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.

The effect of intrathecal medetomidine on small bowel transit in the rat.

BACKGROUND AND OBJECTIVE: Gastrointestinal motility is influenced by abdominal trauma, laparotomy and particularly by intestinal ischaemia. The reflex inhibition of gastrointestinal motility is mediated mainly by the sympathetic nervous system. There are reports on the effects of systemically applied alpha2-adrenoceptor agonists on gastric emptying and recovery of bowel motility, but the effect of spinally applied alpha2-adrenoceptor agonists on intestinal motility has not been studied. The aim of this study was to investigate the effects of intrathecal medetomidine on gastrointestinal transit in rats after transient intestinal ischaemia. METHODS: Forty rats were randomly assigned to four groups of 10 each. Intrathecal catheter insertion and laparotomy were performed on each rat. Saline (10 microL) was injected intrathecally in Groups A and B. Medetomidine (10 microg in 10 microL) was injected intrathecally in Groups C and D. Intestinal ischaemia was induced in Groups B and D. Gastrointestinal transit was determined by measuring the length that a standardized marker meal of activated charcoal had travelled. Intrathecal medetomidine was compared to intrathecal saline in their effect on intestinal motility after 30 min period of bowel ischaemia. RESULTS: Laparotomy and intestinal ischaemia slowed gastrointestinal transit. Intrathecal medetomidine accelerated transit in both ischaemia and non-ischaemia groups. CONCLUSION: Intrathecal medetomidine markedly accelerated small intestinal transit and may also hasten the recovery from post-ischaemic paralytic ileus.