Search

Multiheterocyclic inorganic–organic hybrid phosphazenes have robust inorganic ring systems with the stabilities of the phosphorus nitrogen skeleton and many different substituents bonded to the P atoms. In present study, unsymmetrical dispirocyclotriphosphazenes were prepared due to their potential to depict steric hindrance and electronic rearrangement in creating permanent chirality for certain conformational and configurational isomers. These isomers may have an effect on DNA bindings and activitiy against selected fungi and bacteria, remarkably. Herein, tetrachlorocyclotriphosphazenes (1 and 2) were reacted with 9-ethyl-N-methyl-3-carbazolyl-1,2-diaminoethane (3), 9-ethyl-N-ethyl-3-carbazolyl-1,2-diaminoethane (4) and 9-ethyl-N-methyl-3-carbazolyl-1,3-diaminopropane (5) to give the new unsymmetrical cis/trans-dispirocyclotriphosphazenes, [(ClBz/BzSpiro-6)R1(N3P3)(CzSpiro-n)R2]Cl2 (Cz: Carbazolyl; R1:Me R2:Me or Et; n = 5 or 6; trans 6a–11a and cis 6b–11b). Characterizations, chiralities, and photophysical and biological properties of the new compounds were examined. The molecular and crystal structures of cis-6b, cis-7b, trans-9a, cis-9b, trans-10a and cis-10b were determined by single crystal X-ray crystallography. The chiralities of these compounds with unsymmetrical spiro-architectures were confirmed by X-ray crystallography. These results were further proven by 31P NMR data recorded with the addition of a chiral solvent (CSA). Additionally, circular dichroism (CD) spectra also supported the results. Photophysical measurements indicate that these compounds show emission with lifetimes of approximately 5.6–5.9 ns. In addition, the bioactivities of some isomers were found to be different and quite high against some bacterial and yeast strains. Trans-8a was very active against B. cereus (MBC = 78.1 µM), while cis-6b, trans-9a and cis-9b were very active against the pathogenic yeast C. albicans (MFC = 156.3 µM). [ABSTRACT FROM AUTHOR]

The aim of this research is to synthesize and characterize new organic–inorganic hybrid multi-heterocyclic dichlorodispiro(N/N)cyclotriphosphazenes and to elucidate their antituberculosis activities. To achieve this aim, primarily, trans (6a–11a) and cis (6b–11b) unsymmetrical dichlorodispiro(N/N)cyclotriphosphazenes were obtained from ferrocenyldiamines (4 and 5) and benzyl-pendant armed tetrachloromonospirophosphazenes as starting materials. Several spectroscopic techniques (mass spectrometry, FTIR, and 1H, 13C, and 31P NMR), as well as elemental analysis, were employed to characterize the new phosphazenes. All unsymmetrically substituted phosphazenes are expected to be racemic mixtures (RR′/SS′ and RS′/SR′) due to two different stereogenic P-centers. In addition, the molecular and crystal structures of cis-6b, cis-10b, and cis-11b isomers were elucidated via single-crystal X-ray crystallography. They belong to centrosymmetric C2/c, P21/c, and P1¯ space groups, respectively; thus, their crystal lattices must contain both the enantiomers, RR′/SS′ or SR′/RS′. Moreover, only one oxidation–reduction wave was observed for the ferrocenyl-dispirophosphazenes in the reversible cyclic voltammograms. The HOMO and LUMO energy values of the phosphazenes were calculated using the oxidation potential (Eox) and the optical band gap values using Tauc plots, respectively. To determine the phototunable charge storage properties of the four dispirophosphazenes, their memory functions were investigated under UV illumination. The antituberculosis activities of the dichlorodispiro(N/N)cyclotriphosphazenes trans-6a, cis-6b, trans-10a, and cis-10b against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain were evaluated. The results showed that among these compounds, trans-6a (MIC value 18 μg mL−1) was much more effective than the other phosphazenes. [ABSTRACT FROM AUTHOR]

