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S1
Supporting Information
Stimuli-Responsive Pd2L4 Metallosupramolecular Cages: Towards
Targeted Cisplatin Drug Delivery.
James E. M. Lewis,a Emma L. Gavey, a Scott A. Cameron, a
and James D. Crowley* a
aDepartment of Chemistry, University of Otago, PO Box 56, Dunedin,
New Zealand; Fax: +64 3 479 7906; Tel: +64 3 479 7731.
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
S2
Contents 1 Experimental Procedures ................................................................................................................ 3
1.1 General .................................................................................................................................... 3
1.2 Synthesis of 2(BF4)4 ................................................................................................................. 3
1.3 Synthesis of 2(SbF6)4 ............................................................................................................... 4
1.4 Synthesis of [Pd(DMAP)4](BF4)2 ............................................................................................... 5
1.5 Synthesis of [Pd2(S1)4](BF4)4 .................................................................................................... 7
2 1H DOSY NMR Spectra ..................................................................................................................... 9
2.1 1H DOSY NMR spectrum of 1 (CD3CN, 298 K) .......................................................................... 9
2.2 1H DOSY NMR spectrum of 2(BF4)4 (CD3CN, 298 K) ............................................................... 10
2.3 1H DOSY NMR spectrum of 2(SbF6)4 (CD3CN, 298 K) ............................................................. 11
3 Mass Spectra ................................................................................................................................. 12
3.1 Mass Spectra of 2(BF4)4 ......................................................................................................... 12
3.2 Mass Spectra of 2(SbF6)4 ....................................................................................................... 14
3.3 Mass Spectra of [2⊃(cisplatin)2](BF4)4 .................................................................................. 16
3.4 Mass Spectra of [Pd(DMAP)4](BF4)2 ...................................................................................... 18
4 1H NMR Experiments ..................................................................................................................... 20
4.1 2(BF4)4 + DMAP + Tosylic Acid (TsOH) ................................................................................... 21
4.2 2(BF4)4 + DMAP + Camphor-10-sulfonic acid (CSA). .............................................................. 23
4.3 2(BF4)4 + Bu4NCl + AgSbF6...................................................................................................... 24
4.4 2(BF4)4 + Cisplatin + Bu4NCl ................................................................................................... 25
5 Computer Modelling ..................................................................................................................... 26
5.1 SPARTAN Model of [2⊃(cisplatin)] ........................................................................................ 26
6 X-Ray Crystallographic Data .......................................................................................................... 27
6.1 X-ray data collection and refinement for 2(SbF6)4 ................................................................ 27
6.2 Table 1. Crystal data and structure refinement for 2(SbF6)4. ............................................... 29
6.3 X-ray data collection and refinement for [2⊃(cisplatin)2](BF4)4. .......................................... 30
6.4 Table 2. Crystal data and structure refinement for [2⊃(cisplatin)2](BF4)4. .......................... 32
6.5 Table 3. Squeeze results for [2⊃(cisplatin)2](BF4)4. ............................................................. 33
6.6 Space-filling representations of 2(SbF6)4 and [2⊃(cisplatin)2](BF4)4 ..................................... 34
7 References .................................................................................................................................... 34
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
S3
1 Experimental Procedures
1.1 General Unless otherwise stated, all reagents were purchased from commercial sources and used without further purification. 1H and 13C NMR spectra were recorded on either a 400 MHz Varian 400 MR or Varian 500 MHz VNMRS spectrometer. Chemical shifts are reported in parts per million and referenced to residual solvent peaks (CDCl3: 1H δ 7.26 ppm, 13C δ 77.16 ppm; CD3CN: 1H δ 1.94, 13C δ 1.32, 118.26 ppm, d6-DMSO: 1H δ 2.50 ppm; 13C δ 39.52 ppm). Coupling constants (J) are reported in Hertz (Hz). Standard abbreviations indicating multiplicity were used as follows: m = multiplet, q = quartet, t = triplet, dt = double triplet, d = doublet, dd = double doublet, s = singlet. IR spectra were recorded on a Bruker ALPHA FT-IR spectrometer with an attached ALPHA-P measurement module. Microanalyses were performed at the Campbell Microanalytical Laboratory at the University of Otago. Electrospray mass spectra (ESMS) were collected on a Bruker micro-TOF-Q spectrometer. UV-visible absorption spectra were acquired with a Perkin Elmer Lambda-950 spectrophotometer.
Figure S1: Labelling scheme for 2(X)4.
