Table 1.

Comparisons between Gd-DOTA and Gd-DTPA-BMA

(physical-chemical and thermodynamic characteristics
Complex.
Gd-DOTA Gd-DTPA-BMA

 Macrocyclic.  Open Chain.

 Ionic.  Nonionic.
 Strong Bound.  Weak Bound.
 Lower amount of residual Gd in  Higher amount of residual Gd in
the body. the body.
 Less basic.  More basic.
 Kinect stability is higher.  Kinect stability is lower.
 No Free ligand added.  Has a ligand (Formulation).
 Dissociation half-lives are  Dissociation half-lives are shorter.
markedly longer.  Lower thermodynamic constant (
 Higher thermodynamic constant ( log K yherm ).
log K yherm ).  The complex is more instable
 The complex is more stable than than the radicals are.
the radicals are.  This complex has less of the five-
 This complex has more of the membered rings (six).
five-membered rings (eight).
(n)= are the reference, but I don’t know if you prefer it in the chart or only the number The empty
spaces, without (-), still there, because I am searching for it in the original papers, from they were
referenced (but it is a little bit complicate).

Table 2. Comparisons of stability constants of Gd-DOTA.

(PM= 557.638 g/mol)(12)
Gadolinium species Value (in pH T Medium C
β=( X ) , K =(Y )¿ (°C) (mol L-1)
1. Gd- DOTA(7) 24.03 (X) −¿ 25 Me4NCl 0.1
(14)
2. Gd-DOTA 24.70 (Y) −¿ NaCl 0.15
(6)
3. Gd-DOTA 25.60 (Y) 7.4 0.5
(8)
4.1 Gd-DOTA 24.67 (X) −¿ 25 Me4NCl 0.1
4.2 Gd-DOTA(8) 24.70 (X) −¿ 25 Me4NCl 0.1
(8)
4.3 Gd-DOTA 24.00 (X) −¿ 25 Me4NCl 0.1
(8)
4.4 Gd-DOTA 25.40 (X) −¿ 25 Me4NCl 0.1
4.5 Gd-DOTA(8) 27.00 (X) −¿ 25 NMe4NO3 0.1
4.6 Gd-DOTA(8) 25.30 (X) −¿ 25 NaCl 0.1
(8)
4.7 Gd-DOTA 25.10 (X) −¿ 25 NaCl 0.1
(8)
4.8 Gd-DOTA 26.03 (X) −¿ 25 KCl 0.1
4.9 Gd-DOTA(8) 25.58 −¿ 25 Me4NCl 0.1
4.10 Gd-DOTA(8) 24.99 −¿ 25 Me4NCl 0.1
(4)
5. Gd-DOTA 25.00 (Y) −¿ 25
 Table 3. Comparisons of stability constants of Gd-DTPA-BMA.
(PM= 591.672 g/mol)(11)
Gadolinium species Value pH T Medium C
Log K (°C) (mol L-1)

1. Gd-DTPA-BMA(6) 16.9 7.4 0.5

2. Gd-DTPA-BMA(15) 16.85 −¿ 25 Me4NCl 0.1
3. Gd-DTPA-BMA(4) 16.6 −¿ −¿ −¿ −¿
4. Gd-DTPA-BMA(4) 16.8 −¿ −¿ −¿ −¿
5. Gd-DTPA-BMA(5) 16.85 7.4 25 KCl 0.1
6.1 Gd-DTPA-BMA(1) 16.64 −¿ 25 NaCl 0.15
6.2 Gd DTPA-BMA(1) 16.85 −¿ 25 NaCl 0.15

Table 4. Comparisons of stability constants of Ca(II), Zn(II), Cu(II) and Mg(II) with
the ligand DTPA-BMA.
Element and ligand Value pH T Medium C
Log K (°C) (mol L-1)

1. Ca-DTPA-BMA(5) 7.17 −¿ 25 NaCl 0.1

2. Ca-DTPA-BMA(in) 7.2 −¿ 25 NaCl 0.1
3. Zn-DTPA-BMA(5) 12.04 −¿ 25 NaCl 0.1
4. Zn-DTPA-BMA(1) 12.42 −¿ 25 NaCl 0.15
5. Cu-DTPA-BMA(5) 13.03 −¿ 25 NaCl 0.1
6. Cu-DTPA-BMA(1) 16.30 −¿ 25 NaCl 0.15
7. Mg-DTPA-BMA

