Interferometric Study of S-Substituted Triazinothiocarbamides in 60% Dioxane Water Mixture

Interferometric Study of S-Substituted Triazinothiocarbamides in 60% Dioxane Water Mixture

D. T. Tayadea, A. M. Kshirsagarb*

D.T.Tayadea, Associate Professor,

a Department of Chemistry,

Government Institute of Science and Humanities, Amravati,

S.G.B. Amravati University, (M.S.), India.

A. M. Kshirsagarb*

Assistant Professor

b*Department of Chemistry,

Alamuri Ratnamala Institute of Engineering & Technology, Sapgaon, Taluka-Shahapur, Dist.-Thane (M.S.),

Mumbai University (M.S.), India

Abstract

S-triazine and thiocarbamide group containing drug create their own identity in the drug, pharmaceutical and medicinal sciences in last four decades. Hence, density and sound velocity of some biologically important substituted triazinothiocarbamides were measured at 30°C in 60% dioxane-water mixture. The interferometric measurements of recently synthesized drugs have been carried out for solutions of 1-(4-hydroxy-6- methyl)-S-triazino-3-phenylthiocarbamide(L1),

1-(4-hydroxy-6-methyl)-S-triazino-3-

ethylthiocarbamide (L2) and 1-(4-hydroxy-6- methyl)-S-triazino-3-methylthiocarbamide (L3) at various concentrations. This data have been used to determine various acoustic / thermodynamic parameters viz. adiabatic compressibility (), apparent molal compressibility (k), apparent molal volume (v), intermolecular free length (Lf), relative association (RA) and specific acoustic impedance (Z). These properties are used to interpret weak molecular solute-solvent, solute-

solute interactions in the system. The data and result obtained during this investigation gave detail information regarding drug absorption, transmission, activity and effect of these drugs which is base of pharmacokinetics and pharmacodynamics of any drug. Taking all these things into consideration this research work was carried out. These properties are used to interpret weak molecular solute-solvent, solute-solute interactions in the system.

Keywords

1-(4-Hydroxy-6-methyl)-S-triazino-3- substitutedthiocarbamides; Dioxane-water mixture; Interferometric measurements; Pharmacokinetics; Pharmacodynamics.

1. Introduction

   Most of the modern drugs contain heterocyclic nucleus [1,2]. The S-triazino compounds initiated the new branches of development in the medicinal [3,4], pharmaceutical, agricultural and biochemical fields [7-9]. The successful application of acoustic methods to physiochemical interactions of solution becomes possible after the development of adequate theoretical approaches and methods for precise ultrasonic velocity measurements in small volumes of liquids [10-12]. Most of the information procured from ultrasonic study of fluids is confined to the determination of hydration number and compressibility [13-15]. In the basic sciences, these waves are used to provide information on the behaviour of microscopic particle of matter [16]. The use of ultrasound was proved to be useful probe for generating more information on oregano metallic chemistry, biotechnology, polymerization medicinal use [17-19].

   While studying the pharmacokinetics and pharmacodynamics of any drug the interferometric measurements play an important role in medicinal and drug chemistry [20-22]. The result obtained during this investigation directly through light on the dipole association of compound, intermolecular attraction between solute and solvent, dielectric constant of medium, polarizability, and mutual compensation of dipoles and useful for transmission, stability, activity and effect of drug.

   Hence we were studied the potency of recently synthesized drugs in G.I.S.H., Amravati laboratory in the month of May 2012. The interferometric measurements of 1-(4-hydroxy-6- methyl)-S-triazino-3-phenylthiocarbamide (L1), 1- (4-hydroxy-6-methyl)-S-triazino-3- ethylthiocarbamide (L2), 1-(4-hydroxy-6-methyl)- S-triazino-3-methylthiocarbamides (L3) were studied in 60% dioxane water mixture. S-triazino and thiocarbamido nucleus containing drugs create

   its own identity and significance in drug, pharmaceutical and agricultural chemistry [23-30].

2. Experimental

   1. Materials

      1-(4-Hydroxy-6-methyl)-S-triazino-3- phenylthiocarbamide(L1), 1-(4-hydroxy-6- methyl)-S-triazino-3-ethylthiocarbamid (L2), 1- (4-hydroxy-6-methyl)-S-triazino-3- methylthiocarbamide (L3) were synthesized which were used as ligand [31]. The general structures of substituted thiocarbamides as shown in Fig.1. All the solutions of ligand were prepared fresh in the present investigation.

