Electrochemical study and dependence of ‘ transition state ’ in Co ( II ) and Ni ( II ) complexes with some antibiotics and cephalothin

Abstract: Electrode kinetics and study of ‘transition state’ with applied potential in case of [M – antibiotics – cephalothin] system were reported at pH = 7.30 ± 0.01 at suitable supporting electrolyte at 25.0C. The M = Co or Ni and antibiotics were doxycycline, chlortetracycline, oxytetracycline, tetracycline, minocycline, amoxicillin and chloramphenicol used as primary ligands and cephalothin as secondary ligand. Kinetic parameters viz. transfer coefficient (a), degree of irreversibility (l), diffusion coefficient (D) and rate constant (k) were determined. The values of a and k varied from 0.41 to 0.59 and 2.60 X 10 cm s to 9.67 X 10 cm s in case of [Co – antibiotics – cephalothin] system. In case of [Ni – antibiotics – cephalothin], a and k varied from 0.41 to 0.58 and 2.34 X 10 cm s to 9.19 X 10 cm s respectively confirmed that transition state behaves between oxidant and reductant response to applied potential and it adjusts it self in such a way that the same is located midway between dropping mercury electrode and solution interface. The values of rate constant confirmed the quasireversible nature of electrode processes. The stability constants (logb) of complexes were also determined.


Introduction
Electrode kinetics between dropping mercury electrode and electro active species in solution interface is important in polarography.Delahay and his coworkers [1] have studied the formation of electrical double layer and its structures in the vicinity of electrodes.Trachtenherg et al [2] studied the adsorption kinetics at electrodes.Koryta [3] studied the kinetics of discharge of Zn at the dropping mercury electrode.Matsuda [4] has studied the kinetics between oxidants and reductants at d.m.e.Gellings [5] has applied Lagrange's theorem in electrochemical kinetics.Khan [6] has reported the kinetic parameters of [Mn -antibioticscephaloglycin] system and relates them with transition state and rate constant.On the other hand, Ni and Co are essential elements which play important role in human body.Co as cynocobalamine contributes to the formation of red blood cells and is essential to the normal functioning of all cells, particularly those of bone marrow, nervous and gastro-intestinal systems [7].Ni is a potent activator of several enzymes and probably plays role as a bioligant in iron absorption, regulation of prolactin and in the structure and function of membranes [8].But the excess amount of these metals is toxic.Antibiotics and cephalothin are important drugs which are used against many diseases; therefore, the study of Co and Ni complexes with selected antibiotics and cephalothin has great importance.The present paper deals with the kinetic parameters and stability constants of Ni and Co complexes with doxycycline, chlortetracycline, oxytetracycline, tetracycline, minocycline, amoxicillin and chloramphenicol as primary ligands and cephalothin as a secondary ligands polarographically for which no reference is traced out so far in the literature.

Experimental details Apparatus and reagents
All the chemicals used were of A. R. grade and their solutions were prepared in doubly distilled water.Cobalt nitrate hexahydrate and Nickel chloride hexahydrate (both Fluka) were used for Co and Ni.The antibiotics were Fluka, Sigma and Aldrich products.The concentration of metal in the analyte was 0.5 mmol L -1 while the concentration of antibiotics varied from 0.5 mmol L -1 to 30.0 mmol L -1 at 0.025 mol L -1 and 0.05 mol L -1 of cephalothin.The (0.1 mol L -1 pyridine + 0.1 mol L -1 pyridinium hydrochloride) was used as supporting electrolyte for Co and in case of Ni, 1.00 mol L -1 KSCN was used.In both the cases, dilute solutions of NaOH and HNO 3 (BDH) were used to adjust the pH at 7.30 ± 0.01 at 25 0 C.

Apparatus
Polarograms were recorded on a Polarographic analyzer (Elico, Hyderabad) with capillary of length 5.0 cm and diameter 0.04 mm at m 2/3 t 1/6 = 2.40 mg 2/3 s -1/2 .A m pH meter (Systronics Model -361) was used to measure the pH of the analyte at 7.30 ± 0.01.Potassium dihydrogen phosphatesodium hydroxide buffer was added in the analyte to stabilize the pH of the analyte at 7.30.

