Synthesis , spectral characterization , catalytic and biological studies of new Ru ( II ) carbonyl Schiff base complexes of active amines

The synthesis and characterization of several hexa–coordinated Ru(II) complexes of the type [Ru(CO)(B)(L)] (B = PPh3/AsPh3/py/pip; L = dibasic tetradentate ligand derived from the condensation of isatin with diamines) were reported. IR, electronic, H-NMR, P-NMR of the complexes are discussed. An octahedral geometry has been tentatively proposed for all these complexes. The new complexes have been tested for the catalytic activity in the reaction of oxidation of alcohols in the presence of N-methylmorpholine-N-oxide as co-oxidant. The new complexes were also exhibited antimicrobial investigations.


INTRODUCTION
Transition metal complexes with tetradentate Schiff base ligands have been studied as catalyst for a number of organic oxidation and reduction reactions and electro chemical reduction processes [1,2].The accessibility of ruthenium higher oxidation states [3,4] converts them into excellent catalyst for redox reactions.Particularly, metal complexes of ruthenium have demonstrated to be useful laboratory and industrial homogeneous catalysts in the epoxidation of alkenes and oxidation of alcohols using iodosylbenzene, sodium hypochlorite hydrogen peroxide and N-methylmorpholine-N-oxide as oxygen sources [5][6][7][8].Further the oxidation of organic substrates mediated by high valent ruthenium-oxo species evokes much interest in modeling of cytochrome p.450 [9].Sharpless et al. [10] carried out a yield oriented study of oxidation of cholesterol, geranial etc. catalyzed by ruthenium complexes in the presence of N-methylmorpholine-N-oxide and N, N-dimethylaniline-N-oxide. Furthermore, the catalytic activities of ruthenium complexes containing tertiaryphosphine or arsine ligands are well established [11,12].Tetradentate Schiff base complexes have been employed as catalysts for many reactions and as biological models in understanding the structure of bio molecules and biological process [13,14].
In addition, the chemistry of chelating tetradentate Schiff base ligands with ruthenium has also been extensively studied [15].This is due to the fact that Schiff bases offer opportunities for inducing substrate chirality, tuning metal centered electronic factors, enhancing solubility and stability and their use as either homogeneous or heterogeneous catalysis [16][17][18].The oxidation of primary and secondary alcohols into their corresponding aldehydes and ketones respectively, plays a central role in organic synthesis [19,20].In continuation of our research interest [21] to understand the role of these simple and inexpensive N 2 O 2 donor Schiff base ligands towards ruthenium, the reaction of Schiff bases derived from isatin and diamines with ruthenium(II) precursors containing PPh 3 /AsPh 3 /py/pip has been carried out.Thus, the present work describes the results of synthesis, characterization and properties of hexa coordinated Ru(II) complexes exhibiting a N 2 O 2 ligating core with their catalytic activity towards oxidation of alcohols in the presence of NMO.Further, the antibacterial activity of the Schiff bases and their ruthenium complexes were examined.The following Schiff bases, derived from the condensation of isatin with ethylenediamine/o-phenylenediamine/propylene diamine (Scheme 1), were used to prepare the new ruthenium (II) complexes.

Materials
The Schiff bases were prepared by the reported procedure [21,22].All the reagents used were analytical reagent grade.Solvents were purified and dried according to standard procedures.RuCl

Physical Measurements
The analysis of C, H and N were performed on a Carlo Erba 1160 model 240 Perkin Elmer CHN analyzer, IR spectra were recorded in KBr pellets in the 4000 -400 cm -1 region in a Jasco 400 plus spectrophotometer.Electronic spectra were recorded in CH 2 Cl 2 solution with a Hitachi U -3210 spectrophotometer in the range of 800 -200 nm. 1 H-NMR and 31 P-NMR spectra were recorded on a Burker 400 MHz instrument using TMS as an internal reference.Melting points were recorded with Raaga apparatus and were uncorrected.

Catalytic Oxidation
Catalytic oxidation of alcohols to the corresponding carbonyl compounds by ruthenium(II) carbonyl Schiff base complexes was studied in the presence of NMO as co-oxidant by a typical reaction using the complex [Ru(CO)(B)L] as catalyst, and the alcohol as substrate at a 1:100 molar ratio.For this purpose, a solution of ruthenium complex (0.01 mmol) in 20 cm 3 CH 2 Cl 2 was added to the solution of the substrate (1mmol) and NMO (3 mmol) and the mixture was stirred for 3 -7 hrs at room temperature.The solvent was evaporated from the mother liquor under reduced pressure and the residue was then extracted with petroleum ether (60˚C -80˚C).