   2. Methods

      Carbon dioxide free double distilled water was used. Extra pure (E. Merck) dioxane was further purified by the prescribed procedure [31] and used for preparation of ligand solutions. The densities of the solutions were determined by a bicapillary Pyknometer (±0.2%). Weighing was made on electronic balance, made by Mechaniki Zaktady Precyzyjnej Gdansk Balance, made in Poland (±0.001 gm). A special thermostatic arrangement was done for density.

      Single crystal interferometer (Mittal Enterprises, Model MX-3) with accuracy ±0.03% and frequency 1 MHz was used in the present work. The working of the ultrasonic interferometer [32, 33] was checked by measuring ultrasonic velocity of pure water at 30°C. The measured value is in good agreement with literature value 1510 check value ms-1.as shown in Table No 1. The ultrasonic velocity was calculated for all three ligands the concentration of ligands at various concentration at 30°C in 60% dioxane- water mixture. The molecular interactions were studied with solutes, the effect of these specially related to protic-aprotic nature of solvent, polarity- non polarity of solvent and hydrogen boding in solvent, dielectric constant, density, viscosity and

      surface tension of solvent on solute-solvent, ion- solvent and ion-ion interactions in this investigation.

      1. Data analysis:

         Various acoustic properties were calculated by using following equations,

         1. Adiabatic Compressibility ()

            = 1/ Vs2d 1

         2. Apparent Molar Compressibility (K)

            K = [1000 (sd0 0ds) / mdsd0] + ((sM/ds) 2

         3. Intermolecular Free Length (Lf)

            Lf = K. (s)1/2 3

         4. Relative association (RA)

            RA = ds /d0 [V0/VS]1/3 4

         5. Specific Acoustic Impedance (Z)

            Z = Vs ds 5

         6. Apparent Molar Volume (v)

      V = [1000(d0- ds) / md0ds]+(M/ ds)6

      Where,

      d0 = density of pure solvent ds = density of solution

      m = molality of solution

      M = molecular weight of solute

      0 = adiabatic compressibility of pure solvent and

      s = adiabatic compressibility of solution Lf = Intermolecular Free Length

      K = Jacobsons constant

      V0 = ultrasonic velocities in a solvent Vs = ultrasonic velocity of solution M = molecular weight of solute

      m = molality of solution

3. Result

   An addition of polar solute having a partial positive charge on hydrogen atom, there is every likely hood that there can be a weak interactions

   between this positive charge and negative charge on oxygen atom (due to electro negativity) of dioxane. This weak interaction of the wonder walls forces is expected to introduce the structuredness in the solution i.e. specific arrangement of dioxane molecule may be occurring due to attached solute molecule. Thus, spaces may be created making the solution more compressible as it appears from the higher apparent molar compressibility value in dioxane solvent. Using the values in Tble no 1 and 2, we can calculated the values of all acoustic parameter using the equation 1 to 6 which are shown in Table No. 3 for L1, L2 and L3. The adiabatic compressibility shows the increase association of molecules by lower value. Whereas, apparent molar compressibility also shows the increase association but at the same time the structuredness of the solution by higher

   K values. It is also observed that positive values of K for ligands indicates electro static force in the vicinity of ions [34, 35].

   From the difference in trends in two compressibilitys, adiabatic & apparent molar, it may be predicted that adiabatic compressibility can detect gross changes in interactions but minute changes due to change in structure may only be noticed by apparent molar compressibility (K). It is clear from the graphs shown in Fig 7, Fig. 8, Fig 9. Thus, the structure of solute and the number of atoms present in it will have direct effect on K value. The parameters of solvents which directly affect the values of are due to high density of dioxane as compare to protic nature, polarity, high dielectric constant (24.6).

   Similarly on increasing the concentration of ligands, decreases continuously. The increased concentration of solute will require more and more number of solvent molecules to dissolve it resulting in breaking the electrostriction/ structuredness of solvent consequently decreasing the compressibility. Thus in both the system solute-solvent and solvent-solvent interactions are

   involved which are reflected in the compressibility values.

   The conventional approach based on compressibility is both useful and fundamental; In fact it constitutes an additional probe for studying molecular interactions. Specific acoustic impedance is the complex ration of the effective sound pressure at a point to the effective particle velocity at that point [18].

