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Supporting Information to

Convergent Synthesis of 2nd Generation AB-Type Miktoarm Dendrimers using Click Chemistry Catalyzed by Copper Wire.

Carl N. Urbani, Craig A. Bell, Michael R. Whittaker and Michael J. Monteiro*

Australian Institute of Bioengineering and Nanotechnology, University of Queensland, St Lucia QLD 4072, Brisbane, Australia e-mail: m.monteiro@uq.edu.au

EXPERIMENTAL.................................................................................................................... 3 Materials: ............................................................................................................................ 3 Synthesis of ATRP Initiators: ............................................................................................ 4 Synthesis of 3-hydroxypropyl 2-bromo-2-methylpropanoate 3:. ...................................... 4 Synthesis of polymers using ATRP ................................................................................... 4 Synthesis of PSTY-Br 4:. ................................................................................................... 4 Synthesis of PMA-Br 5: ................................................................................................... 5 Synthesis of PtBA-Br 6: ................................................................................................... 5 Synthesis of HO-PSTY-Br 7: ........................................................................................... 6 Synthesis of polymers with azide functionality ................................................................ 6 Synthesis of PSTY-N3 8: .................................................................................................... 6 Synthesis of 2nd Generation Homo and Miktoarm functional dendrons ....................... 7 Synthesis of functional arm HO-PSTY-(- )2 12 ................................................................ 7 Synthesis of functional arm star G2[G1PSTY-OH, G2PSTY2] 13.................................... 8 Synthesis of functional arm star G2[G1PSTY-Br, G2PSTY2] 16 .................................... 9 Synthesis of functional arm star G2[G1PSTY-N3, G2PSTY2] 19 ................................... 10 Synthesis of functional arm star G2[G1PSTY-(3)2, G2PSTY2] 22 ................................. 10 Synthesis of 2nd Generation Homo and Miktoarm functional dendrimers ................. 11 Synthesis of 3-arm dendrimer G2[G1PSTY3,G2PSTY6] 23 ............................................ 11 Synthesis of G2[G1PSTY3,G2PSTY2-PAA4] 26: .......................................................... 13 Degradation of 3-arm dendrimer G2[G1PSTY3,G2PSTY6] 23:. .................................... 13 Degradation of mikto-arm dendrimer G2[G1PSTY3, G2PSTY2-PtBA4] 25:................... 13 Analytical Methodologies ..................................................................................................... 13 1 H and 13C Nuclear Magnetic Resonance (NMR): ............................................................. 14 Attenuated Total Reflectance Fourier Transform Spectroscopy (ATR-FTIR):................... 14 Size Exclusion Chromatography (SEC):............................................................................. 14 Atomic Absorption Spectroscopy (AAS): .......................................................................... 15 Scheme 1: Synthetic route to azido functional and alkyne functional linear polymers. ........ 16 Scheme 2: Synthetic route to azido functional homo and mikto-arm stars and alkyne functional PSTY stars. ............................................................................................................ 17 Scheme 3: Synthetic route to homo and mikto-arm dendrimers........................................... 18 Table 1: Size exclusion chromatographic data for the synthesis of 3-mikto-arm stars.......... 19 Figure 1: Size exclusion chromatograms using refractive index detection of G2[G1PSTYOH, G2PSTY2] 13 and G2[G1PSTY3,G2PSTY6] 23.. ........................................................... 19 Figure 2: Size exclusion chromatograms using refractive index detection of G2[G1PSTYOH, G2PSTY2] 13 and G2[G1PSTY3,G2PSTY2-PMA4] 24. f .............................................. 20 Figure 3: Size exclusion chromatograms using refractive index detection of G2[G1PSTYOH, G2PSTY2] 13 and G2[G1PSTY3,G2PSTY2-PtBA4] 25. f ............................................... 21 Figure 4: Size exclusion chromatograms using refractive index detection of G2[G1PSTY3,G2PSTY6] 23 and after degradation reaction with NaOCH3........................... 21 Figure 5: Attenuated Total Reflectance Fourier Transform Infrared Spectra (ATR-FTIR) of (a) HO-PSTY-Br 7 (b) HO-PSTY-N3 11 (c) HO-PSTY-(C)2 12 and (d) G2[G1PSTY-OH, G2PSTY2] 13. ......................................................................................................................... 22 Figure 6: 1H NMR spectra of (a) HO-PSTY-Br 7 (b) HO-PSTY-N3 11 and (c) HO-PSTY( )2 13. .................................................................................................................................... 23 Figure 7: 1H NMR spectra of (a) G2[G1PSTY3,G2PSTY2-PtBA4] 25 full spectrum (b) expanded section showing tert-butyl groups and (c) G2[G1PSTY3,G2PSTY2-PAA4] 26 expanded to show loss of tert-butyl groups and addition of trifluoroester. ............................ 24

