Potentiometeric Study of the Diazepam [7- Chloro-1- Methyl-5-Phenyl-3H-1,4- Benzodiazepine -2- One] Fe(III),Cd(II), Co(II), Ni(II), Zn(II) Cations in Aquo-Organic Media

 

Dr. S.G. Sonkamble

Department of Chemistry, Pratishthan Mahavidyalaya Paithan, Dist. Aurangabad (M.S.) 431107, India

*Corresponding Author E-mail: sg_sonkamble@yahoo.co.in

 

ABSTRACT:

The potentiometer studies have been carried out on metal complexes of Fe(III),Cd(II), Co(II), Ni(II), Zn(II) with drug diazepam [ 7- chloro -1- methyl -5- phenyl -3H-1,4- benzodiazepine -2- one ]. The proton ligand, metal ligand and the formation constants have been determined by adopting Irving-Rossotti Method and by computer programming (SCOSS) an ionic strength 0.1 M ethanol – water medium. pK1 and pk2 valve were determined by half –integral method .  Thermodynamic parameter also evaluated at 0.1 M ionic strength.

                                                                            

KEYWORDS: Potentiometer, diazepam, Thermodynamic parameter. The proton ligand, metal ligand formation constants

 

INTRODUCTION:

Diazepam [7-chloro-1-methyl-5-phenyl-3H-1,4- benzodiazepine-2-one are used in pharmacology  as tranquilizing, hypnotic, tranquillizing and anticonvulsant properties1 . Derivatives of 1, 4- benzodiazepine be used in medicine as tranquilizer and sedative hypnotic agent2. The literature survey reveals that a little work has been done on the synthesis and physicochemical studies of transition metal complexes of drug diazepam 3. But, no attempts have been made, to determine the stability constants of metal complexes derived from 1,4–benzodiazepines4-6. There is +I effect hence azomethine nitrogen is more basic7. Some formation constants of metal complexes derived from 1, 4– benzodiazepines have been study8. Studies in Formation Constant of Al(III), Cr(III) and Fe(III) Complexes 9. Studies of Influence of Ionic strengths of Cu (II) metal ion10.The present study describes the result of The proton ligand, metal  ligand stability constant of transition metal ion with drug diazepam by potentiometer method at ionic strength 0.1 M at in aquo-organic media. The literature survey reveals that no systematic work has been done on the dissociation constant and stability constant of metal chelates of this drugs11-13. Study on interaction between Cu, Cr, Nd on substituted drugs14.Influence of dielectric constant studied15. Some interaction studied between Cu, Cr, Ni metal ion16.

 

It was therefore, decided to study in detail, complexation of these chelating reagent in aquo-organic media with reference to various effects. The potentiometric data was utilized for the evaluation of Proton ligand stability constant, metal ligand stability constant at various experimental condition by adopting Irving-Rossotti Method10.

 

EXPERIMENTAL:

All the chemicals used were Analar grade (India make). Metal ion Concentration were determined by using EDTE with suitable indicator and used as chelating reagent.  Eleco -120 model instrument with accuracy in 0.01 unit with glass and saturated calomel electrode was used for the titrations. It was calibrated with the buffer solution of pH 7.00 and 9.20 at 28 ± 0.1 °C before titrations. Titrations were carried out in an inert atmosphere by bubbling a constant flow of nitrogen gas. The binary system were studied by following pH metric titration 

i)         Free acid HNO3 (0.04 M) = A

ii)       Free acid HNO3 (0.04 M) and  ligand (20 x 10-4) = A+R

iii)      Free acid HNO3 (0.04 M) and  ligand (20 x 10-4) and metal ion (4 x 10-4 M) =A+R+M

 

The ionic strength of all the solution was maintained constant (0.1 M) by adding appropriate amount of NaClO4 solution at 298K. The total volume of the test solution was made up to 50 ml . All the titrations were carried out in 60 % ethanol-water mixture by addition of sodium hydroxide. The graph of volume of alkali (NaOH) against pH was plotted.

Table 1-pH Titration of Diazepam in the presence of Metal ion Fe (III),Cd(II),Co(II),Ni(II),Zn(II) 60 % EtOH –Water Medium.

Volume of NaOH

pH Of Solution

HNO3 (A)

HNO3+R

HNO3+R+

Fe(III)

HNO3+R+

Cd(II)

HNO3+R+

Co(II)

HNO3+R

+Ni(II)

HNO3+R+

Zn(II)

