acetate (3 5 ml). The combined organic solution was washed with water (5 ml), and dried with MgS4, and concentrated by rotary evaporation. The residue was purified by column chromatography over silica gel with 5:1 dichloromethane/methanol as the eluent to give a white powder (69 mg,80%). 1 H NMR (600 MHz, DMS-d6/CDCl3 = 1:1, δ): 8.51 (d, J = 2.1 Hz, 1H), 8.17 (dt, J = 8.3, 2.1 Hz, 1H), 7.40 (dd, J = 8.4, 1.8 Hz, 1H), 6.60 (d, J = 5.9 Hz, 1H), 3.13 (t, 1.7 Hz, 2H), 2.13 (t, 1.8 Hz, 2H), 1.59 (m, 1.8 Hz, 2H). 13 C NMR (150 MHz, DMS-d6/CDCl3 = 1:1, δ): 174.2, 164.6, 148.2, 138.0, 130.4, 128.1, 120.0, 51.9, 40.0, 31.5, ESI-MS (m/z): [M-H] - cacld for C11H10N37, ; found, Synthesis of MINPs. MINPs were synthesized according to previously reported procedures. 1 To a micellar solution of surfactant 1 (9.3 mg, 0.02 mmol) in D2 (2.0 ml), divinylbenzene (DVB, 2.8 µl, 0.02 mmol), 4 in DMS (10 µl of a solution of 20.5 mg/ml, mmol), and 2,2- dimethoxy-2-phenylacetophenone (DMPA) in DMS (10 µl of a 12.8 mg/ml, mmol) were added. The mixture was ultrasonicated for 10 min. Compound 2 (4.1 mg, mmol), CuCl2 in D2 (10 µl of 6.7 mg/ml, mmol), and sodium ascorbate in D2 (10 µl of 99 mg/ml, mmol) were then added and the reaction mixture was stirred slowly at room S10

11 temperature for 12 h. Compound 3 (10.6 mg, 0.04 mmol), CuCl2 (10 µl of a 6.7 mg/ml solution in D2, mmol), and sodium ascorbate (10 µl of a 99 mg/ml solution in D2, mmol) were then added and the solution stirred for another 6 h at room temperature. The reaction mixture was transferred to a glass vial, purged with nitrogen for 15 min, sealed with a rubber stopper, and irradiated in a Rayonet reactor for 12 h. 1 H NMR spectroscopy was used to monitor the progress of reaction. The reaction mixture was poured into acetone (8 ml). The precipitate was collected by centrifugation and washed with a mixture of methanol/acetic acid (5 ml/0.1 ml) three times. The off-white product was dried in air to afford the final MINPs in quantitative yield (> 80%). DLS Measurements DLS studies were performed on a PDDLS/ Cool Batch 90 T Dynamic Light Scattering Detector at 25.0 C. The intensity data was analyzed with the PRECISIN DECNVLVE program. The concentration of the sample required for successful measurement is dependent on the size of the scattering particles. Since a large particle will scatter more light than a smaller particle, a lower concentration will be required. If the concentration is too high, multiple scattering can be a problem. In addition, inter-particle interactions makes analysis of the results obtained at high concentration difficult. verall, the scattering intensity was maintained below 1,000,000 counts/sec and optimally between 400,000 and 700,000. The sample time, number of channels, the number of last channels, the run time, and the smoothness parameter were chosen to optimize the correlation curves and afford reproducible results. S11

12 Figure 1S. 1 H NMR spectra of (a) Compound 1 in CDCl3, (b) alkynyl-scm in D2, and (c) MINP(4) in D2. S12

13 (a) (b) (c) Diameter Diameter Diameter Figure 2S. Distribution of the hydrodynamic diameters of the nanoparticles in water as determined by DLS for (a) alkynyl-scm, (b) surface-functionalized SCM, and (c) MINP(4) after purification. (a) (b) Correlation Time Molecular Weight Figure 3S. Distribution of the molecular weights and the correlation curves for MINP(4) from the DLS. The PRECISIN DECNVLVE program assumes the intensity of scattering is proportional to the mass of the particle squared. If each unit of building block for the MINP(4) is assumed to contain one molecule of compound 1 (MW = 465 g/mol), 1.2 molecules of compound 2 (MW = 172 g/mol), one molecule of DVB (MW = 130 g/mol), and 0.8 molecules of compound 3 (MW = 264 g/mol), the molecular weight of MINP(4) translates to 51 [= / ( ] of such units. S13

14 f1 (ppm) Figure 4S. 1 H NMR spectra of (a) Compound 1 in CDCl3, (b) alkynyl-scm in D2, and (c) MINP(5) in D2. (a) (b) (c) Diameter Diameter Diameter Figure 5S. Distribution of the hydrodynamic diameters of the nanoparticles in water as determined by DLS for (a) alkynyl-scm, (b) surface-functionalized SCM, and (c) MINP(5) after purification. S14

