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Dissociation kinetics of cerium(III) and gadolinium(III) complexes of macrocyclic DTPA bis(amide) ligands
Polyhedron Vol. 13, No. 4, pp. 567-571, 1994 Copyright Q 1994 Elsevier Science Ltd Printed in Great Britain. All rights reserved 0277-5387/94 $6.00+0.00
Pergamon
DISSOCIATION KINETICS OF CERIUM(II1) AND GADOLINIUM(II1) COMPLEXES OF MACROCYCLIC DTPA BIS(AMIDE) LIGANDS K&YOUNG CHOI* and KI SUNG KIM Department of Chemistry, Mokwon University, Taejeon 301-729, Korea and
JU CHANG KIM Department of Chemistry, Pusan National University of Technology, Pusan 608-739, Korea (Received 26 July 1993 ; accepted 28 September 1993)
Abstract-The dissociation kinetics of Ce”’ and Gd”’ complexes of macrocyclic DTPA bis(amide) have been studied in aqueous solution using Cu” ions as the scavenger. The measurements were made at 25°C in a solution of 0.100 M (NaClO,) ionic strength. The rates of dissociation of these complexes have been found to be independent of [acetate]. Dissociation of the complexes takes place via both dissociative and associative pathways. The rates of both processes decrease in the order Gd(DTPA)-EAM > Gd(DTPA)-PAM 2: Gd(DTPA)-XAM > Gd(DTPA)-BAM > Gd(DTPA)-PenAM. An increase in ring size of the DTPA bis(amide) ligands leads to an increase in kinetic inertness, reflecting the enhanced participation of the amide carbonyl oxygen in lanthanide(II1) ion coordination. The substitution of an aromatic ring between the two amide nitrogens, however, results in a significant decrease in kinetic inertness of the resulting DTPA-XAM complex.
In recent years, there has been considerable interest in lanthanide complexes with the macrocyclic polyoxa- and polyaza-polycarboxylates, K22DA (1,10-d&a - 4,7,13,16 - tetraazacyclooctadecaneN,N’-diacetic acid), NOTA (1,4,7-triazacyclononane-N,N’,N”-triacetic acid), DOTA (1,4,7, lo-tetraazacyclododecane-N,N’,N”,N”‘-tetraacetic acid), TETA (1,4,&l 1-tetraazacyclotetradecane-N,N’, N”,N”‘-tetraacetic acid) and HEHA (1,4,7,10, 13,16-hexaazacyclooctadecane-N,N’,N”,N”’,N””, N ““‘-hexaacetic acid) because of their use as contrast agents in magnetic resonance imaging (MRI),lA lanthanide ion-selective reagentss7 and radiopharmaceuticals.8,9 The kinetic behaviour of these macrocyclic complexes differs considerably from that of analogous linear polyamino polycarboxylates’@” such as EDTA, DTPA and TTHA (triethylenetetraaminehexaacetic acid) because of the remarkable rigidity of *Author to whom correspondence should be addressed.
macrocyclic aza rings compared to their flexible linear analogues. Kinetic studies’3,‘4 on the lanthanide complexes of polyamino polyoxacarboxylate (K21DA and K22DA) demonstrated the cavity size dependence of the thermodynamic stability and dissociation rates. Brucher el al.” and Brucher and SherryI reported that the dissociation rate of Ce(DOTA)- is slower than that of Ce(NOTA). This likely reflects the thermodynamic stability conferred by the rigidity of the tetraaza ring (DOTA) us the triaza ring (NOTA). Although the difference in the thermodynamic stability between Ce(TETA)- and Ce(NOTA) is not very significant, Ce(NOTA) dissociates more slowly than Ce(TETA)-. This is likely a consequence of the destabilizing effect of the propylene diamine group of the TETA ligand.17 Additional study on the kinetics of formation and dissociation of the Ce3+ complex of HEHA was also reported.18 In this study, although HEHA has an increased ring size (18 cycle) compared to NOTA and DOTA, the rate
561
568
KI-YOUNG CHOI et al. COOH r fiNr”YNA HOOC < 0 o*c > CooH C” \ N N/
Macrocycle DTPA-HAM
n
N
N
HNnNH
DTPA-PAM
HN-NH
DTPA-HAM
HNeNH
DTPA-PenAM HN-NH DTPA-XAM
HNONH
Fig. 1. Structures of the macrocyclic DTPA-bis(amide) ligands.
