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Determination of Stability Constants of Triazole Ligand Carrying Naphthol Group with Heavy Metal Ions in Aqueous Solutions.

Byline: Nurhan GA1/4mrukcA1/4oglu Zekeriyya Bahadir Mirac Ocak and AmmA1/4han Ocak

AbstractInteraction of 4-(2-hydroxy-1-naphthylmethylamino)-3-methyl-5-(4-tolyl)-4H-124-triazole with heavy metal cations such as Cu2+ Co2+ Cd2+ Ni2+ and Pb2+ was investigated by using UV- visible spectrophotometric technique. The complex stability constants (Log AY) were determined in aqueous as well as in methanol: water (1:1) system at 25 0.1C by Buschmann's method and Valeur's methods respectively. The ligand showed good sensitivity for Co2+ with a linear range of210-6M to 310-5M.

Keywords: Triazole; Complex; Stability constant .Introduction

Azole compounds are clinically important antifungal drugs; fluconazole tercanazole voriconazole and posaconazole may be examples for these compounds. They can effectively inhibit the biosynthesis of ergosterol which is the main sterol composition in the fungal cell membrane which needs sterols lacking C-4 methyl groups. The nitrogen of N-4 in triazole compounds binds with the iron of HEM of cytochrome p450 at the molecular level. Thus inhibition of cytochrome p450 is caused to stop the demethylation reaction [1-3]. This mechanism provides antifungal activity of triazole derivatives.

Heterocycles including amino group can be considered as useful intermediates in organic synthesis. The amino group is ready-made nucleophilic center for the synthesis of condensed heterocyclic ring [4-5]. Heterocyclic ligands can be obtained by the condensation reaction of small compounds with suitable reagents [6]. Therefore ester ethoxycarbonylhydrazones are used as starting materials. Many azole derivatives starting from corresponding hydrazones were prepared [7-10].

It is important to investigate metal complexation of triazole compounds in solution because; such type of complexation is present in biological systems. Current efforts are directed toward the investigation of triazole systems which are capable of acting as functional drug mimics and could be used in particular reactions in highly specific manner. Copper (II) aminomethyltriazole shows antiproliferative activity. Similarly aminomethylthioxotriazoline complexes are discussed in literature [11]. Different antiproliferative species are more effective and less toxic anticancer drugs [12-13]. Several 124- triazole compounds having biological activities such as antielastase antiurease antioxidant antibacterial antifungal and antitumor agents have also been synthesized in our laboratories [7-9 14]. The triazole compounds have antimicrobial activity for bacteria and yeast-like fungi [10].

This paper describes the complexation properties of 124-triazole compounds carrying naphthol group with some heavy metal cations by using UV-visible spectrometry. 4-Amino-3-methyl-5-(4-tolyl)-4H-124-triazole was prepared from ethyl N-acetyl-4-methylbenzenecarbohydrazonoate and hydrazine by using the earlier method [10]. The synthesis of certain 4-(2-hydroxy-1- naphthylmethylenamino)-3-methyl-5-(4-tolyl)-4H-124-triazole was carried out by treating the amino compound with 2-hydroxy-1-naphthaldehyde. In early studies the selective reduction of only the imino group of compound 4-alkylidenamino-4H-124-triazole without affecting the rest part of the ring has been reported [9 14-16]. Thus the synthesis of 4-(2-hydroxy-1- naphthylmethylamino)-3-methyl-5-(4-tolyl)-4H-124-triazole was established in good yields by the use of NaBH4 as a selective reducing agent.

ExperimentalChemicals and apparatus

Merck and Fluka were commercial source for all the chemicals that are used in this research. The anhydrous salts Ni(NO3)2.6H2O Pb(NO3)2.2H2O Cu(NO3)2.3H2O Co(NO3)2.6H2O Cd(NO3)2.4H2O had the highest purity available and they were used without further purification in doubly distilled water was used as solvent.

Thermo Scientific Evo 60 spectrophotometer was used to record the absorption spectra of the compound.

MeasurementsBuschmann's methodA spectrophotometric method to determinethe complex stability constants of the ammonium and alkylammonium ions with many of dibenzo crown ethers in aqueous solution was developed by K= [LM ] [L] [Mn+] (2) Buschmann [17]. These compounds are nearly insoluble ligands in aqueous media. Buschmann's method was used to calculate the stability constants of metal complexes with 124-triazoleligand 1 in water. Sufficiently high amounts of the solid ligands were thermostated at 25C and shaken at intervals by adding then into salt solutions (110-3 - 110-2 mol L-1) to ensure the formation of saturated solutions. Before recording their absorption spectra 3 days later they were centrifuged and the resulting clear solutions were filtered through a membrane filter (polycarbonate0.4 m) to remove any undissolved ligand. The maximum absorbance wavelength was used to evaluate complex formation. The stability constants for all metal ions were measured at302 nm.

