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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.

*[email protected]

Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2011

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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


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


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%.


S5

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):


S6

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.


S7

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.


S8

Figure S11: 13C NMR (400 MHz, d6-DMSO) spectrum for S2.


S9

2 1H DOSY NMR Spectra

2.1 1H DOSY NMR spectrum of 1 (CD3CN, 298 K)


S10

2.2 1H DOSY NMR spectrum of 2(BF4)4 (CD3CN, 298 K)


S11

2.3 1H DOSY NMR spectrum of 2(SbF6)4 (CD3CN, 298 K)


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


S13

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


S14

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


S15

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


S16

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]}+.


{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


S17

Figure S20: Experimental (top) and theoretical (bottom) isotope patterns for {2(BF4)3⊃[Pt(NH3)2Cl2]}+.


{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


S18

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


S19

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


S20

4 1H NMR Experiments

Figure S25: Reaction scheme for 1H NMR disassembly/reassembly experiments.


S21

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


S22

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


S23

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


S24

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.).


S25

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.).


S26

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.


S27

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.


S28

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.


S29

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


S30

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).


S31

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.


S32

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


S33

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).


S34

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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