EXPERIMENTAL
Materials: The following monomers were deinhibited before use by passing through a basic alumina column; methyl acrylate (MA: Aldrich, .99%), styrene (STY: Aldrich, >99 %) and tert-butyl acrylate (tBA: Aldrich, >99 %). The following chemicals were used as received; alumina, activated basic alumina (Aldrich: Brockmann I, standard grade, ~ 150 mesh, 58 ), anhydrous magnesium sulfate (MgSO4: Scharlau, extra pure), sodium chloride (NaCl: Univar, 99.9 %), sodium methoxide (NaOCH3: Aldrich, 95%), triethylamine (TEA: Fluka, 98 %), 2-bromoisobutyryl bromide (BIB: Aldrich, 98 %), 1,3-Propanediol (Fluka, >99 %), bromoacetyl bromide (BAB: Fluka, 98 %), sodium azide (NaN3: Aldrich, I 99.5 %) and tripropargylamine (TPA: Aldrich, 98 %). The following solvents were used as received; Acetone (ChemSupply, AR), anisole

(Fluka, 98 %), chloroform (CHCl3: Univar, AR grade), dichloromethane (DCM: Labscan, AR grade), diethyl ether (Univar, AR grade), methanol, anhydrous (MeOH: Mallinckrodt, 99.9 %, HPLC grade), Milli-Q water (Biolab, 18.2 M m), N,N-dimethylformamide (DMF: Labscan, AR grade) and tetrahydrofuran (THF: Labscan, HPLC grade). The following initiators, ligands and metals for the various polymerizations are given below and used as received unless otherwise stated. N,N,N,N,N-

pentamethyldiethylenetriamine (PMDETA: Aldrich, 99 %), copper (I) bromide (CuBr: Aldrich, 99.999 %), copper (II) bromide (CuBr2: Aldrich, 99 %), ethyl-2-bromoisobutyrate (1, EBiB: Aldrich, 98 %) and methyl-2-bromopropionate (2, MBP: Aldrich, 98 %).

Synthesis of ATRP Initiators: Synthesis of 3-hydroxypropyl 2-bromo-2-methylpropanoate 3: 1,3-Propanediol (33.20 g, 0.44 mol) and triethylamine (2.21 g, 0.02 mol) were stirred in THF (60 ml) and cooled in an ice bath. 2-bromoisobutyrylbromide (5.00 g, 0.02 mol) in THF (40 mL) was added dropwise under nitrogen and the reaction mixture was stirred overnight at room temperature. The mixture was filtered and the solvent evaporated on a rotary evaporator. The resultant clear oil was taken up in diethyl ether (200 mL) and the organics washed with 10% (v/v) HCl (1*200 mL), brine (1*200 mL) and water (1*200 mL). The organic layer was dried with magnesium sulphate and the solvent removed on a rotary evaporator. The product was purified by column chromatography (with 40/60 ethyl ether/hexane as eluting solvent), resulting in a clear oil. 1H NMR (CDCl3) 4.60 4.49 (s, br, 1H, OH); 4.17 (t, 1J = 7.96 Hz, 2H, CH2); 3.48 (t, 1J = 6.32

Hz, 2H, CH2); 1.87 (s, 6H, CH3); 1.75 (q, 1J = 6.32 Hz, 2H, CH2).

Synthesis of polymers using ATRP Synthesis of PSTY-Br 4: Freshly purified styrene (15.06 g, 0.145 mol), PMDETA (0.190 mL, 9.09 x 10-4 mol), EBiB (1, 0.145 g, 7.44 x 10-4 mol) and CuBr2 (0.0346 g, 1.55 x 10-4 mol) were added to a 50 mL Schlenk flask equipped with a magnetic stirrer then purged with N2 for 20 min. After stirring for 1 h CuBr (0.109 g, 7.60 x 10-4 mol) was carefully added under positive N2 flow and the reaction mixture purged with N2 for a further 5 min. The flask was placed in a temperature controlled oil bath at 80 oC for 205 min. The reaction was terminated by quenching in liquid nitrogen and then exposure to air. The polymerization mixture was diluted with THF then the copper salts removed by passage through an activated basic alumina column. The solution was concentrated by airflow and the polymer recovered by precipitation into methanol, then filtered and dried for 48 h under high vacuum at 25 oC. The polymer was characterized by SEC (Mn = 5120, PDI = 1.09).