Results and Discussion
The chelating ability of antibiotics and their uses in different diseases crate considerable interest in their metal complexes [9,10].Doxycycline, chlortetracycline, oxytetracycline, tetracycline, minocycline and amoxicillin can make bond with Co and Ni as mentioned in Fig. 1.Co(II) and Ni(II) gave well defined quasireversible [11] waves in (0.1 mol L -1 pyridine and 0.1 mol L -1 pyridinium hydrochloride) and 1.0 mol L -1 KSCN at pH 7.20 to 8.50 at 25 0 C respectively.The natures of complexes were also quasireversible.The metal and ligands were taken in the ratio of 1:40 in case of binary complexes and 1:40:40 in case of ternary complexes and current -voltage curves were determined at different pH values from 7.10 to 8.80, it has been observed that the maximum shifts of E 1/2 were obtained at pH range 7.30 to 8.50 but pH 7.30 was selected on account of studying the complexes at human blood pH [12].De Vries and Kroon method [13] was used to determine the number of electrons involved in the reduction.
The concentration of cephalothin varied from 5.0 mmol L -1 to 30.0 mmol L -1 at 0.5 mmol L -1 of metal i.e.Co and Ni in their analytes.The E 1/2 values became more negative on increasing the concentration of cephalothin to the metal showed complex formation.Gellings method [14] was used to determine the E Lingane method is used to determine the composition and stability constants of binary complexes when overall complex formation is taken place.The number of groups ( j ) attached to the metal ion can be calculated by the following equation d(E 1/2 )c / d logC x = -j 0.0591 / n at 25 0 C (1) Then the values of stability constant of complex MX j is calculated by the equation ( 2) where the symbols have the usual meanings [15].The values of stability constants of Co and Ni complexes were given in Table 1and 2 respectively.

[M -antibiotics] system
The concentration of antibiotics varied from 0.5 mmol L -1 to 30.0 mmol L -1 in each case at 0.50 mmol L -1 of Co or Ni it their respective analytes and polarograms were recorded.After determining the E 1/ 2 reversible values of complexes from E 1/ 2 quasireversible values by Gellings method [14], Deford and Hume method [16] was used to determine the 1:1, 1:2 and 1:3 complexes of Co and Ni with selected antibiotics.The stability constant values of complexes were given in Table 1 and Table 2 respectively.2. Stability constants of [Ni -antibiotics -cephalothin] system.[Ni(II)] = 0.50 mmol L -1 , supporting electrolyte = 1.0 mol L -1 KSCN, pH = 7.30 ± 0.01, T = 25.0 0 C values by Gellings method [14], Deford and Hume method [16] was used to determine the 1:1, 1:2 and 1:3 complexes of Co and Ni with selected antibiotics.The stability constant values of complexes were given in Table 1 and Table 2 respectively In this system, the concentration of antibiotics varied from 0.5mmol L -1 to 30.0 mmol L -1 at 0.50 mmol L -1 of metal at 0.025 mol L -1 and 0.050 mol L -1 of cephalothin and current -voltage curves were determined at pH 7.30 ± 0.01 at 25.
Here [Y] is regarded as maintained constant while [X] is varied.From the equation ( 6), the values of b 11, b 12 and b 21 may be calculated.The values of stability constant of Co and Ni complexes were given in Table 1 and Table 2 respectively.The plots between -[E -RT/nF log(i d -i)/i] vs i for [Codoxycycline -cephalothin] system were given in Fig. 2.The data and plots of F ij [X,Y] vs [X] for (Co -doxycycline -cephalothin) system {where X and Y are doxycycline and cephalothin and i & j are their stoichiometric numbers respectively}were given in Table 3 and Fig. 3