   In case of dioxane, because of its non- polar nature, the compact packing of molecules is already there and when polar solute is added because of its association again free space decreases. Therefore, the Lf values in dioxane must be smaller. When the metal ions are added, the polar-polar associations still increases and the Lf decreases Ultrasonic velocity depends upon intermolecular free length Lf with decrease in free length velocity increases.

   Relative association RA is an acoustic property of understanding interaction, which is influenced by two opposing factors,

   • Breaking of solvent structure on addition of solute to it satisfy decreases in values when

     concentration of ligand L1, L2, L3 in 60% dioxane- water mixture increases for 300C. It was observed that, the value of RA of ligand L1 get affected by the resonance stabilization in benzene while the

     value of ligand L2 get affected by the methylene group attached.

   • Solvation of solute that is simultaneously present by the free solvent molecules. It was clearly observed that the high concentration of solute. The values of RA at high percentage of dioxane are very well explained by second factor.

   In general it is observed that, the value of ,

   v, Lf of ligand L1, L2, L3 clearly indicates effects of resonance stabilization in benzene ring which is a substituent on thiocarbamido nucleus as shown in Fig 4, Fig 5, Fig 6. At the same time bulkier nature of ethyl group may also interfere during these interactions. This clearly indicates that not

   only the bulkier nature and nature of ligand will affect but the molecular weight of solute is also one of an important factor which directly affects the solute-solvent interaction. The change in values of Lf may be due to stronger interaction between ions and solvent molecules at that particular percentage combination of dioxane- water mixture decrease in Lf values indicated weaker interaction between ions and solvent molecules. The intermolecular free length goes on decreasing with increase in concentration of solute indicates decrease in free space between the molecules because of stronger solute-solvent interaction which is in a agreement with on observed value of .

4. Discussion

   These factors may directly interfere the solute-solvent interaction. Measurement of ultrasonic velocity is the best tool to investigate solute-solvent, solute-solute and ion-solvent interactions. Therefore, in last four decades ultrasonic interferometric study created its own identity for determining solute-solvent interactions. By this study , v, K, Lf, RA, Z, etc. acoustic properties were determined which explain how these interactions occur and responsible for breaking and making of the structure in the solution. So in the present work these acoustic parameters were studied for newly synthesized ligands, which were used as solutes.

   To study the pharmacokinetics and pharmacodynamics of any drug relating these ligands, the acoustic parameters of dioxane helps to find out the property of solvent interfere in breaking and making of structure of solvent. From this study it is clear that properties, which are directly or indirectly responsible for these are protic-aprotic nature of solvents, dielectric constant, polarity, density, tendency of forming hydrogen bonding, surface tension, viscosity of solvent, bulkier nature, resonance, reactivity of

   group, size and molecular weight of ligand. All these parameters plays important role in pharmaceutical and medicinal drug chemistry.

   From this study it can be concluded that interferometric technique requires minimum efforts, solutions and is somewhat a direct method and has its own identity and significance in material sciences, which can give idea about effectiveness of solvent. By knowing these parameters the selection of solvent during

   synthesis in organic and coordination chemistry can be predicted. This study is an important basic tool for pharmaceutical, medicinal and biochemical sciences which directly focus on drug activity and drug effect at primary level and then onwards only the characteristics of drug can be decided. This study gave detail information regarding pharmacokinetics and pharmacodynamics of drug.

5. Observations and Calculations

   Table No.1: Average Ultrasonic Velocity of Water at 30C

   Sr. No.	No. of Rotation of Screw	Micrometer Reading (mm)	Difference Between Reading (mm)	Distance Travelled By Screw in One Rotation	Average Ultrasonic Velocity (m/sec)
   1	5	26.7843	3.7654	1.50616	1501.2914
   2	10	23.0189	3.7584	1.50336
   3	15	19.2605	3.7544	1.50176
   4	20	15.5061	3.7002	1.48008
   5	25	11.8059	3.7468	1.49872
   6	30	8.0591	3.7583	1.50332
   7	35	4.3008	3.7891	1.51564
   8	40	0.5117		10.50904

   Table No.2: Average Ultrasonic Velocity of Dioxane at 30C (0)

