TY - JOUR
T1 - Triazoles as T2-Exchange Magnetic Resonance Imaging Contrast Agents for the Detection of Nitrilase Activity
AU - Zhang, Jia
AU - Han, Zheng
AU - Lu, Jiaqi
AU - Li, Yuguo
AU - Liao, Xuhe
AU - van Zijl, Peter C.
AU - Yang, Xing
AU - Liu, Guanshu
N1 - Funding Information:
Financial support from the NIH grants R03EB021573, R01CA211087, R21CA215860, R01EB019934, and R01EB015032, and the Chinese National Thousand Young Talent Programs is acknowledged.
Publisher Copyright:
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2018/10/9
Y1 - 2018/10/9
N2 - We characterized the T2-exchange (T2ex) magnetic resonance imaging (MRI) contrast of azole protons that have large chemical shifts from the water proton resonance as a function of pH, temperature, and chemical modification. Our results showed that 1,2,4-triazoles could be tuned into excellent diamagnetic T2ex contrast agents, with an optimal exchange-based relaxivity r2ex of 0.10 s−1 mm−1 at physiological pH and B0=9.4 T. A fit of r2ex data to the Swift–Connick equation indicated that imino proton exchange of triazoles is dominated by a base-catalyzed process at higher pH values and an acid-catalyzed process at lower pH. The magnitude of r2ex was also found to be heavily dependent on chemical modifications, that is, enhanced by electron-donating groups, such as amines and methyls, or by intramolecular hydrogen bonding between the imino proton and the carboxyl, and weakened by electron-withdrawing groups like bromo, cyano, and nitro. In light of these findings, we applied T2ex MRI to assess the activity of nitrilase, an enzyme catalyzing the hydrolysis of 1,2,4-triazole-3-carbonitrile to 1,2,4-triazole-3-carboxylic acid, resulting in the enhancement of R2ex. Our findings suggest that 1,2,4-triazoles have potential to provide sensitive and tunable diagnostic probes for MRI.
AB - We characterized the T2-exchange (T2ex) magnetic resonance imaging (MRI) contrast of azole protons that have large chemical shifts from the water proton resonance as a function of pH, temperature, and chemical modification. Our results showed that 1,2,4-triazoles could be tuned into excellent diamagnetic T2ex contrast agents, with an optimal exchange-based relaxivity r2ex of 0.10 s−1 mm−1 at physiological pH and B0=9.4 T. A fit of r2ex data to the Swift–Connick equation indicated that imino proton exchange of triazoles is dominated by a base-catalyzed process at higher pH values and an acid-catalyzed process at lower pH. The magnitude of r2ex was also found to be heavily dependent on chemical modifications, that is, enhanced by electron-donating groups, such as amines and methyls, or by intramolecular hydrogen bonding between the imino proton and the carboxyl, and weakened by electron-withdrawing groups like bromo, cyano, and nitro. In light of these findings, we applied T2ex MRI to assess the activity of nitrilase, an enzyme catalyzing the hydrolysis of 1,2,4-triazole-3-carbonitrile to 1,2,4-triazole-3-carboxylic acid, resulting in the enhancement of R2ex. Our findings suggest that 1,2,4-triazoles have potential to provide sensitive and tunable diagnostic probes for MRI.
KW - T-exchange MRI
KW - nitrilase
KW - swift–connick equation
KW - triazoles
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U2 - 10.1002/chem.201802663
DO - 10.1002/chem.201802663
M3 - Article
C2 - 29989227
AN - SCOPUS:85053061852
SN - 0947-6539
VL - 24
SP - 15013
EP - 15018
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 56
ER -