The pH sensitivity of -NH exchange in LnDOTA-tetraamide complexes varies with amide substituent

Ana Christina L Opina, Yunkou Wu, Piyu Zhao, Garry Kiefer, A. Dean Sherry

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The amide proton exchange rates in various lanthanide(III) DOTA-tetraamide complexes were investigated by CEST as a function of variable chemical structures and charges on the amide substituents. Comparisons were made between YbDOTA-(gly) 4 - (Yb-1), YbDOTA-(NHCH 2PO 3) 4 5- (Yb-2) and YbDOTA-(NHCH 2PO 3Et 2) 4 3+ (Yb-3). The general shapes of the CEST vs pH profiles were similar for the three complexes but they showed maximum CEST intensities at different pH values, pH 8.3, 8.8 and 6.9 for Yb-1, Yb-2 and Yb-3, respectively. This indicates that a more negatively charged substituent on the amide helps stabilize the partial positive charge on the amide nitrogen and consequently more base is required to catalyze proton exchange. The chemical shifts of the -NH protons in Yb-1 and Yb-2 were similar (-17ppm) while the -NH proton in Yb-3 was at -13ppm. This shows that the crystal field produced by the amide oxygen donor atoms in Yb-3 is substantially weaker than that in the other two complexes. In an effort to expand the useful range of pH values that might be measured using these complexes as CEST agents, the shapes of the CEST vs pH curves were also determined for two thulium(III) complexes with much larger hyperfine shifted -NH proton resonances. The ratio of CEST from -NH exchange in Tm-1 compared with CEST from -NH exchange in Tm-3 was found to be linear over an extended pH range, from 6.3 to 7.4. This demonstrates a potential advantage of using mixtures of lanthanide(III) DOTA-tetraamides for mapping tissue pH by use of ratiometric CEST imaging.

Original languageEnglish (US)
Pages (from-to)459-464
Number of pages6
JournalContrast Media and Molecular Imaging
Volume6
Issue number6
DOIs
StatePublished - Nov 2011

Fingerprint

Amides
Protons
Lanthanoid Series Elements
glycyl-glycyl-glycyl-glycine
Thulium
Nitrogen
Oxygen

Keywords

  • Amide proton exchange
  • Chemical exchange saturation transfer (CEST) agents
  • Contrast agents
  • MRI
  • Paramagnetic agents
  • pH-responsive agents
  • Ratiometric analysis

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

The pH sensitivity of -NH exchange in LnDOTA-tetraamide complexes varies with amide substituent. / Opina, Ana Christina L; Wu, Yunkou; Zhao, Piyu; Kiefer, Garry; Sherry, A. Dean.

In: Contrast Media and Molecular Imaging, Vol. 6, No. 6, 11.2011, p. 459-464.

Research output: Contribution to journalArticle

Opina, Ana Christina L ; Wu, Yunkou ; Zhao, Piyu ; Kiefer, Garry ; Sherry, A. Dean. / The pH sensitivity of -NH exchange in LnDOTA-tetraamide complexes varies with amide substituent. In: Contrast Media and Molecular Imaging. 2011 ; Vol. 6, No. 6. pp. 459-464.
@article{d13ae651a68641d5b7f3fd5df56647e5,
title = "The pH sensitivity of -NH exchange in LnDOTA-tetraamide complexes varies with amide substituent",
abstract = "The amide proton exchange rates in various lanthanide(III) DOTA-tetraamide complexes were investigated by CEST as a function of variable chemical structures and charges on the amide substituents. Comparisons were made between YbDOTA-(gly) 4 - (Yb-1), YbDOTA-(NHCH 2PO 3) 4 5- (Yb-2) and YbDOTA-(NHCH 2PO 3Et 2) 4 3+ (Yb-3). The general shapes of the CEST vs pH profiles were similar for the three complexes but they showed maximum CEST intensities at different pH values, pH 8.3, 8.8 and 6.9 for Yb-1, Yb-2 and Yb-3, respectively. This indicates that a more negatively charged substituent on the amide helps stabilize the partial positive charge on the amide nitrogen and consequently more base is required to catalyze proton exchange. The chemical shifts of the -NH protons in Yb-1 and Yb-2 were similar (-17ppm) while the -NH proton in Yb-3 was at -13ppm. This shows that the crystal field produced by the amide oxygen donor atoms in Yb-3 is substantially weaker than that in the other two complexes. In an effort to expand the useful range of pH values that might be measured using these complexes as CEST agents, the shapes of the CEST vs pH curves were also determined for two thulium(III) complexes with much larger hyperfine shifted -NH proton resonances. The ratio of CEST from -NH exchange in Tm-1 compared with CEST from -NH exchange in Tm-3 was found to be linear over an extended pH range, from 6.3 to 7.4. This demonstrates a potential advantage of using mixtures of lanthanide(III) DOTA-tetraamides for mapping tissue pH by use of ratiometric CEST imaging.",
keywords = "Amide proton exchange, Chemical exchange saturation transfer (CEST) agents, Contrast agents, MRI, Paramagnetic agents, pH-responsive agents, Ratiometric analysis",
author = "Opina, {Ana Christina L} and Yunkou Wu and Piyu Zhao and Garry Kiefer and Sherry, {A. Dean}",
year = "2011",
month = "11",
doi = "10.1002/cmmi.445",
language = "English (US)",
volume = "6",
pages = "459--464",
journal = "Contrast Media and Molecular Imaging",
issn = "1555-4309",
publisher = "John Wiley and Sons Ltd",
number = "6",

