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Effect of oligomerization on the solvent water proton longitudinal relaxation rates of lanthanide EDTA complexes
Journal of the Less-Common Metals, 126 (1986) 339-342
339
EFFECT OF OLIGOMERIZATION ON THE SOLVENT WATER PROTON LONGITUDINAL RELAXATION RATES OF LANTHANIDE EDTA COMPLEXES*
HARRY
G. BRITTAIN,
S. MANTHA
and MICHAEL
F. TWEEDLE
The Squibb Institute for Medical Research, P.O. Box 191, New Brunswick, NJ08903(lJ.S.A.) (Received March 31,1986)
Summary It has been established through a variety of spectroscopic studies that the lanthanide complexes of EDTA form oligomeric species above pH 10. To investigate further this phenomenon, the relaxivity of Gd(EDTA) was determined as a function of pH. This quantity 2ok1 (having units of M- ’ s- ‘) is defined from A
(solution) --A
(solvent)
= ‘Ok, [Gd(EDTA)]
It was observed that the 2ok1 rate constant changed by a factor of two within the same pH interval associated with the onset of the oligomerization process. Support for the formation of polynuclear species was obtained from measurements of terbium(II1) excitation spectra. It was concluded that the oligomerization resulted in a decrease in the solvent interaction, thus depressing the relaxation properties.
1. Introduction Careful studies of energy transfer among lanthanide complexes containing hexadentate aminopolycarboxylate ligands have revealed that these complexes are capable of forming polynuclear species above pH 10 [l]. Ligands of higher denticity or ligands having a substantial steric requirement were able to prevent the formation of oligomeric species at elevated pH values. Subsequently, it was shown that the circularly polarized luminescence spectra of chiral terbium(II1) aminopolycarboxylate complexes underwent drastic changes above pH 10 [2]. It was concluded from these studies that the formation
*Paper presented at the 17th Rare Earth Hamilton, Ontario, Canada, June 9 ~ 12,1986. 0022-5088/86/$3.50
Research
Conference,
McMaster
0 Elsevier Sequoia/Printed
University,
in The Netherlands
340
of these oligomers was accompanied by large perturbations in the stereochemistry of the coordinated aminopolycarboxylate ligand. Additional proof that lanthanide derivatives of EDTA are capable of undergoing self-association into oligomeric species was obtained from terbium(II1) excitation spectra. It was recently shown that when the terbium(II1) ion is bound in a polymeric environment, terbium(II1) excitation bands near 300 nm increase dramatically in magnitude [S]. The first part of the present investigation therefore deals with the pH dependence of terbium(II1) excitation bands in Tb(EDTA) complexes. Gadolinium(II1) derivatives of certain aminopolycarboxylates have found use as contrast agents in in vivo NMR imaging, based on the ability of these compounds to alter the relaxation times of tissue water. Consequently, it is of interest to quantify the effect on relaxation rates induced by the possible complex oligomerization. In the present work, we report determinations of the relaxivity of Gd(EDTA) as a function of pH and attempt to correlate these observations with the oligomerization reactions. 2. Experimental
details
The lanthanide EDTA complexes were formed by mixing appropriate stock solutions of the desired metal ion and ligand in an exact 1:l ratio. The final concentration of Tb(EDTA) used for luminescence work was 1 mM. pH control over the solutions was effected by the addition of microliter amounts of standard acid or base directly to the solution under study. All luminescence measurements were obtained on a Spex Fluorolog instrument, employing double monochromators on both excitation and emission ends. Proton relaxation rates were measured at 40°C on an IBM 20, 20 MHz Minispectrometer. Relaxation rate enhancement by paramagnetic substances is governed by a second-order rate constant which describes each paramagnet’s ability to relax bulk water protons. The relaxivity of a given paramagnet P as measured at 20 MHz is defined as “k,[P]
=$(P)
-il(water)
(1)
