Spectroscopic and Thermal Characterization of Gliclazide, Glibenclamide and Glimeperide Complexes with Transition and Inner Transition Metals

Introduction

Gliclazide, Glibenclamide and Glimeperide, are bi substituted urea derivatives can exist in keto and enolic form  when dissolved in an organic solvent and react with various metal ions to form intensely coloured metal complexes that provide the basis for their use as a sensitive reagent.

The thermal degradation study of complexes has become a subject of recent interest. It is important property of complexes, which decides the thermal stability and processability of the complexes. The study of thermal behaviour of complexes in air at different temperature provides important information about its practical applicability.

Iqbal S.A. et.a1^l., (2005) synthesized the metal complexes of gliclazide characterized by FTIR, elemental analysis and TGA-DTG parameters. The thermal analysis (TGA) was performed at the heating rate of 10°C/min. in nitrogen atmosphere.

Wilma Cyril et.al²., (2011) studied kinetics and Thermal decomposition of Cu(II) complex of of hydroxyl quinoline-5-sulphonic acid

Thermal data have been analyzed by Freeman Carroll and Sharp-Wentworth method.

Thermal analysis (TGA and DTG) is a typical analytical technique to describe the relationship between physico-chemical changes and temperature.^1-2 In order to synthesize complexes having practical applications. There is a need to investigate the effect of heat on complexes in order to establish thermal stability.

Iqbal and coworkers^3-4 have synthesized and characterized complexes of tolbutamide and glibenclamide by FTIR, elemental analysis and TGA-DTA technique.

Thermal studies of complexes were carried out to determine their mode of decomposition, the activation energy (Ea), order of reaction (n), frequency factor(Z), entropy change (S), Free energy (ΔF) and apparent entropy change (*S). Thermal decomposition curves were discussed with careful attention of minute details. The freeman Carroll and Sharp-Wentworth methods have been used to calculate thermal activation energy and thermal stability.

However, very little work has been carried out on the synthesis and characterization and thermal degradation studies of the metal complexes of gliclazide, glibenclamide and glimeperide.

Hence in this work we prepare complexes of Cu(II), Co(II), Hg(II) and La(II) transition and inner transition metals with gliclazide, glibenclamide and glimeperide drug molecule. The solid complexes were characterized using different physico-chemical methods, like elemental analysis (C, H, N, S and metal content), IR and thermal analysis (TGA and DTG)

Experimental

Materials and Reagents

All chemicals used were of analytical reagent grade (A.R.) and of highest purity. They included gliclazide, glibenclamide and glimeperide (Zim laboratories, Nagpur), Copper(II) Chloride , Lanthanum(II) Chloride heptahydrate (Hi media Lab, Mumbai) organic solvents used are absolute ethyl alcohol, DMF. These solvents were spectroscopic pure from BDH, hydrogen peroxide, hydrochloric and nitric acid (E.Merck) were used. De-ionized water was used in all preparations.

Instruments

Molar conductance of solid complexes in DMF was measured using Systronics conductivity meter, elemental microanalyses of the isolated solid complexes for C,H,N were performed at CDRI, Lucknow, using (HMS-932CLECO) Vario elemental analyzers. Infrared spectra were recorded on Perkin-Elmer, FTIR type 1650 spectrophotometer in wave number 400-4000 cm^-1. The spectra were recorded as KBr pellets.

The thermogravimetric (TG and DTG) analysis was carried out in dynamic nitrogen atmosphere (20 ml.min^-1) with a heating rate of 10°C/min. using shimatzu TGA-50H Thermal Analyzer at IIT Bombay (Mumbai) Electronic spectra recorded at Qualichem Laboratory, Nagpur.

2.3 Synthesis Of Metal Complexes

Metal complexes or synthesized by adding metal salt solution in appropriate solvent to the solution of the ligand. The mixture was refluxed for 3-4 hours. Then the precipitate of metal complexes was obtained. It was filtered, washed and dried in vacuum desiccators.

