Phosphorus–nitrogen compounds part 22. Syntheses, structural investigations, biological activities and DNA interactions of new mono and bis (4-fluorobenzyl) spirocyclophosphazenes

Abstract

The reactions of hexachlorocyclotriphosphazene, N 3P 3Cl 6, with mono ( 1 and 2) and bis(4-fluorobenzyl) diamines ( 3- 5), FPhCH 2NH(CH 2) n NHR (R H or FPhCH 2–), produce mono ( 1a and 2a) and bis(4-fluorobenzyl) monospirocyclophosphazenes ( 3a– 5a). The tetraaminomonospirocyclophosphazenes ( 1b– 2d) are obtained from the reactions of the partly substituted phosphazenes ( 1a and 2a) with excess pyrrolidine, morpholine and 1,4-dioxa-8-azaspiro[4,5]decane (DASD), respectively. The tetrachlorobis(4-fluorobenzyl) monospirocyclophosphazenes ( 4a and 5a) with excess pyrrolidine, morpholine and DASD afford the fully substituted bis(4-fluorobenzyl) monospirocyclophosphazenes ( 4b, 4d– 5d) in boiling THF. In addition, monochlorobis(4-fluorobenzyl) monospirocyclophosphazenes ( 4e and 4f) have also been isolated from the reactions with excess morpholine and DASD in boiling THF. The structural investigations of the compounds have been verified by elemental analyses, MS, FTIR, 1H, 13C, 19F (for 1d and 2d), 31P NMR, HSQC and HMBC techniques. The crystal structures of 3a, 4a, 5a and 2b have been determined by X-ray crystallography. The compounds 2a– 5a, 1b– 2d, 4b, 4d– 5d, 4e and 4f have been screened for antibacterial effects on bacteria and for antifungal activity against yeast strains. The compounds 1b and 4b showed antimicrobial activity against three species of bacteria, Bacillus subtilis, Bacillus cereus and Staphylococcus aureus, and two fungi, Candida albicans and Candida tropicalis. Minimum inhibitory concentrations (MIC) were determined for 1b and 4b. The MIC values were found to be 5000 μM for each bacteria. The most effective compound, 4b has exhibited activity with a MIC of 312 μM for C. albicans and 625 μM for C. tropicalis. DNA-binding and the nature of the interaction with pBR322 plasmid DNA are studied. All of the compounds induce changes on the DNA mobility and intensity. Prevention of HindIII digestion with the compounds indicates that the compounds bind with AT nucleotides in DNA.