of dissociation of Ce(HEHA)3p is much faster than that of NOTA and DOTA. This fact may be attributed to the decrease of macrocycle rigidity by the ligand flexibility and the mismatch caused by the large cavity size. We initiated the kinetic properties to understand the ligand effect, such as number of donor atoms and the size of the macrocyclic ligand cavity. We report herein the systematic dissociation kinetics of Ce3+ and Gd3+ complexes of DTPA bis(amide) derivatives (Fig. 1). EXPERIMENTAL
Reagents and solutions The DTPA-bis(amide) macrocycle ligands 1,4,7tris(carboxymethyl)-9,14-dioxo-1,4,7,10,13-pentaazacyclopentadecane (DTPA-EAM), 1,4,7-tris (carboxymethyl)-9,15-dioxo-1,4,7,10,14-pentaazacyclohexadecane (DTPA-PAM), 1,4,7-tris(carboxymethyl) - 9,16 - dioxo - 1,4,7,10,15 - pentaazacycloheptadecane (DTPA-BAM), 1,4,7-tris(carboxymethyl)-9,17-dioxo- 1,4,7,10,16-pentaazacyclooctadecane (DTPA-PenAM) and 6,9,12-tris(carboxymethyl) - 4,14 - dioxo - 3,6,9,12,15 - pentaazabicyclo [15.2.2]heneicosa - 1(19),18,20 - triene (DTPAXAM) were synthesized by the method of Carvalho et aZ.7 In a typical preparation, the amines (5 mmol) in DMSO-1,5-diazabicyclo [4.3.0]non-5-ene (150/3 cm3) were added neat to DTPA bis(anhydride) (5 mmol) all at once. The mixtures were stirred for 24 h at ambient temperature, concentrated under reduced pressure to an oil, diluted with water (30 cm3) and made to pH 10.0 using 1 N HCl or 1 N NaOH. The solutions were applied to Amberlite IRP-64 ion-exchange resin (1O&500 mesh, carboxylic acid form), the column washed with deionized water and the product eluted with 0.5 N acetic acid to yield the title compounds as white solids after recrystallization (yield 35-50%). The ligands were characterized by ‘H NMR, mass
spectrometry and elemental analysis, All other chemicals used were of analytical grade without further purification. All solutions were made up in deionized water. The stock solutions of Ce3+ and Gd3+ were prepared from CeCl, and Gd203 (Aldrich Co., 99.99% purity). The concentration of the stock solutions was determined by EDTA titration using xylenol orange indicator. The concentration of DTPA bis(amide) stock solutions was determined by titration against a standardized Cu(ClO& solution using murexide as indicator. Complex solutions were made by mixing appropriate amounts of lanthanide perchlorate and ligand (slight excess). The complex concentration in the reaction mixtures was 5.0 x lop5 M, while that of Cu2+ was varied between 2.50 x 10e4 and 1.25 x 10m3M. The buffer solutions were made by using a constant acetate ion concentration and varying the concentration of acetic acid. Measurements The ionic strength was adjusted to 0.100 M with NaClO,. Solution pH measurements were made by a Beckman Model @71 pH meter fitted with a Beckman combination electrode. The hydrogen ion concentrations were calculated from the measured pH value by procedures reported previously.” Kinetic measurements were made with the use of a UVIDEC-610 spectrophotometer interfaced with a Scientific data acquisition system. The temperature of the reaction mixture was maintained at 25.0fO.l”C with the use of a Lauda RM 6 circulatory water bath. As the lanthanide complexes do not show appreciable absorption in the near-UV or visible region, Cu2+ was used as the scavenger of free ligand and the reaction kinetics were followed by monitoring the growth in absorbance due to copper complex at 270 nm. Pseudo-first-order rate constants (kobs,S-‘) were calculated from the absorbance ZIStime data using a first-order model.*’
Ce”’ and Gd”’ complexes
of macrocyclic
RESULTS AND DISCUSSION Since the stability constants of Cu(DTPA)-bis (amide) complexes are much greater than those of the Ln(DTPA)-bis(amide) complexes,’ the displacement of Ln3+ ions from the Ln(DTPA)-bis (amide) complexes is complete in the presence of excess Cu2+ ions :
Ln(DTPA)-bis(amide)
+ Cu*+
---+Cu(DTPA)-bis(amide)-
+ Ln3+.
(1)
The experimental data show excellent pseudo-firstorder reaction rates. The concentration of acetate ion was varied by a factor of 5, and the observed rate constant (kobs) values were within 5% of the average value of kobsat a given [H+]. Such an independence of [acetate] has been observed by other workers in the dissociation kinetics of lanthanide complexes. 2’,22The dependence of kobson [Cu2+] is given in Table 1 at different [H+]. The standard deviations were in the range l-5%. In each case, the data fit straight lines with measurable non-zero intercepts, which confirms the exchange reaction as
Table 1. Pseudo-first-order
rate constants
DTPA-bis(amide)
569
ligands
proceeding via both [Cu’+]-independent and [Cu’+]-dependent pathways. Thus, the kinetic data can be described by kobs=
k~+ku[Cu2+l,
(2)
where the rate constant kd represents spontaneous dissociation of the complexes and kc” reflects the Cu2+-assisted pathway. Both kd and kc, are functions of the acidity, [H+]. The dependence of k,, and k,-” on the concentration of H+ ion is a quadratic expression, as shown in Table 1 and Fig. 2. Based on these results, the overall rate of reaction can be expressed as Rate = k, [LnY] + k2 [LnY] [H+] + k3 [LnY] [WI2 + k4 [LnY] [Cu2+l +k5 [LnY] [Cu2+l [H+l +k6 [LnY] [Cu’+] [H+12.