Synthesis of PMA-Br 5:

Freshly purified methyl acrylate

(25.1261 g, 0.292 mol),

PMDETA (0.262 g, 1.51 x 10-3 mol), EBiB (1, 0.285 g, 1.46 x 10-3 mol) and anisole (10 mL) were added to a 50 mL Schlenk flask equipped with a magnetic stirrer then purged with N2 for 15 min. CuBr (0.099 g, 6.90 x 10-4 mol) and CuBr2 (0.160 g, 7.16 x 10-4 mol) were then carefully added under positive N2 flow and the mixture purged with N2 for a further 10 min. The flask was placed in a temperature controlled oil bath at 60oC and the polymerisation allowed to proceed for 23 h. The reaction was terminated by quenching in liquid nitrogen and then exposure to air. The polymerization mixture was diluted with chloroform and the copper salts removed by passage through an activated basic alumina column. The polymer solution was washed 3 times with water and the organic layer dried over anhydrous MgSO4. The polymer was then recovered by removal of the chloroform under vacuum. The polymer was dried for 24 h under vacuum at 25 oC, and analysed by SEC (Mn = 4200, PDI = 1.06). Synthesis of PtBA-Br 6: Freshly purified tert-butyl acrylate (15.03 g, 0.117 mol),

PMDETA (0.516 mL, 2.47 x 10-3 mol), MBP (2, 0.392 g, 2.35 x 10-3 mol), CuBr2 (0.029 g, 1.30 x 10-4 mol) and acetone (4.2 mL) were added to a 50 mL Schlenk flask, equipped with a magnetic stirrer, and purged with N2 for 20 min. After stirring for 1 h, CuBr (0.338 g, 2.36 x 10-3 mol) was added carefully under positive N2 flow and the mixture purged with N2 for a further 5 min. The flask was placed in a temperature controlled oil bath at 60oC and the polymerisation allowed to proceed for 4 h. The reaction was terminated by quenching with liquid nitrogen and exposure to air. The polymerization mixture was diluted with THF then the copper salts removed by passage through an activated basic alumina column. The solution was concentrated by airflow, and the polymer recovered by precipitation into cold 50 % v/v MeOH/water. The filtrate was dried for 48 h under high vacuum at 25 oC. The polymer was characterized by SEC (Mn = 6180, PDI = 1.10).

Synthesis of HO-PSTY-Br 7: Freshly purified styrene (3.0 g, 2.88 x 10-2 mol), PMDETA (0.026 g, 1.5 x 10-4 mol), pre-formed CuBr2/PMDETA complex (0.00595 g, 1.5 x 10-5 mol), and 3 (0.031 g, 1.38 x 10-4 mol) were added to a 10 mL Schlenk flask equipped with a magnetic stirrer and purged with N2 for 15 min. CuBr (0.0215 g, 1.5 x 10-4 mol) was then carefully added under positive N2 flow and then purged with N2 for a further 10 min. The flask was placed in a temperature controlled oil bath at 80oC for 2 h. The reaction was terminated by quenching in liquid nitrogen and then exposure to air. The polymerization mixture was diluted with THF then the copper salts removed by passage through an activated basic alumina column. The solution was concentrated by airflow and the polymer recovered by precipitation into methanol, then filtered and dried for 48 h under high vacuum at 25 oC. The polymer was characterized by SEC (Mn = 6258 and PDI = 1.10).

Synthesis of polymers with azide functionality Synthesis of PSTY-N3 8: A typical azidation procedure was as follows: NaN3 (0.278 g, 4.3 mmol) was added to a stirred solution of PSTY-Br (4, 2.0 g, 0.39 mmol) in 20 mL of DMF . The reaction mixture was stirred for 24 h at 50 oC in a temperature controlled oil bath. The polymer was precipitated in MeOH, recovered by vacuum filtration and washed exhaustively with water and MeOH. The polymer was dried under high vacuum for 48 h at 25 oC. Similarly, HO-PSTY-N3 (11) was prepared from HO-PSTY-Br (7). PMA-Br (5) and PtBA-Br (6) were azidated using the same procedure as above but purified by precipitation into cold 50 % v/v MeOH/water, filtered and dried under vacuum to give azidated polymers PMA-N3 (9) and PtBA-N3 (10).

Synthesis of 2nd Generation Homo and Miktoarm functional dendrons Synthesis of functional arm HO-PSTY-(- )2 12 Method A: 10 eq. CuBr/PMDETA: HO-PSTY-N3 (11, 1.120 g, 1.78 x 10-4 mol),

PMDETA (0.284 g, 1.64 x 10-3 mol), TPA (0.431 g, 3.29 x 10-3 mol) and 10 mL of DMF was added to a 10 mL Schlenk flask equipped with a magnetic stirrer. The reaction mixture was purged with N2 for 10 min after which CuBr (0.233 g, 1.63 x 10-3 mol) was added under a N2 blanket . The mixture was then purged with N2 for a further 5 min. The reaction mixture was stirred for 2 h at 80 oC in a temperature controlled oil bath. The solution was then diluted with THF, and passed through a basic alumina column. The solution was concentrated under N2 flow and the polymer recovered by precipitation into cold MeOH and then filtered. The polymer was redissolved in DMF (5 mL) and re-precipitated into cold MeOH, filtered and dried under vacuum. Method B: 0.5 eq. CuBr/PMDETA: HO-PSTY-N3 (11, 0.4385 g, 7.01 x 10-5 mol), PMDETA (0.0061 g, 3.49 x 10-5 mol), TPA (0.184 g, 1.40 x 10-3 mol) and 4.4 mL of DMF were added to a 10 mL Schlenk flask equipped with a magnetic stirrer. The reaction mixture was then purged with N2 for 10 min after which CuBr (0.0051 g, 3.55 x 10-5 mol) was acrefully added under a positive flow of N2. The mixture was then purged with N2 for a further 5 min. The reaction mixture was stirred for 2 h at 80 oC in a temperature controlled oil bath. The polymer was recovered by precipitation into MeOH and then filtered. The polymer was redissolved in DMF (4 mL) and re-precipitated into MeOH, filtered and dried under vacuum. Method C: Cu (wire): HO-PSTY-N3 (11, 0.6427 g, 1.17 x 10-4 mol), PMDETA (0.0101 g, 5.84 x 10-5 mol), TPA (0.306 g, 2.33 x 10-3 mol) , Cu (wire, 0.30 g) and 6.4 mL of DMF was added to a 10 mL Schlenk flask equipped with a magnetic stirrer. The reaction mixture was stirred for 4 h at 80 oC in a temperature controlled oil bath. The polymer was recovered by

