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Interaction of metal ions with cytidinetriphosphate
.L inorg, nucl. Chem., 1975, Vol. 37, pp. 771-774. Pergamon Press.
Printed in Great Britain
INTERACTION OF METAL IONS WITH CYTIDINETRIPHOSPHATE M. M. TAQUI KHAN and P. RABINDRA REDDY Department of Chemistry, Nizam College, Hyderabad-500001, India (Received 8 February 1974)
Abstraet--Potentiometric equilibrium measurements have been made at 35° on the combination of anionic species of CTP with Cu(II), Ni(II), Zn(II), Co(II), Mn(II), Mg(II) and Ca(II) in a 1 : 1 ratio of ligand to metal ion. The stabilities for the protonated and normal 1 : 1 complexes decrease in the order Cu(II) > Ni(II) > Zn(II) > Co(II) > Mn(II) > Mg(II) > Ca(II). INTRODUCTION WE HAVE reported earlier[l] on the metal chelates of guanosine triphosphate (GTP) and inosine triphosphate (ITP) and the corresponding thermodynamic quantities with bivalent metal ions. The present paper extends the w o r k to cytidine triphosphate (CTP). Although the metal c o m p l e x e s of adenine nucleotides h a v e been the subject of several studies[2-6], c o m p l e x e s of cytidine triphosphate (CTP) have not been thoroughly investigated. P r e v i o u s investigation by E v a Wallas (7) was restricted to the c o m p l e x e s of C T P with Co(II), Mn(II), Mg(II) and Ca(II) by an ion e x c h a n g e method. C o n s e q u e n t l y detailed physico chemical studies on the c o m p l e x f o r m a t i o n of C T P with bivalent metal ions h a v e been carried out for the first time.
concentration. The electrode system was calibrated by direct titration of acetic acid and the observed pH meter reading was compared to the actual hydrogen ion concentration determined from the pK, values of acetic acid at 35° as tabulated by Harned and Owen [9]. The pH regions below 3.5 and above 10-5 were calibrated by measurements in HCI and NaOH solutions, respectively. CALCULATIONS
The acid dissociation constants for the m o n o s o d i u m salt of C T P (H3L-) are related to the dissociation equilibrium as follows: Ka,K2a
H3L- .
HL3
.
H L 3 - + 2H + K3a
" L4-
+
H+
(1)
(2)
EXPERIMENTAL
Reagents
Cytidine triphosphate was used as the sodium salt and was obtained from Schwarzenbacb-Mann Research Laboratory (U.S.A.). For every titration, fresh solid ligand was weighed out to avoid the possibility of hydrolysis if a stock solution were employed. All transition and alkaline earth metal ions were of AnalaR grade and the metal ions were standardised volumetrically by titration with the disodium salt of EDTA in presence of a suitable indicator as outlined by Schwarzenbach[8]. Carbonate-free sodium hydroxide was prepared and standardised by titration with potassium acid phthalate.
The constants pKa, pK2a w e r e calculated by the graphical solution of Schwarzenbach and Martell [ 10] and pK3 by the usual algebraic method. In order to determine the stability constants of protonated and the normal 1 : 1 c o m p l e x e s f o r m e d during a titration of 1 : 1 mixture of ligand and metal ion, the following equations were used: M 2. + H L 3- . M 2÷ +
Kt&L Kt
L
4-
.
"
" MHL
'-
M L 2-.
(3) (4)
Procedure
Potentiometric titration of the ligand was done with a standard sodium hydroxide solution in the absence and in the presence of the metal ion being investigated. The ionic strength was maintained constant by using 0.10 MKNO3 as the supporting electrolyte and relatively low concentrations of ligand and metal ion. A stream of nitrogen was passed through the solution to exclude the adverse effect of atmospheric carbon dioxide. All titrations were carried out at 35-+ 0.1 °. A Beckmann Model 'G' pH meter with glass and calomel electrodes was used to determine hydrogen ion
Related equilibria may be described as: M 2÷+ H 3 L - - ~ M H L MHL
+ 2H-
+~- M L : - + H L
(5) (6)
The following expressions may be written assuming that a protonated 1 : 1 c o m p l e x species is f o r m e d in the buffer region b e t w e e n a = 0 and 771
M.M. TAQUI KHAN et al.