(3)
Values of the specific rate constants, k,, (n = l-6), calculated from a least square polynomial fit program, are listed in Table 2. The reaction between Ln(DTPA)-bis(amide) complexes and Cu2+ ion
(1 O3kobs, SK’) for the dissociation
of Gd(DTPA)-bis(amide)
complexes”
lO’[H+] (M) Ligand DTPA-EAM
DTPA-PAM
DTPA-BAM
DTPA-PenAM
DTPA-XAM
“At 25.O+O.l”C,
104[cuz+] (M)
1.315
2.565
4.451
6.745
8.492
10.209
12.853
2.5 5.0 7.5 10.0 12.5 2.5 5.0 7.5 10.0 12.5 2.5 5.0 7.5 10.0 12.5 2.5 5.0 7.5 10.0 12.5 2.5 5.0 7.5 10.0 12.5
0.42 0.71 1.07 1.43 1.77 0.38 0.70 1.04 1.39 1.69 0.37 0.69 1.01 1.34 1.68 0.37 0.65 0.98 1.31 1.62 0.38 0.70 1.04 1.40 1.69
0.48 0.87 1.20 1.56 1.97 0.46 0.84 1.16 1.52 1.90 0.45 0.82 1.13 1.48 1.85 0.43 0.79 1.09 1.43 1.79 0.46 0.84 1.15 1.51 1.90
0.71 1.14 1.58 1.96 2.38 0.69 1.06 1.52 1.86 2.30 0.65 1.04 1.47 1.80 2.22 0.63 1.oo 1.39 1.78 2.13 0.69 1.06 1.50 1.85 2.31
1.12 1.66 2.14 2.63 3.12 1.04 1.53 2.00 2.47 2.94 1.00 1.51 1.94 2.37 2.86 0.97 1.50 1.88 2.30 2.80 1.05 1.54 2.03 2.48 2.95
1.56 2.10 2.68 3.30 3.83 1.47 1.98 2.53 3.10 3.62 1.38 1.93 2.44 2.99 3.47 1.36 1.90 2.40 2.93 3.40 1.48 1.98 2.55 3.11 3.63
2.10 2.74 3.41 4.05 4.78 1.90 2.56 3.19 3.78 4.39 1.83 2.46 3.08 3.63 4.24 1.82 2.41 3.00 3.55 4.17 1.92 2.59 3.21 3.80 4.43
3.02 3.91 4.72 5.54 6.36 2.81 3.60 4.37 5.13 5.90 2.72 3.44 4.18 4.93 5.66 2.68 3.40 4.10 4.84 5.56 2.84 3.63 4.39 5.15 5.94
I = 0.100 (NaClO,),
[complex] = 5.0 x 1O-5 M and [acetate] = 1.0 x lo-* M.
570
ICI-YOUNG
40
30 % 7 I ; 2
-:::il 40
20 10
20
5
J
3.5
2.5 "0 -
3.0
2.0
2.5t
105[H+],M
Fig. 2. Plots of k, and kcu us [H+] for the dissociation kinetics of Ce(DTPA)-EAM (m, 0) and Gd(DTPA j EAM (0, 0) ([acetate] = 0.01 M, Z= 0.100 M (NaClO,), T = 25.O”C).
proceeds by reaction paths that are similar to those reported for the exchange of ligand in their polyamino polycarboxylate complexes.23,24 In these
reactions, both dissociative paths (which obviously show an acid-independent and an acid-catalysed contribution) and associative paths are taking place, and the increase of the dissociation rate of the complexes on the H+ ion was interpreted by
CHOI et al. the formation of small amounts of the singly and doubly protonated complexes. The rate-determining step involves the rupture of the Ln-N bond subsequent to the intermediate. The DTPA-bis (amide) ligands liberated on the comparatively slow dissociation of the complexes react very quickly with the Cu2+ ion, present in excess, to yield Cu(DTPA)-bis(amide)- . The structures of the protonated intermediate for the dissociative pathway are not known ; it is probable that the doubly protonated intermediate LnH,Y involves coordination of one of the amine groups of the DTPA-bis(amide) ligand to the Ln3+ ion, while one proton each is bound to the nitrogen atom of the other amine group and to one of its carboxylate groups. The effect of the ligand on the rate constants of dissociation reactions of Ln(DTPA)-bis(amide) can be seen by comparing the values in Table 2 with other linear and macrocyclic polyamino polycarboxylates. The dissociation behaviour of macrocyclic complexes of lathanides differs considerably from that of analogous linear polyamino polycarboxylates such as EDTA, DTPA and TTHA. The dissociation rate of linear complexes is much faster than that of the macrocyclic complexes. This phenomenon may be rationalized by the remarkable rigidity of cycle rings compared to their flexible linear ligands. In the macrocyclic DTPA-bis(amide) series, the consistent decrease in the rate of dissociative and associative pathways of the Ln(DTPA)-EAM complexes from Ce3+ to Gd3+ parallels the thermodynamic stability of these complexes with decreasing ionic size or increasing charge density of Ln 3+. A comparison of the rate
Table 2. Rate constants for dissociation reactions of lanthanide complexes of linear and macrocyclic polyamino polycarboxylates”
Ref.