15 (a) (b) Correlation Time Molecular Weight Figure 6S. Distribution of the molecular weights and the correlation curves for MINP(5) from the DLS. The PRECISIN DECNVLVE program assumes the intensity of scattering is proportional to the mass of the particle squared. If each unit of building block for the MINP(5) is assumed to contain one molecule of compound 1 (MW = 465 g/mol), 1.2 molecules of compound 2 (MW = 172 g/mol), one molecule of DVB (MW = 130 g/mol), and 0.8 molecules of compound 3 (MW = 264 g/mol), the molecular weight of MINP(5) translates to 51 [= / ( ] of such units. S15

16 f1 (ppm) Figure 7S. 1 H NMR spectra of (a) Compound 1 in CDCl3, (b) alkynyl-scm in D2, and (c) MINP(6) in D2. (a) (b) (c) Diameter Diameter Diameter Figure 8S. Distribution of the hydrodynamic diameters of the nanoparticles in water as determined by DLS for (a) alkynyl-scm, (b) surface-functionalized SCM, and (c) MINP(6) after purification. S16

17 (a) (b) Correlation Time Molecular Weight Figure 9S. Distribution of the molecular weights and the correlation curves for MINP(6) from the DLS. The PRECISIN DECNVLVE program assumes the intensity of scattering is proportional to the mass of the particle squared. If each unit of building block for the MINP(6) is assumed to contain one molecule of compound 1 (MW = 465 g/mol), 1.2 molecules of compound 2 (MW = 172 g/mol), one molecule of DVB (MW = 130 g/mol), and 0.8 molecules of compound 3 (MW = 264 g/mol), the molecular weight of MINP(6) translates to 51 [= / ( ] of such units. S17

18 f1 (ppm) Figure 10S. 1 H NMR spectra of (a) Compound 1 in CDCl3, (b) alkynyl-scm in D2, and (c) MINP(7) in D2. (a) (b) (c) Diameter Diameter Diameter Figure 11S. Distribution of the hydrodynamic diameters of the nanoparticles in water as determined by DLS for (a) alkynyl-scm, (b) surface-functionalized SCM, and (c) MINP(7) after purification. S18

19 (a) (b) Correlation Time Molecular Weight Figure 12S. Distribution of the molecular weights and the correlation curves for MINP(7) from the DLS. The PRECISIN DECNVLVE program assumes the intensity of scattering is proportional to the mass of the particle squared. If each unit of building block for the MINP(7) is assumed to contain one molecule of compound 1 (MW = 465 g/mol), 1.2 molecules of compound 2 (MW = 172 g/mol), one molecule of DVB (MW = 130 g/mol), and 0.8 molecules of compound 3 (MW = 264 g/mol), the molecular weight of MINP(7) translates to 51 [= / ( ] of such units. S19

20 f1 (ppm) Figure 13S. 1 H NMR spectra of (a) Compound 1 in CDCl3, (b) alkynyl-scm in D2, and (c) MINP(8) in D2. (a) (b) (c) Diameter Diameter Diameter Figure 14S. Distribution of the hydrodynamic diameters of the nanoparticles in water as determined by DLS for (a) alkynyl-scm, (b) surface-functionalized SCM, and (c) MINP(8) after purification. S20

21 (a) (b) Correlation Time Molecular Weight Figure 15S. Distribution of the molecular weights and the correlation curves for MINP(8) from the DLS. The PRECISIN DECNVLVE program assumes the intensity of scattering is proportional to the mass of the particle squared. If each unit of building block for the MINP(8) is assumed to contain one molecule of compound 1 (MW = 465 g/mol), 1.2 molecules of compound 2 (MW = 172 g/mol), one molecule of DVB (MW = 130 g/mol), and 0.8 molecules of compound 3 (MW = 264 g/mol), the molecular weight of MINP(8) translates to 50 [= / ( ] of such units. S21

22 f1 (ppm) Figure 16S. 1 H NMR spectra of (a) Compound 1 in CDCl3, (b) alkynyl-scm in D2, and (c) MINP(9) in D2. (a) (b) (c) Diameter Diameter Diameter Figure 17S. Distribution of the hydrodynamic diameters of the nanoparticles in water as determined by DLS for (a) alkynyl-scm, (b) surface-functionalized SCM, and (c) MINP(9) after purification. S22

23 (a) (b) Correlation Time Molecular Weight Figure 18S. Distribution of the molecular weights and the correlation curves for MINP(9) from the DLS. The PRECISIN DECNVLVE program assumes the intensity of scattering is proportional to the mass of the particle squared. If each unit of building block for the MINP(9) is assumed to contain one molecule of compound 1 (MW = 465 g/mol), 1.2 molecules of compound 2 (MW = 172 g/mol), one molecule of DVB (MW = 130 g/mol), and 0.8 molecules of compound 3 (MW = 264 g/mol), the molecular weight of MINP(9) translates to 50 [= / ( ] of such units. S23