precipitation into MeOH and then filtered. The polymer was redissolved in DMF (6 mL) and re-precipitated into MeOH, filtered and dried under vacuum.

Synthesis of functional arm star G2[G1PSTY-OH, G2PSTY2] 13 Method A: 10 eq. CuBr/PMDETA: 12 (prepared by Method A, 0.300 g, 4.79 x 10-5mol), PSTY-N3 (8, 0.528 g, 1.03 x 10-4 mol), PMDETA (0.163 g, 9.40 x 10-4 mol) and 8 mL of DMF were added to a 10 mL Schlenk flask equipped with a magnetic stirrer. The reaction mixture was purged with N2 for 10 min after which CuBr (0.133 g, 9.27 x 10-4 mol) was carefully added under a positive flow of N2. The reaction mixture was purged with N2 for a further 5 min. The reaction mixture was stirred for 2 h at 80 oC in a temperature controlled oil bath. The solution was diluted with THF and passed through a basic alumina column. The solution was concentrated under N2 flow, and the polymer precipitated into cold methanol, filtered and dried under vacuum. The above procedure was repeated for the synthesis of the functional mikto-arm stars G2[G1PSTY-OH, G2PMA2] (14) and G2[G1PSTY-OH, G2PtBA2] (15) using PMA-N3 (9) and PtBA-N3 (10) respectively. Method B: 0.5 eq. CuBr/PMDETA: 12 (prepared by Method B, 0.22 g, 3.55 x 10-5 mol), PSTY-N3 (8, 0.40 g, 7.73 x 10-5 mol), PMDETA (0.0066 g, 3.83 x 10-5 mol) and 6 mL of DMF were added to a 10 mL Schlenk flask equipped with a magnetic stirrer. The reaction mixture was purged with N2 for 10 min after which CuBr (0.0055 g, 3.83 x 10-5 mol) was carefully added under a positive flow of N2. The mixture was then purged with N2 for a further 5 min. The reaction mixture was stirred for 3 h at 80 oC in a temperature controlled oil bath.. The polymer was precipitated into cold methanol, filtered and dried under vacuum. The above procedure was repeated for the synthesis of the functional mikto-arm stars G2[G1PSTY-OH, G2PMA2] (14) and G2[G1PSTY-OH, G2PtBA2] (15) using PMA-N3 (9) and

PtBA-N3 (10) respectively. These polymers were purified by precipitation into water, then filtered and dried under vacuum. Method C: Cu (wire): 12 (prepared by Method C, 0.198 g, 3.60 x 10-5 mol), PSTY-N3 (8, 0.4234 g, 7.56 x 10-5 mol), Cu (wire, 1.0 g) and 6 mL of DMF were added to a 10 mL Schlenk flask equipped with a magnetic stirrer. The reaction mixture was stirred for 4 h at 80 oC in a temperature controlled oil bath. The polymer was precipitated into cold methanol, filtered and dried under vacuum. The above procedure was repeated for the synthesis of the functional mikto-arm stars G2[G1PSTY-OH, G2PMA2] (14) and G2[G1PSTY-OH, G2PtBA2] (15) using PMA-N3 (9) and PtBA-N3 (10) respectively. These polymers were purified by precipitation into water, then filtered and dried under vacuum.

Synthesis of functional arm star G2[G1PSTY-Br, G2PSTY2] 16 13 (0.50 g, 2.94 x 10-5 mol), TEA (4.5 L, 3.2 x 10-5 mol) and 1.5 mL of dry DCM were added to a 10 mL Schlenk flask equipped with stirrer bar while purged with N2. BAB (12.7 L, 1.47 x 10-4 mol) in 0.5mL of dry DCM was added dropwise under N2 to the stirred mixture over a period of 20 min. at room temperature. After complete addition the mixture was allowed to stir for a further 16 h at room temperature. The polymer was precipitated in MeOH, then filtered and washed 3 times with MeOH (20 mL). The recovered polymer was dried for 24 h under vacuum. The above procedure was used for the synthesis of the functional mikto-arm stars G2[G1PSTY-Br, G2PMA2] (17) and G2[G1PSTY-Br, G2PtBA2] (18) using G2[G1PSTY-OH, G2PMA2] (14) and G2[G1PSTY-OH, G2PtBA2] (15) respectively.

