Appl. Radiaf. hf. Vol. 42, No. II, pp. 1087-1089, hr. J. Radiat. Appl. Instrum. Part A
1991
0883-2889/91
S3.00 + 0.00
Pergamon Press plc
Primed in Great Britain
Synergistic Effect of Some Pharmaceutical Compounds on Cobalt-60 Complexes K. FARAH’, ‘Radioisotope Atomic Energy
G. EL-SHABOURY’
and A. KANDIL2
Production and Labelled Compounds Department, Nuclear Research Centre, Establishment, P.O. Code 13759, Cairo, Egypt and lDepartment of Chemistry, Faculty of Science, Helwan University, Helwan, Cairo, Egypt
(Received 19 October 1990; received for publication 22 January 1991) Synergism in the extraction of cobalt from acetate 0.1 M aqueous medium, pH = 5.3 has been investigated using a mixture of thenoyl-trifluoro acetone and antipyrine, 4Godoantipyrine or 4-aminopyrine (AAPy), synergism was observed in all the cases. The maximum synergistic effect was observed in the case of 4-(AAPy). The nature of the extracted species has been determined and the equilibrium constants for the adducts have been evaluated. The thermodynamic parameters of these reactions have been calculated to elucidate the mechanism of formation of the extracted species. These compounds were found to be good donors capable in strength to other alkyl phosphorus donors.
Introduction Antipyrine (APy; 1,5-dimethyl-3-oxo-2-phenyl pyrazoline) and aminopyrine (Cdimethyl amino-l,5 dimethyl-3-oxo-2-phenyl pyrazoline) are currently used in medicine as analgesic and antipyretic agents (Clarke, 1978). Also radioiodinated 4-iodoantipyrine (IAPy) has been successfully used for measuring the regional cerebral blood flow as well as to obtain crosssectional images of the human brain (Uszler et al., 1975). It is a well established fact that the activity of the drug increases when administered in the form of metal complexes and a number of metal chelates have been used as antitumor agents. In the cancer treatment, it has been shown that the active species is not the thiosemicarbazone itself but a metal chelate of thiosemicarbazone (Petering and Van Geissen, 1966). The role of mixed ligand complexes in biological process has been well recognized (Beck, 1970). The stabilities of mixed chelates are of great importance in biological systems as many metabolic and toxological functions are dependent upon stability. Many attempts have been made to correlate the stability of the metal ligand complexes with their antimicrobial activity (Anjanyulu el al., 1985). Antipyrine and other substituted pyrazolones of considerable importance in medicine, are also attracting attention as /?-diketones in extraction studies (Malhotra and Sudersanan, 1985; Raghupathy et al., 1985). It is therefore of interest to study the role of APy, IAPy and Caminopyrine (AAPy) as extractants and synergists in the nuclear fuel industry for the
separation of certain metal ions and to elucidate the mechanism of formation of the extracted species. Experimental 4-Iodoantipyrine was synthesized by titrating an antipyrine (940 mg) sodium acetate (2 g) aqueous solution with 10 mL 1 N standard iodine solution. Crystalline needles were separated by filtration and dissolved in chloroform. The chloroform solution was evaporated and the residue was allowed for recrystallization using 90% ethanol, washed by water and oven-dried at 70°C (El-Shaboury and Farah, 1991). The partition coefficient of APy was determined by equilibrating an aqueous solution of APy with an equal volume of benzene and determining the concentrations in the two phases. The partition coefficient was determined to be 0.5 in accordance with that previously reported (Raghupathy et al., 1985). The Co*+ radiotracer was prepared by dissolving the oxide in HCl and transferred to the perchlorate form by successive evaporation and dissolution in dilute HC104. All other chemicals used in this work are high purity grade and the experimental procedure used in this research is previously discussed (Kandil and Farah, 1980). Results and Discussion The extraction of Co2+ by varying thenoyl-trifluoro acetone (HTTA) concentration in benzene from an
1087
1088
K.
FARAHet al.