and is obtained in units of M 1 s-l. The right-hand side of eqn. (1) represents the difference in measured relaxation rates owing to the presence of P and [P] is the concentration of P in moles per liter. Relaxation rates measured in fluid solutions are generally linear in paramagnet concentration over the 0.1-l mM was used exclusively as the range. In the present work, gadolinium(II1) paramagnetic agent. 3. Results and discussion Measurements of energy transfer from Tb(EDTA) to Eu(EDTA) complexes have permitted the deduction of important features associated with the solution
341
phase chemistry. Below pH 10, the complexes remain monomeric and all energy transfer is characteristic of dynamic (collisional) quenching [l]. Above pH 10, the energy transfer process becomes characteristic of static quenching, therefore indicating self-association of the lanthanide EDTA complexes. It has recently been shown that certain terbium(II1) excitation bands around 300 nm become exceedingly intense when this ion becomes bound as part of a polymeric species [3]. We therefore sought verification of the oligomerization process through studies of the pH dependence of Tb(EDTA) complex excitation spectra. The results of these studies are summarized in Fig. 1. The terbium(II1) excitation spectra remained absolutely invariant between pH 4 and 9, but above pH 9.5 the growth of new excitation bands in the 300 nm spectral region was observed. At pH 11, the excitation spectra were found to be dominated by the new features. All these observations are consistent with the trends noted in the energy transfer [l] and circularly polarized luminescence [2] studies.
335 kevel
ength
I’nml
Fig. 1. Terbium(II1) excitation spectra obtained for Tb(EDTA) as a function of pH. Data were obtained at pH 11.1 (full line) and pH 4.3 (broken line). The excitation spectrum obtained at pH 8.0 was identical to that obtained at pH 4.3.
With confirmatory evidence now available supporting oligomerization of lanthanide EDTA complexes above pH 10, we obtained the pH dependence of Gd(EDTA) relaxation rates as a function of pH. The results of these investigations have been collected in Table 1. It should be noted that the relaxivity remains essentially constant until pH 9.5, where it begins to decrease significantly. The correspondence of these pH variations to the known oligomerization trends clearly indicates that the formation of the polynuclear species greatly decreases the relaxation properties of Gd(EDTA). One of the factors governing the relaxation ability of a gadolinium(II1) species is the number of water molecules actually coordinated to the
342
TABLE 1 pH dependence of the relaxivity
associated with Gd(EDTA) complexes
PH
Tl
l/T1
%,(Gd)
5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 11.0 11.5 12.0
0.05947 0.06224 0.05697 0.05979 0.05472 0.05919 0.05781 0.05917 0.05962 0.06551 0.06531 0.07519 0.07415 0.01387
16.82 16.07 17.55 16.72 18.28 16.90 17.39 17.08 16.77 15.27 15.31 13.30 13.49 7.21
5092 4862 5314 5065 5543 5117 5270 5175 5080 4614 4628 4007 4065 2129
gadolinium(II1) ion. In other work we have shown that when all other factors are equal, complexes containing more coordinated water are better relaxation agents [4]. It is therefore implied that the [Gd(EDTA)], oligomers contain fewer waters of hydration than do the monomeric Gd(EDTA) compounds. The number of coordinated water molecules bound to the terbium(II1) and europium(II1) complexes of EDTA has been shown to be 3 [5,6]. The results obtained in the present investigation indicate that formation of the oligomer species results in a reduction of the number of coordinated water molecules. Since it appears that the oligomers are linked by hydroxide bridges [7], this conclusion is completely reasonable.
References L. Spaulding and H. G. Brittain, Inorg. Chem., 22(1983) 3486. H. G. Brittain and K. H. Pearson, Inorg. Chem., 22(1983) 78. A. Rudman, S. Paoletti and H. G. Brittain, Inorg. Chem., 24 (1985) 1283. M. F. Tweedle, G. T. Gaughan, P. W. Wedeking and H. G. Brittain, unpublished results. W. Dew. Horrocks, Jr. and D. R. Sudnick, J. Am. Chem. Sot., 101(1979) 334. H. G. Brittain and M. Ransom, Inorg. Chim. Acta, 95 (1984) 113. R. Prados, L. G. Stadtherr, H. Donato and R. B. Martin, J. Znorg. NucZ. Chem., 36(1974) 689.