Antibacterial Activity Studies
Pathogenic microbials namely Escherichia Coli, Aeromonas hydrophila and Salmonella typhi were used to test the biological potential of the isatin diimine and their carbonyl complexes of ruthenium (II).The antibacterial activities of the complexes were determined by disc diffusion method [26].The bacteria were cultured in nutrient agar medium in petriplates and used inoculums for the study.The complexes to be tested were dissolved in DMSO to a final concentration of 0.25%, 0.5% and 1% and soaked in filter paper disc of 5 mm diameter and of 1 mm thickness.The disc were placed on the previously seeded plates and incubated at 35 ± 2˚C for 24 hrs.The diameter of inhibitory zone around each disc was measured after 24 hrs.Streptomycin was used as a standard.The analytical data for the new complexes agree well with the proposed molecular formula as given in Table 1.In all the reactions it has been observed that the Schiff bases behave as a dibasic tetratentate ligands by substituting the chloride ion, hydride ion and two triphenylphosphine/arsine groups from each mole of the starting complexes to form the mono nuclear complexes.These observations indicate a more labile nature for the Ru-P bond compared to the Ru-N bond of the heterocyclic nitrogen bases in these complexes.The difference in the strength of Ru-P/As and Ru-N bonds may be explained as due to the better σ donation ability of the nitrogen bases compared to that of triphenylphosphine/ arsine.The Schiff base ruthenium(II) complexes are highly colored, stable to air and light and soluble in chloroform, methylene chloride, benzene and DMSO.

I.R. Spectra
The most important IR bands are presented and as-signed in Table 2.The bands appearing at 1740 -1715 cm -1 and 1652 -1619 cm -1 in the ligand spectra were assigned to stretching vibration modes of C = O and C = N respectively.All the bands assigned to stretching vibration modes in the free ligands changed in the spectra of metal complexes.New bands recorded at 1599 -1583 cm -1 and 1637 -1600 cm -1 vibration modes respectively suggest the enolisation of the NH group of isatin and coordination through the oxygen of the C-O group [21,27].The formation of the Ru-O and Ru-N bands is further supported by the appearance of ν M-O and ν M-N band in the regions 576 -541 cm -1 and 492 -475 cm -1 respec-  tively in the spectra of the chelates [21,28,29].The most important conclusion drawn from the infrared spectral evidence is that the diamine bis(isatin) Schiff base ligand is acting as chelating agent towards the central metal ion as dibasic ONNO tetradentate ligand, via the two coordinating sites of nitrogen atoms and two negatively charged oxygen atoms of isatin residues forming fivemembered chelating rings [30].In addition, other characteristic bands due to PPh 3 and AsPh 3 are also present around 1438 cm -1 [31], in the spectra of Schiff base complexes.A medium intensity band is observed in the 1020 cm -1 region, characteristics of the coordinated pyridine or piperidine [21,32].In all the ruthenium complexes the band due to terminally coordinated C ≡ O group appeared at 1900 -1944 cm -1 [33].

Electronic Spectra
The electronic spectra of all the complexes in dichloromethane showed three to four bands in the region 246 -600 nm.All the Schiff base ruthenium complexes are diamagnetic, indicating the presence of ruthenium in the +2 oxidation state.The ground state of ruthenium(II) in an octahedral environment is 1 A 1g from the t 6 2g configuration and excited states corresponding to the t 5 2g e 1 g configurations are 3 T 1g , 3 T 2g , 1 T 1g and 1 T 2g .Hence four bands corresponding to the transition 1 A 1g → 3 T 1g , 1 A 1g → 3 T 2g , 1 A 1 g→ 3 T 1g and 1 A 1g → 1 T 2g are possible in the order of increasing energy.The bands around 600 -550 nm and 463 -403 nm are assigned to 1 A 1g → 1 T 1g [34,35] and the charge transfer reactions respectively are listed in Table 2.The charge transfer bands observed in all the complexes due to M → L transitions are possible in the visible region [36][37][38].Moreover the presence of carbonyl, triphenylphosphine/arsine and heterocyclic bases as ligands, which are capable of producing strong ligand field in e g * which is relatively higher energy levels.This band has been assigned to the charge-transfer transition arising from the excitation of an electron from the metal t 2g level to the unfilled molecular orbital's derived from the e g * level of the ligands should appear in the relatively high energy region compared to those due to t 2g → e g * transitions [34][35][36].The other high energy bands have been designated as π-π * and n-π * transitions for the electrons localized on the azomethine group of Schiff bases [32].The pattern of the electronic spectra of all the complexes indicated the presence of an octahedral environment around the ruthenium(II) ion, similar to that of other octahedral ruthenium(II) complexes [37].

