title: QSAR and CAMM study of amphiphilic antimicrobially active 2,2'-bipyridyl monoammonium salts.
abstract: 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, aggregation properties and antimicrobial activity (QSAR) of these derivatives. It was found that using the applied synthetic route the monoammonium salt is prepared free of bis-ammonium salt. While in the case of the unsubstituted 2,2'-bipyridyl the energy difference between s-cis and s-trans conformers is minor and the transition from one state into the other one is possible with s-trans state apparently being preferred, after quaternisation the exclusive conformer is s-cis that is in this state fixed except of steric hindrance between the alkyl substituent bonded to the N+ atom and the hydrogen bonded to 3'C also by a weak hydrogen interaction C-H ... N between the hydrogen of the first carbon of the alkyl chain and the nitrogen of the adjacent ring. This finding is supported also by the results of calculation of point electric charges, dipole moments, 2C-2'C distance and torsion angles of non-quaternised as well as bipyridinium cations. It follows from quantitative dependencies between lipophilicity (expressed by means of aggregation properties-by critical concentration of micelle formation ck, and chromatographic factor RM), structure (length of alkyl chain m) and antimicrobial activity (minimum inhibition concentration, MIC) that the maximum of activity is achieved with compounds of chain length m = 13 to 16 with ck about 1.10(-3) mol/l. It follows from the comparison with simple alkylpyridinium salts that the mechanism of biological activity at the bacterial level will not differ in 2,2'-dipyridyl derivatives from the mechanism of activity of other ammonium salts.
authors.affiliation: Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic.
authors.forename: F
authors.initials: F
authors.lastname: Devínsky
authors.forename: J
authors.initials: J
authors.lastname: Zámocka
authors.forename: I
authors.initials: I
authors.lastname: Lacko
authors.forename: M
authors.initials: M
authors.lastname: Polakovicova
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D003198:Computer Simulation; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013500:Surface Tension
chemical_list: D000900:Anti-Bacterial Agents; D015082:2,2'-Dipyridyl