339
EFFECT OF OLIGOMERIZATION ON THE SOLVENT WATER PROTON LONGITUDINAL RELAXATION RATES OF LANTHANIDE EDTA COMPLEXES*
HARRY
G. BRITTAIN,
S. MANTHA
and MICHAEL
F. TWEEDLE
The Squibb Institute for Medical Research, P.O. Box 191, New Brunswick, NJ08903(lJ.S.A.) (Received March 31,1986)
Summary It has been established through a variety of spectroscopic studies that the lanthanide complexes of EDTA form oligomeric species above pH 10. To investigate further this phenomenon, the relaxivity of Gd(EDTA) was determined as a function of pH. This quantity 2ok1 (having units of M- ’ s- ‘) is defined from A
(solution) --A
(solvent)
= ‘Ok, [Gd(EDTA)]
It was observed that the 2ok1 rate constant changed by a factor of two within the same pH interval associated with the onset of the oligomerization process. Support for the formation of polynuclear species was obtained from measurements of terbium(II1) excitation spectra. It was concluded that the oligomerization resulted in a decrease in the solvent interaction, thus depressing the relaxation properties.
1. Introduction Careful studies of energy transfer among lanthanide complexes containing hexadentate aminopolycarboxylate ligands have revealed that these complexes are capable of forming polynuclear species above pH 10 [l]. Ligands of higher denticity or ligands having a substantial steric requirement were able to prevent the formation of oligomeric species at elevated pH values. Subsequently, it was shown that the circularly polarized luminescence spectra of chiral terbium(II1) aminopolycarboxylate complexes underwent drastic changes above pH 10 [2]. It was concluded from these studies that the formation
*Paper presented at the 17th Rare Earth Hamilton, Ontario, Canada, June 9 ~ 12,1986. 0022-5088/86/$3.50
Research
Conference,
McMaster
0 Elsevier Sequoia/Printed
University,
in The Netherlands
340
of these oligomers was accompanied by large perturbations in the stereochemistry of the coordinated aminopolycarboxylate ligand. Additional proof that lanthanide derivatives of EDTA are capable of undergoing self-association into oligomeric species was obtained from terbium(II1) excitation spectra. It was recently shown that when the terbium(II1) ion is bound in a polymeric environment, terbium(II1) excitation bands near 300 nm increase dramatically in magnitude [S]. The first part of the present investigation therefore deals with the pH dependence of terbium(II1) excitation bands in Tb(EDTA) complexes. Gadolinium(II1) derivatives of certain aminopolycarboxylates have found use as contrast agents in in vivo NMR imaging, based on the ability of these compounds to alter the relaxation times of tissue water. Consequently, it is of interest to quantify the effect on relaxation rates induced by the possible complex oligomerization. In the present work, we report determinations of the relaxivity of Gd(EDTA) as a function of pH and attempt to correlate these observations with the oligomerization reactions. 2. Experimental
details
The lanthanide EDTA complexes were formed by mixing appropriate stock solutions of the desired metal ion and ligand in an exact 1:l ratio. The final concentration of Tb(EDTA) used for luminescence work was 1 mM. pH control over the solutions was effected by the addition of microliter amounts of standard acid or base directly to the solution under study. All luminescence measurements were obtained on a Spex Fluorolog instrument, employing double monochromators on both excitation and emission ends. Proton relaxation rates were measured at 40°C on an IBM 20, 20 MHz Minispectrometer. Relaxation rate enhancement by paramagnetic substances is governed by a second-order rate constant which describes each paramagnet’s ability to relax bulk water protons. The relaxivity of a given paramagnet P as measured at 20 MHz is defined as “k,[P]
=$(P)
-il(water)
(1)
and is obtained in units of M 1 s-l. The right-hand side of eqn. (1) represents the difference in measured relaxation rates owing to the presence of P and [P] is the concentration of P in moles per liter. Relaxation rates measured in fluid solutions are generally linear in paramagnet concentration over the 0.1-l mM was used exclusively as the range. In the present work, gadolinium(II1) paramagnetic agent. 3. Results and discussion Measurements of energy transfer from Tb(EDTA) to Eu(EDTA) complexes have permitted the deduction of important features associated with the solution
341
phase chemistry. Below pH 10, the complexes remain monomeric and all energy transfer is characteristic of dynamic (collisional) quenching [l]. Above pH 10, the energy transfer process becomes characteristic of static quenching, therefore indicating self-association of the lanthanide EDTA complexes. It has recently been shown that certain terbium(II1) excitation bands around 300 nm become exceedingly intense when this ion becomes bound as part of a polymeric species [3]. We therefore sought verification of the oligomerization process through studies of the pH dependence of Tb(EDTA) complex excitation spectra. The results of these studies are summarized in Fig. 1. The terbium(II1) excitation spectra remained absolutely invariant between pH 4 and 9, but above pH 9.5 the growth of new excitation bands in the 300 nm spectral region was observed. At pH 11, the excitation spectra were found to be dominated by the new features. All these observations are consistent with the trends noted in the energy transfer [l] and circularly polarized luminescence [2] studies.