IC I-
D,
D
0
@15°C 25’C 4 35*c 0 45Y
12'C
l
. 25’C 4 35-c II 45-c 0: [APy
CHTTAI
Fig. 1. The extraction of Co2+ by HTTA in benzene from 0.1 M CH,COONa, pH = 5.3 at various temperatures. phase of 0.1 M CH,COONa buffered to pH = 5.3 at different temperatures (Fig. 1) indicated that the extraction mechanism of Co*+ can be represented by: aqueous
Co*+ (8) + 2HTTA &Co(TTA),,,,
+ 2H&
where a and o stand for the aq. and org. phases, respectively. Table 1 gives the log K, value and the thermodynamic parameters of the free energy AC, enthalpy AH and entropy AS. The positive enthalpy change reflects an endothermic reaction for the formation of Co(TTA), chelate resulting from the release of H,O molecules in the dehydration process. The formation constant log K, and the thermodynamic parameters of the species Co(TTA), are in excellent agreement with those previously reported (Kandil and Ramadan, 1980). Figures 2, 3 and 4 show the effect of temperature on the extraction of Co*+ from an aqueous phase of 0.1 M CH,COONa, pH = 5.3 by a fixed 0.03 M HTTA in benzene mixed with various concentrations of either APy, IAPy or AAPy respectively. It was
10-z
10-3
100 0.1
0.0 1
1
Fig. 2. The effect of APy concentration on the extraction of Co2+ at const. 0.03 M HTTA in benzene from 0.1 M CH,COONa, pH = 5.3 at various temperatures.
found that the extraction increases linearly with increase of concentration and a slope of 1 is observed indicating the formation of a synergistic adduct. At a higher concentration range, a slight increase in the slope is observed which does not correspond to slope 2, indicating the formation possibly, of two adducts. It is thus concluded that the species that is initially formed is Co(TTA), . S where S =APy,IAPy The extraction
or
mechanism
can be represented
Co;$ + ZHTTA,,, + S,,,ACo(TTA),(S),,,
AG Ion K
Co(nA), -8.61 f 0.05 Co(I-I’A),.APy -4.44 * oo4 Co(l-TA),.lAPy -5.51 f 0.04 Co(TTA),.AAPy -2.35 f 0.03 Species toa B, &(-PTA), APy 4.17kO.06 Co(lTA), IAPy Co(TTA),.AAPy
3.10 + 0.06 6.22 + 0.05
(kJ/mol)
49.41 25.45 31.60 13.46 AG -23.96 - 17.81 - 35.95
AH (kJ/mol)
37.20 17.32 26.96 12.71
D
AH -19.88 - 10.24 -24.49
13.68 25.39 38.44
+ 2H&.
1
. 25’C
AS (J/dea/moll
-40.86 - 27.28 - 15.57 -2.52 AS
by:
IC
Table I. Formation constants and thermodynamic parameters for the formation of Co(lTA),, Co(TTA),‘APy, Co(TTA),.IAPy and Co(TTA), AAPy Species
AAPy
A 35’C 0 45-c
_. 1
o-’
10-Z
?O-'
[IAPyl
Fig. 3. The effect of IAPy concentration on the extraction of Co2+ at const. 0.03 M HTTA benzene from 0.1 M CH,COONa, pH = 5.3 at various temperatures.
Effect of pharmaceutical
compounds
on cobalt-60
complexes
1089
The log B, values and the thermodynamic parameters of the above reactions are listed in Table 1 with:
0.1
I
I
I 1o-4
10-5
10-6
CAAPy 1 Fig. 4. The effect of AAPy concentration on the extraction of Co*+ at const. 0.03 M HTTA in benzene from 0.1 M CH,COONa, pH = 5.3 at various temperatures.
The log K2 values and the thermodynamic parameters of these reactions are also contained in Table I. The AH values are calculated from the slope of the log K vs l/T relationship and the entropy change is obtained from the relation AG = AH - TAS. The synergistic reactions that occur in the organic phase and lead to the formation of Co(TTA),.S are thus: Co(TTA),,,, 10
+ S,,,&Co(TTA),
S(a).
r
0.11
I
I 0.01
0.1
CTTAI
Fig. 5. The effect of HTTA cont. in benzene on the extraction of Co2+ at const. APy, IAPy and AAPy from 0.1 M CH,COONa, pH = 5.3 at 25°C.
That the addition of APy, IAPy and AAPy does not lead to the release of any TTA molecules is evident from Fig. 5 where a plot of the distribution ratio vs [HTTA] at fixed [APy]. [IAPy] or [AAPy] leads to a slope of 2. An enhancement in the Co*+ extraction using a mixture of HTTA and either APy or AAPy is seen to be over lo4 and lo6 respectively. This indicates that synergism is quite pronounced in these systems as compared to donors like tributyl phosphate or other phosphine oxide systems (Kandil and Ramadan, 1980). The thermodynamic data of the enthalpy accompanying the formation of the Co(TTA),.S, shown in Table 1, indicates an exothermic reaction explained by the formation of strong metal-O bonding. The coordination number of Co2+ is thus increased from 4 to 5, in accordance with our previous conclusion in this system (Kandil and Ramadan, 1980). The synergistic reaction in all three cases studied is seen to be entropy driven. The steric hindrance is least in APy and largest in AAPy as to be expected from the structure of these ligands. A lower AH value in the case of IAPy is explained by the presence of I in IAPy which increases the electron density at the 0 in IAPy, therefore a weaker adduct is formed. In conclusion, we indicate the suitability and the advantage of using APy, IAPy and AAPy as neutral donors in extraction studies.