All selected metals forms 1:2 complexes with gliclazide, glibenclamide and glimeperide, were confirmed by Jobs method of continuous variation⁵  as modified by Turner and Anderson⁶.

Estimation Of  Metals In Complexes

An accurately weighed portion of the different complexes ranged from 10 to 30 mg was placed in Kjeldhal flask. A measured volume of concentrated nitric acid ranged from 5 to 10 ml was added initially to the powdered complexes to start the fast wet oxidation digestion. This mixture had been digested with some drops of H₂O₂ solution using a gradual heating. This treatment was conducted until most of the powdered complexes were dissolved and the remaining solution had the colour of the corresponding metal salt. This solution was then diluted upto a 50 ml. with distilled water and the metal content was determined by titration against standard EDTA solution at a suitable pH value using the suitable indicator.

Results and Discussion

Composition And Structures Of Metal Complexes.

The isolated solid complexes of Cu(II), Co(II) ions with GLZ ligand, and GLB ligand while Hg(II), La(II) ions with GLM ligands were subjected to elemental analysis (C, H, N, S. and metal content), I.R., Molar conductance, thermal analysis (TG and DTG) to support the  tentative structure. The results of elemental analysis listed in table (1) suggest the formulae [Co(GLZ)₂]2H₂O, [Cu(GLZ)₂], [Co(GLB)₂]2H₂O, [Cu(GLB)₂], [Hg(GLM)₂]2H₂O and [La(GLM)₂]2H₂O for respective complexes.

TABLE 1: ANALYTICAL AND PHYSICAL DATA OF GLICLAZIDE, GLIBENCLAMIDE,AND GLIMEPERIDE METAL COMPLEXES.

Complexes	Colour	% (Yield)	m.p. (°C)	Elemental Analysis					Molar conductance ‘Am’ (Ω-1Mole-1cm-1)
				C	H	N	S	M
[CC          (C15H20N3O3S)2Cu	Blue	74	189	49.67 (46.25)	5.12 (5.65)	8.12 (11.86)	6.05 (9.14)	7.18 (8.61)	13.18
(C15H20N3O3S)2Co.2H2O	Pink	70	195	48.91 (45.25)	5.42 (5.00)	9.10 (10.50)	6.66 (8.00)	6.20 (6.75	18.56
(C23H27O5ClN3S)2Cu	Blue	76	205	48.41 (52.62)	4.80 (5.15)	7.42 (8.00)	5.62 (6.10)	5.43 (5.81)	24.51
(C23H27O5ClN3S)2Co2H2O	Blue	75	188	49.40 (51.11)	5.33 (5.83)	6.91 (7.84)	6.32 (6.32)	5.00 (5.00)	18.88
(C24H33N4O6S)2Hg	White	65	189	49.08 (50.47)	4.02 (5.57)	8.02 (9.81)	6.18 (6.41)	12.46 (14.08)	22.1
(C24H33N4O6S)2La2H2O	White	64	188	50.12 (50.91)	4.92 (5.50)	9.26 (9.90)	7.23 (6.99)	9.01 (10.07)	30.10

 

Molar Conductance

The complexes were dissolved in DMF and the molar conductivities of 10^-3M of their solutions at 298 K are measured. It is concluded from results listed in table (1) that the complexes are found to have molar conductance values of 13.18 to 30.15Ω^-1 mole^-1 am^-2 indicating that all the metal complexes are non-electrolytes.

Ir Spectral Studies

The IR data of the spectra of GLZ, GLB, GLM ligand and there complexes are listed in table (2). The IR spectra of the complexes are compared with those of the free GLZ, GLB, GLM ligands in order to determine the coordination sites that may be involved in complexation^7-14 The tautomeric equilibrium depends on the extent of conjugation, nature and position of the substituent, polarity of the solvent etc.

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