Complex Ce(DTPAtEAM Gd(DTPAkEAM Gd(DTPA)-PAM Gd(DTPAkBAM Gd(DTPA)-PenAM Gd(DTPA)-XAM Ce(NOTA) Ce(DOTA)Ce(TETA) Ce(HEHA)3Ce(EDTA) La(DTPA)‘Eu(TTHA)~ “At 25.0fO.l”C “Not observed.
8.20 x 3.04 x 2.62 x 2.37 x 1.91 x 2.45 x 2.5x
1O-4 1O-5 10-j 1O-5 lo-’ lo-’ 1O-5
1.26 x 10’ 1.24 x 10-l 3.87 x lo-’ 2.03 x lo-* 1.50 x lo-’ 3.58 x lo-* 4.3x lo-* 8 x 10m4 b 9.13 x 1o-4 2.22 1.76 x 1O-3 2.44 x 10’ 1.38 x lo3 b b 7.5 x 10’ 3.40 2.05 x lo3
and Z = 0.100 (NaClO,).
3.03 x lo6 1.31 x lo5 1.22 x lo5 1.18 x 10’ 1.17 x lo5 1.24x lo5 b 2 x 10-j
8.09 1.30 1.27 1.24 1.20 1.27
b
3.79
b
b
b
b
b
b
b
b
10
b
24 12
b
3.5 x 10’ b
1.06 x 4.06 x 3.91 x 3.79 x 3.73 x 3.94 x
lo5 lo3 103 103 lo3 lo3
2.40 x 9.09 x 7.90 x 7.37 x 7.25 x 7.92 x
b
b
b
b
b
b
b
9.7 x 10’ b
3.2 x lo3 b
b
lo9 IO’ 10’ 10’ IO’ 10’ 16 15 17 18
Ce”’ and Gd”’ complexes of macrocyclic DTPA-bis(amide) constants of the Gd3+ complexes of macrocyclic DTPA-bis(amide) demonstrates the order Gd (DTPAkEAM > Gd(DTPAFPAM N Gd(DTPA) -XAM > Gd(DTPA)-BAM > Gd(DTPA)PenAM. The rate constants of both the dissociative and associative pathways are significantly affected by ring size and the number of carbons between two amide nitrogens. An increase in ring size from 15 (DTPA-EAM) to 18 (DTPA-PenAM) leads to an increase in kinetic inertness. This probably reflects the increase of thermodynamic stability (log j? = 11.15-15.94) by the enhanced participation of the amide carbonyl oxygens in metal ion coordination.’ However, an acidcatalysed rate of dissociative pathway of Ce(HEHA)3dissociates about two or four orders of magnitude faster than that for Ce(NOTA) and Ce(DOTA)-, even though the HEHA ligand has the greatest number of donor atoms (nitrogen and oxygen) and an increased ring size (18 cycle). This may be attributed to the decrease of macrocycle rigidity by the flexibility of the HEHA ligand and the mismatch caused by the large cavity size. The dissociation rate of Gd(DTPA)-XAM was found to be faster than that of Gd(DTPA)-BAM and Gd(DTPA)-PenAM complexes. This fact may be attributed to the decrease in the cavity size of the macrocycle by the aromatic ring and the lower basicity of DTPA-XAM (CpK, = 17.42) relative to other DTPA-bis(amide) macrocycles (CpK, = 18.39-18.54). paper was supported by Non Directed Research Fund, Korea Research Foundation, 1993.
Acknowledgement-This
REFERENCES
ligands
571
3. C. A. Chang, P. F. Sieving, A. D. Watson, T. M. Dewey, T. B. Karpishin and K. N. Raymond, J. Magn. Reson. Imaging 1992,2,95.