Series1
The trend of stability constant of complexes was doxycycline < chlortetracycline < oxytetracycline < tetracycline < minocycline < amoxicillin < chloramphenicol.All the tetracycline including doxycycline and minocycline are having the same structures except in the difference in R 1 and R 2 positions [18].They all made bond with oxygen of 1, C and oxygen of amide (CONH 2 ) group at 2, C atom with Co and Ni.The doxycycline formed the complexes of minimum stability with metal ions.The lesser stability of chlortetracycline complexes [Co -doxycycline -cephalothin] system, [cephalothin] = 0.05 M 1:1:1 complex in [Co -chlortetracycline -cephalothin] and 1:2 complex in [Ni-amoxicillin -cephalothin] systems were not formed; therefore, the log K m values were not calculated for these systems.
than that of oxytetracycline complexes is due to the presence of more electrons withdrawing Cl at R 1 in the former in place of H in the latter [19].In case of tetracycline, H is present both at R 1 and R 2 therefore; there is the least electronic disturbance in tetracycline in comparison to other tetracycline complexes.This order supported the order of their pK values also [20].The stability of minocycline complexes is lesser than that of amoxicillin complexes is owing to the presence of 6 membered ring with two double bonds in former while the later made 5 membered

Series1
saturated ring together with b -lactam ring with metal ions.The complex with saturated 5 membered ring is more stable than complex with unsaturated 6 membered ring [21].The chloramphenicol made complexes of the maximum stability is due to the fact that this complex system has maximum shift of E 1/2 that might be the result of the formation of one  4.The values of a and k were varied from 0.41 to 0.59 and 2.60 X 10 -3 cm s -1 to 9.67 X 10 -3 cm s -1 in case of [Coantibiotics -cephalothin] system while in case of [Ni -antibiotics -cephalothin], a and k were varied from 0.41 to 0.58 and 2.34 X 10 -3 cm s -1 to 9.19 X 10 -3 cm s -1 confirmed that transition state behaves between oxidant and reductant response to applied potential and energy barrier adjusts it self in such a way that it locates always midway between dropping mercury electrode and solution interface.The values of rate constant were of the order of 10 -3 cms -1 confirmed the quasireversible nature of electrode processes.A small variation in rate constant (k) not only affects the rate of the electrochemical reaction but also the rate constant greatly.
0 0 C. The E 1/2 values increased with the addition of [cephalothin] to [M -antibiotics] showed ternary complex formation.After determining the E 1/2 reversible values from E 1/2quasireversible values of complexes by Gellings method, Schaap and McMaster method[17] was used to deter-

4 and one 5
membered ring with Co and Ni [22].The polarograms of [Co -doxycycline -cephalothin] system at [cephalothin] = 0.025 M were given in Fig. 4. In the case of cephalothin, O of the COOH and N of the b-lactam ring may take part in bond formation with Co or Ni.Electrode Kinetics Consider the electrochemical reaction at d.m.e k red O(s) + e(d.m.e.) = R(s) -----(i) k ox Where O(s) is the metal complex species.The current flowing is given by the following equations i a = -FAk ox.[R] o ---(2) and I c = -FAk red.[O]o ---(3) where the terms have the usual meanings[22].To establish how the rate constant k Red and k Ox are affected by applied potential, transition state theory is used in which we consider that the reaction is precede via an energy barrier.In electrochemical reactions, free energy is a function of the applied potential which derive electro active species from solution interface to the transition state and form reductants after gaining electrons from d.m.e.Using these concepts, the corresponding rate constants are given by the following equations k Red.= Ze [(-DG Red ./RT)(-aFV)/RT] (4).and k Ox. = Ze [(-DG Ox ./RT)(1-a)FV/RT] (5).But at anode, the electrode reactions are almost negligible because the concentration of depolarizer is lesser than 1.0 mM [23-24].The parameter a is called the transfer coefficient which has a value of 0.50.Physically, it provides an inside into the way the 'transition state' is influenced by the applied potential.A value of 0.5 means that the 'transition state'is a function of applied potential.It also defines the symmetric behaviour of energy barrier.A small variation in potential not only affects the rate of the electrochemical reaction but also rate constant greatly.The values of kinetic parameters were determined by Tamamushi and Tanaka methods [23, 24] by plotting (E 1/2 r -E) vs log (Z-1) for metals complexes by equation (7).ln (I d -I / I ) = x + loge Z (6) ln (Z -1) = log e 1.13 / l t 1/2 -(1 -a) x (7) Where x = nF / RT (E-E 1/2 r ).The values of Z can be calculated by the following equation [23] Z = antilog [nF / RT (E 11) for [Co-doxycycline -cephalothin] were given in Fig. 5(a) and 5(b) respectively while the values of kinetic parameters were given in Table