1.2 Synthesis of 2(BF4)4 To a stirring solution of 1 (0.141 g, 0.50 mmol, 2 eq.) in acetonitrile (10 mL) was added dropwise a solution of [Pd(CH3CN)4](BF4)2 (0.111 g, 0.25 mmol, 1 eq.) in acetonitrile (5 mL). The resulting solution was stirred at room temperature for 1 hour before filtering through cotton wool and the product precipitated by vapour diffusion of diethyl ether over 36 hours. The supernatant was decanted off and the solid dried in vacuo to give 2(BF4)4 as a tan solid. Yield 0.200 g (0.12 mmol, 95%). 1H NMR (400 MHz, d6-DMSO) δ: 9.54 (s, 2H, Ha), 9.38 (dd, J = 1.5, 5.9 Hz, 2H, Hb), 8.35 (dt, J = 1.5, 8.2 Hz, 2H, Hd), 8.01 (t, J = 7.5 Hz, 1H, Hf), 7.86 (dd, J = 5.9, 8.1 Hz, 2H, Hc), 7.79 (d, J = 7.8 Hz, 2H, He). 1H NMR (400 MHz, CD3CN) δ: 9.34 (d, J = 1.5 Hz, 2H, Ha), 9.08 (dd, J = 1.2, 5.8 Hz, 2H, Hb), 8.17 (dt, J = 1.4, 8.0 Hz, 2H, Hd), 7.87 (t, J = 7.8 Hz, 1H, Hf), 7.68 (d, J = 7.8 Hz, 2H, He), 7.66 (dd, J = 5.8, 8.0
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
S4
Hz, 2H, Hc). 13C NMR (500 MHz, d6-DMSO) δ: 153.3 (Ca), 151.1(Cb), 143.5 (Cd), 141.8, 138.3 (Cf), 128.6 (Ce), 127.4 (Cc), 121.5, 93.3, 83.6. IR (ATR): υ (cm-1) 3087, 1575, 1558, 1483, 1444, 1420, 1199, 1046, 803, 727, 690, 572, 558, 520. HRESI-MS (CH3CN): m/z = 1598.1482 [Pd2(C19H11N3)4(BF4)3]+ calc. 1598.2022; 756.0795 [Pd2(C19H11N3)4(BF4)2]2+ calc. 756.0989. UV-Vis (DMSO, ε [M-1.cm-1]): λmax nm = 314 (1.02 × 105), 268 (1.20 × 105). Anal. Calc for 2(BF4)4.(CH3CN)3(H2O)3: C, 52.88; H, 3.19; N, 11.28%. Found: C, 52.67; H, 3.02; N, 11.40%.
Figure S2: 1H NMR (400 MHz, d6-DMSO) spectrum for 2(BF4)4.
Figure S3: 13C NMR (500 MHz, d6-DMSO) spectrum for 2(BF4)4.
1.3 Synthesis of 2(SbF6)4 AgSbF6 (0.172 g, 0.50 mmol, 2 eq.) and Pd(CH3CN)2Cl2 (0.065 g, 0.25 mmol, 1 eq.) were stirred in acetone (dry, 10 mL) under N2 in the dark for 30 minutes. The reaction was filtered through celite (dried in oven) to give a red solution that was added dropwise to a stirring solution of 1 (0.141 g, 0.50 mmol, 2 eq.) in acetone (dry, 10 mL). After stirring for 1 hour the reaction solution was filtered through cotton wool and the product precipitated by vapour diffusion of diethyl ether over 48 hours. The supernatant was decanted off and the solid dried in vacuo to give 2(SbF6)4 as a tan solid. Yield 0.225 g (0.10 mmol, 79%). 1H NMR (400 MHz, CD3CN) δ: 9.27 (s, 2H, Ha), 9.00 (dd, J = 1.1, 5.9 Hz, 2H, Hb), 8.17 (dt, J = 1.5, 8.1 Hz, 2H, Hd), 7.87 (t, J = 8.2 Hz, 1H, Hf), 7.68 (d, J = 7.8 Hz, 2H, He), 7.66 (dd, J = 5.8, 7.6 Hz, 2H, Hc). 13C NMR (400 MHz, CD3CN) δ: 154.5 (Ca), 151.4 (Cb), 144.5 (Cd), 143.3, 138.7 (Cf), 129.4 (Ce), 128.5 (Cc), 124.1, 94.6, 83.5. IR (ATR): υ (cm-1) 3069, 1579, 1557, 1482, 1448, 1417, 1239, 811, 696. HRESI-MS (CH3CN/CH3OH): m/z = 2044.8478 [Pd2(C19H11N3)4(SbF6)3]+ calc. 2044.8741; 904.9749 [Pd2(C19H11N3)4(SbF6)2]2+ calc. 904.9897. UV-Vis (DMSO, ε [M-1.cm-1]): λmax nm = 317 (9.10 × 104), 270 (1.05 × 105). Anal. Calc for 2(SbF6)4.(CH3COCH3)5: C, 42.50; H, 2.90; N, 6.54%. Found: C, 42.70; H, 3.11; N, 6.40%.