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10. T. Ryhl, Acta Chem. Stand. 1972,26,3955. 11. K. Y. Choi and G. R. Choppin, J. Coord. Chem. 1991, 24, 19. 12. K. Y. Choi and G. R. Choppin, Znorg. Chem. (submitted for publication). 13. V. C. Sekhar and C. A. Chang, Znorg. Chem. 1986, 25, 206 1. 14. C. A. Chang and V. C. Sekhar, Znorg. Chem. 1987, 26, 1981. 15. E. Brucher, G. Laurenczy and Z. S. Makra, Znorg. Chim. Acta 1987, 139, 141.
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23. E. Brucher and I. Banyai, J. Znorg. Nucl. Chem. 1980, 1. R. B. Lauffer, Chem. Rev. 1987,87,901. 2. C. A. Chang, Eur. J. Solid State Znorg. Chem. 1991, 28,237.
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Pergamon
DISSOCIATION KINETICS OF CERIUM(II1) AND GADOLINIUM(II1) COMPLEXES OF MACROCYCLIC DTPA BIS(AMIDE) LIGANDS K&YOUNG CHOI* and KI SUNG KIM Department of Chemistry, Mokwon University, Taejeon 301-729, Korea and
JU CHANG KIM Department of Chemistry, Pusan National University of Technology, Pusan 608-739, Korea (Received 26 July 1993 ; accepted 28 September 1993)
Abstract-The dissociation kinetics of Ce”’ and Gd”’ complexes of macrocyclic DTPA bis(amide) have been studied in aqueous solution using Cu” ions as the scavenger. The measurements were made at 25°C in a solution of 0.100 M (NaClO,) ionic strength. The rates of dissociation of these complexes have been found to be independent of [acetate]. Dissociation of the complexes takes place via both dissociative and associative pathways. The rates of both processes decrease in the order Gd(DTPA)-EAM > Gd(DTPA)-PAM 2: Gd(DTPA)-XAM > Gd(DTPA)-BAM > Gd(DTPA)-PenAM. An increase in ring size of the DTPA bis(amide) ligands leads to an increase in kinetic inertness, reflecting the enhanced participation of the amide carbonyl oxygen in lanthanide(II1) ion coordination. The substitution of an aromatic ring between the two amide nitrogens, however, results in a significant decrease in kinetic inertness of the resulting DTPA-XAM complex.
In recent years, there has been considerable interest in lanthanide complexes with the macrocyclic polyoxa- and polyaza-polycarboxylates, K22DA (1,10-d&a - 4,7,13,16 - tetraazacyclooctadecaneN,N’-diacetic acid), NOTA (1,4,7-triazacyclononane-N,N’,N”-triacetic acid), DOTA (1,4,7, lo-tetraazacyclododecane-N,N’,N”,N”‘-tetraacetic acid), TETA (1,4,&l 1-tetraazacyclotetradecane-N,N’, N”,N”‘-tetraacetic acid) and HEHA (1,4,7,10, 13,16-hexaazacyclooctadecane-N,N’,N”,N”’,N””, N ““‘-hexaacetic acid) because of their use as contrast agents in magnetic resonance imaging (MRI),lA lanthanide ion-selective reagentss7 and radiopharmaceuticals.8,9 The kinetic behaviour of these macrocyclic complexes differs considerably from that of analogous linear polyamino polycarboxylates’@” such as EDTA, DTPA and TTHA (triethylenetetraaminehexaacetic acid) because of the remarkable rigidity of *Author to whom correspondence should be addressed.
macrocyclic aza rings compared to their flexible linear analogues. Kinetic studies’3,‘4 on the lanthanide complexes of polyamino polyoxacarboxylate (K21DA and K22DA) demonstrated the cavity size dependence of the thermodynamic stability and dissociation rates. Brucher el al.” and Brucher and SherryI reported that the dissociation rate of Ce(DOTA)- is slower than that of Ce(NOTA). This likely reflects the thermodynamic stability conferred by the rigidity of the tetraaza ring (DOTA) us the triaza ring (NOTA). Although the difference in the thermodynamic stability between Ce(TETA)- and Ce(NOTA) is not very significant, Ce(NOTA) dissociates more slowly than Ce(TETA)-. This is likely a consequence of the destabilizing effect of the propylene diamine group of the TETA ligand.17 Additional study on the kinetics of formation and dissociation of the Ce3+ complex of HEHA was also reported.18 In this study, although HEHA has an increased ring size (18 cycle) compared to NOTA and DOTA, the rate
561
568
KI-YOUNG CHOI et al. COOH r fiNr”YNA HOOC < 0 o*c > CooH C” \ N N/
Macrocycle DTPA-HAM
n
N
N
HNnNH
DTPA-PAM
HN-NH
DTPA-HAM
HNeNH
DTPA-PenAM HN-NH DTPA-XAM
HNONH
Fig. 1. Structures of the macrocyclic DTPA-bis(amide) ligands.
