Spectral , Electrochemical and Molecular Modeling Studies of Some 3-( 2-Hydroxy benzalhydrazino-4-thiazolyl ) coumarins

Spectral, cyclic voltammetric and molecular modeling studies have been carried out on some 3-(2-hydroxybenzalhydrazino-4-thiozolyl)coumarins (1), to understand their solution and electrochemical characteristics. These investigations reveal structural alterations in the conjugates of their acid-base equilibria as indicated by considerable bathochromic shift in electronic spectra and changes in electron transfer properties with rise in pH. The pKa values and electrochemical data such as Ep, ip, αna, k o h, etc., of 1 were evaluated. Further, the compound 1 is found to be good chelating ligands. Molecular modeling studies were also performed to correlate the spectral and electrochemical observations. Voltammetric analysis of 1 is also presented.


Introduction
Schiff bases are known for their biological importance, especially in antimicrobial 1,2 and antitumour 3 activities and in the physiology of vision 4 .They are widely used as ligands for complexation [5][6][7][8][9] .They are also known to undergo hydrolysis readily in aqueous media 10,11 .Some of the Schiff bases with OH group in ortho position to the imino group exhibit tautomerism [5][6][7][8][9]12 . Howver, the electrochemical characterization of Schiff bases is not consummate to their other studies.In this paper, we present the spectral, electrochemical and preliminary molecular modeling studies of 1 which are Schiff bases arising from salicylaldehyde and hydrazinyl thiazocoumarins.

Experimental
All the three compounds, 1a-1c, have been prepared based on the reported 12 procedure.A typical case is presented here.

Synthesis of 1a
A mixture of 3-(2-bromoacetyl)coumarin (0.01 mol), thiosemicarbazide (0.01 mol) and salicylaldehyde (10 mL) was thoroughly stirred for 5 min at room temperature in a 50 mL RB flask at 60 o C. The solid mass was filtered and recrystallized from methanol.
A millimolar stock solution of 1 was prepared in methanol.1 mL of the stock solution was made up to 25 mL by the Britton-Robinson buffer of the desired pH (ionic strength = 0.02 M) for the purpose of spectral or electrochemical run.An ATI Orion Model 902 Ion Meter was used for the pH-metry whereas an AnalytikJena Specord 205 Spectrophotometer for UV-vis spectral and a Metrohm 663 VA Stand for voltammetric and a BAS CV-27 Voltammograph for coulometric studies.Molecular modeling was carried out on a ChemOffice ® Ultra Pro 10.0 platform.

Spectral studies
Even though salicylidinimine Schiff bases are known to undergo hydrolysis readily in aqueous buffers 10,11,13,14 , no such instability has been observed for 1.However, compounds, 1, suffer structural change with pH. Figure 1 shows such time-independent but pH-dependent spectra for the case of 1a.The compounds exhibit bathochromic shift from ~ 325 nm to ~ 370 nm with a well defined isosbestic point at ~350 nm.Many hydrazones are famous to undergo Wolff-Kishner reaction in alkaline media 15 with a mechanism shown in Scheme 1 converting the azomethine carbon into a carbanion.In the present case of 1 too, we propose the generation of a carbanion upon deprotonation at elevated pH.Additional stability for this anion comes from the extended conjugation running from the phenyl group to the thiazolyl coumarin ring via the azo moiety besides Huckel's aromaticity encompassing all the three rings with n=6 in the 4n+2 rule that includes the carbanion's lone pair.In other words, the azo moiety and the carbanion are stabilized at high pH.The acid-base equilibria for 1 as an extension of Scheme 1 are shown in Scheme 2.

Scheme 2
The presence of isosbestic points at ~275 and ~350 nm is a strong evidence for the fact that there are only two absorbing species, 1 and 1 -in equilibrium.The pK a of 1 were obtained by plotting absorbance vs. pH at the two λ max as shown in Figure 2. It is worth comparing the spectral behaviour of 2 with that of 1. Spectral variation with pH was observed 16 to be negligible for 2. This compound is analogous to 1 with phenolic group absent.Hence, we suggest the deprotonation at the phenolic group is more probable than that at the hydrazone.The bathochromic shift in the spectra of 1 is attributed to the involvement of tautomerism that is not possible in 2.

