Study of Stability Constant of Some Transition Metal Complexes Formed With 4-[(1R)-2-amino-1-hydroxyethyl] benzene-1, 2-diol.
Dr. Jaishri Kaushik1*, Dr. Namita Bharadwaj2, Pratyush Jaiswal3
1Assistant Professor, Department of Chemistry, LCIT College of Commerce & Science, Bilaspur (C.G.) India.
2Professor, Department of Chemistry, Dr. C.V. Raman University, Kota-495113, Dist-Bilaspur, (C.G.) India.
3Research Scholar, Department of Chemistry, Dr. C.V. Raman University, Kota-495113,
Dist-Bilaspur, (C.G.) India.
*Corresponding Author E-mail: kaushik.jaishri08@gmail.com
ABSTRACT:
The Simple, selective, and expeditious spectrophotometric methods have been developed for the determination of complexation of 4-[(1R)-2-amino-1-hydroxyethyl] benzene-1,2-diol with metal ions in pharmaceutical field. The method was based on complex formation between the antihypotensive drug and transition metal ions in a basic medium (pH 9.2). The colored complexes were measured at 280 nm wavelength for 4-[(1R)-2-amino-1-hydroxyethyl] benzene-1, 2-diol. The different experimental parameters affecting the development and stability of the colour were carefully studied and optimized. The stability constant of complex were calculated to be Ag(Ι)-4-[(1R)-2-amino-1-hydroxyethyl] benzene-1,2-diol is 4.34, Pd (ΙΙ)-4-[(1R)-2-amino-1-hydroxyethyl] benzene-1,2-diol is 5.75 & Cd (ΙΙ) - 4-[(1R)-2-amino-1-hydroxyethyl] benzene-1,2-diol is 3.82 by job’s continuous variation method. The stoichiometry of the complexes formed between the antihypotensive drugs and the metal ions was 1:1 M/L ratio. The proposed method was further applied to the determination of drug in pure and dosage forms. The results obtained were in good agreement with those obtained by a reference to UV–Visible Spectrophotometric method.
KEYWORDS: Complexation, Antihypotensive drug, Stability constant, Job’s method, Spectrophotometer.
INTRODUCTION:
The introduction of metal ions or metal ion binding components into a biological system for the treatment of diseases is one of the main subdivisions in the field of bioinorganic chemistry 6,7. A wide range of biological activities8,9,10. Metals and metal complexes had played an important role in the development of the pharmaceutical drugs11,12.
Every year many new drugs and newer drug combinations enter the pharmaceutical area13.Spectroscopy deals with the study of measurement of interaction between radiation energy and matter particles and it can also be used to measure the stability constants14.
Noradrenaline (4-[(1R)-2-amino-1hydroxyethyl] benzene-1, 2-diol (fig: 1) are catecholamine neurotransmitters produced by the nervous system. They are also known as epinephrine and norepinephrine15 and are involved in several physiological functions including regulation of blood pressure, vasoconstriction16,17,18,19. Noradrenaline is mainly produced by neurons within the locus coeruleus (LC) and takes part in diverse motor and mental functions including locomotion control, motivation, attention, cognition, and memory formation 20. Among the most important heterocyclic units indole nucleus has received major attention as a key structural building block due to their medicinal and pharmaceutical applications 21. Further 3-thioindole motifs are very common in various drugs for the treatment of heart disease, allergies 22,23.
The complex formation is confirmed by using Job’s variation method at a fixed temperature 24. The Job’s method of continuous variation used for the determination of metal ligand stability constant 25.
Figure 1 Chemical structure of 4-[(1R)-2-amino-1-hydroxyethyl] benzene-1, 2-diol
MATERIAL AND METHODS:
Chemicals and reagents:
Stock solution (0.01 M) of 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1, 2-diol was prepared by dissolving the accurately weighed amount in deionized water. Metal stock solution (0.01 M) was prepared by dissolving the appropriate amount of Silver nitrate (Merck), Palladium chloride (Merck) and Cadmium chloride (Merck) in deionized water. Working solutions were prepared by suitable dilutions with deionized water. The universal phosphate buffer solutions of varying pH values were prepared 28.
Instrumentation:
The proposed work was carried out on the Systronic UV/Vis double beam spectrophotometer with 1 cm quartz cells was used to measure the absorbance 26. The pH measurements were made with systronic pH meter model 371 all measurements were performed at room temperature (35 ±0.01°C) 27.
