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.
Işiklan
Muhammet
M
Department of Chemistry, Kirikkale University, Kirikkale, Turkey.
Asmafiliz
Nuran
N
Ozalp
Ezgi Elif
EE
Ilter
Elif Ece
EE
Kiliç
Zeynel
Z
Coşut
Bünyemin
B
Yeşilot
Serkan
S
Kiliç
Adem
A
Oztürk
Asli
A
Hökelek
Tuncer
T
Bilir
L Yasemin Koç
LY
Açik
Leyla
L
Akyüz
Emel
E
D001419:Bacteria / Q000187:drug effects; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D004262:DNA Restriction Enzymes / Q000378:metabolism; D005658:Fungi / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009584:Nitrogen / Q000737:chemistry*; D010758:Phosphorus / Q000737:chemistry*; D011789:Quantum Theory; D012997:Solvents / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D013237:Stereoisomerism
D012997:Solvents; D013141:Spiro Compounds; D010758:Phosphorus; D004247:DNA; D004262:DNA Restriction Enzymes; D009584:Nitrogen