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
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Figure S4: 1H NMR (400 MHz, CD3CN) spectrum for 2(SbF6)4.
Figure S5: 13C NMR (400 MHz, CD3CN) spectrum for 2(SbF6)4.
1.4 Synthesis of [Pd(DMAP)4](BF4)2
Figure S6: Labelling scheme for [Pd(DMAP)4](BF4)2.
[Pd(CH3CN)4](BF4)2 (0.022 g, 0.05 mmol, 1 eq.) and 4-dimethylaminopyridine (0.024 g, 0.2 mmol, 4 eq.) were stirred in acetonitrile (2.5 mL) for 30 minutes. The product was precipitated as a light yellow crystalline solid by vapour diffusion of diethyl ether over a period of 24 hours. Yield 0.032 g (0.04 mmol, 84%). 1H NMR (400 MHz, d6-DMSO) δ: 8.22 (d, J = 7.1 Hz, 2H, Ha), 6.71 (d, J = 7.3 Hz, 2H, Hb), 2.96 (s, 6H, Hd). 1H NMR (400 MHz, CD3CN) δ: 7.97 (d, J = 7.4 Hz, 2H, Ha), 6.55 (d, J = 7.4 Hz, 2H, Hb), 2.98 (s, 6H, Hd). 13C NMR (400 MHz, CD3CN) δ: 156.1 (Ca), 150.0 (Cb), 109.2 (Cc), 39.59 (Cd). IR (ATR): υ (cm-1) 1617, 1544, 1444, 1392, 1351, 1224, 1049, 1017, 944, 806, 520. HRESI-MS (MeCN):
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
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m/z = 681.2381 [Pd(C7H10N2)4(BF4)]+ calc. 681.2449; 297.1205 [Pd(C7H10N2)4]2+ calc. 297.1196. Anal. Calc for C28H40B2F8Pd: C, 43.75; H, 5.24; N, 14.58%. Found: C, 44.05; H, 5.36; N, 14.67%.
Figure S7: 1H NMR (400 MHz, CD3CN) spectrum for [Pd(DMAP)4](BF4)2.
Figure S8: 13C NMR (400 MHz, CD3CN) spectrum for [Pd(DMAP)4](BF4)2.
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
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1.5 Synthesis of [Pd2(S1)4](BF4)4
Figure S9: Self-assembly of cage complex S2 from ligand S1.
To a stirring solution of [Pd(CH3CN)4](BF4)2 (0.66 g, 1.49 mmol, 1 eq.) in acetonitrile (dry, 5 mL) was added S1 (0.833 g, 2.97 mmol, 2 eq.). The reaction mixture was heated at 50 °C for 30 minutes. The product was precipitated as a pale yellow solid by vapour diffusion of diethyl ether into the cooled reaction mixture. Yield 0.98 g (0.58 mmol, 78%). 1H NMR (400 MHz, d6-DMSO) δ: 9.60 (s, 2H, Ha), 9.36 (d, J = 5.0 Hz, 2H, Hb), 8.28 (d, J = 8.0 Hz, 2H, Hd), 7.95 (s, 2H, Hg), 7.82 (dd, J = 5.9, 7.9 Hz, 2H, Hc), 7.73 (dd, J = 1.4, 7.9 Hz, 2H, He), 7.58 (t, J = 7.8, 1H, Hf). 13C NMR (400 MHz, d6-DMSO) δ: 153.2, 151.1, 143.5, 141.8, 138.3, 128.6, 127.4, 121.6, 109.6, 93.3, 83.6. IR (ATR): υ (cm-1) 3566, 3210, 1718, 1600, 1562, 1488, 1413, 1295, 1198, 1163, 1050, 809, 796, 680, 520, 418. HRESI-MS (CH3CN/CH3OH): m/z = 1594.2218 [Pd2(C20H12N2)4(BF4)3]+ calc. 1594.2213; 754.1044 [Pd2(C20H12N2)4(BF4)2]2+ calc. 754.1085; 333.5552 [Pd2(C20H12N2)4]4+ calc. 333.5521. UV-Vis (DMSO, ε [M-1.cm-1]): λmax nm = 286 (1.75 × 105). Anal. Calc for C80H48N8B4F16Pd: C, 61.01; H, 3.03; N, 7.11%. Found: C, 53.45; H, 3.03; N, 6.18%.
Figure S10: 1H NMR (400 MHz, d6-DMSO) spectrum for S2.
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
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Figure S11: 13C NMR (400 MHz, d6-DMSO) spectrum for S2.