Both starting phosphazenes, tetrachloromono- and tetrachlorobis-(4-fluorobenzyl)monospiro(N/N)cyclotriphosphazenes (1 and 2) were synthesized by the substitution reactions of hexachlorocyclotriphosphazene, N3P3Cl6 (trimer; HCCP) with N-(4-fluorobenzyl)-1,3-diaminopropane (L1) and N,N′-bis(4-fluorobenzyl)-1,3-diaminopropane (L2), respectively. Tetraaminomono-(1a and 1b) and bis-(4-fluorobenzyl)spiro(N/N)cyclotriphosphazenes (2a and 2b) were prepared by the condensation reactions of spiro 1 and 2 with the excess of ethyl piperazine and phenylpiperazine, respectively, in boiling THF. Elemental analysis, FTIR, ESI-MS, 31P, 13C and 1H NMR data identified the structures of the new products. In addition, the solid-state structure of 2b was confirmed by X-ray crystallography. Hirshfeld surface analysis of 2b indicates that the most important contributions for the crystal packing are from H⋯H (61.2%), H⋯C/C⋯H (24.8%) and H⋯F/F⋯H (9.3%) interactions. On the other hand, the inhibitory effects of these cyclotriphosphazenes on the esterase activities of hCA I and hCA II isoenzymes were investigated in vitro. It was determined that compound 2b exhibited a stronger inhibitory effect than compound 2a. [ABSTRACT FROM AUTHOR]

In this research, the starting compounds tetrachloromonospirocyclotriphosphazenes, (BzSpiro-5)R1(N3P3)Cl4 [Bz: Benzyl; R1: Me (1) and R1: Et (2)], were synthesized from the reactions of hexachlorocyclotriphosphazene, N3P3Cl6 (HCCP, trimer) with N/N-donor type benzyldiamines. Both phosphazenes were reacted with 9-ethyl-N-methyl-3-carbazolyldiamines (3 and 4) to form dichloro trans/cisN/N-dispirocyclotriphosphazenes, [(BzSpiro-5)R1(N3P3)(CzSpiro-n)R2]Cl2 (Cz: Carbazolyl; R1, R2: Me or Et; n = 5 or 6; (5a–8a and 5b–8b), containing unsymmetrical diamino precursors. The structure of the cis-5b was clarified by single-crystal X-ray crystallography. The space group of the chiral cis-5b isomer is P−1, which is centrosymmetric, and both enantiomers must be present in the unit cell. Since the absolute configuration of an enantiomer is found as SR′ according to the X-ray crystallography, the other must be RS′. The chiralities of the compounds were also confirmed by 31P NMR spectroscopy recorded upon the addition of chiral solvating agent [(S)-(+)-2,2,2-trifluoro-1-(9′-anthryl)ethanol; CSA] (for 5a, 5b and 8b) and the circular dichroism (CD) (for 5a, 5b, 6a and 6b) spectra. All N/N-dispirocyclotriphosphazenes (5a–8b) bearing carbazole units exhibited a fluorescence profile with a lifetime of about 4.9–6.5 ns and a quantum yield in the range of 0.11–0.20. On the other hand, P. aeruginosa was sensitive to compounds 5b, 7a, 8a and 8b, while E. coli was sensitive to most of the phosphazenes. The cytotoxic activities of phosphazenes against Vero cells (healthy) and MDA-MB-231 breast cancer cells were determined. In addition, compounds 5a and 5b appear to have very high antioxidant activity with respect to radical scavenging activities of 55.1% and 68.3%, respectively. [ABSTRACT FROM AUTHOR]