1 H-NMR Spectra
The 1 H NMR spectra of some complexes were recorded to confirm the bonding of the Schiff base to the ruthenium ion and given in the Table 3. Multiplets are observed around 7.2 -7.8 ppm in all the complexes and have been assigned to the aromatic protons of triphenylphophine, triphenylarsine, pyridine, piperidine and isatin Schiff base ligands [29].A singlet appears in the region 1.36 -1.4 ppm for the methylene protons [39].In the complexes [Ru(CO)(PPh 3 )(L 3 )] and [Ru(CO)(AsPh 3 )(L 3 )] an extra singlet was found in the region at 2.05 ppm, which has been assigned to the extra methylene group present in the Schiff base.The 1 H NMR spectra of the neutral diamagnetic chelates of the type [Ru(CO)(B)(L)] are similar to those of the ligands, excepting that the signal due to NH proton of isatin disappears.This proves the deprotonation of NH group upon complexation and supports the above NMR spectral data suggesting that the ligand acts as dibasic tetra dentate chelating agent.

31 P-NMR Spectra
The 31 P-NMR spectra for a few of the complexes have been recorded in order to confirm the presence of triphenylphosphine group and to determine the geometry of the complexes (Table 3).The appearance of singlet at 28.78, 28.75 and 28.70 ppm for the complexes [Ru(CO)(PPh 3 )(L 1 )], [Ru(CO)(PPh 3 )(L 2 )] and [Ru(CO)(PPh 3 )(L 3 )] respectively indicates the presence of one triphenylphosphine group in these complexes.

Catalytic Activity of the Complexes
Catalytic oxidation of primary alcohols and secondary alcohols by the synthesized ruthenium(II) carbonyl Schiff base complex [Ru(CO)(B)(L)]was carried out in CH 2 Cl 2 in the presence of NMO.Results of the present investigation suggest that the complex is able to react efficiently with NMO to yield a high valent rutheniumoxo species [15,40] capable of transferring oxygen atom to alcohols.The oxidation of benzylalcohol to benzaldehyde resulted in 89% yield.Further, the complex effectively catalyzes the oxidation of aliphatic alcohols such as butane-2-ol, to the corresponding ketones effectively and is evident from Table 4.Moreover, the complex effectively catalyzes the oxidation of five and six membered cyclic alcohols to the corresponding ketones with the conversion rates to the extent of 90% and 82% respectively.The reaction provides a new environment friendly route to the conversion of alcoholic functions to carbonyl group and water is the only byproduct during the course of the reaction.It has been concluded that the complexes have a better catalytic efficiency in the case of oxidation of primary and secondary alcohols in the presence of NMO.

Antibacterial Studies
The in vitro antibacterial screening of the ligands and their ruthenium complexes have been carried out against Escherichia Coli, Aeromonas hydrophila and Salmonella typhi using a nutrient agar medium by disc diffusion method.The results (Table 5) showed the complexes exhibit moderate activity against Escherichia Coli, Aeromonas hydrophila and Salmonella typhi.The toxicity of ruthenium chelates increases on increasing the concentration [41].The increase in the antibacterial activity of metal chelates may be due to the effect of the metal ion on the normal cell process.A possible mode of the toxicity increase may be considered in light of Tweeds chelation theory [42].Chelation considerably reduces the polarity of the metal ion because of partial sharing of its positive charge with the donor groups and possible πelectron delocalization over the whole chelate ring.Such chelation could enhance the lipophilic character of the central metal atom, which subsequently favors its per-meation through the lipid layers of cell membrane.Furthermore, the mode of action of the compounds may involve in the formation of a hydrogen bond through the azomethine (>C = N) group with the active centers of cell constituents, resulting in interference with the normal cell processes [42].Though the complexes possess activity, it could not reach the effectiveness of the standard drug streptomycin.The variation in the effectiveness of the different compounds against different organisms depend either on the impermeability of the cells of the microbes or differences in ribosomes of microbial cells [40,41].
Based on the analytical, spectral (IR, electronic, 1 H NMR and 31 P-NMR) data, Scheme 3 octahedral structure has been tentatively proposed for all the new carbonyl Schiff base complexes of ruthenium (II).

CONCLUSIONS
A new family of carbonyl complexes of ruthenium(II) containing N 2 O 2 donor Schiff bases incorporating triphenylphosphine/triphenylarsine/pyridine/piperidine ligands were synthesized and characterized.The new complexes were tested as a new and efficient catalyst for the oxidation of primary and secondary alcohols to their corresponding aldehydes and ketones with excellent yields in the presence of N-methylmorpholine-N-oxide.Further the possible explanations for the mode of action of these complexes against three different microbes are described.

Scheme 2 .
Preparation of new Ru(II) Schiff base complexes.

Table 1 .
Analytical data of new Ru(II) complexes.

Table 2 .
IR and UV -Visible Spectral data for the ligands and new Ru(II) complexes.

Table 3 .
NMR Spectral data of new Ru(II) complexes.

Table 4 .
Catalytic oxidation of alcohols by Ru(II) complexes.

Table 5 .
Antibacterial activity of ligands and Ru(II) complexes (diameter of inhibition zones-mm).
Scheme 3. Structure of New Ru(II) complexes.