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
S9
2 1H DOSY NMR Spectra
2.1 1H DOSY NMR spectrum of 1 (CD3CN, 298 K)
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
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2.2 1H DOSY NMR spectrum of 2(BF4)4 (CD3CN, 298 K)
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
S11
2.3 1H DOSY NMR spectrum of 2(SbF6)4 (CD3CN, 298 K)
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
S12
3 Mass Spectra
3.1 Mass Spectra of 2(BF4)4
Figure S12: HR-ESI Mass Spectrum (+ve ion, MeCN) of 2(BF4)4. m/z = 1598.1482 [Pd2(1)4(BF4)3]+;
756.0795 [Pd2(1)4(BF4)2]2+.
300.0890
385.9911
547.5397
687.0769
1006.45631599.1474
+MS, 0.2-1.0min #(10-59)
0.0
0.5
1.0
1.5
2.0
5x10Intens.
500 1000 1500 2000 2500 m/z
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
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Figure S13: Experimental (top) and theoretical (bottom) isotope patterns for [Pd2(1)4(BF4)3]+.
Figure S14: Experimental (top) and theoretical (bottom) isotope patterns for [Pd2(1)4(BF4)2]2+.
751.0019 751.4981 752.0030 752.5327
753.0733
753.5755
754.0790
754.5787
755.0793755.5801
756.0794
756.5807
757.0784
757.5808
758.0803
758.5798
759.0916
759.5795
+MS, 0.1-0.9min #(6-54)
752.5996
753.0992
753.5989
754.0987
754.5988
755.0988755.5990 756.0989
756.5994
757.0991
757.5997
758.0995
758.6001
759.1004759.6010
(C19H11N3)4Pd2(BF4)2, M ,1510.190.0
0.5
1.0
1.5
4x10Intens.
0
500
1000
1500
2000
752 754 756 758 760 m/z
1592.1484
1593.1497
1594.1476
1595.1460
1596.1460
1597.1454
1598.14811599.1472
1600.1482
1601.1506
1602.1534
1603.1515
1604.1529
1605.15201606.1410
+MS, 0.1-0.9min #(6-54)
1592.2039
1593.2030
1594.2023
1595.2017
1596.2018
1597.20191598.2022
1599.2021
1600.2028
1601.2023
1602.2033
1603.2031
1604.2042
1605.2047
1606.2059
(C19H11N3)4Pd2(BF4)3, M ,1597.200
2000
4000
6000
8000Intens.
0
500
1000
1500
2000
1590.0 1592.5 1595.0 1597.5 1600.0 1602.5 1605.0 1607.5 1610.0 m/z
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
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3.2 Mass Spectra of 2(SbF6)4
Figure S15: HR-ESI Mass Spectrum (+ve ion, MeCN) of 2(SbF6)4. m/z = 2044.8478 [Pd2(1)4(SbF6)3]+;
904.9749 [Pd2(1)4(SbF6)2]2+.
282.1049
387.9998
444.0296
563.5140
671.0928
+MS, 11.5-15.7min #(683-937)
0.0
0.2
0.4
0.6
0.8
1.0
6x10Intens.
200 400 600 800 1000 1200 1400 m/z
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
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Figure S16: Experimental (top) and theoretical (bottom) isotope patterns for [Pd2(1)4(SbF6)3]+.
Figure S17: Experimental (top) and theoretical (bottom) isotope patterns for [Pd2(1)4(SbF6)2]2+.
2037.8326
2038.8382
2039.8439
2040.8500
2041.8562
2042.8628
2043.84082044.8478
2045.85512046.8338
2047.8415
2048.8495
2049.8578
2050.8375
2051.8462
+MS, 11.5-15.7min #(683-937)
2037.8735
2038.8726
2039.8735
2040.8731
2041.8739
2042.8736
2043.8745
2044.8741
2046.8746
2047.8760
2048.8753
2049.8767
2050.8763
2051.8776
2052.87772053.8788
(C19H11N3)4Pd2(SbF6)3, M ,2040.870
100
200
300
400
500
Intens.
0
500
1000
1500
2000
2035 2040 2045 2050 2055 m/z
897.9633
898.9632
899.9645
900.9647
901.9693
902.4829
902.9718
903.4837
903.9749
904.4837
904.9749
905.4844
905.9763
906.4849
906.9749
907.4850
907.9752
908.9731
+MS, 11.5-15.7min #(683-937)
900.9890
901.4893
901.9889
902.4893
902.9892
903.4896
903.9894
904.9897
905.4903
906.4907
906.9904
907.4911
907.9911
908.4917908.9921
Pd2(C19H11N3)4(SbF6)2, M ,1805.980.00
0.25
0.50
0.75
1.00
1.25
4x10Intens.