24 (a) (b) (c) (d) Model: nesites N ±0.04 K 19.6E4 ±1.1E4 H E3 ±1.17E3 S Model: nesites N 1.06 ± 0.05 K 6.11E4 ± 0.511E4 H ± 248 S Model: nesites N 1.21 ± K 2.94E4 ± 0.80E4 H ± 689 S Model: nesites N 1.17 ± K 4.87E3 ± 176 H ± 335 S Figure 19S. ITC titration curves obtained at 298 K for the titration of MINP(4) with (a) 4, (b) 5, (c) 6, and (d) 7 in Millipore water. The data correspond to entries 1 4, respectively, in Table 1. The top panel shows the raw calorimetric data. The area under each peak represents the amount of heat generated at each ejection and is plotted against the molar ratio of MINP to the substrate. The solid line is the best fit of the experimental data to the sequential binding of N equal and independent binding sites on the MINP. The heat of dilution for the substrate, obtained by adding the substrate to water, was subtracted from the heat released during the binding. Binding parameters were auto-generated after curve fitting using Microcal rigin 7. S24

25 (a) (b) (c) (d) Model: nesites N 0.91 ± 0.12 K 7.11E4 ± 0.13E4 H ± 868 S Model: nesites N 0.91 ± 0.03 K 4.08E4 ± 0.22E4 H ± 199 S Model: nesites N 1.09 ± 0.25 K 1.84E4 ± 0.47E4 H ± 91.7 S Model: nesites N 1.15 ± 0.05 K 0.83E4 ± 0.02E4 H ± 75 S Figure 20S. ITC titration curves obtained at 298 K for the titration of MINP(5) with (a) 5, (b) 4, (c) 6, and (d) 7 in Millipore water. The data correspond to entries 5 8, respectively, in Table 1. The top panel shows the raw calorimetric data. The area under each peak represents the amount of heat generated at each ejection and is plotted against the molar ratio of MINP to the substrate. The solid line is the best fit of the experimental data to the sequential binding of N equal and independent binding sites on the MINP. The heat of dilution for the substrate, obtained by adding the substrate to water, was subtracted from the heat released during the binding. Binding parameters were auto-generated after curve fitting using Microcal rigin 7. S25

26 (a) (b) Model: nesites N 1.11 ± 0.08 K 6.50E4 ± 0.46E4 H ± 120 S Model: nesites N 0.90 ± K 1.90E4 ± 0.68E4 H ± 495 S Figure 21S. ITC titration curves obtained at 298 K for the titration of (a) MINP(6) with 6 and (b) MINP(7) with 7 in Millipore water. The data correspond to entries 9 10, respectively, in Table 1. The top panel shows the raw calorimetric data. The area under each peak represents the amount of heat generated at each ejection and is plotted against the molar ratio of MINP to the substrate. The solid line is the best fit of the experimental data to the sequential binding of N equal and independent binding sites on the MINP. The heat of dilution for the substrate, obtained by adding the substrate to water, was subtracted from the heat released during the binding. Binding parameters were auto-generated after curve fitting using Microcal rigin 7. S26

27 (a) (b) Model: nesites N 0.82 ± K 0.53E4 ± 0.033E4 H ± S Model: nesites N 0.91 ± 0.19 K 9.21E3 ± 913 H ± S Figure 22S. ITC titration curves obtained at 298 K for the titration of (a) MINP(8) with 8 and (b) MINP(9) with 9 in Millipore water. The data correspond to entries 11 12, respectively, in Table 1. The top panel shows the raw calorimetric data. The area under each peak represents the amount of heat generated at each ejection and is plotted against the molar ratio of MINP to the substrate. The solid line is the best fit of the experimental data to the sequential binding of N equal and independent binding sites on the MINP. The heat of dilution for the substrate, obtained by adding the substrate to water, was subtracted from the heat released during the binding. Binding parameters were auto-generated after curve fitting using Microcal rigin 7. S27

28 (a) Figure 23S. ITC titration curve obtained at 298 K for the titration of (a) 4 into 10 mm HEPES buffer. The data correspond to background titration in Table 1. The top panel shows the raw calorimetric data. The area under each peak represents the amount of heat generated at each ejection and is plotted against the molar ratio of MINP to the substrate. This is the heat of dilution for the substrate, was subtracted from the heat released during the binding. Binding parameters were auto-generated after curve fitting using Microcal rigin 7. S28

29 1 H and 13 C NMR spectra S29

30 S f1 (ppm) NH N H H HN HN 4 NH N H H HN HN 4

31 S31

32 S32

33 S33

34 S34

35 S35

36 d2o f1 (ppm) S36

37 2 N N H N 2 NH 17 N 2 N 2 2 N N H N 2 NH 17 N 2 N 2 S37

38 f1 (ppm) S38

39 S39

40 S40