Solution structures, stabilities, kinetics, and dynamics of DO3A and DO3A-sulphonamide complexes

Anett Takács, Roberta Napolitano, Mihály Purgel, A. Bényei, László Zékány, E. Brücher, Imre Tóth, Z. Baranyai, Silvio Aime

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Abstract

The Gd3+-DO3A-arylsulphonamide (DO3A-SA) complex is a promising pH-sensitive MRI agent. The stability constants of the DO3A-SA and DO3A complexes formed with Mg2+, Ca2+, Mn2+, Zn 2+, and Cu2+ ions are similar, whereas the logK LnL values of Ln(DO3A-SA) complexes are 2 orders of magnitude higher than those of the Ln(DO3A) complexes. The protonation constant (log K MHL) of the sulphonamide nitrogen in the Mg2+, Ca 2+, Mn2+, Zn2+, and Cu2+ complexes is very similar to that of the free ligand, whereas the logKLnHL values of the Ln(DO3A-SA) complexes are lower by about 4 logK units, indicating a strong interaction between the Ln3+ ions and the sulphonamide N atom. The Ln(HDO3A-SA) complexes are formed via triprotonated*Ln(H 3DO3A-SA) intermediates which rearrange to the final complex in an OH--assisted deprotonation process. The transmetalation reaction of Gd(HDO3A-SA) with Cu2+ is very slow (t1/2 = 5.6 × 103 h at pH = 7.4), and it mainly occurs through proton-assisted dissociation of the complex. The 1H and 13C NMR spectra of the La-, Eu-, Y-, and Lu(DO3A-SA) complexes have been assigned using 2D correlation spectroscopy (COSY, EXSY, HSQC). Two sets of signals are observed for Eu-, Y-, and Lu(DO3A-SA), showing two coordination isomers in solution, that is, square antiprismatic (SAP) and twisted square antiprismatic (TSAP) geometries with ratios of 86-14, 93-7, and 94-6%, respectively. Line shape analysis of the 13C NMR spectra of La-, Y-, and Lu(DO3A-SA) gives higher rates and lower activation entropy values compared to Ln(DOTA) for the arm rotation, which indicates that the Ln(DO3A-SA) complexes are less rigid due to the larger flexibility of the ethylene group in the sulphonamide pendant arm. The fast isomerization and the lower activation parameters of Ln(DO3A-SA) have been confirmed by theoretical calculations in vacuo and by using the polarizable continuum model. The solid state X-ray structure of Cu(H2DO3A-SA) shows distorted octahedral coordination. The coordination sites of Cu 2+ are occupied by two ring N- and two carboxylate O-atoms in equatorial position. The other two ring N-atoms complete the coordination sphere in axial positions. The solid state structure also indicates that a carboxylate O atom and the sulphonamide nitrogen are protonated and noncoordinated.

Original languageEnglish
Pages (from-to)2858-2872
Number of pages15
JournalInorganic Chemistry
Volume53
Issue number6
DOIs
Publication statusPublished - Mar 17 2014

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Sulfonamides
Atoms
Kinetics
kinetics
carboxylates
atoms
Nitrogen
Chemical activation
Nuclear magnetic resonance
activation
Ions
solid state
nitrogen
nuclear magnetic resonance
Deprotonation
rings
Protonation
Entropy
Isomerization
Isomers

ASJC Scopus subject areas

  • Inorganic Chemistry
  • Physical and Theoretical Chemistry
  • Medicine(all)

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Solution structures, stabilities, kinetics, and dynamics of DO3A and DO3A-sulphonamide complexes. / Takács, Anett; Napolitano, Roberta; Purgel, Mihály; Bényei, A.; Zékány, László; Brücher, E.; Tóth, Imre; Baranyai, Z.; Aime, Silvio.

In: Inorganic Chemistry, Vol. 53, No. 6, 17.03.2014, p. 2858-2872.