Selection of Solvents:
On the basis of solubility study deionized water was selected as the solvent for dissolving 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol and metal chlorides.
EXPERIMENT:
Spectrometric determination of 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol with Ag(I) complex: In a series of 10 ml volumetric flasks, the concentrations of 4-[(1R)-2-amino-1-hydroxyethyl] benzene-1, 2-diol ranged from (0.5- 3.5) ml : (3.5-0.5) ml of 0.01M Ag (Ι) was added along with 9.2 pH phosphate buffer and the solutions were diluted . The mixture was allowed to stand for 10 min 29. The absorbance of the resulting solutions was measured at 280 nm against an appropriate blank in which the drug is omitted.
Spectrometric determination of 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol with Pd(Il) complex:
In a series of 10 ml volumetric flasks, the concentrations of 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol ranged from (0.5- 3.5) ml : (3.5-0.5) ml of 0.01 M Pd (ΙI) was added along with 9.2 pH phosphate buffer and the solutions were diluted . The mixture was allowed to stand for 10 min. The absorbance of the resulting solutions was measured at 280 nm against an appropriate blank in which the drug is omitted.
Spectrometric determination of 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol with Cd(IΙ) complex:
In a series of 10 ml volumetric flasks, the concentrations of 4-[(1R)-2-amino-1-hydroxyethyl] benzene-1, 2-diol ranged from (0.5- 3.5) ml: (3.5-0.5) ml of 0.01 M Cd (ΙΙ) was added along with 9.2 pH phosphate buffer and the solutions were diluted . The mixture was allowed to stand for 10 min. The absorbance of the resulting solutions was measured at 280 nm against an appropriate blank in which the drug is omitted.
The Stoichiometry of 4-[(1R)-2-amino-1-hydroxyethyl] benzene-1, 2-diol complexes formed in the solution was determined spectrophotometrically applying the continuous variation 30. The obtained results revealed the formation of 1:1 (M: L) 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diolcomplexeswith Ag (I), Pd (ΙΙ) & Cd (ΙΙ) metal ions.
The logarithmic constants (log βn) and the free energy changes (ΔG) of the formed complexes were calculated from the data of continuous variation method by applying equations 1 and 2 31.
𝛽𝑛 = A/Am / 1- [A/Am]n+1 C1n N2 .................................(1)
ΔG = -2.303 RT log βn ...............................................(2)
Where βn is the stability constant of the metal chelate, A is the absorbance at ligand concentration Cl, Am is the absorbance at full color developed, n is the order of the complex formed, T is the absolute temperature and R is the gas constant.
RESULT AND DISCUSSION:
When the ligand solutions are mixed with the metal ions above 6.5 pH solution then it was observed that the color of solutions changes to light yellow from colourless. This confirms the complex formation between metal ion and ligand species. To prevent the oxidation of the ligand at higher pH during spectrophotometric measurements, the optical density measured immediately after the preparation of the solution. The absorption data obtained are used to plot the curves. The curves plotted between wavelength (nm) and optical density (O.D.). The change occur in log K values due to the factors such as effective nuclear charge, oxidation number, size of metal ion are also affect complex formation 32. The order of magnitude of the stability of complexes formed by Noradrenalin with the cations here investigated and comparing it to information from the literature, it is possible to hypothesize that for our systems as well, the interaction should occur via the phenolic oxygen(s) of the two phenol groups, excluding the amine group of the lateral chain 33.
The values of βn for drugs 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1 2-diol and metal ions lies between 0.5 to 3.5 and 3.5 to 0.5 which indicate 1:1 complexes are formed by the ligands with transition metal ions. (Table 1) (Table 2) (Table 3). The stability constant value for complex of 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol with Ag(Ⅰ), Pd(Ⅱ) and Cd(Ⅱ) metal ions by spectrophotometrically (figure 2).
