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Chapter 4

Conversion of the prepared compound into surfactant

77

4.1 Introduction to surfactant

Surfactants are having wide array of pharmaceutical applications. Day

by day demand of surfactants is increasing drastically due to its recent

prevelance in developing formulations. Owing to the higher water

solubility of one of the most widely used surfactant (sodium lauryl

sulphate), interest have recently arisen to synthesize a compound

bearing quinazoline nucleus with lauryl group. Synthesized compound

when analyzed by QSAR exhibits the low water solubility which is a

major impediment in achieving low MIC values. Thus only few

compounds having higher antibacterial activity were transformed into

surfactant. These synthesized compounds can be further screened for

antimicrobial activity. The synthesized surfactant was further evaluvated

for physicochemical properties like surface tension, cloud point, foaming

height, wetting time and emulsification power which was used to improve

the stability of the whole system.

4.2 Experimental Work

4.2.1 Development of QD surfactant

On the basis of antibacterial activity, we emphasized on the synthesis of

new compounds such as QD-6 and QD-7 with improved water solubility.

However due to the poor yield and lack of knowledge regarding the

synthesis of QD-7, QD-6 were selected for further synthesis. Additionally

the structure of compound was deterimed by TLC, IR, Mass and NMR.

78

A solution of compound QD-6 (0.01M) and Sodium Lauryl

Sulphate (0.01 mole) were refluxed 12 hrs in boiling Ethanol (20ml) in

the presence of potassium hydroxide (Scheme 2). Then mixtures were

concentrated on water bath and finally recrystallized by ethanol. Yield:

45%; UV λmax: 245 nm; Rf: 0.77 (Pet.ether: ethyl acetate: methanol);

Mpt: 1600C

N

N

O

N

F

SO4C12H25

N

N

O

N

F

F

NaSO4C12H25 KOH

Ehanol

Reflux for 12 hrs

Surfactant3-{[bis(4-fluorophenyl)methylidene]amino}-2-phenylquinazolin-4(3H)-one

Scheme 2: Synthesis of surfactant

4.2.2 Determination of physical properties

4.2.2.1 Surface tension

Surface tension was measured using Stalgmometer with 0.1 % (w/v)

aqueous solution of surfactant at room temperature (25oC) {1}.

4.2.2.2 Cloud point

This can be envisaged by gradually heating 0.1 % (w/v) solution in a

controlled temperature bath and recording the time at which the clear or

nearly clear solutions became definitely turbid. The reproducibility of this

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temperature was checked by cooling the solutions until they become

clear again {2}.

4.2.2.3 Wetting time

Wetting time was determined by immersing a sample of cotton fabric in a

0.1 % (w/v) aqueous solution of surfactant {3}. So, they can find a wide

application in textile industry

4.2.2.4 Foaming properties

This method follows traditional method in which a 25 ml solution 0.1%

(w/v) was shaken vigorously for 10 seconds in a 100 ml glass stopper,

graduated cylinder, at 250C. The solution was allowed to stand for 30

seconds, and the foam height was measured {4}.

4.2.2.5 Emulsification stability

10 ml of a 0.1% (w/v) aqueous solution of surfactant and 5 ml of liquid

paraffin at 400C was prepared for Emulsification stability. The

emulsifying property was determined by the time it took for an aqueous

volume separating from the emulsion layer to reach 9 ml. counting from

the moment the shaking was stopped {5}.

4.2.2.6 Determination of Critical Micelle Concentration (CMC)

The critical micelle concentration of surfactant was determined by

plotting surface tension values against the concentration of each

surfactant.

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4.3 Biological activity

The antimicrobial activities of some synthesized compounds were

determined in vitro using the Cup plate method {6}. Different species of

Gram positive and Gram negative bacteria were used for screening

antibacterial activity. The compound in question was dissolved in

Dimethyl Formamide (DMF) and different concentrations were chosen

(10-250 μg/ml). Fresh broth culture of Gram positive and Gram negative

bacteria were used to inoculated uniform Agar plates. The discs were

incubated at 280C for 24 h. The formed zones of inhibition was measured

in mm scale.

4.4 Result and Discussion

Prior to this study () various related wok was done to improve the anti-

microbila activity of a compound by introducing new molecular

parameter such as heteroatoms {7}, chemical functions {8–11}, aromatics

{12} or non aromatic cyclic substituents {13}. In our study attempts were

made to synthesize a whole system wich acts as a drug as well as

surfactant.

4.4.1 Physicochemical properties

The investigation of the surface active properties of the compound has

been done in the neutral medium (pH 7.3), at a concentration of 0.1 %

(w/v) and 250C. These types of surfactants are especially interesting

81

because they are not the most common. Therefore the traditional

procedure was used to follow up the properties.

4.4.1.1 Surface tension

The surface tension of prepared compound is shown in Table 4.1. This

compound has low surface activity due to electrostatic repulsion between

ions in molecule.

4.4.1.2 Cloud point

An understanding of the property called cloud point is a very important

factor. This property can be used in various applications of surfactants

in aqueous system. The cloud point of the prepared surfactant is less

than 1000C because of presence of long alkyl chain. Its hydrophobicity

increase with increase in the alkyl chain.