Table 5. Comparisons of stability constants of Ca(II), Zn(II), Cu(II) and Mg(II) with
the ligand DTPA.
Element and ligand. Value pH T Medium C
Log K (°C) (mol L-1)
1.1 Ca-DTPA(14) 10.63 −¿ 20 NaClO4 0.1
1.2 Ca-DTPA(14) 10.89 ± 0.1 −¿ 20 NaClO4 0.1
1.3 Ca-DTPA(14) 10.74 −¿ 25 NaClO4 0.1
1.4 Ca-DTPA(14) 10.6 −¿ 25 NaClO4 0.1
1.5 Ca-DTPA(14) 10.58 −¿ −¿ NaClO4 0.1
1.6 Ca-DTPA(14) 9.82±0.008 −¿ 37 NaClO4 0.15
1.7 Ca-DTPA(14) 9.06± 0.03 −¿ 25 NaClO4 0.7
2. Ca-DPTA(3) 10.75 −¿ 25 NaCl 0.1
(2)
3. Ca-DPTA 10.75 −¿ 25 NaCl 0.1
(10)
4. Zn-DTPA 18.29 −¿
4. Zn-DTPA(5) 18.70 −¿ 25 NaCl 0.15
(1)
4. Zn-DTPA 17.58 −¿ 25 NaCl 0.15
(1)
7. Cu-DTPA 23.40 −¿ 25 NaCl 0.15
(2)
8. Cu-DTPA 21.38 −¿ 25 NaCl 0.1
(10)
9. Cu-DTPA 21.38 −¿ 25 NaCl 0.1
(1)
10. Cu-DTPA 21.5 −¿ 25 NaCl 0.15
(14)
11.1 Mg-DPTA 9.03 −¿ 20 NaClO4 0.1
(14)
11.2 Mg-DPTA 9.3 −¿ 25 NaClO4 0.1
(14)
11.3 Mg-DPTA 8.56±0.016 −¿ 37 NaClO4 0.1
(14)
11.4 Mg-DPTA 7.70±0.02 −¿ 25 NaClO4 0.1
12.1 Gd-DTPA 22.46±0.07 −¿ 25 NaClO4 0.1
12.2 Gd-DTPA 22.46 −¿ 25 NaClO4 0.1
12.3 Gd-DTPA 20.73±0.06 −¿ 25 NaClO4 0.5
12.4 Gd-DTPA 20.68±0.07 −¿ 25 NaClO4 0.7
12.5 Gd-DTPA 21.15±0.02 −¿ 25 NaClO4 2

Table 6. Comparisons of stability constants of Ca(II), Zn(II), Cu(II) and Mg(II) with
the ligand DOTA.
Element and ligand. Value pH T Medium C
Log K (°C) (mol L-1)
 1. Ca-DOTA(3) 17.50 −¿
1. Ca-DOTA(10) 17.23 −¿
1. Ca-DOTA(9) 16.37 −¿ 25 KCl 1
1. Zn-DOTA(9) 18.17 −¿ 25 KCl 1
1. Zn-DOTA(3) 21.00 −¿
1. Zn-DOTA(10) 21.05 −¿
1. Cu-DOTA(10) 22.63 −¿
1. Cu-DOTA(1) 22.00 −¿ 25 NaCl 0.15
1. Cu-DOTA(1) 22.21 −¿ 25 NaCl 0.15
1. Cu-DOTA(9) 22.72 −¿ 25 KCl 1
1. Mg-DOTA(9) 11.15 −¿ 25 KCl 1

Equations:
M
β111= is a reported value in charts.
Keff= is a value you may have to calculate.
M
β112= is a reported value in charts
It is also worth mentioning that the equations only mention the final products, not the
intermediaries.