of dissociation of Ce(HEHA)3p is much faster than that of NOTA and DOTA. This fact may be attributed to the decrease of macrocycle rigidity by the ligand flexibility and the mismatch caused by the large cavity size. We initiated the kinetic properties to understand the ligand effect, such as number of donor atoms and the size of the macrocyclic ligand cavity. We report herein the systematic dissociation kinetics of Ce3+ and Gd3+ complexes of DTPA bis(amide) derivatives (Fig. 1). EXPERIMENTAL
Reagents and solutions The DTPA-bis(amide) macrocycle ligands 1,4,7tris(carboxymethyl)-9,14-dioxo-1,4,7,10,13-pentaazacyclopentadecane (DTPA-EAM), 1,4,7-tris (carboxymethyl)-9,15-dioxo-1,4,7,10,14-pentaazacyclohexadecane (DTPA-PAM), 1,4,7-tris(carboxymethyl) - 9,16 - dioxo - 1,4,7,10,15 - pentaazacycloheptadecane (DTPA-BAM), 1,4,7-tris(carboxymethyl)-9,17-dioxo- 1,4,7,10,16-pentaazacyclooctadecane (DTPA-PenAM) and 6,9,12-tris(carboxymethyl) - 4,14 - dioxo - 3,6,9,12,15 - pentaazabicyclo [15.2.2]heneicosa - 1(19),18,20 - triene (DTPAXAM) were synthesized by the method of Carvalho et aZ.7 In a typical preparation, the amines (5 mmol) in DMSO-1,5-diazabicyclo [4.3.0]non-5-ene (150/3 cm3) were added neat to DTPA bis(anhydride) (5 mmol) all at once. The mixtures were stirred for 24 h at ambient temperature, concentrated under reduced pressure to an oil, diluted with water (30 cm3) and made to pH 10.0 using 1 N HCl or 1 N NaOH. The solutions were applied to Amberlite IRP-64 ion-exchange resin (1O&500 mesh, carboxylic acid form), the column washed with deionized water and the product eluted with 0.5 N acetic acid to yield the title compounds as white solids after recrystallization (yield 35-50%). The ligands were characterized by ‘H NMR, mass
spectrometry and elemental analysis, All other chemicals used were of analytical grade without further purification. All solutions were made up in deionized water. The stock solutions of Ce3+ and Gd3+ were prepared from CeCl, and Gd203 (Aldrich Co., 99.99% purity). The concentration of the stock solutions was determined by EDTA titration using xylenol orange indicator. The concentration of DTPA bis(amide) stock solutions was determined by titration against a standardized Cu(ClO& solution using murexide as indicator. Complex solutions were made by mixing appropriate amounts of lanthanide perchlorate and ligand (slight excess). The complex concentration in the reaction mixtures was 5.0 x lop5 M, while that of Cu2+ was varied between 2.50 x 10e4 and 1.25 x 10m3M. The buffer solutions were made by using a constant acetate ion concentration and varying the concentration of acetic acid. Measurements The ionic strength was adjusted to 0.100 M with NaClO,. Solution pH measurements were made by a Beckman Model @71 pH meter fitted with a Beckman combination electrode. The hydrogen ion concentrations were calculated from the measured pH value by procedures reported previously.” Kinetic measurements were made with the use of a UVIDEC-610 spectrophotometer interfaced with a Scientific data acquisition system. The temperature of the reaction mixture was maintained at 25.0fO.l”C with the use of a Lauda RM 6 circulatory water bath. As the lanthanide complexes do not show appreciable absorption in the near-UV or visible region, Cu2+ was used as the scavenger of free ligand and the reaction kinetics were followed by monitoring the growth in absorbance due to copper complex at 270 nm. Pseudo-first-order rate constants (kobs,S-‘) were calculated from the absorbance ZIStime data using a first-order model.*’
Ce”’ and Gd”’ complexes
of macrocyclic
RESULTS AND DISCUSSION Since the stability constants of Cu(DTPA)-bis (amide) complexes are much greater than those of the Ln(DTPA)-bis(amide) complexes,’ the displacement of Ln3+ ions from the Ln(DTPA)-bis (amide) complexes is complete in the presence of excess Cu2+ ions :
Ln(DTPA)-bis(amide)
+ Cu*+
---+Cu(DTPA)-bis(amide)-
+ Ln3+.
