Polymethylene bis( 4-dimethylaminopyridinium bromide) synthesis, electrochemical and biological investigation

A series of bis(4-dimethylaminopyridinium)alkane dibromides (1-7) were prepared from the reaction between 4-dimethylaminopyridine (OMAP) and dibromoalkane(s). Electrochemical studies on 1-7 showed two irreversible reduction po· tentials, which indicated the presence of two DMAP moieties in a compound. Antibacterial and antifungal activities of these compounds were screened.

Quaternary ammonium salt is usually called as Quat, which is highly reactive and generates nitrogen cation in water. Nitrogen cation is Iipophlic and surface active 1 . These two properties made the quat to be useful in the fields of phar-maceuticals2, agrochemicals 2 · 3 and organic and bioorganic synthesis 4 • 5 . Pyridinium salts are served as better medicinal antiseptics, germicides, disinfectants and sanitizing agents 6 . Some diquats and paraquats are found to be good herbicides 7 . For the past two decades, much attention have been given to the quat salt containing DMAP moiety. As a result, DMAP quats are used directly in organic and biochemical reactions such as benzoylation 8 , acetylation 9 , tritylation 10 , tosylation 11 , benzyloxylation 12 , cyanylation 13 and silylation 14 . A few bispyridinium salts obtained from DAMP with anticancer, antiviral, antiparasitic, antifungal and antibacterial activity have been reported 15 · 1 6. In continuation of our research on the quat salt of DAMP 17 , we made an attempt to prepare title compounds from DAMP with dibromoalkanes. Further it is planned to study their electrochemical properties and antimicrobial activity.

Reaction between DAMP and dibromoalkanes(s):
The reaction between DAMP and active halide(s) containing electron withdrawing group ato halogen to give pyridinium salt(s) was reported elsewhere 18 . On the similar way, the reaction between two mole of DAMP and one mole of dibromoalkane(s) has been carried out to give the bispyridinium bromide(s) (1-7) (Scheme I).
The progress of the reaction was followed by TLC test using methanol as eluent. The physical data of 1-7 and the time required for a reaction to give the isolated yield of the product are presented in the experimental section. Schemel reaction of DAMP with dibromomethane took long time ( 144 h) to give I with the yield of 79%. This is due to serious steric effect felt by bulky DMAP while tends to displace the bromine atoms at the carbon of dibromomethane. Thus the formation of 1 is found to be too slow compared to the formation of 2-7 by the reaction between DMAP and higher dibromoalkane(s). The increase of distance between two bromine atoms in dibromoalkane by increasing the chain length is favored for the formation of 2-7. The reaction time is diminished to about half for each addition of carbon atom into the alkyl chain.
Assigments of the structure of the compounds are based on their spectral data. 1 H and 13 C NMR spectra of1-7 show only one type of pyridinium cation. UV -absorption of certain compounds (1-3 and 5) with higher molar extinction cofficient is due to 1t-1t*. The mass spectral data and elemental analysis are consistent with the assigned structure for 1-7. Though the compounds 2 and 3 have been previously described 16 , we have obtained the same with the yield of 83 and 88% against the reported yield of 40 and 54% respectively.

Electrochemistry :
The results of cyclic voltammetric (CV) studies per-Note formed on compounds 1-7 as shown in the Experimental section. The reduction potentials are given in experimental section. The cyclic voltammograms exhibit two irreversible reduction peaks. These reductions were found irreversible even when scanning was done just upro the point of reduction. This observation is very similar to reported one 18 . The two-reduction potentials indicate the presence of two pyridine moieties in a compound and also represent successive reduction of pyridinium ions one after the other.
Antimicrobial screening : The compounds 1-6 were screened for their antibacterial activity against Staphylococcus aureus, Eschorichia coli, Porleus vulgaris and Bacillus pumilis by employing filter paper disc method at 100 and 200 )..tg/ml in DMF 19 . At similar conditions, penicillin was used as reference drug. Antifungal activity of these compounds was tested against Aspergillus niger and Aspergillus flavus by standard method 19 . Nystatin was used as a reference drug. The significant biological results are presented in Table I. All the compounds are found to be moderately to highly active against test organisms at 200 )..tg/ml. The activity of 2, 4, 6 against E. coli and 2, 6 against P. vulgaris are significant. spectra of the compounds 1-7 were recorded on a Perkin-Elmer 1600 FT spectrophotometer, 1 H and ' 13 c NMR spectra in DMSO-d 6 or D 2 0 on a Bruker, 200 MHz spectrometer using TMS as standard, and mass spectra on a Shimadzu QP 5000 mass spectrometer.

Electrochemistry :
Cyclic voltammetry was performed on EG & G Princeton Applied Research (PAR) Model 273 potentiostat. For all the compounds best results were obtained in aqueous solution. Platinum sphere, platinum plate and Ag/ Ag+ were used as a working electrode, counter electrode and reference electrode respectively. Aqueous samples were run at a concentration of 0.001 mol dm-3 in 0.1 mol dm-3 KCI as supporting electrolyte. Multiple scans were recorded for each compound with little or no variation between scans.  The antifungal activity of 2 and 6 is high, whereas, 1, 3, 4, and 5 is moderate.