Synthesis of functional arm star G2[G1PSTY-N3, G2PSTY2] 19 NaN3 (0.0166 g, 2.67 x 10-4 mol) was added to a stirred solution of 16 (0.450 g, 2.67 x 10-5 mol) in 2 mL DMF. The reaction mixture was stirred for 24 h at 50 oC in a temperature controlled oil bath. The polymer was precipitated in water with vigorous stirring, filtered and dried under high vacuum. The above procedure was used for the synthesis of the functional mikto-arm stars G2[G1PSTY-N3, G2PMA2] (20) and G2[G1PSTY-N3, G2PtBA2] (21) using G2[G1PSTY-Br, G2PMA2] (17) and G2[G1PSTY-Br, G2PtBA2] (18) respectively.

Synthesis of functional arm star G2[G1PSTY-(3)2, G2PSTY2] 22 Method A: 10 eq. CuBr/PMDETA: 19 (prepared by Method A, 0.200 g, 1.18 x 10-5 mol), PMDETA (25 L, 1.20 x 10-4 mol), TPA (34 L, 2.35 x 10-4 mol) and 2mL of DMF was added to a 10 mL Schlenk flask equipped with magnetic stirrer. The reaction mixture was purged with N2 for 20 min after which CuBr (0.0168 g, 1.17 x 10-4 mol) was carefully added under a positive flow of N2. The mixture was then purged with N2 for a further 5 min. The reaction mixture was stirred for 2 h at 80 oC in a temperature controlled oil bath. The solution was then diluted with THF and passed through a basic alumina column. The solution was concentrated under N2 flow, and the polymer precipitated into cold methanol then filtered. The polymer was redissolved in DMF (5 mL) and re-precipitated in cold MeOH, filtered and dried under vacuum. Method B: 0.5 eq. CuBr/PMDETA: 19 (prepared by Method B, 0.1498 g, 9.25 x 10-6 mol),TPA (26 L, 1.84 x 10-4 mol) and 1 mL of DMF were added to a 10 mL Schlenk flask equipped with magnetic stirrer. The solution was then purged with N2 for 20 min. To the reaction mixture was carefully added a 100 L aliquot of a deoxygenated solution containing, PMDETA (49 L, 2.34 x 10-4 mol) and CuBr (0.033 g, 2.30 x 10-4 mol) in 5 mL DMF, under

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positive N2 flow and the reaction mixture was then purged with N2 for a further 5 min. The reaction mixture was stirred for 3 h at 80 oC in a temperature controlled oil bath. The polymer was precipitated into cold methanol then filtered. The polymer was redissolved in DMF (2 mL) and re-precipitated in cold MeOH, filtered and dried under vacuum. Method C: Cu (wire): 19 (prepared by Method C, 0.2366 g, 1.34 x 10-5 mol), TPA (38 L, 2.69 x 10-4 mol), Cu (wire, 0.355 g) and 2.5 mL of DMF were added to a 10 mL Schlenk flask equipped with magnetic stirrer. The reaction mixture was stirred for 4 h at 80 oC in a temperature controlled oil bath. The polymer was precipitated into cold methanol then filtered. The polymer was redissolved in DMF (2.5 mL) and re-precipitated in cold MeOH, filtered and dried under vacuum.

Synthesis of 2nd Generation Homo and Miktoarm functional dendrimers Synthesis of 3-arm dendrimer G2[G1PSTY3,G2PSTY6] 23 Method A: 10 eq. CuBr/PMDETA: 22 (prepared by Method A, 5.3 mg, 3.12 x 10-7 mol), 19 (prepared by Method A, 11.2 mg, 6.59 x 10-7 mol), PMDETA (1.4 L, 6.47 x 10-6 mol) and 0.5 mL of DMF was added to a 10 mL Schlenk flask equipped with a magnetic stirrer. The solution was purged with N2 for 10 min after which CuBr (1.3 mg, 9.1 x 10-6 mol) was carefully added under a positive flow of N2. and the reaction mixture was then purged with N2 for a further 5 min. The flask was placed in a temperature controlled oil bath and stirred at 80
o

C for 2 h, at which a sample removed for SEC analysis. The star dendrimer was then purified

from the bulk reaction by fractionation using SEC. The fractionated polymer 23f was then analysed by SEC. The above procedure was used for the synthesis of the mikto-arm dendrimers G2[G1PSTY3,G2PSTY2-PMA4] (24 and 24f) and G2[G1PSTY3,G2PSTY2-PtBA4] (25 and 25f) using G2[G1PSTY-N3, G2PMA2] (20) and G2[G1PSTY-N3, G2PtBA2] (21) respectively.