0
500
1000
1500
2000
896 898 900 902 904 906 908 910 912 914 m/z
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
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3.3 Mass Spectra of [2⊃(cisplatin)2](BF4)4
Figure S18: Experimental (top) and theoretical (bottom) isotope patterns for
{2(BF4)3⊃2[Pt(NH3)2Cl2]}+.
Figure S19: Experimental (top) and theoretical (bottom) isotope patterns for
{2(BF4)2⊃2[Pt(NH3)2Cl2]}2+.
2183.2888 2191.1793
2192.1637
2193.1593
2194.1608
2195.1640
2196.1619
2198.1578
2199.1594
2200.1607
2201.1643
2202.1625
2203.1591
2204.1663
2205.1698
2206.17962207.1759
+MS, 0.5-1.5min #(27-88)
2190.1105
2191.1102
2192.1100
2193.1098
2194.1096
2195.1095
2196.1094
2198.1093
2200.1093
2201.1093
2202.1094
2203.1095
2204.1096
2205.1097
2206.10992207.1100
(C19H11N3)4Pd2(BF4)3(PtN2H6Cl2)2, M ,2195.11
500
1000
1500
2000
Intens.
0
500
1000
1500
2000
2180 2185 2190 2195 2200 2205 2210 2215 m/z
1049.5346 1051.54561052.0549
1052.5600
1053.0650
1053.5679
1054.0693
1054.5700
1055.5713
1056.5710
1057.0710
1057.5709
1058.0707
1058.5690
1059.0682
1059.5651
1060.0615
1060.5532
+MS, 0.5-1.5min #(27-88)
1051.55291052.0528
1052.5528
1053.0527
1053.5526
1054.0526
1054.5526
1055.5526
1056.5526
1057.0526
1057.5527
1058.0527
1058.5528
1059.0528
1059.5530
1060.0530
(C19H11N3)4Pd2(BF4)2(PtN2H6Cl2)2, M ,2108.110
1000
2000
3000
4000
5000
6000
Intens.
0
500
1000
1500
2000
2500
1048 1050 1052 1054 1056 1058 1060 1062 1064 1066 m/z
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Figure S20: Experimental (top) and theoretical (bottom) isotope patterns for {2(BF4)3⊃[Pt(NH3)2Cl2]}+.
Figure S21: Experimental (top) and theoretical (bottom) isotope patterns for
{2(BF4)2⊃[Pt(NH3)2Cl2]}2+.
1880.2052 1891.2056
1892.2041
1893.1978
1894.2003
1895.1988
1896.1983
1897.1974
1898.1980
1899.1978
1900.1982
1901.1982
1902.2003
1903.2013
1904.2021
1905.2041
1906.21001907.2170
1912.2236 1916.2346 1918.2385
+MS, 0.5-1.5min #(27-88)
1891.1571
1892.1566
1893.1562
1894.1560
1895.1558
1896.1558
1898.1559
1900.1560
1901.1560
1902.1563
1903.1563
1904.1568
1905.1568
1906.1574
(C19H11N3)4Pd2(BF4)3(PtN2H6Cl2), M ,1896.15
1000
2000
3000
4000
Intens.
0
500
1000
1500
2000
1880 1885 1890 1895 1900 1905 1910 1915 m/z
898.1528
900.0044 900.9962 902.0838
902.5922
903.0916
903.5924
904.0922
904.5934
905.0923905.5928
906.5933
907.0926
907.5922
908.0922
908.5935
909.0905
909.5919910.0830
+MS, 0.5-1.5min #(27-88)
902.0762
902.5760
903.0758
903.5758
904.0757
904.5758
905.5758
906.5760
907.0759
907.5761
908.0761
908.5764
909.0764
909.5767
(C19H11N3)4Pd2(BF4)2(PtN2H6Cl2), M ,1809.150.0
0.2
0.4
0.6
0.8
1.0
4x10Intens.
0
500
1000
1500
2000
898 900 902 904 906 908 910 912 914 m/z
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
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3.4 Mass Spectra of [Pd(DMAP)4](BF4)2
Figure S22: HR-ESI Mass Spectrum (+ve ion, MeCN) of [Pd(DMAP)4](BF4)2. m/z = 681.2381
[Pd(C7H10N2)4(BF4)]+; 297.1205 [Pd(C7H10N2)4]2+.
297.1196
350.0720
491.1532
681.2381
395.0664
+MS, 0.1-2.8min #(8-168)
0
2
4
6
8
4x10Intens.
400 600 800 1000 1200 1400 1600 1800 2000 2200 m/z
Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011
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Figure S23: Experimental (top) and theoretical (bottom) isotope patterns for [Pd(DMAP)4](BF4)+.
