Glycosylated copper(II) ionophores as prodrugs for β ... · Supporting Information Glycosylated...
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Supporting Information Glycosylated copper(II) ionophores as prodrugs for β-glucosidase activation in targeted cancer therapy. Valentina Oliveri 1 , Maurizio Viale 2 , Giulia Caron 3 , Cinzia Aiello 2 , Rosaria Gangemi 2 and Graziella Vecchio 1* 1 University of Catania, Dipartimento di Scienze Chimiche, Viale A. Doria, 6, 95125 – Catania (Italy). 2 IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, U.O.C. Terapia Immunologia, L.go R. Benzi, 10, 16132 – Genova (Italy) 3 University of Torino, BMSS, Via Quarello, 11, 10135 – Torino (Italy) TABLE OF CONTENTS: Figure S1-S6: The 1 H NMR, COSY, TOCSY, gHSQCAD, ESI-MS spectra of GluMeHQ Figure S7-S16: The 1 H NMR, COSY, gHSQCAD, gHMBC and ESI-MS spectra of GluClHQ Figure S17-S23: The 1 H NMR, COSY, gHSQCAD, gHMBC and ESI-MS spectra of GluCl 2 HQ Figure S24-S26: : Enzymatic kinetic assay of GluClHQ, GluCl 2 HQ and GluMeHQ in the presence of β-glucosidase Electronic Supplementary Material (ESI) for Dalton Transactions This journal is © The Royal Society of Chemistry 2012
Transcript of Glycosylated copper(II) ionophores as prodrugs for β ... · Supporting Information Glycosylated...
Supporting Information
Glycosylated copper(II) ionophores as prodrugs for β-glucosidase
activation in targeted cancer therapy.
Valentina Oliveri1, Maurizio Viale
2, Giulia Caron
3, Cinzia Aiello
2, Rosaria Gangemi
2 and Graziella
Vecchio1*
1 University of Catania, Dipartimento di Scienze Chimiche, Viale A. Doria, 6, 95125 – Catania
(Italy).
2 IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul
Cancro, U.O.C. Terapia Immunologia, L.go R. Benzi, 10, 16132 – Genova (Italy)
3 University of Torino, BMSS, Via Quarello, 11, 10135 – Torino (Italy)
TABLE OF CONTENTS:
Figure S1-S6: The 1H NMR, COSY, TOCSY, gHSQCAD, ESI-MS spectra of GluMeHQ
Figure S7-S16: The 1H NMR, COSY, gHSQCAD, gHMBC and ESI-MS spectra of GluClHQ
Figure S17-S23: The 1H NMR, COSY, gHSQCAD, gHMBC and ESI-MS spectra of GluCl2HQ
Figure S24-S26: : Enzymatic kinetic assay of GluClHQ, GluCl2HQ and GluMeHQ in the presence
of β-glucosidase
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
Figure S1: 1H NMR spectrum of GluMeHQ (500 MHz, CD3OD)
Figure S2: COSY spectrum of GluMeHQ (500 MHz, CD3OD)
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
Figure S3: TOCSY spectrum of GluMeHQ (500 MHz, CD3OD)
Figure S4: gHSQCAD spectrum of GluMeHQ (500 MHz, CD3OD)
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
glumehq #12-289 RT: 0.29-5.63 AV: 75 NL: 6.47E7T: + p ESI Full ms [ 200.00-2000.00]
300 350 400 450 500 550 600 650
m/z
0
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100
Re
lative
Ab
un
da
nce
322.00
664.67
344.07
359.87 680.80383.93 495.60479.40 543.13 660.00405.80 427.80 621.80564.73 606.00
Figure S5. ESI-MS spectrum of GluMeHQ (CH3OH)
glumehq #76-106 RT: 1.91-2.35 AV: 31 NL: 5.08E7T: + p ESI Z ms [ 316.90-326.90]
319 320 321 322 323 324 325 326 327 328 329
m/z
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Re
lative
Ab
un
da
nce
321.94
322.94
323.97324.91 325.99321.46319.80318.99 320.39 326.81
Figure S6. Zoom scan spectrum of GluMeHQ
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
Figure S7: 1
H NMR spectrum of GluClHQ (500 MHz, CD3OD)
Figure S8: 1
H-1H COSY spectrum of GluClHQ (500 MHz, CD3OD)
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
Figure S9: gHSQCAD spectrum of GluClHQ (500 MHz, CD3OD)
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
Figure S10: gHMBC spectrum of GluClHQ (aromatic region, 500 MHz, CD3OD)
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
Figure S11: gHMBC spectrum of GluClHQ (aliphatic region, 500 MHz, CD3OD)
Figure S12: 13
C NMR spectrum of GluClHQ (125 MHz, CD3OD)
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