(1)
The experimental data show excellent pseudo-firstorder reaction rates. The concentration of acetate ion was varied by a factor of 5, and the observed rate constant (kobs) values were within 5% of the average value of kobsat a given [H+]. Such an independence of [acetate] has been observed by other workers in the dissociation kinetics of lanthanide complexes. 2’,22The dependence of kobson [Cu2+] is given in Table 1 at different [H+]. The standard deviations were in the range l-5%. In each case, the data fit straight lines with measurable non-zero intercepts, which confirms the exchange reaction as
Table 1. Pseudo-first-order
rate constants
DTPA-bis(amide)
569
ligands
proceeding via both [Cu’+]-independent and [Cu’+]-dependent pathways. Thus, the kinetic data can be described by kobs=
k~+ku[Cu2+l,
(2)
where the rate constant kd represents spontaneous dissociation of the complexes and kc” reflects the Cu2+-assisted pathway. Both kd and kc, are functions of the acidity, [H+]. The dependence of k,, and k,-” on the concentration of H+ ion is a quadratic expression, as shown in Table 1 and Fig. 2. Based on these results, the overall rate of reaction can be expressed as Rate = k, [LnY] + k2 [LnY] [H+] + k3 [LnY] [WI2 + k4 [LnY] [Cu2+l +k5 [LnY] [Cu2+l [H+l +k6 [LnY] [Cu’+] [H+12.
(3)
Values of the specific rate constants, k,, (n = l-6), calculated from a least square polynomial fit program, are listed in Table 2. The reaction between Ln(DTPA)-bis(amide) complexes and Cu2+ ion
(1 O3kobs, SK’) for the dissociation
of Gd(DTPA)-bis(amide)
complexes”
lO’[H+] (M) Ligand DTPA-EAM
DTPA-PAM
DTPA-BAM
DTPA-PenAM
DTPA-XAM
“At 25.O+O.l”C,
104[cuz+] (M)
1.315
2.565
4.451
6.745
8.492
10.209
12.853
2.5 5.0 7.5 10.0 12.5 2.5 5.0 7.5 10.0 12.5 2.5 5.0 7.5 10.0 12.5 2.5 5.0 7.5 10.0 12.5 2.5 5.0 7.5 10.0 12.5
0.42 0.71 1.07 1.43 1.77 0.38 0.70 1.04 1.39 1.69 0.37 0.69 1.01 1.34 1.68 0.37 0.65 0.98 1.31 1.62 0.38 0.70 1.04 1.40 1.69
0.48 0.87 1.20 1.56 1.97 0.46 0.84 1.16 1.52 1.90 0.45 0.82 1.13 1.48 1.85 0.43 0.79 1.09 1.43 1.79 0.46 0.84 1.15 1.51 1.90
0.71 1.14 1.58 1.96 2.38 0.69 1.06 1.52 1.86 2.30 0.65 1.04 1.47 1.80 2.22 0.63 1.oo 1.39 1.78 2.13 0.69 1.06 1.50 1.85 2.31
1.12 1.66 2.14 2.63 3.12 1.04 1.53 2.00 2.47 2.94 1.00 1.51 1.94 2.37 2.86 0.97 1.50 1.88 2.30 2.80 1.05 1.54 2.03 2.48 2.95
1.56 2.10 2.68 3.30 3.83 1.47 1.98 2.53 3.10 3.62 1.38 1.93 2.44 2.99 3.47 1.36 1.90 2.40 2.93 3.40 1.48 1.98 2.55 3.11 3.63
2.10 2.74 3.41 4.05 4.78 1.90 2.56 3.19 3.78 4.39 1.83 2.46 3.08 3.63 4.24 1.82 2.41 3.00 3.55 4.17 1.92 2.59 3.21 3.80 4.43
3.02 3.91 4.72 5.54 6.36 2.81 3.60 4.37 5.13 5.90 2.72 3.44 4.18 4.93 5.66 2.68 3.40 4.10 4.84 5.56 2.84 3.63 4.39 5.15 5.94
I = 0.100 (NaClO,),
[complex] = 5.0 x 1O-5 M and [acetate] = 1.0 x lo-* M.
570
ICI-YOUNG
40
30 % 7 I ; 2
-:::il 40
20 10
20
5
J
3.5
2.5 "0 -
3.0
2.0
2.5t
105[H+],M
Fig. 2. Plots of k, and kcu us [H+] for the dissociation kinetics of Ce(DTPA)-EAM (m, 0) and Gd(DTPA j EAM (0, 0) ([acetate] = 0.01 M, Z= 0.100 M (NaClO,), T = 25.O”C).