Electrochemical investigations
The cyclic voltammograms recorded for 1 on SMDE over a wide pH range are shown in Figure 3.The voltammograms indicate irreversible but pH-dependent reduction profiles.In the pH range, 1-6, the compounds exhibit a single irreversible reduction peak with an n value of 2. The plot of E p vs. pH, in this range is used to evaluate the number of H + ions involved in the reduction process 17,18 .(4) In Figure 4 is shown the effect of scan rate on the cyclic voltammetric response of 1a at a pH of 3. The electrochemical response for the reaction, (4), is observed, as expected, at low scan rate as a cathodic shoulder because of the finite life for product of 2a.At faster scan rates the potential needed for 2b is too quickly reached to allow any scope for (3).Hence, the response of ( 4) disappears with increased scan rate and the cyclic voltammograms manifest only the reaction, (2), a single 2-electron step.The linearity of the plots of peak current, i p , vs. ν 1/2 , the square root of the scan rate, suggests that the electrochemical reduction in the pH range, 1-6, is diffusion-controlled.The cathodic shift of peak potential, E p , with increased scan rate also supports the irreversible nature of the electrode reaction.From plots of E p vs. log ν, at different pH values, the transfer coefficients were evaluated.The cyclic voltammograms for 1 in the basic pH range are also shown in Figure 3.One gets an altogether different set of voltammograms showing a sharp and intense peak at ~ -0.7 V. Based on Scheme 2 one expects an electrochemical reduction mechanism characteristic to an azo group in this pH range.It is reported vastly in literature that stilbenes and azobenzenes exhibit reduction processes that are not diffusion controlled but adsorption complicated 21,22 .The i p vs. ν 1/2 for the sharp peak at ~ -0.75V are not linear but those of i p vs. ν are. Figure 5 shows the linear effect of scan rate on the current signal.Based on the plots of E p vs. pH and coulometry, the electrochemical reduction of 1 in alkaline buffers is proposed as -NH-NH--N=N-+ 2e -+ 2H + (5) A consolidated set of electron transfer processes shown in Scheme 3 is proposed for 1 while all their relevant electrochemical data are collected in Table 1.

Metal coordination of 1
Compounds, 1, have several coordinating atoms that can bind to metal ions.Differential pulse polarography and electronic spectra have been used to elucidate complexation scheme for 1 with a few bivalent metal ions.The Job's plots give metal to ligand ratio as 1:2 for Cu(II) and Ni(II) and 1:3 for Co(II) ions.The plausible structures are shown in 3. Detailed characterization of these complexes is underway.

Molecular modeling studies
Molecular modeling studies were done on 1 using CambridgeSoft ChemOffice.The global energy-minimized structure of 1a is shown in Figure 6.The dihedral angles about 4 relevant bonds are given in Table 1.Torsional energy plots of 1a over a few dihedrals are presented in Figure 7.It is evident from this figure that the phenol prefers hydrogen bond engagement with the azomethine nitrogen than with the distant hydrazine nitrogen.# with 1 at 2.75 x 10 -5 M on SMDE of 2.75 x 10 -6 m 2 surface area at ν = 100 mVs -1 The quantum mechanical HOMO-LUMO energy calculations have been used for computing the expected gas-phase electronic transitions.These values are collected in Table 2 along with the experimental spectral data whose trends are in good agreement.The thermodynamic and electrical dipole moment data obtained by modeling are also collected in Table 2 for the conjugate acid-base forms of 1.It is noteworthy that the standard heats of formation of 1H + and 1 -are lower than that of 1.  16) bonds (c.f. Figure 6 for numbering scheme for atoms) ∆H o f are MM2-wise energy-minimized standard heats of formation; φ a-b-c-d is angle between abc and bcd planes of the contiguous a-b-c-d atomic chain; * λ max are experimental values (mostly from Table 3).
Table 3. Spectral and thermodynamic data # of 1.
# λ in nm; ε (in lt mol -1 cm -1 ); K a and ∆G o (in kJ mol -1 ) are for the process, 1→ 1 -; λ const is unchanging high energy wavelength while λ low and λ high are wave lengths below and above the isosbestic wave length, λ iso , respectively.
et al.

Figure 2 .
Figure 2. Effect of pH on the absorptivities of 1a at (a) 326 and (b) 370 nm.The solid lines are curv-fitted for pK a = 8.6.
et al.

Figure 6 .
Figure 6.Stereographic view of 1a after global minimization along with the numbering scheme of the atoms.Table1.Electrochemical data of 1.