772
a = 2. If TL represents the total concentration of various ligand species and TM that of all metal species; then: TL = [H3L-] + [H2L 2-] + [HL 3-] + [ M H L - ] TM= [M 2÷] 4- [MHL-].
(7)
where /3 = (l - a)TL - [H ÷] + [OH ] and
(8)
A = [H+] k3a "
The total amount of titrable hydrogen The value of [L 4-] is used to calculate the value of [M 2+] from the relationship
[H +] = [H2L 2-] + 2[HL 3-] + 2 [ M H L - ] - a TL
(9) [M 2+] = [L4-IB Where " a " represents, moles of base added per mole of CTP present. Solving, we have for [L'-]: ot
[L'-] = -~
(10)
where B
[H+] ' 1.
= K3---~-~The value of [M 2÷] and [L 4 ] thus obtained are combined with Eqns (11-13) to calculate K1 from Eqn (4).
where a = (2 - a) TL - [H +] + [OH-] and
RESULTS
y
2[H+]-.-.-~ 3 + [H+]___.~ 2
Determination of p K values of CTP
K~K2~K3~ K~K2a"
The potentiometric titration curves of CTP [H3L-] shown in Fig. 1 indicates a simultaneous dissociation of two protons from the ligand between a = 0 and a = 2 and a separate neutralization reaction between a - - 2 and a =3. The dissociation constants were calculated from Eqns (1) and (2) and the constants are given in Table 1. Schematically the dissociations are represented in Fig. 1. Figure 2 shows the titration curves for CTP chelates of Cu(II), and Mg(II) in a 1:1 ratio of ligand to metal ion at 35°C. Similar curves were obtained for Ni(II), Co(II), Zn(II), Mn(II) and Ca(II) with CTP. The curves show an inflection at a = 2 and a = 3, indicating the dissociation of two protons and one proton respectively from the ligand in two separate steps. Mathematical treatment of the buffer region between a = 0 and a = 2 assuming formation of diprotonated and monoprotonated 1:1 complexes of CTP gave negative results. It was, therefore, assumed that only monoprotonated 1 : 1 complexes of CTP are formed (in the first buffer region) during the titration of above mentioned metal ions with the ligand. The constants so calculated are listed in Table 1. The constants decrease in the order C u ( I I ) > N i ( I I ) > Zn(II) > Co(II) > Mn(II) > Mg(II) > Ca(II). In the buffer region between a = 2 and a = 3 dissociation of the monoprotonated 1 : 1 species to a normal 1:1 metal chelate species had been assumed, and the stability constants of the normal 1 : 1 chelate species calculated. The data presented in Table 1 decrease in the order C u ( I I ) > N i ( I I ) > Zn(II) > Co(II) > Mn(II) > Mg(II) > Ca(II).
Equation (10) is solved for [L 4-] and may be related to [M 2+] by the expression.
[M2+]=[L'-]X where X=
[H+]3
K~K2oK3.
4- [H+]2 ~ [H+]
~
K3~ "
The value of [M 2+] and [L 4-] may then be used with Eqns (7-9) to calculate the unknowns in Eqn (3) and the value of K~mL u determined. In the buffer region between a = 2 and a = 3, it was assumed that a simple dissociation of the [ M H L - ] species to [ML 2-] had taken place. The following material balance equations may be set up for the dissociation. TL = [HL 3-] + [L 4-] + [ M H L - ] + [ML:-] TM= [M 2÷] + [ M H L - ] + [ML2-].