References Anjanyulu Y., Swamy R. Y. and Prabhakara Rao (1985) Studies on some mixed ligand complexes of Cu(II) with 8-hydroxyquinoline and salicylic acids. Relation between stability constants and antimicrobial activity. J. Indian Chem. Sot. LXII, 346. Beck M. T. (1970) Chemistry of Complex Equilibria. Van Nostrand Reinhold, London. Clark E. G. G. (1978) Isolation and Identification of Drugs. The Pharmaceutical Press, London. El-Shabourv G. and Farah K. (1991) Recent studv on radioiodination of [4-iZ71]iodoantipyrine via isotope exchange in dry states up to melt. Appl. Radiut. ISOI. 42, 1091. Kandil A. T. and Farah K. (1980) Thermodynamic studies of TOP0 adducts of europium and terbium tri-TTA chelates. J. Inorg. Nucl. Chem. 42, 1491. Kandil A. T. and Ramadan A. (1980) The synergistic solvent extraction of Co’+. Radiochim. Acta 21, 229. Malhotra R. K. and Sudersanan M. (1985) Synergism in the extraction of lanthanides, copper and thorium in presence of HTTA and antipyrine. Proc. Indian Acad. Sci. 95, 333. Petering H. G. and Van Geissen G. J. (1966) The Biochemistry of C&per. Academic Press, New York. Raahuoathv S.. Ranaaraian J. and Sudersanan M. (1985) S;nergism in extr&tion of europium in presence of antipyrine and a B-diketone. Indian J. Chem. 24, 898. Uszler J. M., Bennet L. R., Mena I. et al. (1975) Human CNS perfusion scanning with ‘2’I-iodoantipyrine. Radiology 115, 197.
1991
0883-2889/91
S3.00 + 0.00
Pergamon Press plc
Primed in Great Britain
Synergistic Effect of Some Pharmaceutical Compounds on Cobalt-60 Complexes K. FARAH’, ‘Radioisotope Atomic Energy
G. EL-SHABOURY’
and A. KANDIL2
Production and Labelled Compounds Department, Nuclear Research Centre, Establishment, P.O. Code 13759, Cairo, Egypt and lDepartment of Chemistry, Faculty of Science, Helwan University, Helwan, Cairo, Egypt
(Received 19 October 1990; received for publication 22 January 1991) Synergism in the extraction of cobalt from acetate 0.1 M aqueous medium, pH = 5.3 has been investigated using a mixture of thenoyl-trifluoro acetone and antipyrine, 4Godoantipyrine or 4-aminopyrine (AAPy), synergism was observed in all the cases. The maximum synergistic effect was observed in the case of 4-(AAPy). The nature of the extracted species has been determined and the equilibrium constants for the adducts have been evaluated. The thermodynamic parameters of these reactions have been calculated to elucidate the mechanism of formation of the extracted species. These compounds were found to be good donors capable in strength to other alkyl phosphorus donors.