Organic–inorganic hybrid multi-heterocyclic unsymmetrical cis/trans dispirocyclotriphosphazenes with different pendant arms were obtained and their spectral, stereogenic, photophysical and bioactivity properties were investigated. To prepare these phosphazenes, the starting compounds tetrachloro(4-chlorobenzyl)spiro(N/N)cyclotriphosphazenes, (ClBzSpiro-5)R1(N3P3)Cl4 [Bz: Benzyl; R1: Me (1) and R1: Et (2)], were prepared regioselectively from the reactions of hexachlorocyclotriphosphazene, N3P3Cl6 (HCCP, trimer) with N-methyl/ethyl-N′-(4-chlorobenzyl)-1,2-diaminoethanes. Reactions of tetrachlorocyclotriphosphazenes (1 and 2) and 9-ethyl-N-methyl-3-carbazolyl-1,2-diaminoethane (3) or 9-ethyl-N-methyl-3-carbazolyl-1,3-diaminopropane (4) produce new cis/trans-dispirocyclotriphosphazenes, [(ClBzSpiro-5)R1(N3P3)(CzSpiro-n)R2]Cl2 (Cz: Carbazolyl; R1, R2: Me or Et; n = 5 or 6; (5a–8a and 5b–8b), containing unsymmetrical spiro-architectures. In addition, the structures of trans-7a and cis-7b isomers were clarified by single crystal X-ray crystallography. The chiralities of trans-7a and cis-7b were confirmed using X-ray crystal structures, 31P NMR spectra recorded upon the addition of chiral solvating agent [(S)-(+)-2,2,2-trifluoro-1-(9′-anthryl)ethanol; CSA], and circular dichroism (CD) spectra. Moreover, the photophysical properties of phosphazenes showed a fluorescence profile with lifetimes of about 4.9–6.6 ns and quantum yields in the range of 0.10–0.14. Additionally, the antibacterial and antifungal activities of the newly synthesized phosphazenes against some bacteria and yeast strains and their interactions with pBR322 plasmid DNA were investigated. The bacterial strain most susceptible (MIC = 156.3 μM) to compounds 5a and 8a was P. aeruginosa. However, it was found that the yeast strain most susceptible (MIC = 156.3 μM) to compounds 5b, 7a, 7b and 8b was C.albicans. The cytotoxic activities of 5a, 5b, 7b and 8a against L929 fibroblast and MCF-7 breast cancer cells were determined. However, cis-5b showed reasonable antioxidant activity with a radical scavenging value of 35.20%. [ABSTRACT FROM AUTHOR]

The reaction of octachlorocyclotetraphosphazene, N4P4Cl8 (1) (OCCP, tetramer), with an equimolar amount of sodium 3-(N-ferrocenylmethylamino)-1-propanoxide (L1) resulted in the formation of ferrocenyl-spiro-(2) and ferrocenyl-2-cis-4-dichloro-ansa-(3) cyclotetraphosphazenes. Both of the starting compounds were used to produce the new inorganic–organic hybrid multiheterocyclic-spiro and ansa cyclotetraphosphazenes. Spiro (2) was treated with excess N-(4-fluorobenzyl)-N′-ethyl-1,2-diaminoethane (L2) to give 2-trans-6-dispiro (trans-2a) and 2-trans-4-cis-6-trans-8-tetraspiro (tetraspiro-2a) cyclotetraphosphazenes. Spiro (2) was also reacted with excess sodium 3-(4-fluorobenzylamino)-1-propanoxide (L3) to produce 2-trans-6-dispiro (trans-2b), 2-cis-6-dispiro (cis-2b), 2-cis-4-trans-6-trispiro (trans-2c), 2-cis-4-cis-6-trispiro (cis-2c), 2-cis-4-dichloro-ansa-4-trans-6-spiro(N/O) (ansa-2b) and 2-cis-4-dichloro-ansa-6-trans-8-dispiro(N/O) (ansa-2c). The reactions of 2,4-ansa (3) with excess L2 led to the formation of 2-cis-4-dichloro-ansa-2-trans-6-spiro(N/N) (trans-3a) and 2-cis-4-dichloro-ansa-2-cis-6-spiro(N/N) (cis-3a) cyclotetraphosphazenes. However, the reactions of 2,4-ansa (3) with excess L3 afforded monospiro {2-cis-4-dichloro-ansa-4-trans-6-spiro(N/O) (trans-3b) and 2-cis-4-dichloro-ansa-4-cis-6-spiro(N/O) (cis-3b)} and dispiro {2-cis-4-dichloro-ansa-6-trans-8-dispiro(N/O) (trans-3c) and 2-cis-4-dichloro-ansa-6-cis-8-dispiro(N/O) (cis-3c)}. The obtained products were characterized by spectroscopic techniques. The crystal structures of trans-2b and cis-3b were clarified by single crystal X-ray analysis. The products had stereogenic P-centres except for trans-2a , tetraspiro-2a , trans-2b and cis-2b. The stereogenic properties of tetrameric phosphazenes were evaluated by X-ray crystallography and chiral high performance liquid chromatography (HPLC) methods. The structure of cis-3b revealed the absolute configurations of the enantiomers (SS′R′′/RR′S′′). The broad HPLC peak of cis-3b indicates that it may exist as a resamate in solution. The cytotoxic activities of the cyclotetraphosphazenes were evaluated using an MTT assay against L929 mouse fibroblasts, A549 non-small lung cancer and Caco-2 colorectal adenocarcinoma cells. Compound cis-3b was found to be very effective in all cell lines up to 104.1 μM. [ABSTRACT FROM AUTHOR]