(11) (12)
The total amount of titrable hydrogen [H ÷] = [Z 4-] 4- [ M H L - ] + [ML 2-] - aTL + [OH-]. (13) The above equations are solved for [L4-]: [L 4-] =
Interaction of metal ions with cytidinetriphosphate Table 1. Equilibrium constants for the interaction of CTP with various metal ions
NH2
I
II
o//C "N/C--H
1 lO...
O
O
O
II
II
II
HC CH--CH~O--P--O--P--O--P~OH I I I H C - - C/ H O O OH
I
HO
77
I
OH
l
pk~ ~ 2.62
NH2
o / /.,N..1/o.. CC - - H HC
O
O
O
II
II
II
\
/
I
P
O-
I
HO
I
Ca(II) Mg(II) Mn(II) Co(II) Zn(II) Ni(II) Cu(II)
3.81 3.93 4.10 4-36 4.48 4.61 5-45
4.13 4-21 4.43 4.96 5.12 5.58 6.61
I
O-
OH
O
O
O
II
II
II
constant of C T P reported in this investigation may c o r r e s p o n d to the ionization of a proton f r o m the N3H + group and the first and third dissociation constants to those f r o m the phosphate chain. It may be seen f r o m Table 1 that the stabilities of m o n o p r o p o n a t e d 1 : 1 and normal 1 : 1 metal chelate species of C T P follow the Irving-Williams order. Of the sites, base, ribose and phosphate i n v o l v e d in the chelation of bivalent metal ions, ribose appears
OH
lp
NH2 N,-~",, C __H [ II ~H o//C "N/ C
[/o\
HC
CH--CH20--P--O--P--O~P--
H \C - - C/ H
I
I
O-
I
HO
I
O-
0
J
OH
OH
l
II --
pk3o =9.99
NH2
C
8 l-
II
o / /" N1/o\ C/ C - - H \
Log K~*
*The constants are accurate to +0.06 log K units, t = 35°; p~ = 0.10 M(KNO3): pKo = 2-62]÷ pK~ = 4.22~_ 0.02. pKg. = 9.99)
k2a = 4"22
HC
Log K~r~L*
CH--CH20--P--O~P--O--P--O-
HC--CH
I
Metalion
O
O
O
II
II
II
C H - - C H 2 0 - - P - - O - - P - - O - - P - - O-
/
HC--CH f HO OH
I
O
I
O-
t
O-
,/
1"
I 5 4
Fig. 1.
DISCUSSION
The dissociation constants of C T P are listed in Table 1. The second dissociation constant (pK2a = 4.22) is comparable to the first dissociation constant of cytosine (pKa = 4.2). F o r cytosine, on the basis fo N M R data, the proton ionization site was suggested to be the N3H + group by J a r d e t z k y et a l . [ l l , 12]. This was also supported by aqueous N M R studies[13, 14] and absorption spectroscopic studies of cytosine [15, 16]. The second dissociation
0[
t
r
2
5
Fig. 2. Potentiometric titration of CTP with Cu(II) and Mg(II) in 1:1 ratio of ligand to metal ion t = 35° (~z = 0.10 M(KNO~) A = Free ligand; B = Mg(II); C = Cu(II); a = moles of base added per mole of CTP.
774
M.M. TAQUIKHAN et al.