proceeds by reaction paths that are similar to those reported for the exchange of ligand in their polyamino polycarboxylate complexes.23,24 In these
reactions, both dissociative paths (which obviously show an acid-independent and an acid-catalysed contribution) and associative paths are taking place, and the increase of the dissociation rate of the complexes on the H+ ion was interpreted by
CHOI et al. the formation of small amounts of the singly and doubly protonated complexes. The rate-determining step involves the rupture of the Ln-N bond subsequent to the intermediate. The DTPA-bis (amide) ligands liberated on the comparatively slow dissociation of the complexes react very quickly with the Cu2+ ion, present in excess, to yield Cu(DTPA)-bis(amide)- . The structures of the protonated intermediate for the dissociative pathway are not known ; it is probable that the doubly protonated intermediate LnH,Y involves coordination of one of the amine groups of the DTPA-bis(amide) ligand to the Ln3+ ion, while one proton each is bound to the nitrogen atom of the other amine group and to one of its carboxylate groups. The effect of the ligand on the rate constants of dissociation reactions of Ln(DTPA)-bis(amide) can be seen by comparing the values in Table 2 with other linear and macrocyclic polyamino polycarboxylates. The dissociation behaviour of macrocyclic complexes of lathanides differs considerably from that of analogous linear polyamino polycarboxylates such as EDTA, DTPA and TTHA. The dissociation rate of linear complexes is much faster than that of the macrocyclic complexes. This phenomenon may be rationalized by the remarkable rigidity of cycle rings compared to their flexible linear ligands. In the macrocyclic DTPA-bis(amide) series, the consistent decrease in the rate of dissociative and associative pathways of the Ln(DTPA)-EAM complexes from Ce3+ to Gd3+ parallels the thermodynamic stability of these complexes with decreasing ionic size or increasing charge density of Ln 3+. A comparison of the rate
Table 2. Rate constants for dissociation reactions of lanthanide complexes of linear and macrocyclic polyamino polycarboxylates”
Ref.
Complex Ce(DTPAtEAM Gd(DTPAkEAM Gd(DTPA)-PAM Gd(DTPAkBAM Gd(DTPA)-PenAM Gd(DTPA)-XAM Ce(NOTA) Ce(DOTA)Ce(TETA) Ce(HEHA)3Ce(EDTA) La(DTPA)‘Eu(TTHA)~ “At 25.0fO.l”C “Not observed.
8.20 x 3.04 x 2.62 x 2.37 x 1.91 x 2.45 x 2.5x
1O-4 1O-5 10-j 1O-5 lo-’ lo-’ 1O-5
1.26 x 10’ 1.24 x 10-l 3.87 x lo-’ 2.03 x lo-* 1.50 x lo-’ 3.58 x lo-* 4.3x lo-* 8 x 10m4 b 9.13 x 1o-4 2.22 1.76 x 1O-3 2.44 x 10’ 1.38 x lo3 b b 7.5 x 10’ 3.40 2.05 x lo3
and Z = 0.100 (NaClO,).
3.03 x lo6 1.31 x lo5 1.22 x lo5 1.18 x 10’ 1.17 x lo5 1.24x lo5 b 2 x 10-j
8.09 1.30 1.27 1.24 1.20 1.27
b
3.79
b
b
b
b
b
b
b
b
10
b
24 12
b
3.5 x 10’ b
1.06 x 4.06 x 3.91 x 3.79 x 3.73 x 3.94 x
lo5 lo3 103 103 lo3 lo3
2.40 x 9.09 x 7.90 x 7.37 x 7.25 x 7.92 x
b
b
b
b
b
b
b
9.7 x 10’ b
3.2 x lo3 b
b
lo9 IO’ 10’ 10’ IO’ 10’ 16 15 17 18
Ce”’ and Gd”’ complexes of macrocyclic DTPA-bis(amide) constants of the Gd3+ complexes of macrocyclic DTPA-bis(amide) demonstrates the order Gd (DTPAkEAM > Gd(DTPAFPAM N Gd(DTPA) -XAM > Gd(DTPA)-BAM > Gd(DTPA)PenAM. The rate constants of both the dissociative and associative pathways are significantly affected by ring size and the number of carbons between two amide nitrogens. An increase in ring size from 15 (DTPA-EAM) to 18 (DTPA-PenAM) leads to an increase in kinetic inertness. This probably reflects the increase of thermodynamic stability (log j? = 11.15-15.94) by the enhanced participation of the amide carbonyl oxygens in metal ion coordination.’ However, an acidcatalysed rate of dissociative pathway of Ce(HEHA)3dissociates about two or four orders of magnitude faster than that for Ce(NOTA) and Ce(DOTA)-, even though the HEHA ligand has the greatest number of donor atoms (nitrogen and oxygen) and an increased ring size (18 cycle). This may be attributed to the decrease of macrocycle rigidity by the flexibility of the HEHA ligand and the mismatch caused by the large cavity size. The dissociation rate of Gd(DTPA)-XAM was found to be faster than that of Gd(DTPA)-BAM and Gd(DTPA)-PenAM complexes. This fact may be attributed to the decrease in the cavity size of the macrocycle by the aromatic ring and the lower basicity of DTPA-XAM (CpK, = 17.42) relative to other DTPA-bis(amide) macrocycles (CpK, = 18.39-18.54). paper was supported by Non Directed Research Fund, Korea Research Foundation, 1993.
Acknowledgement-This
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ligands
571
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