gluclhq #3-52 RT: 0.57-1.35 AV: 31 NL: 1.92E7T: + p ESI Full ms [ 200.00-2000.00]
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lative
Ab
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704.60
364.00
341.93
543.20641.27 668.53 754.00413.00 581.33 772.67320.80 451.27 481.00 520.33
Figure S13. ESI-MS spectrum of GluClHQ (CH3OH)
gluclhq #58-111 RT: 1.47-2.27 AV: 54 NL: 6.07E6T: + p ESI Z ms [ 336.90-346.90]
337 338 339 340 341 342 343 344 345 346
m/z
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lative
Ab
un
da
nce
341.85
343.80
342.83
344.78
345.79339.07 340.38338.12 341.14337.10 346.78339.51
Figure S14. ESI-MS spectrum (zoom scan) of GluClHQ (CH3OH)
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
gluclhq #145-234 RT: 3.03-4.39 AV: 90 NL: 1.76E6T: + p ESI Z ms [ 358.90-368.90]
359 360 361 362 363 364 365 366 367 368
m/z
0
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100
Re
lative
Ab
un
da
nce
363.92
365.89
364.92
366.90368.34
367.90360.30 362.83361.01359.08 362.06
Figure S15. ESI-MS spectrum (zoom scan) of GluClHQ (CH3OH)
gluclhq #276-379 RT: 5.33-6.88 AV: 104 NL: 4.08E6T: + p ESI Z ms [ 699.60-709.60]
700 701 702 703 704 705 706 707 708 709
m/z
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Ab
un
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nce
704.61
706.43
705.51
707.51
703.53701.47699.89 702.94700.97 708.41 709.27
Figure S16. ESI-MS spectrum (zoom scan) of GluClHQ (CH3OH)
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
Figure S17: 1H NMR spectrum of GluCl2HQ (500 MHz, CD3OD)
Figure S18: 1H-
1H COSY spectrum of GluCl2HQ (500 MHz, CD3OD)
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
Figure S19: gHSQCAD spectrum of GluCl2HQ (500 MHz, CD3OD)
Figure S20: HMBC spectrum of GluCl2HQ (500 MHz, CD3OD)
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
Figure S21: 13
C NMR spectrum of GluCl2HQ (125 MHz, CD3OD) glucl2hq #22-35 RT: 0.67-1.02 AV: 14 NL: 2.11E7T: + p ESI Full ms [ 200.00-2000.00]
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m/z
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Re
lative
Ab
un
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nce
397.87
774.47
375.73
490.80 790.53626.67413.00 441.80 746.07560.13 675.53 722.40537.93371.47 599.87307.93
Figure S22: ESI-MS spectrum of GluCl2HQ (CH3OH)
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
glucl2hqbis #1-24 RT: 0.01-0.36 AV: 24 NL: 1.85E6T: + p ESI Z ms [ 370.70-380.70]
371 372 373 374 375 376 377 378 379 380
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375.85
377.81
376.82
378.78 379.78
370.92 372.03 372.92 374.99373.87 380.13
Figure S23: ESI-MS spectrum (zoom scan) of GluCl2HQ (CH3OH)
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
(nm)
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Ab
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1.2
Figure S24: Enzymatic kinetic assay of GluClHQ (6 x10-5
M) in the presence of glucosidase
(1.1x10-6
M) at pH 7.4 (phosphate buffer 5 mM). UV-vis spectra were recorded every 12 min.
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
(nm)
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1.5
2.0
Figure S25: Enzymatic kinetic assay of GluCl2HQ (6 x10-5
M) in the presence of glucosidase
(1.1x10-6
M) at pH 7.4 (phosphate buffer 5 mM). UV-vis spectra were recorded every 9 min.
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
(nm)
250 300 350 400 450 500
Ab
s
0.0
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1.0
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Figure S26: Enzymatic kinetic assay of GluMeHQ (6 x10
-5 M) in the presence of glucosidase
(1.1x10-6
M)and copper (II) at pH 7.4 (phosphate buffer 5 mM). UV-vis spectra were recorded
every 12 min. No significant hydrolysis was observed.
Electronic Supplementary Material (ESI) for Dalton TransactionsThis journal is © The Royal Society of Chemistry 2012
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