Syntheses, spectroscopic and crystallographic characterizations of cis- and trans-dispirocyclic ferrocenylphosphazenes: molecular dockings, cytotoxic and antimicrobial activities

Hokelek, Tuncer/0000-0002-8602-4382; Unver, Huseyin/0000-0003-3968-4385; Asmafiliz, Nuran/0000-0002-9335-4101; Tumer, Yasemin/0000-0002-2460-9414WOS: 000423702900026New cis-(4-6) and trans-dispirocyclic ferrocenylphosphazene derivatives (7-9) were obtained by reactions of hexachlorocyclotriphosphazene (N3P3Cl6) with N-alkyl-N-monoferrocenyldiamines of the formula FcCH(2)NH(CH2)(n)NHR [n = 2, R = CH3 (1); n = 2, R = C2H5 (2) and n = 3, R = CH3 (3)]. Characterizations of the products were performed using MS, FTIR, H-1, C-13 and P-31 NMR techniques. The crystal structures of 5 (with 8), 6, 7 and 9 were determined by X-ray crystallography. The most important result of this study was that the trans chiral phosphazenes crystallized as only one enantiomer. Studies of the antibacterial and antifungal activity of the phosphazenes (4-9) showed that compounds 6 and 7 were effective against P. vulgaris and K. pneumoniae. The cytotoxic activities of 4-9 against L929 fibroblasts and DLD-1 colon cancer cells were investigated. The necrotic effects of 4 and 7 were greater in the DLD-1 cell line than those in the L929 cell line. DFT calculations were carried out using the B3LYP functional with the LANL2DZ basis set to determine the energies, the orientations of the molecular orbitals (HOMOs and LUMOs) and the molecular electrostatic potential (MEP) surfaces of the partly substituted cyclotriphos-phazenes (6, 7 and 9). The results for 6, 7 and 9 revealed that these bonded to the active sites of A-DNA and B-DNA by weak non-covalent interactions, which was also supported by molecular docking investigations.Scientific and Technical Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [216Z182]; Turkish Academy of Sciences (TUBA)Turkish Academy of Sciences; Hacettepe University Scientific Research Project UnitHacettepe University [013 D04 602 004]The authors acknowledge the Scientific and Technical Research Council of Turkey Grant No. 216Z182. The authors also acknowledge the Scientific and Technological Research Application and Research Center, Sinop University, Turkey, for the use of the Bruker D8 QUEST diffractometer. Z. K. thanks the Turkish Academy of Sciences (TUBA) for partial support of this work. T. H. is grateful to the Hacettepe University Scientific Research Project Unit (Grant No. 013 D04 602 004)