)(Mβ111) (Gd(H 2 O)38+¿+L ⇌ GdL(H ¿¿2 O)+7 H O ¿ ¿)

−¿ ¿
4−¿⇋ GdHL

Equation of Gd+DOTA (Gd3 +¿+H L

¿
¿ 2

1.- G d 3+¿+¿¿

PM=157.25 mol L-1 PM=400.388 mol L-1 PM= 557.638 mol L-1
2.- G d ( H 2 O)3+¿+¿
8
¿

PM= 175.265 mol L-1 PM=400.388 mol L-1 PM= 575.653 mol L-1 PM= 126.105mol L-1

2.- K eff =[ GdL ] ¿¿ ¿

3−¿⇋Gd H2 L ¿

Equation of Gd+DTPA+BMA (Gd3 +¿+H L 2 ¿

)(Mβ112)

3.- G d 3+¿+¿¿
 PM=157.25 mol L-1 PM= 415.403 mol L-1 PM= 572.653 mol L-1

Chemical structures:
I made these two structures, I also have it in 3D, but I want to show you, so you may
choose the best position for it.
Scheme 1. Gd-DTPA-BMA (2D).
O

N
HN NH
N N
Gd
O O

O O O O
H2O

Scheme 2. Gd-DTPA-BMA (3D).

Scheme 3. Gd-DOTA- (2D).

 -*
OH2

O
O
O

N N O

Gd
O
N N

O
O

Scheme 4. Gd-DOTA (3D).

Chemical reactions.
DOTA(8).
Part one:

OH2 +**
O O O
O
O H2O O
Gd + NH N OH
fast
HO
N NH OH2 NH N O
O Gd
O
O N
O NH
H2O
O
O
OH2 O
 Part two:
+** OH2 +* +*
OH2 OH2
O (H)
O O H 2O O H2 O O
O O O H2O O
H
OH2 NH N O Slow N N O Slow N N O
Gd Gd Gd
O O O
N NH N N N N
H 2O
O O H O
OH2 O OH2 O OH2 O
O O O
(H)

+ 2 H+
-
+2H
+ 2 OH- fast

OH2 -*

O O H2O O

N N O
Gd
O
N N
O
OH2 O
O

Part three.
-*
OH2 OH2 -*
O O O
H2O O O O

+2H+ N N O
slow N N O
Gd Gd
O O
N N N N
O O
OH2 O O
O O

DTPA-BMA(13).
O O O O

+ NH4OH +
C CH2 H CH2 C H2N C CH2 H CH2 C

O N H2C H2C N CH2 CH2 N

O
+ NH4OH
Gd+3 N H2C H2C N CH2 CH2 N + H2O

- - -
C CH2 CH 2 C O CH2 C O C CH2 CH2 C O CH2 C O

O O O O O O
Information about the complexes.
The Gd-DOTA complex has a higher stability constant than Gd-DTPA-BMA, this is
because the first complex is has micro-cycling ring that helps him to be more stable,
also the literature mention that the Gd-DOTA complex has a higher global negative
charge, which results in a stronger electrostatic metal-ligand interaction than that in non-
ionic chelates (6).
Another point that make Gd-DTPA-BMA less stable is that this complex has non-ionic
donor atoms, these atoms are less basic and consequently more weakly bound to
gadolinium than ionic donor atoms (6).
Statistic information.
Comparison Value of R2 Equation Value of Mg
between.
DTPA and DTPA-BMA 0.8753 y=1.0691 x+ 4.2019
DOTA and DTPA-BMA 0.9118 y=0.7127 x +12.364
DTPA and DOTA 0.8406 y=1.0939 x−5.1175 N/A
|Graphics.
The colors represent a different element (Gadolinium, Calcium, Zinc, copper and
Magnesium) complex with each ligand.
f(x) = 0
R² = 0 Comparison of DTPA-BMA and DOTA with diferents metals
27

25

23
Log K DOTA

21

19

17

15
6 8 10 12 14 16
Log K DTPA-BMA

Comparison of DTPA-BMA and DTPA wiht diferents metals

24

22
f(x) = 1.07 x + 4.2
20 R² = 0.88

18
Log DTPA

16

14

12

10

8
6 8 10 12 14 16 18
Log DTPA-BMA.
 Comparison of DTPA and DOTA with diferent metals
24

22 f(x) = 1.09 x − 5.12

R² = 0.84

20

18
Log K DTPA

16

14

12

10

8
10 12 14 16 18 20 22 24 26 28

Log K DOTA

References
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