to be the weakest donor group and the triphosphate chain the strongest group for transition and alkaline earth metal ions. Hence it is of interest to compare the stability constants of normal 1:1 chelates of CTP with the corresponding stability constants of adenosine triphosphate (ATP), guanosine triphosphate (GTP) and inosine triphosphate (ITP) with bivalent metal ions. The stabilities show no regular trend as compared to the basicities of the ligand. The sum of the p K values of ligands CTP, GTP, ITP and ATP are respectively 10.83, 9.94, 9.27 and 10.92117, 18] indicating the order C T P > A T P > GTP > ITP. The stability constants of these ligands with bivalent metal ions show no correlation whatsoever, with the basicities of the ligand [17, 19]. The lack of the expected order in the stabilites of the I : 1 complexes of these ligands may be due to differences in the nature of bonding of the ligand with the divalent metal ions which varies from ligand to ligand and also metal ion to metal ion. Philips [20] and Weser [21] suggested the possibility of the metal ions forming a large chelate ring in ATP by simultaneous coordination of the triphosphate and the base. Perhaps in some cases the triphosphate chain and the base are involved in the binding of the metal ion and in other cases only the triphosphate chain. In all the cases studies CTP forms complexes of lower stability than those of GTP[17] though a reverse trend would have been expected from the basicities of two ligands. It may therefore be concluded that the binding sites involved in GTP and CTP complexes may be different. Microscopic information on the binding sites of CTP cannot yet be ascertained from existing data.
REFERENCES
1. M. M. Taqui Khan and P. Rabindra Reddy, J. inorg. nucl. Chem. 35, 2813 (1973). 2. A. E. Martell and G. Schwarzenbach, Heir. Chim. Acta 76, 653 (1956). 3. R. M. Smith and R. A. Alberty, J. Am. chem. Soc. 78, 2376 (1956). 4. L. B. Naninga, J. phys. Chem. 61, 1144 (1957). 5. M. M. Taqui Khan and A. E. Martell, J. phys. Chem. 66, 10 (1962). 6. M. M. Taqui Khan and A. E. Martell, J. Am. chem. Soc. 84, 3037 (1962). 7. E. Wallas, Acta. chem. scand. 12, 528 (1958). 8. G. Schwarzenbach, Complexometric Titrations, pp. 77, 82. Interscience, New York (1957). 9. H. S. Harned and B. B. Owen, Physical Chemistry of Electrolytic Solution, 3rd Edn, pp 638, 752. Reinhold, New York (1958). 10. A. E. Martell and M. Calvin, Chemistry of the Metal Chelate Compounds. Prentice-Hall, New York (1952). 11. C. D. Jardetzky and O. Jardetzky, J. Am. chem. Soc. 82, 222 (1960). 12. O. Jardetzky, P. Pappas and N. G. Wade, J. Am. chem. Soc. 85, 1657 (1963). 13. H. T. Mites, R. B. Bradely and F. D. Becker, Science 142, 1569 (1963). 14. A. R. Katrizky and A. J. Waring, J. chem. Soc. 3046 (1963). 15. T. Veda and J. J. Fox, J. Am. chem. Soc. 85, 1348 (1963). 16. P. Brookes and P. D. Lawley, J. chem. Soc. 1348 (1962). 17. M. M. Taqui Khan and P. Rabindra Reddy, J. inorg. nucl. Chem. 35, 2813 (1973). 18. M. M. Taqui Khan and P. Rabindra Reddy, J. inorg. nucl. Chem. 34, 967 (1972). 19. M. M. Taqui Khan and A. E. Martell, J. Am. chem. Soc. 84, 668 (1966). 20. R. Phillips, Chem. Rev. 66, 501 (1966). 21. U. Weser, Structure and Bonding 5, 41 (1968).