Introduction Antipyrine (APy; 1,5-dimethyl-3-oxo-2-phenyl pyrazoline) and aminopyrine (Cdimethyl amino-l,5 dimethyl-3-oxo-2-phenyl pyrazoline) are currently used in medicine as analgesic and antipyretic agents (Clarke, 1978). Also radioiodinated 4-iodoantipyrine (IAPy) has been successfully used for measuring the regional cerebral blood flow as well as to obtain crosssectional images of the human brain (Uszler et al., 1975). It is a well established fact that the activity of the drug increases when administered in the form of metal complexes and a number of metal chelates have been used as antitumor agents. In the cancer treatment, it has been shown that the active species is not the thiosemicarbazone itself but a metal chelate of thiosemicarbazone (Petering and Van Geissen, 1966). The role of mixed ligand complexes in biological process has been well recognized (Beck, 1970). The stabilities of mixed chelates are of great importance in biological systems as many metabolic and toxological functions are dependent upon stability. Many attempts have been made to correlate the stability of the metal ligand complexes with their antimicrobial activity (Anjanyulu el al., 1985). Antipyrine and other substituted pyrazolones of considerable importance in medicine, are also attracting attention as /?-diketones in extraction studies (Malhotra and Sudersanan, 1985; Raghupathy et al., 1985). It is therefore of interest to study the role of APy, IAPy and Caminopyrine (AAPy) as extractants and synergists in the nuclear fuel industry for the
separation of certain metal ions and to elucidate the mechanism of formation of the extracted species. Experimental 4-Iodoantipyrine was synthesized by titrating an antipyrine (940 mg) sodium acetate (2 g) aqueous solution with 10 mL 1 N standard iodine solution. Crystalline needles were separated by filtration and dissolved in chloroform. The chloroform solution was evaporated and the residue was allowed for recrystallization using 90% ethanol, washed by water and oven-dried at 70°C (El-Shaboury and Farah, 1991). The partition coefficient of APy was determined by equilibrating an aqueous solution of APy with an equal volume of benzene and determining the concentrations in the two phases. The partition coefficient was determined to be 0.5 in accordance with that previously reported (Raghupathy et al., 1985). The Co*+ radiotracer was prepared by dissolving the oxide in HCl and transferred to the perchlorate form by successive evaporation and dissolution in dilute HC104. All other chemicals used in this work are high purity grade and the experimental procedure used in this research is previously discussed (Kandil and Farah, 1980). Results and Discussion The extraction of Co2+ by varying thenoyl-trifluoro acetone (HTTA) concentration in benzene from an
1087
1088
K.
FARAHet al.
IC I-
D,
D
0
@15°C 25’C 4 35*c 0 45Y
12'C
l
. 25’C 4 35-c II 45-c 0: [APy
CHTTAI
Fig. 1. The extraction of Co2+ by HTTA in benzene from 0.1 M CH,COONa, pH = 5.3 at various temperatures. phase of 0.1 M CH,COONa buffered to pH = 5.3 at different temperatures (Fig. 1) indicated that the extraction mechanism of Co*+ can be represented by: aqueous
Co*+ (8) + 2HTTA &Co(TTA),,,,
+ 2H&
where a and o stand for the aq. and org. phases, respectively. Table 1 gives the log K, value and the thermodynamic parameters of the free energy AC, enthalpy AH and entropy AS. The positive enthalpy change reflects an endothermic reaction for the formation of Co(TTA), chelate resulting from the release of H,O molecules in the dehydration process. The formation constant log K, and the thermodynamic parameters of the species Co(TTA), are in excellent agreement with those previously reported (Kandil and Ramadan, 1980). Figures 2, 3 and 4 show the effect of temperature on the extraction of Co*+ from an aqueous phase of 0.1 M CH,COONa, pH = 5.3 by a fixed 0.03 M HTTA in benzene mixed with various concentrations of either APy, IAPy or AAPy respectively. It was
10-z
10-3
100 0.1
0.0 1
1
Fig. 2. The effect of APy concentration on the extraction of Co2+ at const. 0.03 M HTTA in benzene from 0.1 M CH,COONa, pH = 5.3 at various temperatures.
found that the extraction increases linearly with increase of concentration and a slope of 1 is observed indicating the formation of a synergistic adduct. At a higher concentration range, a slight increase in the slope is observed which does not correspond to slope 2, indicating the formation possibly, of two adducts. It is thus concluded that the species that is initially formed is Co(TTA), . S where S =APy,IAPy The extraction
or
mechanism
can be represented
Co;$ + ZHTTA,,, + S,,,ACo(TTA),(S),,,
AG Ion K
Co(nA), -8.61 f 0.05 Co(I-I’A),.APy -4.44 * oo4 Co(l-TA),.lAPy -5.51 f 0.04 Co(TTA),.AAPy -2.35 f 0.03 Species toa B, &(-PTA), APy 4.17kO.06 Co(lTA), IAPy Co(TTA),.AAPy
3.10 + 0.06 6.22 + 0.05
(kJ/mol)
49.41 25.45 31.60 13.46 AG -23.96 - 17.81 - 35.95
AH (kJ/mol)
37.20 17.32 26.96 12.71
D
AH -19.88 - 10.24 -24.49
13.68 25.39 38.44
+ 2H&.