0.00

2.23

2.24

2.23

2.23

2.22

2.22

2.18

0.60

2.27

2.29

2.27

2.27

2.25

2.24

2.25

1.20

2.35

2.35

2.32

2.32

2.30

2.30

2.32

1.80

2.45

2.43

2.40

2.40

2.38

2.36

2.39

2.40

2.50

2.50

2.50

2.50

2.49

2.45

2.49

2.80

2.56

2.60

2.58

2.50

2.56

2.56

2.58

3.20

2.70

2.69

2.68

2.58

2.67

2.70

2.67

3.60

2.80

2.80

2.49

2.68

2.75

2.95

2.80

4.00

3.05

3.00

2.95

2.79

3.00

3.00

2.98

4.10

3.10

3.04

3.00

3.00

3.03

3.08

3.03

4.20

3.20

3.13

3.07

3.04

3.08

3.13

3.10

4.25

3.22

3.18

.011

3.08

3.11

3.16

3.13

4.30

3.25

3.22

3.15

3.12

3.15

3.20

3.18

4.35

3.32

3.27

3.20

3.16

3.22

3.26

3.22

4.40

3.40

3.30

3.23

3.21

3.26

3.32

3.26

4.45

3.45

3.37

3.27

3.26

3.32

3.39

3.32

4.50

3.53

3.44

3.32

3.31

3.37

3.46

3.37

4.55

3.61

3.53

3.36

3.35

3.46

3.54

3.43

4.60

3.72

3.63

3.41

3.45

3.53

3.66

3.55

4.65

3.88

3.70

3.48

3.50

3.62

3.77

3.64

4.70

4.10

3.92

3.55

3.59

3.75

4.10

3.76

4.75

4.60

4.20

3.65

3.65

3.90

4.45

3.94

4.80

6.40

4.70

3.80

3.88

4.18

5.45

4.20

4.85

7.30

6.40

3.88

4.11

4.80

6.65

4.77

4.90

8.40

7.25

4.25

4.59

6.55

7.25

6.47

4.95

11.55

8.12

4.38

6.20

7.46

7.70

6.92

5.00

11.80

10.80

5.20

7.20

8.05

8.20

7.00

5.05

12.00

11.10

 

 

8.25

 

7.28

5.10

 

11.30

 

 

 

 

 

Figure 1-4  shows graph of pH vs  volume of NaOH of Diazepam  and  metal ions.

Fig.1

 

Fig.2

 

Fig.3

 

Fig.4

Form above Figure 1-4 shows graph of pH vs.  volume of NaOH of Diazepam  and  metal ions which is V1, V2 are measure.                                         

 

Plot of nA vs pH for Diazepam in 60 % EtOH –Water  Medium at 0.1 M ionic Strength.

 

Fig.5

 

Table 2.pK and Log K of Metal chelate of Diazepam in EtOH –Water Medium at different ionic Strength.

% (v/v)

Ionic Strength

0.1M

0.25M

0.5M

pK1

3.30

3.25

3.15

pK2

11.48

11.38

11.25

Fe(III)

11.10

2.76

11.00

2.70

10.85

2.65

CdII)

9.75

2.35

9.65

-

9.50-

Co(II)

9.75

3.01

9.60

9.55

-

Ni(II)

11.26

-

11.14

2.65

10.96

2.50

Zn(II)

11.25

2.64

11.15

2.60

10.84

2.55

 

Table 3: Stepwise stability constant Diazepam in EtOH at 298 k  at 0.1 M ionic strength

%→

60%

Metal↓

Log K1

Log K2

Fe(III)

11.40

3.80

CdII)

11.34

3.33

Co(II)

11.37

4.05

Ni(II)

11.50

4.18

Zn(II)

11.56

4.28

 

Table 4: Activation Parameter of  Diazepam in EtOH at 298 k  at 0.1 M ionic strength

1:1

Fe(III)

65.04

1.40

0.213

CdII)

63.33

2.63

0.206

Co(II)

63.85

2.98

0.204

Ni(II)

64.70

2.10

0.210

Zn(II)

63.80

1.05

0.210

 

RESULTS AND DISCUSSION:

Proton-ligand stability constants:

The binary complex of Diazepam [ 7- chloro -1- methyl -5- phenyl -3H-1,4- benzodiazepine -2- one)ware studied in aquo-organic media in presence of Fe(III),Cd(II), Co(II), Ni(II), Zn(II) metal ions by pH metric measurements  at various temperature at 0.1 M ionic strength .The Diazepam [ 7- chloro -1- methyl -5- phenyl -3H-1,4- benzodiazepine -2- one Diazepam [ 7- chloro -1- methyl -5- phenyl -3H-1,4- benzodiazepine -2- one was monobasic acids having only one dissociable H+ ion from OH group. It can therefore, be represented as HL

 

k1

                   HL  H+ + L-

 

Proton ligand stability constant kiH is represented as;

                            H

 

The proton-ligand formation number ( nA ) were calculated by Irving and Rossotti expression.

 

 

Where,

V0             = Initial volume of solution

E0              = Initial concentration of free acid

T              = Concentration of ligand

Γ              = Number of replaceable  protons

N              = Avagadros Number

 

(V2 – V1) = Volume of alkali  N ,consumed by acid and ligand on the given . 5).

 

The experimental result obtained were utilized for evaluation of dissociation and stability constant. the chelate of the sedative drugs having analgesic tranquilizing , hypnotic ,tranquillizing and anticonvulsant activity were identified in solution. The observed pK and Log K for diazepam in EtOH –Water Medium are shown in Table 3. It Would be seen from above Table 4 that the stability constant increase with increase in percentage of the solvents, and also decrease with increase in ionic strength.   It could be seen from table 5 ∆G and ∆H were found to be highly negative, while ∆S valve were to be positive .Science the Log K are found to be very high, there must be strong interaction between the metal ion and the chelating reagents. The positive entropy valve were accounted towards the interaction with positive and negative ions.,

 

ACKNOWLEDGEMENTS:

We are very much thankful to Late Dr. V.G. Dongra Ex Professor, Department of Chemistry, Mumbai University, Mumbai and Late Dr. V. Kamble, Deputy Director, Forensic Lab., Aurangabad for their valuable guidance and supports for research work.

 

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Received on 06.08.2014         Modified on 22.08.2014

Accepted on 26.08.2014         © AJRC All right reserved

Asian J. Research Chem. 7(8): August 2014; Page 722-725