Research output: Contribution to journalArticle

Takács, Anett ; Napolitano, Roberta ; Purgel, Mihály ; Bényei, A. ; Zékány, László ; Brücher, E. ; Tóth, Imre ; Baranyai, Z. ; Aime, Silvio. / Solution structures, stabilities, kinetics, and dynamics of DO3A and DO3A-sulphonamide complexes. In: Inorganic Chemistry. 2014 ; Vol. 53, No. 6. pp. 2858-2872.
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abstract = "The Gd3+-DO3A-arylsulphonamide (DO3A-SA) complex is a promising pH-sensitive MRI agent. The stability constants of the DO3A-SA and DO3A complexes formed with Mg2+, Ca2+, Mn2+, Zn 2+, and Cu2+ ions are similar, whereas the logK LnL values of Ln(DO3A-SA) complexes are 2 orders of magnitude higher than those of the Ln(DO3A) complexes. The protonation constant (log K MHL) of the sulphonamide nitrogen in the Mg2+, Ca 2+, Mn2+, Zn2+, and Cu2+ complexes is very similar to that of the free ligand, whereas the logKLnHL values of the Ln(DO3A-SA) complexes are lower by about 4 logK units, indicating a strong interaction between the Ln3+ ions and the sulphonamide N atom. The Ln(HDO3A-SA) complexes are formed via triprotonated*Ln(H 3DO3A-SA) intermediates which rearrange to the final complex in an OH--assisted deprotonation process. The transmetalation reaction of Gd(HDO3A-SA) with Cu2+ is very slow (t1/2 = 5.6 × 103 h at pH = 7.4), and it mainly occurs through proton-assisted dissociation of the complex. The 1H and 13C NMR spectra of the La-, Eu-, Y-, and Lu(DO3A-SA) complexes have been assigned using 2D correlation spectroscopy (COSY, EXSY, HSQC). Two sets of signals are observed for Eu-, Y-, and Lu(DO3A-SA), showing two coordination isomers in solution, that is, square antiprismatic (SAP) and twisted square antiprismatic (TSAP) geometries with ratios of 86-14, 93-7, and 94-6{\%}, respectively. Line shape analysis of the 13C NMR spectra of La-, Y-, and Lu(DO3A-SA) gives higher rates and lower activation entropy values compared to Ln(DOTA) for the arm rotation, which indicates that the Ln(DO3A-SA) complexes are less rigid due to the larger flexibility of the ethylene group in the sulphonamide pendant arm. The fast isomerization and the lower activation parameters of Ln(DO3A-SA) have been confirmed by theoretical calculations in vacuo and by using the polarizable continuum model. The solid state X-ray structure of Cu(H2DO3A-SA) shows distorted octahedral coordination. The coordination sites of Cu 2+ are occupied by two ring N- and two carboxylate O-atoms in equatorial position. The other two ring N-atoms complete the coordination sphere in axial positions. The solid state structure also indicates that a carboxylate O atom and the sulphonamide nitrogen are protonated and noncoordinated.",
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T1 - Solution structures, stabilities, kinetics, and dynamics of DO3A and DO3A-sulphonamide complexes

AU - Takács, Anett

AU - Napolitano, Roberta

AU - Purgel, Mihály

AU - Bényei, A.

AU - Zékány, László

AU - Brücher, E.

AU - Tóth, Imre

AU - Baranyai, Z.

