Phosphorus-nitrogen compounds: part 53-synthesis, characterization, cytotoxic and antimicrobial activity, DNA interaction and molecular docking studies of new mono- and dispirocyclotriphosphazenes with pendant arm(s).

Mono-/dispirocyclotriphosphazenes with pendant arm(s) are robust, but they are less investigated inorganic ring systems. In this study, a series of mono (3 and 4)- and dispirocyclotriphosphazenes with 4-chloro-benzyl pendant arm(s) (13-16) was obtained from the Cl exchange reactions of hexachlorocyclotriphosphazene with sodium (N-benzyl)aminopropanoxides (1 and 2). When compound (3) reacted with excess pyrrolidine, morpholine, tetra-1,4-dioxa-8-azaspiro[4,5]decane (DASD) and piperidine, the fully substituted monospirocyclotriphosphazenes (7, 9, 10 and 12) occurred. But, the reactions of 4 with excess piperidine and morpholine produced the gem-piperidino (5)- and morpholino (6)-substituted monospirocyclotriphosphazenes, whereas the reactions of 4 with excess pyrrolidine and DASD gave the fully substituted monospirocyclotriphosphazenes (8) and (11). However, it should be indicated that these derivatives were obtained to be used for the investigation of their spectral, stereogenic and biological properties. The structures of 5, 7 and 14 were determined crystallographically. X-ray data of 5 and 14 displayed that both of compounds were chiral in solid state, and their absolute configurations were assigned as R and RR. Additionally, the antimicrobial activities of phosphazenes were investigated. Minimum inhibitory concentrations, minimal bacterial concentrations and minimum fungicidal concentrations of phosphazenes were determined. The interactions of phosphazenes with plasmid DNA were evaluated by agarose gel electrophoresis. The cytotoxic activities of compounds were studied against L929 fibroblast and DLD-1 colon cancer cells. In addition, density functional theory calculations of 5, 7 and 14 were reported, and their molecular docking studies with DNA, E. coli DNA gyrase and topoisomerase IV were presented.

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, N(3)P(3)Cl(6), 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 (31)P 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.