Figure S24: Experimental (top) and theoretical (bottom) isotope patterns for [Pd(DMAP)4]2+.
678.2416
679.2390
680.2392
681.2381
682.2399
683.2376
684.2399
685.2390
686.2415
+MS, 0.2-2.8min #(9-166)
677.2456678.2476
679.2442
680.2452
681.2449
682.2468
683.2440
684.2472685.2452
686.2485
(C7H10N2)4Pd(BF4), M ,681.240
2000
4000
6000
Intens.
0
500
1000
1500
2000
670 675 680 685 690 695 m/z
295.1187
296.1187
296.6197
297.1196
297.6199
298.1191
298.6201
299.1194
299.6208
300.1221
+MS, 0.2-2.8min #(9-166)
295.1211
296.1203
296.6208
297.1205
297.6217
298.1202
298.6219
299.1208
299.6225
(C7H10N2)4Pd(BF4)0, M ,594.240.0
0.5
1.0
1.5
2.0
2.5
3.04x10
Intens.
0
500
1000
1500
2000
292 294 296 298 300 302 304 m/z
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4 1H NMR Experiments
Figure S25: Reaction scheme for 1H NMR disassembly/reassembly experiments.
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4.1 2(BF4)4 + DMAP + Tosylic Acid (TsOH) To a 17 mM solution of 2(BF4)4 in d6-DMSO (0.75 mL) was added DMAP (0.012 g, 0.1 mmol). After stirring for 5 minutes a 1H NMR spectrum was obtained showing disassembly of the cage complex and formation of [Pd(DMAP)4](BF4)2. The formation of Pd(DMAP)4 and the presence of free ligand was confirmed by ESI-MS (Fig. S27). TsOH (0.017 g, 0.1 mmol) was added and the suspension gently heated until all solids were dissolved. A further 1H NMR spectrum was obtained revealing protonation of DMAP and reassembly of 2.
Figure S26: Stacked 1H NMR (500 MHz, d6-DMSO) spectra of a) 1, b) 2(BF4)4, c) 2(BF4)4 plus DMAP
(8 eq.), and d) 2(BF4)4 plus DMAP plus TsOH (8 eq.). N.B. the signals for the reassembled cage differ slightly from the original due to interactions between the palladium cations and the sulfonate
anions. This type of interaction has been studied and exploited extensively by Shionoya and co-workers.1-3
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Figure S27: Experimental (top) and theoretical (bottom) isotope patterns for [1H]+, [1Na]+, and
[Pd(DMAP)4](BF4) + (left to right respectively).
280.0817
282.1005
283.1005
284.1026
282.1026
283.1059
280 285
304.0769
305.0747
306.0267
304.0845
305.0878
306.0912
304 306
681.2306
683.2281
685.2295
681.2449
683.2440
685.2452
680 685
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4.2 2(BF4)4 + DMAP + Camphor-10-sulfonic acid (CSA). To a 4 mM solution of 2(BF4)4 in CD3CN (0.75 mL) was added DMAP (0.003 g, 0.02 mmol). After stirring for 5 minutes a 1H NMR spectrum was obtained showing disassembly of the cage complex and formation of [Pd(DMAP)4](BF4)2. CSA (0.006 g, 0.02 mmol) was added and the solution stirred for 5 minutes. A further 1H NMR spectrum was obtained revealing protonation of DMAP. After 17 hours complete reassembly of 2 was observed.
Figure S28: Stacked 1H NMR (400 MHz, CD3CN) spectra of a) 1, b) 2(BF4)4, c) 2(BF4)4 plus DMAP
(8 eq.), and d) 2(BF4)4 plus DMAP plus CSA (8 eq.). N.B. the signals for the reassembled cage differ slightly from the original due to interactions between the palladium cations and the sulfonate
anions. This type of interaction has been studied and exploited extensively by Shionoya and co-workers.1-3
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4.3 2(BF4)4 + Bu4NCl + AgSbF6 To a 4 mM solution of 2(BF4)4 in d6-DMSO (0.75 mL) was added Bu4NCl (0.007 g, 0.02 mmol). A precipitate was observed to form. A 1H NMR spectrum was obtained showing disassembly of the cage complex. Upon addition of AgSbF6 (0.008 g, 0.02 mmol) no change in the 1H NMR spectrum was observed. Subsequent addition of further AgSbF6 (0.020 g, 0.06 mmol) resulted in the reassembly of the cage complex.
Figure S29: Stacked 1H NMR spectra (400 MHz, d6-DMSO) of a) 1, b) 2(BF4)4, c) plus Bu4NCl (8 eq.), d) plus AgSbF6 (8 eq.), and e) plus further AgSbF6 (20 eq.).