The phosphazenium salts (protic ionic liquids, PILs/protic molten salts, PMOSs) (6a-6d and 7a) of the free phosphazene bases (4a-4d and 5a) have been prepared by the reactions of the corresponding cyclotriphosphazenes with the bulky gentisic acid. The structures of the PMOS have been evaluated using the elemental analyses, FTIR, 1H, 13C{1H} and 31P{1H} NMR data. The molecular and crystal structures of 4a and 6c are established by X-ray crystallography. The thermal properties of the PMOS are determined using TG and DTA techniques. On the other hand, the antimicrobial activities of the free phosphazene bases (4a-4d and 5a-5d) and PMOSs (6a-6d and 7a) are screened against the selected bacteria and yeast strains. The antimicrobial activities of the free phosphazene bases and the PMOSs are compared. The interactions of the phosphazenes and their salts with plasmid DNA are elucidated by the agarose gel electrophoresis. The evaluations of the cytotoxic activities of these compounds are also studied against to L929 fibroblast and breast cancer cells (MDA-MB-231). [ABSTRACT FROM AUTHOR]

The reaction of N4P4Cl8 (1) with one equimolar amount of the sodium salt of an N/O donor-type bidentate ligand (2) afforded two kinds of derivatives, namely, mono-ferrocenyl-2-cis-4-dichloro-ansa- (2,4-ansa; 3) and mono-ferrocenyl-spiro- (spiro; 4) hexachlorocyclotetraphosphazenes. The reaction yield (35%) of 4 was significantly larger than that of 3 (14%). The 2,4-ansa compound (3) was reacted with excess secondary amines to produce 2-cis-4-dichloro-ansa-cyclotetraphosphazenes (3a–3d). On the other hand, the spiro compound (4) gave fully substituted mono-ferrocenyl-spiro-cyclotetraphosphazenes (4a–4d) with excess monoamines as well. The tetrameric phosphazene derivatives were characterized by ESI-MS and/or HRMS, FTIR, HSQC, HMBC, 1H, 13C, and 31P NMR spectroscopy and X-ray crystallography (for 4). It is observed that the 2,4-ansa and spiro-cyclotetraphosphazenes have different thermal stabilities. Additionally, the CVs of the new mono-ferrocenyl pendant-armed cyclotetraphosphazenes revealed electrochemically reversible one-electron oxidation of the Fe-redox centre. The 2,4-ansa phosphazenes (3 and 3a–3d) have two different stereogenic P centers indicating that they are expected to be in racemic mixtures (RR′/SS′). The chiralities of 3a and 3c were investigated by chiral HPLC. The manuscript also deals with the antimicrobial activities against G(+)/G(−) bacteria and fungi, the interactions with plasmid DNA, the in vitro cytotoxic activities against L929 fibroblast and MCF7 breast cells, and the antituberculosis activities against Mycobacterium tuberculosis H37Rv of the cyclotetraphosphazenes. [ABSTRACT FROM AUTHOR]