Printed in Great Britain
INTERACTION OF METAL IONS WITH CYTIDINETRIPHOSPHATE M. M. TAQUI KHAN and P. RABINDRA REDDY Department of Chemistry, Nizam College, Hyderabad-500001, India (Received 8 February 1974)
Abstraet--Potentiometric equilibrium measurements have been made at 35° on the combination of anionic species of CTP with Cu(II), Ni(II), Zn(II), Co(II), Mn(II), Mg(II) and Ca(II) in a 1 : 1 ratio of ligand to metal ion. The stabilities for the protonated and normal 1 : 1 complexes decrease in the order Cu(II) > Ni(II) > Zn(II) > Co(II) > Mn(II) > Mg(II) > Ca(II). INTRODUCTION WE HAVE reported earlier[l] on the metal chelates of guanosine triphosphate (GTP) and inosine triphosphate (ITP) and the corresponding thermodynamic quantities with bivalent metal ions. The present paper extends the w o r k to cytidine triphosphate (CTP). Although the metal c o m p l e x e s of adenine nucleotides h a v e been the subject of several studies[2-6], c o m p l e x e s of cytidine triphosphate (CTP) have not been thoroughly investigated. P r e v i o u s investigation by E v a Wallas (7) was restricted to the c o m p l e x e s of C T P with Co(II), Mn(II), Mg(II) and Ca(II) by an ion e x c h a n g e method. C o n s e q u e n t l y detailed physico chemical studies on the c o m p l e x f o r m a t i o n of C T P with bivalent metal ions h a v e been carried out for the first time.
concentration. The electrode system was calibrated by direct titration of acetic acid and the observed pH meter reading was compared to the actual hydrogen ion concentration determined from the pK, values of acetic acid at 35° as tabulated by Harned and Owen [9]. The pH regions below 3.5 and above 10-5 were calibrated by measurements in HCI and NaOH solutions, respectively. CALCULATIONS
The acid dissociation constants for the m o n o s o d i u m salt of C T P (H3L-) are related to the dissociation equilibrium as follows: Ka,K2a
H3L- .
HL3
.
H L 3 - + 2H + K3a
" L4-
+
H+
(1)
(2)
EXPERIMENTAL
Reagents
Cytidine triphosphate was used as the sodium salt and was obtained from Schwarzenbacb-Mann Research Laboratory (U.S.A.). For every titration, fresh solid ligand was weighed out to avoid the possibility of hydrolysis if a stock solution were employed. All transition and alkaline earth metal ions were of AnalaR grade and the metal ions were standardised volumetrically by titration with the disodium salt of EDTA in presence of a suitable indicator as outlined by Schwarzenbach[8]. Carbonate-free sodium hydroxide was prepared and standardised by titration with potassium acid phthalate.
The constants pKa, pK2a w e r e calculated by the graphical solution of Schwarzenbach and Martell [ 10] and pK3 by the usual algebraic method. In order to determine the stability constants of protonated and the normal 1 : 1 c o m p l e x e s f o r m e d during a titration of 1 : 1 mixture of ligand and metal ion, the following equations were used: M 2. + H L 3- . M 2÷ +
Kt&L Kt
L
4-
.
"
" MHL
'-
M L 2-.
(3) (4)
Procedure
Potentiometric titration of the ligand was done with a standard sodium hydroxide solution in the absence and in the presence of the metal ion being investigated. The ionic strength was maintained constant by using 0.10 MKNO3 as the supporting electrolyte and relatively low concentrations of ligand and metal ion. A stream of nitrogen was passed through the solution to exclude the adverse effect of atmospheric carbon dioxide. All titrations were carried out at 35-+ 0.1 °. A Beckmann Model 'G' pH meter with glass and calomel electrodes was used to determine hydrogen ion
Related equilibria may be described as: M 2÷+ H 3 L - - ~ M H L MHL
+ 2H-
+~- M L : - + H L
(5) (6)
The following expressions may be written assuming that a protonated 1 : 1 c o m p l e x species is f o r m e d in the buffer region b e t w e e n a = 0 and 771
M.M. TAQUI KHAN et al.
772
a = 2. If TL represents the total concentration of various ligand species and TM that of all metal species; then: TL = [H3L-] + [H2L 2-] + [HL 3-] + [ M H L - ] TM= [M 2÷] 4- [MHL-].