Table -1 Experimental Data For Complexation of Ag(I)-4-[(1R)-2-amino-1hydroxyethyl]benzene-1,2-diol by Spectrophotometer Method:
|
S.N |
Metal concentration 1×10-2mol |
Ligand concentration 1×10-2mol |
O.D at 280 nm |
|
1 |
0.5 |
3.5 |
0.829 |
|
2 |
1.0 |
3.0 |
0.855 |
|
3 |
1.5 |
2.5 |
0.863 |
|
4 |
2.0 |
2.0 |
1.271 |
|
5 |
2.5 |
1.5 |
0.870 |
|
6 |
3.0 |
1.0 |
0.861 |
|
7 |
3.5 |
0.5 |
0.882 |
Table 2: Experimental Data for Complexation of Pd(II)-4-[(1R)-2-amino-1hydroxyethyl]benzene-1,2-diol by Spectrophotometer Method
|
SN |
Metal concentration 1×10-2 mol |
Ligand concentration 1×10-2mol |
O.D at 280 nm |
|
1 |
0.5 |
3.5 |
1.209 |
|
2 |
1.0 |
3.0 |
1.212 |
|
3 |
1.5 |
2.5 |
1.262 |
|
4 |
2.0 |
2.0 |
1.520 |
|
5 |
2.5 |
1.5 |
1.268 |
|
6 |
3.0 |
1.0 |
1.252 |
|
7 |
3.5 |
0.5 |
1.223 |
Table -3 Experimental Data for Complexation of Cd (II)-4-[(1R)-2-amino-1hydroxyethyl]benzene-1,2-diol by Spectrophotometer Method:
|
SN |
Metal concentration 1×10-2mol |
Ligand concentration 1×10-2mol |
O.D. at 280 nm |
|
1 |
0.5 |
3.5 |
0.865 |
|
2 |
1.0 |
3.0 |
0.857 |
|
3 |
1.5 |
2.5 |
0.877 |
|
4 |
2.0 |
2.0 |
0.942 |
|
5 |
2.5 |
1.5 |
0.832 |
|
6 |
3.0 |
1.0 |
0.863 |
|
7 |
3.5 |
0.5 |
0.853 |
Figure 2: Job’s plot for the reaction of drug and metal ions at maximum wavelength 280 nm. (a) Drug with Ag (Ι) metal ion. (b) Drug with Pd (ΙΙ) metal ion. (c) Drug with Cd (ΙΙ) metal ion.
The stability constants of the binary complexes formed between drug and the transition metal ions. The order of their stabilities, which was in the expected Irving–Williams such behavior of drug, may be due to its bidentate structure that coordinates through the oxygen atom of phenol group 34.
The UV region exhibits maximum absorbance at 280 nm for M/L Complexation. The order of stability constant is Pd (Ⅱ) > Ag (Ⅰ) >Cd (Ⅱ) are 5.61 > 4.34 > 3.82 respectively (Table 4). It’s commonly observed the stability constants of transition metal complexes obtained follows the usual natural order (Irving William natural order) of stability.
Table –4 Spectrophotometric Analysis Characteristic OF 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol Complexes with Ag (Ι), Pd(ΙΙ) and Cd(ΙΙ) Metal ions.
|
SN |
Metal ions |
λ max |
M/L Ratio |
βn |
-ΔG |
|
1 |
Ag (Ι) |
280 nm |
1:1 |
4.34 |
3.75 |
|
2 |
Pd (ΙΙ) |
280 nm |
1:1 |
5.61 |
4.47 |
|
3 |
Cd (ΙΙ) |
280 nm |
1:1 |
3.82 |
3.43 |
CONCLUSION:
In summary it is successfully shows that the stoichiometric ratio of 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol –Ag, Pd, Cd (M/L) was 1:1 ratio. The development of the new antihypotensive drug with enlarged biological activity can be possible by progress in the field of antihypotensive complexes. The proposed method is simple, fairly and sensitive when compared with already reported methods especially those which are based on non-aqueous medium and expensive technique such as chromatographic instruments and do not require any pretreatment of the drugs. It has a good accuracy and precision. Transition metal complexes find their application in catalysis, material synthesis, and photochemistry. Various chemical, optical, and magnetic properties of the metal complexes of some drug have been studied by using a wide range of techniques.
AKNOWLEDGEMENT:
The Authors are thankful to Department of Chemistry Dr. C.V. Raman University for provided the laboratory facilities during the research work.
CONFLICT OF INTEREST:
The author declares no conflict of interest.
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Received on 15.01.2021 Modified on 18.05.2021
Accepted on 23.08.2021 © RJPT All right reserved
Research J. Pharm. and Tech. 2022; 15(5):2268-2272.
DOI: 10.52711/0974-360X.2022.00377