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Method B: 0.5 eq. CuBr/PMDETA: 22 (prepared by Method B, 4.9 mg, 3.03 x 10-7 mol) and 19 (prepared by Method B, 10.8 mg, 6.67 x 10-7 mol) in 0.5 mL of DMF was added to a 10 mL Schlenk flask equipped with a magnetic stirrer bar. The solution was purged with N2 for 10 min after which a 100 L aliquot of a deoxygenated solution containing PMDETA (7 L, 3.35 x 10-5 mol) and CuBr (4.8 mg, 3.35 x 10-5 mol) in 10 mL DMF was dispensed into the reaction under a positive N2 flow. The reaction solution was then purged with N2 for a further 5 min. The reaction mixture was stirred for 4 h at 80 oC in a temperature controlled oil bath after which a sample was removed for SEC analysis. The above procedure was used for the synthesis of the mikto-arm dendrimers G2[G1PSTY3,G2PSTY2-PMA4] (24) and G2[G1PSTY3,G2PSTY2-PtBA4] (25) using

G2[G1PSTY-N3, G2PMA2] (20) and G2[G1PSTY-N3, G2PtBA2] (21) respectively. The reactions were maintained at 80 oC for 19 h. Method C: Cu (wire): 22 (prepared by Method C, 5.0 mg, 2.82 x 10-7 mol), 19 (prepared by Method C, 10.5 mg, 5.93 x 10-7 mol), Cu (wire, 50.0 mg) and 0.5 mL of DMF was added to a 10 mL Schlenk flask equipped with magnetic stirrer. The reaction mixture was stirred for 4h at 80 oC in a temperature controlled oil bath and then a sample was removed for SEC analysis. The star dendrimer was then purified from the bulk reaction by fractionation using SEC. The fractionated polymer 23f was then analysed by SEC. The above procedure was used for the synthesis of the mikto-arm dendrimers G2[G1PSTY3,G2PSTY2-PMA4] (24 and 24f) and G2[G1PSTY3,G2PSTY2-PtBA4] (25 and 25f) using G2[G1PSTY-N3, G2PMA2] (20) and G2[G1PSTY-N3, G2PtBA2] (21) respectively. Method D: Cu (wire): 22 (prepared by Method B, 5.0 mg, 3.08 x 10-7 mol) and 19 (prepared by Method B, 11.0 mg, 6.79 x 10-7 mol), Cu (wire, 50.0 mg) and 0.5 mL of DMF was added to a 10 mL Schlenk flask equipped with magnetic stirrer. The reaction mixture was

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stirred for 4h at 80 oC in a temperature controlled oil bath and then a sample was removed for SEC analysis. The above procedure was used for the synthesis of the mikto-arm dendrimers G2[G1PSTY3,G2PSTY2-PMA4] (24) and G2[G1PSTY3,G2PSTY2-PtBA4] (25) using

G2[G1PSTY-N3, G2PMA2] (20) and G2[G1PSTY-N3, G2PtBA2] (21) respectively.

Synthesis of G2[G1PSTY3,G2PSTY2-PAA4] 26: G2[G1PSTY3,G2PSTY2-PtBA4] (25, 10 mg, 3.43 10-5 mol. tBA groups) was dissolved in 0.5 mL of DCM. TFA (20 mg, 1.72 10-4 mol) was added and the solution was stirred overnight at 25 oC after which the solution was dried with a nitrogen stream. The material was then further dried for 48 h at 25oC in a high vacuum oven. Hydrolysis of the tBA groups was confirmed by the loss of the tert-butyl groups in the 1H spectrum situated at 1.35ppm.

Degradation of 3-arm dendrimer G2[G1PSTY3,G2PSTY6] 23: To a 250 L aliquot of the reaction mixture from the synthesis of G2[G1PSTY3,G2PSTY6] 23 was added THF (1 mL) and NaOCH3 (10 mg, 1.85 x 10-4 mol). The mixture was stirred at room temperature for 16 h, then diluted with THF and analysed by SEC.

Degradation of mikto-arm dendrimer G2[G1PSTY3, G2PSTY2-PtBA4] 25: G2[G1PSTY3, G2PSTY2-PtBA4] (25, 2 mg) was dissolved in 1 mL of THF. NaOCH3 (0.1 mg, 1.85 x 10-6 mol) was added and the solution stirred for 16 h at room temperature. The mixture was then analysed by SEC.