}

TY - JOUR

T1 - The pH sensitivity of -NH exchange in LnDOTA-tetraamide complexes varies with amide substituent

AU - Opina, Ana Christina L

AU - Wu, Yunkou

AU - Zhao, Piyu

AU - Kiefer, Garry

AU - Sherry, A. Dean

PY - 2011/11

Y1 - 2011/11

N2 - The amide proton exchange rates in various lanthanide(III) DOTA-tetraamide complexes were investigated by CEST as a function of variable chemical structures and charges on the amide substituents. Comparisons were made between YbDOTA-(gly) 4 - (Yb-1), YbDOTA-(NHCH 2PO 3) 4 5- (Yb-2) and YbDOTA-(NHCH 2PO 3Et 2) 4 3+ (Yb-3). The general shapes of the CEST vs pH profiles were similar for the three complexes but they showed maximum CEST intensities at different pH values, pH 8.3, 8.8 and 6.9 for Yb-1, Yb-2 and Yb-3, respectively. This indicates that a more negatively charged substituent on the amide helps stabilize the partial positive charge on the amide nitrogen and consequently more base is required to catalyze proton exchange. The chemical shifts of the -NH protons in Yb-1 and Yb-2 were similar (-17ppm) while the -NH proton in Yb-3 was at -13ppm. This shows that the crystal field produced by the amide oxygen donor atoms in Yb-3 is substantially weaker than that in the other two complexes. In an effort to expand the useful range of pH values that might be measured using these complexes as CEST agents, the shapes of the CEST vs pH curves were also determined for two thulium(III) complexes with much larger hyperfine shifted -NH proton resonances. The ratio of CEST from -NH exchange in Tm-1 compared with CEST from -NH exchange in Tm-3 was found to be linear over an extended pH range, from 6.3 to 7.4. This demonstrates a potential advantage of using mixtures of lanthanide(III) DOTA-tetraamides for mapping tissue pH by use of ratiometric CEST imaging.

AB - The amide proton exchange rates in various lanthanide(III) DOTA-tetraamide complexes were investigated by CEST as a function of variable chemical structures and charges on the amide substituents. Comparisons were made between YbDOTA-(gly) 4 - (Yb-1), YbDOTA-(NHCH 2PO 3) 4 5- (Yb-2) and YbDOTA-(NHCH 2PO 3Et 2) 4 3+ (Yb-3). The general shapes of the CEST vs pH profiles were similar for the three complexes but they showed maximum CEST intensities at different pH values, pH 8.3, 8.8 and 6.9 for Yb-1, Yb-2 and Yb-3, respectively. This indicates that a more negatively charged substituent on the amide helps stabilize the partial positive charge on the amide nitrogen and consequently more base is required to catalyze proton exchange. The chemical shifts of the -NH protons in Yb-1 and Yb-2 were similar (-17ppm) while the -NH proton in Yb-3 was at -13ppm. This shows that the crystal field produced by the amide oxygen donor atoms in Yb-3 is substantially weaker than that in the other two complexes. In an effort to expand the useful range of pH values that might be measured using these complexes as CEST agents, the shapes of the CEST vs pH curves were also determined for two thulium(III) complexes with much larger hyperfine shifted -NH proton resonances. The ratio of CEST from -NH exchange in Tm-1 compared with CEST from -NH exchange in Tm-3 was found to be linear over an extended pH range, from 6.3 to 7.4. This demonstrates a potential advantage of using mixtures of lanthanide(III) DOTA-tetraamides for mapping tissue pH by use of ratiometric CEST imaging.

KW - Amide proton exchange

KW - Chemical exchange saturation transfer (CEST) agents

KW - Contrast agents

KW - MRI

KW - Paramagnetic agents

KW - pH-responsive agents

KW - Ratiometric analysis

UR - http://www.scopus.com/inward/record.url?scp=83155185495&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=83155185495&partnerID=8YFLogxK

U2 - 10.1002/cmmi.445

DO - 10.1002/cmmi.445

M3 - Article

C2 - 22144023

AN - SCOPUS:83155185495

VL - 6

SP - 459

EP - 464

JO - Contrast Media and Molecular Imaging

JF - Contrast Media and Molecular Imaging

SN - 1555-4309

IS - 6

ER -