Phosphorus−Nitrogen Compounds. 21. Syntheses, Structural Investigations, Biological Activities, and DNA Interactions of New N/O Spirocyclic Phosphazene Derivatives. The NMR Behaviors of Chiral Phosphazenes with Stereogenic Centers upon the Addition of Chiral Solvating Agents

The reactions of hexachlorocyclotriphosphazatriene, N3P3Cl6, with N/O-donor-type N-alkyl (or aryl)-o-hydroxybenzylamines (1a−1e) produce mono- (2a−2e), di- (3a−3d), and tri- (4a and 4b) spirocyclic phosphazenes. The tetrapyrrolidino monospirocyclic phosphazenes (2f−2i) are prepared from the reactions of partly substituted compounds (2a−2d) with excess pyrrolidine. The dispirodipyrrolidinophosphazenes (3e−3h) and trispirophosphazenes (3i−3k) are obtained from the reactions of trans-dispirophosphazenes with excess pyrrolidine and sodium (3-amino-1-propanoxide), respectively. Compounds 3a−3d have cis and trans geometric isomers. Only the trans isomers of these compounds are isolated. Compounds 3a−3h have two stereogenic P atoms. They are expected to be in cis (meso) and trans (racemic) geometric isomers. In the trans trispiro compounds (3i−3k), there are three stereogenic P atoms. They are expected to be in racemic mixtures. The stereogenic properties of 3a−3k are confirmed by 31P NMR spectroscopy upon the addition of the chiral solvating agent; (S)-(+)-2,2,2-trifluoro-1-(9′-anthryl)ethanol. The molecular structures of 3i−3k, 4a, and 4b look similar to a propeller, where the chemical environment of one P atom is different from that of others. Additionally, 4a and 4b are also expected to exist as cis−trans−trans and cis−cis−cis geometric isomers, but both of them are found to be in cis−trans−trans geometries. The solid-state structures of 2a, 2e, 2f, 3e, and 3f are determined by X-ray crystallography. The compounds 2f−2i, 3e−3i, and 3k are screened for antibacterial activity against Gram-positive and Gram-negative bacteria and for antifungal activity against yeast strains. These compounds (except 3f) have shown a strong affinity against most of the bacteria. Minimum inhibitory concentrations (MIC) are determined for 2f−2i, 3e−3i, and 3k. DNA binding and the nature of interaction with pUC18 plasmid DNA are studied. The compounds 2f−2i, 3e−3i, and 3k induce changes on the DNA mobility. The prevention of BamHI and HindIII digestion (except 2g) with compounds indicates that the compounds bind with nucleotides in DNA.