Valeur's method

Modified Valeur's method was used to determine the complex stability constants in solution [18]. Stock solutions of the ligand and the metal salt were prepared in methanol and water respectively. The absorbance of the solutions containing a fixed concentration of ligand (510-6M) was measured at 206 nm with various saltconcentrations using 1-cm long absorption cell. These concentrations were obtained by appropriate dilution of a 110-4 M stock solution.

Synthesis

Ligand 1 was prepared according to the earlier method [10].

Results and DiscussionTreatment of the experimental data forBuschmann's method

Equation (1) may represent the formation of a 1:1 complex between a ligand L and a cation Mn+.If only the ligand and the complex formed absorb at a given wavelength the experimentally measured absorptivity A' for an optical path length d is given by equation (3).Where ei and e2 are the molar absorptivities of the ligand and complex respectively. The first term in Equation (3) is constant because the salt solution is saturated with the ligand. Consequently:Where [L]sat denotes the solubility of the ligand in the pure solvent. The material balances (5) and (6) can be derivated by using Equation (2). Plotting (A/Ao)-1 as a function of the total salt concentration csalt one gets a straight line with slope b. From this slope the stability constant of the complex formed in solution can be calculated according to Equation (8).The stability constant K is given by slopeb if molar absorptivities are nearly similar and thesolubility of the ligand is low. The correctness of these assumptions has already been showed for some macrocyclic ligands such as benzo and aza crown ethers cryptands and cucurbit[n]urils [19-23].

Treatment of the experimental data for Valeur's method

In order to determine the complex stability constant the ratio of Ao/(Ao-A) was plotted against1/[M] which gave a good straight line. Ao and Aare the absorbance of the free ligand and theabsorbance of the solution containing the cation respectively. The stability constant was calculated from the ratio intercept/slope [18].The complex stability constants of the ligand