(7)
where /3 = (l - a)TL - [H ÷] + [OH ] and
(8)
A = [H+] k3a "
The total amount of titrable hydrogen The value of [L 4-] is used to calculate the value of [M 2+] from the relationship
[H +] = [H2L 2-] + 2[HL 3-] + 2 [ M H L - ] - a TL
(9) [M 2+] = [L4-IB Where " a " represents, moles of base added per mole of CTP present. Solving, we have for [L'-]: ot
[L'-] = -~
(10)
where B
[H+] ' 1.
= K3---~-~The value of [M 2÷] and [L 4 ] thus obtained are combined with Eqns (11-13) to calculate K1 from Eqn (4).
where a = (2 - a) TL - [H +] + [OH-] and
RESULTS
y
2[H+]-.-.-~ 3 + [H+]___.~ 2
Determination of p K values of CTP
K~K2~K3~ K~K2a"
The potentiometric titration curves of CTP [H3L-] shown in Fig. 1 indicates a simultaneous dissociation of two protons from the ligand between a = 0 and a = 2 and a separate neutralization reaction between a - - 2 and a =3. The dissociation constants were calculated from Eqns (1) and (2) and the constants are given in Table 1. Schematically the dissociations are represented in Fig. 1. Figure 2 shows the titration curves for CTP chelates of Cu(II), and Mg(II) in a 1:1 ratio of ligand to metal ion at 35°C. Similar curves were obtained for Ni(II), Co(II), Zn(II), Mn(II) and Ca(II) with CTP. The curves show an inflection at a = 2 and a = 3, indicating the dissociation of two protons and one proton respectively from the ligand in two separate steps. Mathematical treatment of the buffer region between a = 0 and a = 2 assuming formation of diprotonated and monoprotonated 1:1 complexes of CTP gave negative results. It was, therefore, assumed that only monoprotonated 1 : 1 complexes of CTP are formed (in the first buffer region) during the titration of above mentioned metal ions with the ligand. The constants so calculated are listed in Table 1. The constants decrease in the order C u ( I I ) > N i ( I I ) > Zn(II) > Co(II) > Mn(II) > Mg(II) > Ca(II). In the buffer region between a = 2 and a = 3 dissociation of the monoprotonated 1 : 1 species to a normal 1:1 metal chelate species had been assumed, and the stability constants of the normal 1 : 1 chelate species calculated. The data presented in Table 1 decrease in the order C u ( I I ) > N i ( I I ) > Zn(II) > Co(II) > Mn(II) > Mg(II) > Ca(II).
Equation (10) is solved for [L 4-] and may be related to [M 2+] by the expression.
[M2+]=[L'-]X where X=
[H+]3
K~K2oK3.
4- [H+]2 ~ [H+]
~
K3~ "
The value of [M 2+] and [L 4-] may then be used with Eqns (7-9) to calculate the unknowns in Eqn (3) and the value of K~mL u determined. In the buffer region between a = 2 and a = 3, it was assumed that a simple dissociation of the [ M H L - ] species to [ML 2-] had taken place. The following material balance equations may be set up for the dissociation. TL = [HL 3-] + [L 4-] + [ M H L - ] + [ML:-] TM= [M 2÷] + [ M H L - ] + [ML2-].
(11) (12)
The total amount of titrable hydrogen [H ÷] = [Z 4-] 4- [ M H L - ] + [ML 2-] - aTL + [OH-]. (13) The above equations are solved for [L4-]: [L 4-] =
Interaction of metal ions with cytidinetriphosphate Table 1. Equilibrium constants for the interaction of CTP with various metal ions
NH2
I
II
o//C "N/C--H
1 lO...