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4.4 2(BF4)4 + Cisplatin + Bu4NCl To a 4 mM solution of 2(BF4)4 in CD3CN (0.75 mL) was added cisplatin (0.002 g, 0.005 mmol) and the mixture sonicated for 10 minutes. A downfield shift and broadening of the Ha and Hb signals was observed in the 1H NMR spectrum, indicative of encapsulation of cisplatin within 2. Bu4NCl (0.007 g, 0.02 mmol) was added to the reaction mixture. A precipitate was observed to form. A 1H NMR spectrum was obtained showing disassembly of the host-guest complex.
Figure S30: Stacked 1H NMR spectra (400 MHz, CD3CN) of a) 1, b) 2(BF4)4, c) host-guest adduct
[2⊃(cisplatin)2](BF4)4, and d) plus Bu4NCl (8 eq.).
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5 Computer Modelling
5.1 SPARTAN Model of [2⊃(cisplatin)]
Figure S31: MMFF force field energy minimised SPARTAN model of [2⊃(cisplatin)]. Ball-and-stick representations viewed from a) the side, and b) the top; space-fill representations viewed from
c) the side, and b) the top.
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6 X-Ray Crystallographic Data
6.1 X-ray data collection and refinement for 2(SbF6)4
X-ray data for 2(SbF6)4 were collected at 89 K on a Bruker Kappa Apex II area detector diffractometer using monochromated Mo Kα radiation. The structure was solved by direct methods and refined against F2 using anisotropic thermal displacement parameters for all non-hydrogen atoms (except where noted below) using APEX II software. Hydrogen atoms were placed in calculated positions and refined using a riding model. The structure was solved in the primitive triclinic space group P1̄ and refined to an R1 value of 5.2%. Present in the asymmetric unit were two ligands bound orthogonally to a single Pd(II) atom, two hexafluoroantimonate counteranions (one of which is rotationally disordered), and multiple disordered solvent molecules (H2O, acetone and MeOH). The rotationally disordered hexafluoroantimonate counteranion was disordered over two sites with occupancies of 75% (F3 through F6) and 25% (F7 through F10). Sb1, F1 and F2 were all full occupancy. FLAT command was used to restrain F3 through F10 in the same plane. The quarter occupancy fluorine atoms did not behave well when refined anisotropically, thus were made isotropic.
Figure S32: Ball-and-stick model of the rotationally disordered hexafluoroantimonate counteranion.
Inside the cage cavity were present four water and one methanol molecules. All were refined as full occupancy. Outside the cage were present three partial occupancy methanol molecules, a full occupancy methanol molecule disordered over three sites, and a full occupancy acetone molecule.
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Figure S33: Ball-and-stick representation of the crystal structure of 2(SbF6)4 showing disordered solvent molecules. SbF6 counteranions and non-solvent hydrogen atoms have been removed for
clarity.
Figure S34: Ball-and-stick representation of the crystal structure of 2(SbF6)4 showing disordered solvent molecules within the internal cavity of the cage complex. SbF6 counteranions, external
solvent molecules and non-solvent hydrogen atoms have been removed for clarity.
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6.2 Table 1. Crystal data and structure refinement for 2(SbF6)4.
Identification code eg273
Empirical formula C44.10 H48.40 F12 N6 O8.10 Pd Sb2
Formula weight 1369.99
Temperature 293(2) K
Wavelength 0.71069 Å
Crystal system Triclinic
Space group P1̄
Unit cell dimensions a = 12.850(5) Å α= 66.868(5)°.
b = 15.422(5) Å β= 88.549(5)°.
c = 16.768(5) Å γ = 80.667(5)°.
Volume 3012.7(18) Å3
Z 2
Density (calculated) 1.510 Mg/m3
Absorption coefficient 1.270 mm-1
F(000) 1352
Crystal size 0.45 x 0.13 x 0.12 mm3
Theta range for data collection 1.46 to 20.68°.