4.4.1.3 Wetting time

For the prepared compound, at all points of the investigation, the

synthesized surfactant was efficient wetting agent.

4.4.1.4 Foam power

Foam power was also investigated for surfactant and is generally rated as

foamy. The foam height of the prepared surfactant was measured. A low

foaming height has an application in the dyeing industry {15}.

4.4.1.5 Emulsion stability

Studies are still being carried out on the use of surfactant in emulsion

formation which is of immense importance to technological development.

It was proven that the emulsifying stability of the prepared surfactant

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containing heterocyclic nucleus exhibit moderate emulsifying properties.

The results might lead to the application of the surfactant of choice in

the manufacturing of cosmetics.

Table 4.1 Physical properties of Surfactant

PHYSICAL PROPERTIES VALUE

Color White crystal

pH 7.3

CMC 0.4 %

Surface Tension (0.3%) 27 (dyne/cm)

Foam Height (0.1%) 3 cm

Emulsion Stability (0.1%) 25 min

Wetting Time 10 sec

Cloud point 600C

Log P 3.12

4.4.1.6 Critical Micelle Concentration

The surface tension decreases from its original value to a lower constant

one, which is attained at the CMC. The value of CMC for drug was found

to be 0.4 % (Fig. 4.1). Hydrophobic group is an important driving force in

micellization. Increase in hydrophobicity, decrease in CMC value. The

number of carbon atoms was found to be a determining factor in the

values of CMC {16}.

83

0

10

20

30

40

50

60

70

0.00% 0.10% 0.20% 0.30% 0.40% 0.50% 0.60% 0.70%

conc.

surf

ace

tens

ion(

dyne

/cm

)

Series1

Figure 4.1 Effect of varying the concentration of drug on the surface

tension

4.5 Biological activity

Most of the antibiotics act by specific mechanism by showing

intereferance in the metabolic processes of micro organism. By keeping

this in view we here synthesized a compound which acts through specific

mechanism. Structure activity relationship of the designed compound is

basically depends on two factors.

The presence of heterocyclic moiety and the length of aliphatic chain

regulate the anti-microbial activity of synthesized product. Among the

two factors Carbon chain length plays a greater role by exhihibiting

absorption at the interface of cell membrane, which is responsible for the

decrease in permeability of cell leading to altered biological process and

cause cell death.

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Table 4.2 Zone of inhibition with different microbes

Micro-organism Zone of Inhibition

(mm)*

Ciprofloxacin DMF

S.aureus6571 25 25 -------

B.subtilisATCC6051 21 26 --------

S.dysenteriaeK12 29 29 ---------

E.coli6 20 22 --------

*Conc: 125µg/ml

0

5

10

15

20

25

30

35

S.aureus

B.subtilis

S.dysenteria

eE.co

li

zone

of in

hibi

tion

(mm

)

Zone of Inhibition(mm)*Ciprofloxacin

Figure 4.2 Activity of compound for different microbes

85

4.6 Conclusion

Our previous work lead to the conclusion that prepared surfactant

constituting hydrophilic (sulfate ion) and hydrophobic (long alkyl chain)

properties in a single frame work, demonstrates good emulsifing or

surface active properties which can be used as a topical agent as well as

anti-bacterial formulations.

86

4.7 References

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1040 (1963).

2. Wiel J. K., Smith F. D., Stirton A. J and Bistine R. G. J. Am. Oil. Chem.

Soc., 40, 538-541 (1963).

3. Draves C. Z. and Clarkso R. J. Am. Dye Stuff Reporter, 20, 201 (1931).

4. El-Sukkary M. A., El-Sawy A. A. and El-Dib Hungarian J. Ind.Chem.

15, 317-320 (1987).

5. Takeshi H. Bull. Chem. Soc., 43, 2236-2239 (1970).

6. Rosen M. J. 2th Ed., John Wiley & Sons, New York, 286-294 (1989).

7. Skrzypcak A, Brycki B, Mirska I and Pernak J. Eur J Med Chem, 32,

661–668 (1997).

8. Diz M., Manresa A., Pinazo A., Erra P. and Infante M.R. J Chem Soc

Perkin Trans, 2, 1871–1876 (1994).

9. Pavlikova-Moricka M., Lacko Y., Devinsky F. and Mlynarcik D. Collect

Czech Chem Commun, 60, 1213–1227 (1995).

10. Pavlikova-Moricka M., Lacko Y., Devinsky F., Masarova L and

Mlynarcik D. Folia Microbiol, 39, 176–180 (1994).

11. Bell J. P., Doyle A. K., Farmer R. F., Gadberry F. J., Lucas D. and

Mirviss R. B. International Patent Number WO/1999/043212 (1999).

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(1999).

13. Kim Y.H., Choi H. M. and Yoon J. H. Text Res J , 68, 428–434 (1998).

87

14. Mao J European Patent Number EP0937912A2 (1999).

15. Somaya A. R., Eissa A. M. F, Nadia A. and Ahmad M. N. J. Pharm.

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16. Mohamed M. Z. and Mohamed A. S. J Surfact Deterg, 12, 345–

349(2009).