O
O
O
II
II
II
HC CH--CH~O--P--O--P--O--P~OH I I I H C - - C/ H O O OH
I
HO
77
I
OH
l
pk~ ~ 2.62
NH2
o / /.,N..1/o.. CC - - H HC
O
O
O
II
II
II
\
/
I
P
O-
I
HO
I
Ca(II) Mg(II) Mn(II) Co(II) Zn(II) Ni(II) Cu(II)
3.81 3.93 4.10 4-36 4.48 4.61 5-45
4.13 4-21 4.43 4.96 5.12 5.58 6.61
I
O-
OH
O
O
O
II
II
II
constant of C T P reported in this investigation may c o r r e s p o n d to the ionization of a proton f r o m the N3H + group and the first and third dissociation constants to those f r o m the phosphate chain. It may be seen f r o m Table 1 that the stabilities of m o n o p r o p o n a t e d 1 : 1 and normal 1 : 1 metal chelate species of C T P follow the Irving-Williams order. Of the sites, base, ribose and phosphate i n v o l v e d in the chelation of bivalent metal ions, ribose appears
OH
lp
NH2 N,-~",, C __H [ II ~H o//C "N/ C
[/o\
HC
CH--CH20--P--O--P--O~P--
H \C - - C/ H
I
I
O-
I
HO
I
O-
0
J
OH
OH
l
II --
pk3o =9.99
NH2
C
8 l-
II
o / /" N1/o\ C/ C - - H \
Log K~*
*The constants are accurate to +0.06 log K units, t = 35°; p~ = 0.10 M(KNO3): pKo = 2-62]÷ pK~ = 4.22~_ 0.02. pKg. = 9.99)
k2a = 4"22
HC
Log K~r~L*
CH--CH20--P--O~P--O--P--O-
HC--CH
I
Metalion
O
O
O
II
II
II
C H - - C H 2 0 - - P - - O - - P - - O - - P - - O-
/
HC--CH f HO OH
I
O
I
O-
t
O-
,/
1"
I 5 4
Fig. 1.
DISCUSSION
The dissociation constants of C T P are listed in Table 1. The second dissociation constant (pK2a = 4.22) is comparable to the first dissociation constant of cytosine (pKa = 4.2). F o r cytosine, on the basis fo N M R data, the proton ionization site was suggested to be the N3H + group by J a r d e t z k y et a l . [ l l , 12]. This was also supported by aqueous N M R studies[13, 14] and absorption spectroscopic studies of cytosine [15, 16]. The second dissociation
0[
t
r
2
5
Fig. 2. Potentiometric titration of CTP with Cu(II) and Mg(II) in 1:1 ratio of ligand to metal ion t = 35° (~z = 0.10 M(KNO~) A = Free ligand; B = Mg(II); C = Cu(II); a = moles of base added per mole of CTP.
774
M.M. TAQUIKHAN et al.
to be the weakest donor group and the triphosphate chain the strongest group for transition and alkaline earth metal ions. Hence it is of interest to compare the stability constants of normal 1:1 chelates of CTP with the corresponding stability constants of adenosine triphosphate (ATP), guanosine triphosphate (GTP) and inosine triphosphate (ITP) with bivalent metal ions. The stabilities show no regular trend as compared to the basicities of the ligand. The sum of the p K values of ligands CTP, GTP, ITP and ATP are respectively 10.83, 9.94, 9.27 and 10.92117, 18] indicating the order C T P > A T P > GTP > ITP. The stability constants of these ligands with bivalent metal ions show no correlation whatsoever, with the basicities of the ligand [17, 19]. The lack of the expected order in the stabilites of the I : 1 complexes of these ligands may be due to differences in the nature of bonding of the ligand with the divalent metal ions which varies from ligand to ligand and also metal ion to metal ion. Philips [20] and Weser [21] suggested the possibility of the metal ions forming a large chelate ring in ATP by simultaneous coordination of the triphosphate and the base. Perhaps in some cases the triphosphate chain and the base are involved in the binding of the metal ion and in other cases only the triphosphate chain. In all the cases studies CTP forms complexes of lower stability than those of GTP[17] though a reverse trend would have been expected from the basicities of two ligands. It may therefore be concluded that the binding sites involved in GTP and CTP complexes may be different. Microscopic information on the binding sites of CTP cannot yet be ascertained from existing data.
REFERENCES
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