Index ranges -12<=h<=12, -15<=k<=15, -16<=l<=16
Reflections collected 55742
Independent reflections 6112 [R(int) = 0.0854]
Completeness to theta = 20.68° 98.6 %
Absorption correction Semi-empirical from equivalents
Max. and min. transmission 0.7445 and 0.6373
Refinement method Full-matrix least-squares on F2
Data / restraints / parameters 6112 / 17 / 695
Goodness-of-fit on F2 1.096
Final R indices [I>2sigma(I)] R1 = 0.0517, wR2 = 0.1386
R indices (all data) R1 = 0.0670, wR2 = 0.1498
Largest diff. peak and hole 1.145 and -0.684 e.Å-3
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6.3 X-ray data collection and refinement for [2⊃(cisplatin)2](BF4)4. X-ray data for [2⊃(cisplatin)2](BF4)4 were collected at 89 K on a Bruker Kappa Apex II area detector diffractometer using monochromated Mo Kα radiation. The structure was solved by direct methods and refined against F2 using anisotropic thermal displacement parameters for all non-hydrogen atoms using APEX II software. Hydrogen atoms were placed in calculated positions and refined using a riding model. The structure was solved in the primitive triclinic space group P1̄ and refined to an R1 value of 7.5%. One molecule of the host-guest adduct is present in the unit cell. ISOR command was used for atoms C1, C2 and C3. The tetrafluoroborate counteranions and solvent of crystallisation molecules were deemed too disordered to model. SQUEEZE was used to remove the aforementioned disorder, resulting in a void electron count of 374. With four tetrafluoroborate counteranions present totalling 168 electrons, the remaining 206 electrons can be accounted for by a variety of solvent molecule combinations from those solvents present, i.e. MeCN, DMF, Et2O and H2O (e.g. (MeCN)2(DMF)3(Et2O); (MeCN)8(H2O)3). In the asymmetric unit two ligands are bound orthogonally to a single Pd(II) atom and one cisplatin molecule is present. In the crystal lattice the molecules are arranged in an interlocking fashion with a centroid-centroid distance between the central pyridine moieties of 4.67 Å.
Figure S35: Ball-and-stick representation of the asymmetric unit cell of [2⊃(cisplatin)2](BF4).
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Figure S36: Capped-stick representation of interlocking between adjacent host-guest molecules in
the crystal lattice of [2⊃(cisplatin)2](BF4)4. Hydrogen atoms have been removed for clarity.
Figure S37: Space-fill representation of interlocking between adjacent host-guest molecules in the
crystal lattice of [2⊃(cisplatin)2](BF4)4. Hydrogen atoms have been removed for clarity.
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6.4 Table 2. Crystal data and structure refinement for [2⊃(cisplatin)2](BF4)4.
Identification code jl_merged
Empirical formula C76 H56 Cl4 N16 Pd2 Pt2
Formula weight 1938.15
Temperature 89(2) K
Wavelength 0.71073 Å
Crystal system Triclinic
Space group P1̄
Unit cell dimensions a = 11.9663(19) Å α= 76.455(9)°.
b = 12.3450(19) Å β= 83.846(10)°.
c = 17.495(3) Å γ = 85.135(10)°.
Volume 2493.3(7) Å3
Z 1
Density (calculated) 1.291 Mg/m3
Absorption coefficient 3.299 mm-1
F(000) 940
Crystal size 0.32 x 0.32 x 0.31 mm3
Theta range for data collection 1.20 to 26.47°.
Index ranges -14<=h<=14, -15<=k<=15, -21<=l<=21
Reflections collected 53506
Independent reflections 10143 [R(int) = 0.0729]
Completeness to theta = 26.47° 98.4 %
Absorption correction Semi-empirical from equivalents
Max. and min. transmission 0.4278 and 0.4183
Refinement method Full-matrix least-squares on F2
Data / restraints / parameters 10143 / 18 / 454
Goodness-of-fit on F2 1.093
Final R indices [I>2sigma(I)] R1 = 0.0748, wR2 = 0.2226
R indices (all data) R1 = 0.0965, wR2 = 0.2379
Largest diff. peak and hole 4.948 and -1.483 e.Å-3
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6.5 Table 3. Squeeze results for [2⊃(cisplatin)2](BF4)4. Platon squeeze void nr 1 Platon squeeze void average x 0.500 Platon squeeze void average y 0.238 Platon squeeze void average z 0.923 Platon squeeze void volume 908 Platon squeeze void count electrons 374 Platon squeeze void content Highly disordered BF4 anions and solvent. The number of
electrons is consistent with a number of combinations of solvent (H2O, DMF, Et2O and/or MeCN).
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6.6 Space-filling representations of 2(SbF6)4 and [2⊃(cisplatin)2](BF4)4
Figure S38: Space-filling representations of the crystal structures of 2(SbF6)4 viewed from a) the side, and b) the top, and of [2⊃(cisplatin)2](BF4)4 viewed from c) the side, and d) the top. Counterions and
solvent molecules had been removed for clarity.
7 References (1) Clever, G. H.; Tashiro, S.; Shionoya, M. Angew. Chem. Int. ed. 2009, 48, 7010. (2) Sakata, Y.; Hiraoka, S.; Shionoya, M. Chem. Eur. J. 2010, 16, 3318. (3) Clever, G. H.; Tashiro, S.; Shionoya, M. J. Am. Chem. Soc. 2010, 132, 9973.
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