• New tetrachloro and tetraamino(2-furanylmethyl)spiro(N/N)cyclotriphosphazenes were prepared. • The characteristic NMR spectral data of the compounds were elucidated. • The crystal structures of five phosphazenes were determined crystallographically. • The antiproliferative and antimigratory activities of the phosphazenes were discussed. In this research, the Schiff bases prepared from the condensation reactions of furfural with N-ethyl-1,2-diaminoethane and N-methyl-1,3-diaminopropane were reduced to N/N-donor type diamines (1 and 2) to obtain the starting diamines. The tetrachloro(2-furanylmethyl)spiro-(N/N)cyclotriphosphazenes (3 and 4) were formed regioselectively in excellent yields, when the hexachlorocyclotriphosphazene, N 3 P 3 Cl 6 (HCCP , trimer), was reacted with the diamines. The Cl replacement reactions of 3 and 4 with pyrrolidine and piperidine yielded tetrapyrrolidino (3a and 4a) and tetrapiperidino (3b and 4b) cyclotriphosphazenes, respectively. The structures of all cyclotriphosphazenes were proven by FT-IR, HRMS, 1H, 13C, and 31P NMR data. The crystal structures of 3, 4, 3a, 3b and 4b were elucidated using single crystal X-ray crystallography. Tetraamino(2-furanylmethyl)spiro(N/N)cyclotriphosphazenes (3a, 3b, 4a and 4b) were tested by MTT assay for their ability to inhibit the growth of human breast cancer MCF-7, prostate cancer PC-3 and colon cancer HT-29 cells. Besides, the antimigratory activities of these compounds on three cell lines were also investigated by in vitro scratch analysis. The results show that the compounds have varying degrees of success in inhibiting the growth and migration of various cancer cells. However, the most effective phosphazene derivatives against these cancer cell lines were the five-membered N-ethyl phosphazenes (3a and 3b). [Display omitted] [ABSTRACT FROM AUTHOR]