   D-W %	Sr. No.	No. of Rotation of Screw	Micrometer Reading (mm)	Difference Between Reading	Distance Travelled By Screw in One Rotation	Average Ultrasonic Velocity (v0) (m/sec)	Density (d0) (Kg.m-3)	0 x 10-10 (Pa-1)
   60	1	5	20.0328	3.7055	1.4822	1477.72	1026.2	4.4625
   	2	10	16.3273	3.7255	1.4902
   	3	15	12.6018	3.6907	1.4763
   	4	20	8.9111	3.6555	1.4622
   	5	25	5.2556
   					5.9109

   Table No.3: Acoustic Parameters at Different Concentration of Ligand L1, L2, L3 at 30C

   Ligand	Conc. C (Mole/lit)	Average Ultrasonic Velocity V (m/sec )	Density ds (Kg.m-3)	sx10-10 (pa-1)	V (m3mol-1)	k x10-10	Lf (A0)	RA	Z * 104 (Kgm-2sec-1)
   L1	0.1	1683.89	1023.6	3.4454	0.2797	-8.9475	0.0117	0.9550	172.3630
   	0.075	1582.9	1023.4	3.8998	0.2817	-6.1779	0.0125	0.9747	161.9940
   	0.056	1434.675	1023.1	4.7487	0.2846	6.4420	0.0138	1.0069	146.7816
   	0.042	1286.695	1022.8	5.9055	0.2876	35.4424	0.0153	1.0438	131.6032
   L2	0.1	1583.89	1033.9	3.8554	0.1799	-5.4015	0.0124	0.9845	163.7584
   	0.075	1421.975	1029.4	4.8043	0.2233	5.2410	0.0138	1.0161	146.3781
   	0.056	1278.675	1026.1	5.9606	0.2085	27.3144	0.0154	1.0493	131.2048
   	0.042	1130.175	1021.8	7.6620	0.2504	76.5963	0.0175	1.0888	115.4813
   L3	0.1	1734.53	1036	3.2083	0.0999	-11.9013	0.0113	0.9570	179.6973
   	0.075	1620.3	1033	3.6873	0.1285	-9.6772	0.0121	0.9762	167.3770
   	0.056	1417.525	1029	4.8364	0.1669	7.2126	0.0139	0.9939	156.1533
   	0.042	1356.765	1024	5.3051	0.2153	20.8428	0.0145	1.0267	138.9327

6. Figures

   The Ligands used during investigation are as below,

   Figure-1: L1:

   1-(4-Hydroxy-6-methyl)-S-triazino-3- phenylthicarbamide

7. Graphs

   Plot Between Apparent molar volume (v) Vs concentration (C) for Ligand L1, L2 and L3 at 30C in 60% dioxane- water mixture

   Figure 4 : L1 at 30C for V

   HN C

   S

   N N

   NH Ph

   H3C N OH

   Figure-2: L2:

   1-(4-Hydroxy-6-methyl)-S-triazino-3- ethylthiocarbamide

   HN C

   S

   N N

   NH C2H5

   H3C

   N OH

   Figure 5 : L2 at 30C for V

   Figure-3: L3:

   1-(4-Hydroxy-6-methyl)-S-triazino-3- methylthiocarbamide

   HN C

   S

   N N

   NH CH3

   H3C

   N OH

   Figure 6 : L3 at 30C for V

   Plot between Apparent molar compressibility (k) Vs concentration (C) for Ligand L1, L2 and L3 at 30C in 60% dioxane-water mixture

   Figure 7 : L1 at 30C for K

   Figure 8 : L2 at 30C for K

   Figure 9 : L3 at 30C for K

8. Conclusion

   As at high percentages of dioxane in dioxane-water system indicate the protic nature, polarity, dielectric constant and tendency of formation of hydrogen bonding in solvent in the system decreases. Hence, it may cause decreases values of for L1, L2 and L3.

   Hence from the above discussion, it was clear that bulky substituent on the molecule was not only factor in trend but tautomeric conversion as well as electron donating nature, electron clouds, nature of hetero atom present in compounds and compactness in the molecule will directly hampered results and trends. It means that when the high percentage of dioxane in the solute-solvent interactions

   i.e. interaction of compounds (drugs) and dioxane which may be stabilize the drug activity. This consider as basic study for any drug through the point of medicinal chemistry From this it can be concluded that the drug absorption, drug transmission and drug effect of compounds L1, L2 and L3 is effective at high concentration of dioxane. This study may become a milestone in the drug, medicinal and pharmaceutical chemistry of triazino thiocarbamides.

9. Acknowledgment

   I am very thankful to Dr. D. T. Tayade for checking & giving valuable suggestions in my research papers.

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