QSAR AND CAMM STUDY OF AMPHIPHILIC ANTIMICROBIALLY ACTIVE 2,2'-BIPYRIDYL MONOAMMONIUM SALTS

Preparation of 2,2'-bipyridyl monoammonium salts is described as well as their conformation study using computer aided molecular modelling ( CAMM) methods and quantitative relations between structure, aggregatio n properties and antimicrobial activity (QSAR) of these derivatives. I t was found that using the applied synthetic route the monoammonium sa lt is prepared free of bis-ammonium salt. While in the case of the uns ubstituted 2,2'-bipyridyl the energy difference between s-cis and s-tr ans conformers is minor and the transition from one state into the oth er one is possible with s-trans state apparently being preferred, afte r quaternisation the exclusive conformer is s-cis that is in this stat e fixed except of steric hindrance between the alkyl substituent bonde d to the N+ atom and the hydrogen bonded to 3'C also by a weak hydroge n interaction C-H ... N between the hydrogen of the first carbon of th e alkyl chain and the nitrogen of the adjacent ring. This finding is s upported also by the results of calculation of point electric charges, dipole moments, 2C - 2'C distance and torsion angles of non-quaternis ed as well as bipyridinium cations. It follows from quantitative depen dencies between lipophilicity (expressed by means of aggregation prope rties - by critical concentration of micelle formation c(k), and chrom atographic factor R(M)), structure (length of alkyl chain m) and antim icrobial activity (minimum inhibition concentration, MIC) that the max imum of activity is achieved with compounds of chain length m = 13 to 16 with c(k) about 1 . 10(-3) mol/l. It follows from the comparison wi th simple alkylpyridinium salts that the mechanism of biological activ ity at the bacterial level will not differ in 2,2'-dipyridyl derivativ es from the mechanism of activity of other ammonium salts.