• Dispirocyclotriphosphazenes with unsymmetrical pendant arms were obtained. • Crystal structures of four dispirophosphazenes were enlightened by X-ray technique. • Electrochemical behaviors of the phosphazenes compounds were evaluated. • The usability of the dispirophosphazenes in DSSCs was investigated. • Antituberculosis activities of three compounds were determined. In this study, dichlorobisspiro(N/N)cyclotriphosphazenes with 4-chlorobenzyl and ferrocenyl-pendant arms were prepared to investigate their spectroscopic and crystallographic characterizations, and antituberculosis activities. The chlorine replacement reactions of tetrachloro(4-chlorobenzyl)spiro(N/N)cyclotri-phosphazenes with ferrocenyldiamines (4 and 5) lead to dichlorobispiro(N/N)cyclotriphosphazenes, containing unsymmetrical diaminospirorings. All cyclotriphosphazenes were characterized by mass spectrometry, FTIR and 31P NMR spectroscopies. Two different stereogenic P-centers are present in the unsymmetrically substituted inorganic-organic fused hybrid rings. These compounds may be in the form of racemic mixtures (RR'/SS' and RS'/SR'). The molecular and crystal structures of trans (6a and 7a) and cis (6b and 7b) isomers were elucidated by single-crystal X-ray structural crystallography. The space groups of trans- 6a , cis- 6b , trans- 7a and cis- 7b are centrosymmetric P -1, P bca, P 2 1 /n and P bca, respectively. Therefore, the crystal lattices contain both enantiomers. The absolute configurations of P2 atoms of 6a, 6b, 7a and 7b are R, R, S and S, respectively. It was determined that the most effective compound was 6b against Mycobacterium tuberculosis H37Rv (ATCC 27,294) strain among the phosphazenes 6a, 6b and 10b. Among the compounds, In the reversible cyclic voltammograms of ferrocenyl-dispirophosphazenes , only one oxidation–reduction wave was observed. The HOMO energy values of the compounds were figured out using the oxidation potential (Eox). Whereas, the LUMO energy values were figured out from the optical band gap values using Tauc plots. In addition, it was determined that the most effective compound that can be used in dye-sensitized solar cells (DSSCs) is cis- 11b. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ditopic, tritopic and tetratopic phosphaza-crown ether ligands were synthesized. • Sodium complexes of monoferrocenylspirocyclotriphosphaza-crown ethers were obtained. • The structures of the compounds were investigated using spectroscopic methods. • The crystal structures of the two compounds were determined by X-ray crystallography. • The chirality of the cyclophosphazenes were discussed. In the present investigation, it is observed that condensation reactions of hexachlorocyclotriphosphazene, N 3 P 3 Cl 6 (HCCP , trimer) and four different diamines (1 – 4) yielded tetrachloromono (5 , 7 and 8) and bisferrocenyl (6) spirocyclotriphosphazenes. Reactions of 5 , 7 and 8 with two equimolar amounts of 1-aza-15-crown-5 ether (L) produced new monoferrocenylspirocyclotriphosphazabis(crown ethers) (9, 10 and 12) in THF, respectively. The only monoferrocenylspirocyclotriphosphazatris(crown ether) (13) was obtained from the reaction of 8 with three equimolar amounts of L. However, reactions of 7 and 8 with four equimolar amounts of L resulted in the formation of monoferrocenylspirocyclotriphosphaza-tetrakis(crown ethers) 11 and 14. In addition, the complexation reactions of ditopic phosphaza-crown ethers (9 , 10 and 11) with NaClO 4 yielded novel mononuclear sandwich-type sodium complexes (9a , 10a and 11a). Tri- and tetranuclear complexes (13a and 14a) were obtained as a result of the complexation reactions of tri- and tetratopic phosphaza-crown ethers (13 and 14) with NaClO 4. Characterizations of phosphaza-crown ethers and complexes were performed using elemental analysis, mass spectrometry, FTIR, and 1H, 13C and 31P NMR techniques. Ditopic phosphazenes (9 , 10 and 12) and complexes (9a , 10a and 11a) have a stereogenic P center. While the tritopic ligand (13) and complex (13a) have two stereogenic P centers. They are expected to be in racemic mixtures. In addition, crystal structures of phosphazenes 6 and 9 were elucidated using X-ray crystallography. The absolute configurations of the enantiomers of 9 were determined as R and S. Furthermore, intermolecular interactions in crystal structures of 6 and 9 were determined by Hirshfeld surface (HS) analysis. [ABSTRACT FROM AUTHOR]

Graphical abstract The Cl exchange reactions of hexachlorocyclotriphosphazene, N 3 P 3 Cl 6 , were carried out with the bidentate ligands to obtain the new phosphazene derivatives. The spectroscopic and crystallographic properties of the compounds were investigated in detail. The absolute configurations of the two compounds were unambiguously established using X-ray crystallographic data. In addition, the interactions of the compounds with plasmid DNA indicated that these compounds caused a decrease in the mobilities and intensities of form I and form II DNA. The tested compounds inhibited enzyme cleavage indicating compound bindings to the specific G/G and A/A nucleotides. Highlights • New dispirocyclotriphosphazenes were prepared. • The crystal structures of three compounds were established by X-ray crystallography. • The absolute configurations of the products were unambiguously determined. • The compounds caused the changes and damages in DNA conformation. Abstract The Cl exchange reactions of hexachlorocyclotriphosphazene, N 3 P 3 Cl 6 , with two equimolar amounts of N -alkyl-N′-mono(4-fluorobenzyl)diamines (1 – 3), FC 6 H 4 CH 2 NH(CH 2) n NHR 1 (n = 2 and 3, R 1 = CH 3 or C 2 H 5), and N -alkyl-N′-mono(4-nitrobenzyl)diamines (4 and 5), NO 2 C 6 H 4 CH 2 NH(CH 2) n NHR 1 (n = 2, R 1 = CH 3 or C 2 H 5), led to the formation of the mono(4-fluorobenzyl) (1a - 3a) and mono(4-nitrobenzyl) (4a and 5a) spirocyclotriphosphazenes as minor products, and trans -bis(4-fluorobenzyl) (1b - 3b) and trans -bis(4-nitrobenzyl) (4b and 5b) spirocyclotriphosphazenes as major products. The bis(4-fluorobenzyl)spirocyclotriphosphazene (1b) reacted with excess pyrrolidine to give fully substituted (1c) phosphazene. The structures of the new compounds were elucidated by elemental analyses, ESI-MS, FTIR, 1H, 13C, and 31P NMR techniques. The molecular and crystal structures of 1a , 3b and 6 were identified by single crystal X-ray crystallography. The absolute configurations of 3b and 6 were unambiguously established as SS and R respectively, using X-ray crystallographic data. On the other hand, the interactions of 1b , 1c , 3b - 5b and 6 with plasmid DNA indicated that compounds 3b , 4b , and 5b caused a decrease in the mobilities and intensities of form I and form II DNA. Compounds 1b , 1c and 6 caused a double strand break of plasmid DNA. All of the tested compounds inhibited enzyme cleavage indicating compound bindings to the specific G/G and A/A nucleotides. [ABSTRACT FROM AUTHOR]

