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Preliminary evaluation of PARACEST MRI agents for the detection of nitric oxide synthase (NOS)

Mojmír Suchý,a.b Alex X. Li,b Yin Liu,c Qingping Feng,c Robert Bartha,b and Robert H. E. Hudson*a,d

aDepartment of Chemistry and dThe Centre for Advanced Materials and Biomaterials

Research, The University of Western Ontario, London, Ontario, Canada, N6A 5B7

b Robarts Research Institute, The University of Western Ontario, London, Ontario,

Canada, N6A 5K8

cDepartment of Physiology and Pharmacology, The University of Western Ontario,

London, Ontario, Canada, N6A 5C1

E-mail: rhhudson@uwo.ca Tel: 519-661-2111 ext. 86349 Fax: 519-661-3022

(ELECTRONIC SUPPLEMENTARY INFORMATION)

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CONTENTS1H and 13C NMR spectra of 9, 10a and 10b......................................................................SI31H NMR spectra of DOTAM-Cit-OMe and DOTAM-Gly-Cit-OMe...............................SI9

HR-ESI-MS spectra of DOTAM-Cit-OMe, DOTAM-Gly-Cit-OMe, 11, 12a and 12b...SI11

HPLC chromatograms of the reaction mixtures containing DOTAM-Cit-OMe and DOTAM-

Gly-Cit-OMe.....................................................................................................................SI16

UPLC traces of purified complexes Dy3+DOTAM-Cit-OH, Dy3+DOTAM-Gly-Cit-OH and

Tm3+DOTAM-Gly-Cit-OH................................................................................................SI17

SI2

Figure SI1: 1H NMR spectrum of L-Cit-OMe · HCl (9) in D2O

SI3

Figure SI2: 13C NMR spectrum of L-Cit-OMe · HCl (9) in D2O

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Figure SI3: 1H NMR spectrum of N-chloroacetyl-Cit-OMe (10a) in DMSO-D6

SI5

3.63

water

Figure SI4: 13C NMR spectrum of N-chloroacetyl-Cit-OMe (10a) in DMSO-D6

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Figure SI5: 1H NMR spectrum of N-chloroacetyl-Gly-Cit-OMe (10b) in DMSO-D6

SI7

3.62

water

Figure SI6: 13C NMR spectrum of N-chloroacetyl-Gly-Cit-OMe (10b) in DMSO-D6

SI8

SI9

Figure SI7: 1H NMR spectrum of the free ligand DOTAM-Cit-OMe in DMSO-D6

SI10

3.62

water

Figure SI8: 1H NMR spectrum of the free ligand DOTAM-Gly-Cit-OMe in DMSO-D6

SI11

3.62

Figure SI9: HR-ESI-MS spectrum of DOTAM-Cit-OMe, note the charge state envelope 1089.6 (M+), 545.3 (M2+)

Figure SI10: HR-ESI-MS spectrum of DOTAM-Cit-OMe, expanded view of 1089.6 (M+) charge state, observed (bottom), simulated (top)

SI12

Figure SI11: HR-ESI-MS spectrum of DOTAM-Gly-Cit-OMe, note the charge state envelope 1317.6 (M+), 659.3 (M2+), 439.9 (M3+)

Figure SI12: HR-ESI-MS spectrum of DOTAM-Gly-Cit-OMe, expanded view of 1317.6 (M+) charge state, observed (bottom), simulated (top)

SI13

Figure SI13: HR-ESI-MS spectrum of Dy3+ DOTAM-Cit-OH (7), note the charge state envelope 1192.4 (M+), 597.7 (M2+), 398.8 (M3+)

Figure SI14: HR-ESI-MS spectrum of Dy3+ DOTAM-Cit-OH (7), expanded view of 597.7 (M2+) charge state, observed (bottom), simulated (top)

SI14

Figure SI15: HR-ESI-MS spectrum of Dy3+ DOTAM-Gly-Cit-OH (8a), note the charge state envelope 1421.5 (M+), 711.7 (M2+), 474.8 (M3+)

Figure SI16: HR-ESI-MS spectrum of Dy3+ DOTAM-Gly-Cit-OH (8a), expanded view of 711.8 (M2+) charge state, observed (bottom), simulated (top)

SI15

Figure SI17: HR-ESI-MS spectrum of Tm3+ DOTAM-Gly-Cit-OH (8b), note the proper charge state envelope 1427.5 (M+), 714.2 (M2+), 476.5 (M3+)

Figure SI18: HR-ESI-MS spectrum of Tm3+ DOTAM-Gly-Cit-OH (8b), expanded view of 714.3 (M2+) charge state, observed (bottom), simulated (top)

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5.370

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Figure SI19: HPLC chromatogram (Method A) of the mixture containing DOTAM-Cit-OMe (tR 5.4 min)

4.265

AU

0.00

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Figure SI20: HPLC chromatogram (Method A) of the mixture containing DOTAM-Gly-Cit-OMe (tR 4.3 min).

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Figure SI21. UPLC trace of Dy3+DOTAM-Cit-OH, 7, UV monitoring at = 220 nm.

Figure SI22. UPLC trace of Dy3+DOTAM-Gly-Cit-OH, 8a, UV monitoring at = 220 nm.

Figure SI22. Tm3+DOTAM-Gly-Cit-OH, 8b, UV monitoring at = 220 nm.

SI18