Recently Buschmann has shown that the determination of the total concentration of a ligand in a salt solution by using UV-Vis spectroscopy allows the determination of the stability constant of the complex formed in solution. It is not necessary to know definitely the relation between the measured signals and the ligand. The measured signal only has to be directly proportional [17]. The molar absorptivities of the ligand and complex ei and e2 should be nearly the same to apply the method. In the earlier study this approach was used to determine the complex stability constants of some 124-triazole ligands contaning substituted benzylidenamino group and their appropriate wavelength in which the enhancements of absorbance are regular when metal concentration increases. The regular evolution between (A/A0)-1 and csalt for the tested metal ions was observed. Therefore the complex stability constants were calculated for the cations with the triazole ligands.In this study the complex stability constants for Cu2+ Co2+ Cd2+ Ni2+ and Pb2+ cations with a 124-triazole ligand carrying naphthole amino group (Fig. 1) have been reported. Firstly Buschmann's method was used to determine the complex stability constants in aqueous solution. For Cu2+ Co2+ Cd2+ Ni2+ and Pb2+ cations straight lines were found in accordance with Eq. (7). Owing to the complex formation the total concentration of the ligand in solution monitored by spectrophotometric measurements increased. The quantity (A/A0)-1 was plotted against csalt and the stability constant was obtained from the slope. (Fig. 2a) shows the variation of the absorption spectra of ligand 1 with increasing Co(II) concentration. A linear response of (A/A0)-1 versus cCo2+ for ligand 1with Co2+ was given by equation y=13026- 1.43212 with a correlation coefficient of 0.9992 in (Fig. 2b).Figure 3a shows the absorption spectra of ligand 1 in methanol:water (1:1) with increasing concentrations of Cu2+. The complex stability constant (AY) was calculated according to Valuer's method [18]. Accordingly the quantity A0/(A0-A) was plotted against [Cu2+]-1 with the stability constant given by the ratio of intercept/slope. (Fig. 3b) a plot of A0/(A0-A) versus [Cu2+]-1 for ligand 1 shows satisfactory linearity. Similar linearity for all metal cations with ligand 1 was obtained.A regular absorbance increase was detected for Co2+ in the spectrophotometric titration with ligand 1 at 206 nm. A linear response of the absorbance as a function of Co2+ concentration at this wavelength was observedfrom 210-6 to 310-5M where R2 was 0.9925 (Fig. 4). Also Job method was used to determine the complex composition. Figure 5 shows Job plot for Co2+-ligand complex. As seen from (Fig. 5) Co2+ forms 1:1 complex with the ligand. The isosbestic point in (Fig. 5) verifies the equilibrium between Co2+-ligand.To propose a mode of metal-ligand coordination 1H NMR spectroscopic method was applied. DMSO-d6 and metal nitrate was used in this experiment. As an example Cd2+-ligand interaction was investigated with this technique. While NH proton was observed at 6.70 ppm in 1H NMR spectra of free ligand it appeared in 6.89 ppm in case of equivalent Cd2+-ligand mixture. Therefore it is decided Cd2+ interacted with the NH nitrogen in the triazole ring. A reasonable change in the chemical shift of the OH proton after cadmium nitrate was added to the free ligandsolution was not observed. Therefore one can decide that hydroxyl group was not effective in the complexation. Also the pH values of the solutions were measurement during the spectrophotometric titrations and no reasonable change in pH values indicating that there is no proton release during the complexation. This result shows that metal ion is covalently coordinated to nitrogen atoms in the triazole ring. (Fig. 6) shows the proposed mode ofmetal-ligand coordination for Co2+ ion.Table 1 shows the stability constants with Log AY determined by means of both methods for Cu2+ Co2+ Cd2+ Ni2+ and Pb2+ ions with ligand 1. For these cations the value of the stability constants decreased in the order Co2+ greater than Ni2+ greater than Cu2+greater than Cd2+ greater than Pb2+ in aqueous solution. In methanol:water (1:1) nearly the same order iswhere the Cu(II) complex (log AY: 4.25) is more stable than the Ni(II) complex (log AY: 3.99) (see Table 1). However in water the log AY value is 3.50 for Cu(II) while it is 3.72 for Ni(II). The most stable complex is the Co (II) complex in water. The value of log AY is 4.11 for this complex. The reason of this may be preference of Co (II) more water molecules binding to the ligand with respect to the other metal cations. This manner provides the most complex formation. The lowest log AY value of 3.29 belongs to Pb(II) complex. Interestingly methanol increases complex stability for all metal cations. The Co (II) complex is the most stable complex (4.77) in methanol: water (1:1) with an increase of 16% in log AY value. However the highest increase i.e. 21% in log AY value was observed for Cu(II) ion when solvent changed from water to methanol:water (1:1). This result shows that a change in solvent polarity is very important for Cu(II) complexation with ligand 1.

Table 1. Stability constants (Log ) for ligand 1 with metal salts in###

solution at 25Ca.

###Cation###Log

###Solvent

###Water###Methanol: Water (1:1)

###Cd2+###3.380.09###3.670.09

###Co2+###4.110.10###4.770.05

###Cu2+###3.500.04###4.250.08

###Ni2+###3.720.05###3.990.05###

###2+

###Pb###3.290.04###3.600.06

In the present study it was clearly demonstrated that the feasibility to quantitatively study the complexation reaction between a 124- triazole ligand carrying naphthole group and metal cations even if the ligand is nearly insoluble in water as in such earlier study with some substituted 124- triazole compounds [24]. Because of their nearly insoluble nature in water under the abovementioned conditions very small quantities of 124-triazole ligand are sufficient to perform the spectrophotometric titrations according to Buschmann's method which is more appropriate for the determination of complex stability constants in aqueous solutions in comparison to fast and simple Valeur's method for which the ligand should be soluble in a proper solvent. Another advantage of Buschmann's method is the recovery of the ligand after the procedure. Because of the biological activity of124-triazole compounds demonstration of their complexation properties with metal ions in aqueous phase is noteworthy to utilize them in physiological studies.

Conclusions

The spectrophotometric titrations of triazole ligand 1 carrying naphthol group with Cu2+ Co2+ Cd2+ Ni2+ and Pb2+ cations point outthe complexation properties of the ligand in aqueous solutions and methanol:water media (1:1) by using Buschmann and Valeur's methods respectively. The most stable complex was the cobalt complex according to both methods. The log AY values were 4.11 and 4.77 in water and methanol:water (1:1) respectively. The work presents the complex stability constants for these metal cations calculated from two different methods. Job method shows 1:1 complex composition for the cobalt complex. NMRspectroscopic data reveals a probable complexationmodel over nitrogen donor atomsReferences

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Publication:Pakistan Journal of Analytical and Environmental Chemistry
Date:Dec 31, 2013
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