Analytical Methodologies

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H and

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C Nuclear Magnetic Resonance (NMR): All NMR spectra were recorded on a

Bruker DRX 500 MHz spectrometer using an external lock (CDCl3) and utilizing a standard internal reference (solvent reference).
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C NMR spectra were recorded by decoupling the

protons and all chemical shifts are given as positive downfield relative to these internal references. Attenuated Total Reflectance Fourier Transform Spectroscopy (ATR-FTIR): ATR-FTIR spectra were recorded between 4000 and 550 cm-1 in a Perkin Elmer FT-2000 FTIR spectrometer equipped with a single reflection diamond window. Each spectrum had a 32 scan accumulation using a spectral resolution of 8 cm-1. Size Exclusion Chromatography (SEC): The molecular weight distributions of nanoparticles were measured by SEC. All polymer samples were dried prior to analysis in a vacuum oven for two days at 40 oC. The dried polymer was dissolved in tetrahydrofuran (THF) (Labscan, 99%) to a concentration of 1 mg/mL. This solution was then filtered through a 0.45 m PTFE syringe filter. Analysis of the molecular weight distributions of the polymer nanoparticles was accomplished by using a Waters 2695 Separations Module, fitted with two Ultrastyragel linear columns (7.8 x 300 mm) kept in series. These columns were held at a constant temperature of 35oC for all analyses. The columns used separate polymers in the molecular weight range of 500 2 million g/mol with high resolution. THF was the eluent used at a flow rate of 1.0 mL/min. Calibration was carried out using narrow molecular weight PSTY standards (PDI ~ 1.1) ranging from 500 2 million g/mol. Data acquisition was performed using Waters Millenium software (ver. 3.05.01) and molecular weights were calculated by using a 5th order polynomial calibration curve.

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Atomic Absorption Spectroscopy (AAS): Prior to analysis, all polymer samples were digested in 3 mL of 70 % HNO3 and heated for 30 min until evolution of red NO2 fumes ceased. After cooling, these solutions were then filtered through filter paper and transferred quantitatively into 25 mL volumetric flasks, and filled up to the mark with Milli-Q water. Sample concentrations were diluted where necessary so as to be calculated against Cu(NO3)2 standards (0.1-1 ppm). An Analyst 100 Perkin Elmer multi-elemental atomic absorption spectrometer (AAS) equipped with hollow cathode lamps was used for the copper determination. The AAS instrument was adjusted for the optimum conditions. The sample solutions obtained were directly aspirated in order to determine copper concentrations.

15

Schemes, Tables & Figures

O O

O
Br

Br

HO

Br

1
O O

2
O O

O O Br n
O

O Br n O O

O O O Br n
HO O

O Br n

4
NaN3 DMF, 50oC

5
NaN3 DMF, 50oC

6
NaN3 DMF, 50oC

7
NaN3 DMF, 50oC

O O N n3
O

O N n3 O O

O O O N n3 O
HO O

O N n 3

10

11

O HO O

N N N n

12

Scheme 1: Synthetic route to azido functional and alkyne functional linear polymers.

16

O HO O

N N N n

12 8
N N n N O HO O N N N n O N O N N N n O O

9
O N N n N O HO O N N N n O N O N N N n O O O O O

10
O N N n N O HO O N N N n O N O N N N n O O O O O

13
O Br Br Br
TEA, DCM

14
O Br

15
O Br Br
TEA, DCM
O O O

TEA, DCM

O
N N O Br O O O N N N N O N O N N N O O

O N N N O Br O O O N N N

O O O

N N O Br O O O N N N

N O N N N O O O

N O N N N O O O

16
NaN3 DMF, 50oC

17
NaN3 DMF, 50oC

18
NaN3 DMF, 50oC
O O O N O N N N O O O

O
N N O N3
O

O O O
O N3 O O O N N N N N N

N O

N N O N3 O O O N N N

O O

N N N

N O N N N O

N O N N N O O O

19

20

21

N
N N n N N N N N O O O O N N N n O N O N N N n O O

22

Scheme 2: Synthetic route to azido functional homo and mikto-arm stars and alkyne functional PSTY stars.

17

O O O O O OH
n N N N
n N N N

O O O

N N N n

O O O O O N O N N N N N N O O N N N O O

N N n

N N N Nn

O O

OH

O O

N N N N N n O OH

OH O

N N nN

O O O O n N N N

TFA, DCM

O O O O
n

O N N N N N O N N N N n
n N N

N N n O O O O N N N N N N N N N N O O O O

N N O N N
n

21

O O O

O
n N

O O

N N N N n O O O

O O O

N N nN

N N

N N

N N N
O O N O O
n

N
O

O O O n N N N O N N N O N N N N n
n N N

N N
n

N N n O

O O O N N N N N N N O O N N N O O O O

N N O N N
n

22
O O
n

20

O O

N N N N n O O O

O O

N N nN

N N

O O
O

N N N
O

O
n N N

N O O N N N N n
n N N

O
n N

N N N

N N n O O O O N N N N N N N O O N N N O O O O

N N N Nn O O

19

O O
n

N N N N Nn

N N nN O

O O

Scheme 3: Synthetic route to homo and mikto-arm dendrimers.

