TY - JOUR
T1 - Structural and spectroscopic insight into the metal binding properties of the
T2 - O -aminophenol- N, N, O -triacetic acid (APTRA) chelator: Implications for design of metal indicators
AU - Brady, Michael
AU - Piombo, Sebastian D.
AU - Hu, Chunhua
AU - Buccella, Daniela
N1 - Funding Information:
This work was supported in part by the National Science Foundation (CHE-1555116). The authors acknowledge Tal Moriah for her assistance in acquiring spectrophotometric data. The Bruker Avance-400 and Avance-500 NMR spectrometers were acquired through the support of the National Science Foundation under Award Number CHE-01162222. The Bruker AXS SMART APEXII single crystal diffractometer was acquired through the support of the Molecular Design Institute in the Department of Chemistry at New York University.
Publisher Copyright:
© 2016 The Royal Society of Chemistry.
PY - 2016
Y1 - 2016
N2 - The o-aminophenol-N,N,O-triacetic acid (APTRA) chelator is employed extensively as a metal-recognition moiety in fluorescent indicators for biological free Mg2+, as well as in low-affinity indicators for the detection of high levels of cellular Ca2+. Despite its widespread use in sensor design, the limited metal selectivity of this chelating moiety can lead to binding of competing cations that complicate the fluorescence-based detection of metals of interest in complex samples. Reported herein are the structural characterization of APTRA complexes with various biologically relevant cations, and the thermodynamic analysis of complex formation with Mg2+, Ca2+ and Zn2+. Our results indicate that the low affinity of APTRA for Mg2+, which makes it a suitable metal-recognition moiety for sensitive analysis of typical millimolar levels of this metal in cells, stems from a much higher enthalpic cost of Mg2+ binding compared to that of other cations. The results are discussed in the context of indicator design, highlighting the aspects that may aid the future development of fluorescent sensors with enhanced metal selectivity profiles.
AB - The o-aminophenol-N,N,O-triacetic acid (APTRA) chelator is employed extensively as a metal-recognition moiety in fluorescent indicators for biological free Mg2+, as well as in low-affinity indicators for the detection of high levels of cellular Ca2+. Despite its widespread use in sensor design, the limited metal selectivity of this chelating moiety can lead to binding of competing cations that complicate the fluorescence-based detection of metals of interest in complex samples. Reported herein are the structural characterization of APTRA complexes with various biologically relevant cations, and the thermodynamic analysis of complex formation with Mg2+, Ca2+ and Zn2+. Our results indicate that the low affinity of APTRA for Mg2+, which makes it a suitable metal-recognition moiety for sensitive analysis of typical millimolar levels of this metal in cells, stems from a much higher enthalpic cost of Mg2+ binding compared to that of other cations. The results are discussed in the context of indicator design, highlighting the aspects that may aid the future development of fluorescent sensors with enhanced metal selectivity profiles.
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U2 - 10.1039/c6dt01557c
DO - 10.1039/c6dt01557c
M3 - Article
AN - SCOPUS:84982729053
SN - 1477-9226
VL - 45
SP - 12458
EP - 12464
JO - Dalton Transactions
JF - Dalton Transactions
IS - 31
ER -