• The cis and trans benzylspiro(N/N)cyclotriphosphazenes were synthesized. • The spectral analyses of all the phosphazenes were presented. • The absolute configurations of the two compounds were examined by X-ray crystallography. • Chirality of the phosphazenes was interpreted using 31P NMR upon the addition of CSA. • Hirshfeld surface analysis was carried out for two compounds. In the present study, dichloro trans-(7, 8 and 9) and cis-(10, 11 and 12) bis(benzylspiroN/N)cyclo-triphosphazenes were prepared by the reaction of hexachlorocyclotriphosphazene, N 3 P 3 Cl 6 (HCCP ; trimer) with the corresponding diamines (1, 2 and 3). The reactions of 7, 9 and 10 with excess pyrrolidine yielded trans-(13 and 14) and cis-(15) geminal-phosphazenes. Cis-derivatives (10, 11, 12 and 15) are to be in the meso form (RS/SR). Since the two benzyl groups are in the trans position in compounds 7, 8, 9, 13 and 14 , they are only expected to be in the form of a racemic mixture (RR/SS). The space groups of 7 and 13 were found to be P 2 1 /n and P 2 1 /c, respectively. These two space groups are centrosymmetric and both enantiomers must exist in the crystal lattices of the compounds. Since the absolute configurations of enantiomers of 7 and 13 are respectively found as RR and SS by X-ray crystallography, the others must be SS and RR. The chiralities of 7 and 13 were also confirmed using 31P NMR spectroscopy recorded upon the addition of chiral solvating agent [(S)-(+)-2,2,2-trifluoro-1-(9'-anthryl)ethanol, CSA]. In addition, Hirshfeld surface (HS) analysis indicated van der Waals interactions as leading intermolecular interactions in the crystal structures. [Display omitted] [ABSTRACT FROM AUTHOR]