18

Table 1: Size exclusion chromatographic data for the synthesis of 3-mikto-arm stars
G2 dendrons PDI 13 14 15 1.17 1.22 1.15 Method A Mp 18200 19080 14960 Mp,theory 18170 20310 15730 PDI 1.17 1.27 1.19 Method B Mp 16440 17000 12300 Mp,theory 18170 20310 15730 PDI 1.27 1.31 1.27 Method C Mp 16650 18480 12880 Mp,theory 16800 18940 14360

(a)
80000
d(Log(w(M)))

(b) 13 23 23 9
3 3.5 4 4.5 5 5.5
80000

60000 40000 20000 0

d(Log(w(M)))

60000 40000 20000 0

13

23

9
3 3.5 4 LogMw 4.5 5 5.5

(c)
80000 60000 40000 20000 0 3 3.5 4

LogM w

(d)
100000

13 9

23
d(Log(w(M)))

80000 60000 40000 20000 0

d(Log(w(M)))

13

23

23

9
3 3.5 4 LogM w 4.5 5 5.5

LogM w

4.5

5.5

Figure 1: Size exclusion chromatograms using refractive index detection of G2[G1PSTYOH, G2PSTY2] 13 and G2[G1PSTY3,G2PSTY6] 23. fAfter fractionation by SEC. (a) Method A: 10 eq. CuBr/PMDETA (b) Method B: 0.5 eq. CuBr/PMDETA (c) Method C: Cu (wire) (d) Method D: Cu (wire).

19

(a)
80000 60000 40000 20000 0 3 3.5 4

(b) 13
80000

d(Log(w(M)))

d(Log(w(M)))

24
f

13 24 9
3 3.5 4 LogMw 4.5 5 5.5

60000 40000 20000 0

9
LogMw 4.5

24
5

5.5

(c)
80000 60000 40000 20000 0 3 3.5 4

(d)
80000

13 9

24
d(Log(w(M)))

d(Log(w(M)))

60000 40000 20000 0

13 24 9
3 3.5 4 4.5 5 5.5

24f

LogMw

4.5

5.5

LogMw

Figure 2: Size exclusion chromatograms using refractive index detection of G2[G1PSTYOH, G2PSTY2] 13 and G2[G1PSTY3,G2PSTY2-PMA4] 24. fAfter fractionation by SEC. (a) Method A: 10 eq. CuBr/PMDETA (b) Method B: 0.5 eq. CuBr/PMDETA (c) Method C: Cu (wire) (d) Method D: Cu (wire).

20

(a)
80000 60000 40000 20000 0 3 3.5 4 LogMw 4.5 5

(b)
80000

13

d(Log(w(M)))

d(Log(w(M)))

25

60000 40000 20000 0

13

25f
5.5

9
3 3.5 4

25
4.5 5 5.5

LogM w

(c)
80000 60000 40000 20000 0 3 3.5 4 LogM w 4.5 5

(d)
80000

13 9

d(Log(w(M)))

d(Log(w(M)))

25 25f
5.5

60000 40000 20000 0 3 3.5

13

25

9
4 4.5 5 5.5

LogM w

Figure 3: Size exclusion chromatograms using refractive index detection of G2[G1PSTYOH, G2PSTY2] 13 and G2[G1PSTY3,G2PSTY2-PtBA4] 25. fAfter fractionation by SEC. (a) Method A: 10 eq. CuBr/PMDETA (b) Method B: 0.5 eq. CuBr/PMDETA (c) Method C: Cu (wire) (d) Method D: Cu (wire).

80000

23
60000

d(Log(w(M)))

After Degradation

40000

20000

0 3 3.5 4 LogM w 4.5 5 5.5

Figure 4: Size exclusion chromatograms using refractive index detection of G2[G1PSTY3,G2PSTY6] 23 and after degradation reaction with NaOCH3.

21

(a)
100
% Transmittance

90 80 70 60 50 40 500 1000 1500 2000


Wavenumbers (cm-1)
HO O R O Br n
2 200 270 0 32 00 W ave numb e r s ( cm - 1 )

2500

3000

3500

(b)
% Transmittance

97

N a 3
87 1700

N3

2200

2700
Wavenumbers (cm-1)

3200

(c)
% Transmittance

97
R

N N N
N

b C :C-H

87 1700

2200

2700
Wavenumbers (cm-1)

3200

(d)
% Transmittance

97
N R N N N N N N N N N

13
87 1700 2200

O O

2700
Wavenumbers (cm-1)

3200

Figure 5: Attenuated Total Reflectance Fourier Transform Infrared Spectra (ATR-FTIR) of (a) HO-PSTY-Br 7 (b) HO-PSTY-N3 11 (c) HOPSTY-(C)2 12 and (d) G2[G1PSTY-OH, G2PSTY2] 13.

22

(a)

(b)

(c)

Figure 6: 1H NMR spectra of (a) HO-PSTY-Br 7 (b) HO-PSTY-N3 11 and (c) HOPSTY-( )2 13.

23

(a)

(b)

(c)

Figure 7: 1H NMR spectra of (a) G2[G1PSTY3,G2PSTY2-PtBA4] 25 full spectrum (b) expanded section showing tert-butyl groups and (c) G2[G1PSTY3,G2PSTY2-PAA4] 26 expanded to show loss of tert-butyl groups and addition of trifluoroester.

24

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