AU - Aime, Silvio

PY - 2014/3/17

Y1 - 2014/3/17

N2 - The Gd3+-DO3A-arylsulphonamide (DO3A-SA) complex is a promising pH-sensitive MRI agent. The stability constants of the DO3A-SA and DO3A complexes formed with Mg2+, Ca2+, Mn2+, Zn 2+, and Cu2+ ions are similar, whereas the logK LnL values of Ln(DO3A-SA) complexes are 2 orders of magnitude higher than those of the Ln(DO3A) complexes. The protonation constant (log K MHL) of the sulphonamide nitrogen in the Mg2+, Ca 2+, Mn2+, Zn2+, and Cu2+ complexes is very similar to that of the free ligand, whereas the logKLnHL values of the Ln(DO3A-SA) complexes are lower by about 4 logK units, indicating a strong interaction between the Ln3+ ions and the sulphonamide N atom. The Ln(HDO3A-SA) complexes are formed via triprotonated*Ln(H 3DO3A-SA) intermediates which rearrange to the final complex in an OH--assisted deprotonation process. The transmetalation reaction of Gd(HDO3A-SA) with Cu2+ is very slow (t1/2 = 5.6 × 103 h at pH = 7.4), and it mainly occurs through proton-assisted dissociation of the complex. The 1H and 13C NMR spectra of the La-, Eu-, Y-, and Lu(DO3A-SA) complexes have been assigned using 2D correlation spectroscopy (COSY, EXSY, HSQC). Two sets of signals are observed for Eu-, Y-, and Lu(DO3A-SA), showing two coordination isomers in solution, that is, square antiprismatic (SAP) and twisted square antiprismatic (TSAP) geometries with ratios of 86-14, 93-7, and 94-6%, respectively. Line shape analysis of the 13C NMR spectra of La-, Y-, and Lu(DO3A-SA) gives higher rates and lower activation entropy values compared to Ln(DOTA) for the arm rotation, which indicates that the Ln(DO3A-SA) complexes are less rigid due to the larger flexibility of the ethylene group in the sulphonamide pendant arm. The fast isomerization and the lower activation parameters of Ln(DO3A-SA) have been confirmed by theoretical calculations in vacuo and by using the polarizable continuum model. The solid state X-ray structure of Cu(H2DO3A-SA) shows distorted octahedral coordination. The coordination sites of Cu 2+ are occupied by two ring N- and two carboxylate O-atoms in equatorial position. The other two ring N-atoms complete the coordination sphere in axial positions. The solid state structure also indicates that a carboxylate O atom and the sulphonamide nitrogen are protonated and noncoordinated.

AB - The Gd3+-DO3A-arylsulphonamide (DO3A-SA) complex is a promising pH-sensitive MRI agent. The stability constants of the DO3A-SA and DO3A complexes formed with Mg2+, Ca2+, Mn2+, Zn 2+, and Cu2+ ions are similar, whereas the logK LnL values of Ln(DO3A-SA) complexes are 2 orders of magnitude higher than those of the Ln(DO3A) complexes. The protonation constant (log K MHL) of the sulphonamide nitrogen in the Mg2+, Ca 2+, Mn2+, Zn2+, and Cu2+ complexes is very similar to that of the free ligand, whereas the logKLnHL values of the Ln(DO3A-SA) complexes are lower by about 4 logK units, indicating a strong interaction between the Ln3+ ions and the sulphonamide N atom. The Ln(HDO3A-SA) complexes are formed via triprotonated*Ln(H 3DO3A-SA) intermediates which rearrange to the final complex in an OH--assisted deprotonation process. The transmetalation reaction of Gd(HDO3A-SA) with Cu2+ is very slow (t1/2 = 5.6 × 103 h at pH = 7.4), and it mainly occurs through proton-assisted dissociation of the complex. The 1H and 13C NMR spectra of the La-, Eu-, Y-, and Lu(DO3A-SA) complexes have been assigned using 2D correlation spectroscopy (COSY, EXSY, HSQC). Two sets of signals are observed for Eu-, Y-, and Lu(DO3A-SA), showing two coordination isomers in solution, that is, square antiprismatic (SAP) and twisted square antiprismatic (TSAP) geometries with ratios of 86-14, 93-7, and 94-6%, respectively. Line shape analysis of the 13C NMR spectra of La-, Y-, and Lu(DO3A-SA) gives higher rates and lower activation entropy values compared to Ln(DOTA) for the arm rotation, which indicates that the Ln(DO3A-SA) complexes are less rigid due to the larger flexibility of the ethylene group in the sulphonamide pendant arm. The fast isomerization and the lower activation parameters of Ln(DO3A-SA) have been confirmed by theoretical calculations in vacuo and by using the polarizable continuum model. The solid state X-ray structure of Cu(H2DO3A-SA) shows distorted octahedral coordination. The coordination sites of Cu 2+ are occupied by two ring N- and two carboxylate O-atoms in equatorial position. The other two ring N-atoms complete the coordination sphere in axial positions. The solid state structure also indicates that a carboxylate O atom and the sulphonamide nitrogen are protonated and noncoordinated.

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