New tetraamino-bis(4-fluorobenzyl)-spiro(N/N)cyclotriphosphazenes are synthesized. The salient features of the spectroscopic data of the compounds are presented. The solid-state crystal structures of two compounds are verified by the X-ray crystallography method, and intermolecular interactions are determined with HS analysis. In addition, the investigations of the antibacterial, antifungal, antioxidant and DNA cleavage activities of these compounds are examined. [Display omitted] • New three tetraamino-bis(4-fluorobenzyl)-spiro(N/N)cyclotriphosphazenes were prepared. • The characteristic spectral data of the compounds were elucidated. • The crystal structures of two phosphazenes were determined crystallographically. • Phosphazenes interact with DNA and inhibit the enzyme digestion showing a bind to A/A and G/G. • MIC, MBC and MFC values of the compounds ranged from 312.5 and > 2500 µM. Substitution reaction of hexachlorocyclotriphosphazatriene (trimer; N 3 P 3 Cl 6 ; HCCP) with N , N '-bis(4-fluorobenzyl)ethane-1,2-diamine (1) gave the starting compound tetrachlorobis(4-fluorobenzyl)monospiro(N/N)cyclotriphosphazene (2). Tetraaminobis(4-fluorobenzyl)spiro(N/N) cyclotriphosphazenes (2a - 2c) were synthesized from the substitution reactions of spiro (2) with excess piperidine, ethylpiperazine and phenylpiperazine, respectively, in boiling THF. Elemental analysis, ESI-MS, FTIR, 1H, 13C and 31P NMR data verified the structures of new compounds; and the solid-state crystal structures of 2a and 2b were elucidated using the X-ray crystallography method. Hirshfeld surface (HS) analyses were performed to figure out the intermolecular interactions in these crystals as well. Moreover, the minimum inhibitory, bactericidal and fungicidal concentrations (MIC, MBC and MFC) were determined using the microdilution method, which was used to detect the compounds that have the antimicrobial effects on microorganisms exhibited the effect at which concentration. It was concluded that MIC, MBC and MFC values ranged from 312.5 and > 2500 µM. Furthermore, DNA cleavage and unwinding properties of 2a , 2b and 2c with pBR322 plasmid DNA were examined by agarose gel electrophoresis. Also, compound-DNA incubation and Bam HI and Hind III restriction enzyme digestions were realized to provide more insight into changes in DNA conformation. Finally, the antioxidant activity was determined that 2c had the highest antioxidant capacity with a 38.38% radical scavenging activity value. [ABSTRACT FROM AUTHOR]

The reactions of hexachtorocyclotriphosphazatriene, N3P3Cl6, with N/O-donor-type Al-alkyl (or aryl)-o-hydroxybenzy- famines (1a-1e) produce mono- (2a-2e), di- (3a-3d), and tri- (4a and 4b) spirocyclic phosphazenes. The tetrapyrrotidino monospirocyclic phosphazenes (2f-2i) are prepared from the reactions of partly substituted compounds (2a-2d) with excess pyrrolidine. The dispirodipynotidinophosphazenes (3e-3h) and tnispirophospha- zenes (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 lobe 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 30 have shown a strong affinity against most of the bacteria. Minimum inhibitory concentrations (MIC) are determined for 2f-2i, 3e-31, 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 BamHl and HindII digestion (except 2g) with compounds indicates that the compounds bind with nucleotides in DNA. [ABSTRACT FROM AUTHOR]

The N/N donor-type bromobenzyldiamines (1 – 3) were successively prepared by reduction of Schiff bases formed as a result of condensation reactions of 4-bromobenzaldehyde with aliphatic diamines. The Cl exchange reactions of hexachlorocyclotriphosphazene (HCCP; trimer; N 3 P 3 Cl 6 ; 4) with the bidentate ligands (1 – 3) produced the new monospiro- (5 – 7) and dispirocyclotriphosphazenes (8 – 13) containing 4-bromo-benzyl pendant arm(s). The tetrachloro phosphazenes (5 – 7) were reacted with pyrrolidine, tetra-1,4-dioxa-8-azaspiro [4.5]decane (DASD) and piperidine to give the tetraamino substituted monospirophosphazenes (5a - 7c). The spectral analyses of all the phosphazenes were made using appropriate spectroscopic methods; such as FTIR, 1H, 13C, 31P NMR and ESI-MS. The molecular and crystal structures of 5 , 6 , 7 and 12 were also determined by X-ray crystallography. On the other hand, the antimicrobial activities of the phosphazenes were evaluated against G (−) and G (+) bacteria and fungi. Some of the tetraaminophosphazenes were found to be very active against several bacteria and fungi. Besides, the interactions of the cyclotriphosphazenes with plasmid DNA were investigated using agarose gel electrophoresis. Image 1 • The mono/dispirocyclotriphosphazenes with 4-bromobenzyl pendant arms were obtained. • The spectral analyses of the new phosphazenes were made. • The crystal structures of four phosphazenes were examined by X-ray crystallography. • The one of the cis -dispiro compound crystallizes forming racemic (RS/SR) mixture. • The antimicrobial activities of the phosphazenes were discussed. [ABSTRACT FROM AUTHOR]