1
. 25’C
AS (J/dea/moll
-40.86 - 27.28 - 15.57 -2.52 AS
by:
IC
Table I. Formation constants and thermodynamic parameters for the formation of Co(lTA),, Co(TTA),‘APy, Co(TTA),.IAPy and Co(TTA), AAPy Species
AAPy
A 35’C 0 45-c
_. 1
o-’
10-Z
?O-'
[IAPyl
Fig. 3. The effect of IAPy concentration on the extraction of Co2+ at const. 0.03 M HTTA benzene from 0.1 M CH,COONa, pH = 5.3 at various temperatures.
Effect of pharmaceutical
compounds
on cobalt-60
complexes
1089
The log B, values and the thermodynamic parameters of the above reactions are listed in Table 1 with:
0.1
I
I
I 1o-4
10-5
10-6
CAAPy 1 Fig. 4. The effect of AAPy concentration on the extraction of Co*+ at const. 0.03 M HTTA in benzene from 0.1 M CH,COONa, pH = 5.3 at various temperatures.
The log K2 values and the thermodynamic parameters of these reactions are also contained in Table I. The AH values are calculated from the slope of the log K vs l/T relationship and the entropy change is obtained from the relation AG = AH - TAS. The synergistic reactions that occur in the organic phase and lead to the formation of Co(TTA),.S are thus: Co(TTA),,,, 10
+ S,,,&Co(TTA),
S(a).
r
0.11
I
I 0.01
0.1
CTTAI
Fig. 5. The effect of HTTA cont. in benzene on the extraction of Co2+ at const. APy, IAPy and AAPy from 0.1 M CH,COONa, pH = 5.3 at 25°C.
That the addition of APy, IAPy and AAPy does not lead to the release of any TTA molecules is evident from Fig. 5 where a plot of the distribution ratio vs [HTTA] at fixed [APy]. [IAPy] or [AAPy] leads to a slope of 2. An enhancement in the Co*+ extraction using a mixture of HTTA and either APy or AAPy is seen to be over lo4 and lo6 respectively. This indicates that synergism is quite pronounced in these systems as compared to donors like tributyl phosphate or other phosphine oxide systems (Kandil and Ramadan, 1980). The thermodynamic data of the enthalpy accompanying the formation of the Co(TTA),.S, shown in Table 1, indicates an exothermic reaction explained by the formation of strong metal-O bonding. The coordination number of Co2+ is thus increased from 4 to 5, in accordance with our previous conclusion in this system (Kandil and Ramadan, 1980). The synergistic reaction in all three cases studied is seen to be entropy driven. The steric hindrance is least in APy and largest in AAPy as to be expected from the structure of these ligands. A lower AH value in the case of IAPy is explained by the presence of I in IAPy which increases the electron density at the 0 in IAPy, therefore a weaker adduct is formed. In conclusion, we indicate the suitability and the advantage of using APy, IAPy and AAPy as neutral donors in extraction studies.
References Anjanyulu Y., Swamy R. Y. and Prabhakara Rao (1985) Studies on some mixed ligand complexes of Cu(II) with 8-hydroxyquinoline and salicylic acids. Relation between stability constants and antimicrobial activity. J. Indian Chem. Sot. LXII, 346. Beck M. T. (1970) Chemistry of Complex Equilibria. Van Nostrand Reinhold, London. Clark E. G. G. (1978) Isolation and Identification of Drugs. The Pharmaceutical Press, London. El-Shabourv G. and Farah K. (1991) Recent studv on radioiodination of [4-iZ71]iodoantipyrine via isotope exchange in dry states up to melt. Appl. Radiut. ISOI. 42, 1091. Kandil A. T. and Farah K. (1980) Thermodynamic studies of TOP0 adducts of europium and terbium tri-TTA chelates. J. Inorg. Nucl. Chem. 42, 1491. Kandil A. T. and Ramadan A. (1980) The synergistic solvent extraction of Co’+. Radiochim. Acta 21, 229. Malhotra R. K. and Sudersanan M. (1985) Synergism in the extraction of lanthanides, copper and thorium in presence of HTTA and antipyrine. Proc. Indian Acad. Sci. 95, 333. Petering H. G. and Van Geissen G. J. (1966) The Biochemistry of C&per. Academic Press, New York. Raahuoathv S.. Ranaaraian J. and Sudersanan M. (1985) S;nergism in extr&tion of europium in presence of antipyrine and a B-diketone. Indian J. Chem. 24, 898. Uszler J. M., Bennet L. R., Mena I. et al. (1975) Human CNS perfusion scanning with ‘2’I-iodoantipyrine. Radiology 115, 197.