335 kevel
ength
I’nml
Fig. 1. Terbium(II1) excitation spectra obtained for Tb(EDTA) as a function of pH. Data were obtained at pH 11.1 (full line) and pH 4.3 (broken line). The excitation spectrum obtained at pH 8.0 was identical to that obtained at pH 4.3.
With confirmatory evidence now available supporting oligomerization of lanthanide EDTA complexes above pH 10, we obtained the pH dependence of Gd(EDTA) relaxation rates as a function of pH. The results of these investigations have been collected in Table 1. It should be noted that the relaxivity remains essentially constant until pH 9.5, where it begins to decrease significantly. The correspondence of these pH variations to the known oligomerization trends clearly indicates that the formation of the polynuclear species greatly decreases the relaxation properties of Gd(EDTA). One of the factors governing the relaxation ability of a gadolinium(II1) species is the number of water molecules actually coordinated to the
342
TABLE 1 pH dependence of the relaxivity
associated with Gd(EDTA) complexes
PH
Tl
l/T1
%,(Gd)
5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 11.0 11.5 12.0
0.05947 0.06224 0.05697 0.05979 0.05472 0.05919 0.05781 0.05917 0.05962 0.06551 0.06531 0.07519 0.07415 0.01387
16.82 16.07 17.55 16.72 18.28 16.90 17.39 17.08 16.77 15.27 15.31 13.30 13.49 7.21
5092 4862 5314 5065 5543 5117 5270 5175 5080 4614 4628 4007 4065 2129
gadolinium(II1) ion. In other work we have shown that when all other factors are equal, complexes containing more coordinated water are better relaxation agents [4]. It is therefore implied that the [Gd(EDTA)], oligomers contain fewer waters of hydration than do the monomeric Gd(EDTA) compounds. The number of coordinated water molecules bound to the terbium(II1) and europium(II1) complexes of EDTA has been shown to be 3 [5,6]. The results obtained in the present investigation indicate that formation of the oligomer species results in a reduction of the number of coordinated water molecules. Since it appears that the oligomers are linked by hydroxide bridges [7], this conclusion is completely reasonable.
References L. Spaulding and H. G. Brittain, Inorg. Chem., 22(1983) 3486. H. G. Brittain and K. H. Pearson, Inorg. Chem., 22(1983) 78. A. Rudman, S. Paoletti and H. G. Brittain, Inorg. Chem., 24 (1985) 1283. M. F. Tweedle, G. T. Gaughan, P. W. Wedeking and H. G. Brittain, unpublished results. W. Dew. Horrocks, Jr. and D. R. Sudnick, J. Am. Chem. Sot., 101(1979) 334. H. G. Brittain and M. Ransom, Inorg. Chim. Acta, 95 (1984) 113. R. Prados, L. G. Stadtherr, H. Donato and R. B. Martin, J. Znorg. NucZ. Chem., 36(1974) 689.