The Spectroscopic and Thermal Properties, Antimicrobial Activities and DNA Interactions of 4-(Fluorobenzyl)Spiro(N/O) Cyclotriphosphazenium Salts

Abstract

The protic ionic liquids (PILs) (3a-3d) were synthesized from the reactions of tetraamino-4-(fluorobenzyl)spiro(N/O)cyclotriphosphazenes (2a-2d) with the gentisic acid in THF. The structures of the PILs were verified by elemental analyses, Fourier transform infrared (FTIR), ¹H, ¹³C {¹H} and ³¹P {¹H} NMR techniques. The thermal properties of the PILs were evaluated using TG/DTG/DTA instrument. On the other hand, the antimicrobial activities of the PILs were examined against some bacteria and fungi, and the obtained results were compared with the evaluations of the corresponding fully substituted cyclotriphosphazene bases. The interactions between the PILs and supercoiled PBR322 DNA were also scrutinized, and it was determined that they exhibited significant conformational changes.

Keywords

• PILs,Thermal analysis,Spectroscopy,Antimicrobial activity,DNA binding

References

1. Referans1. Stewart FF. Phosphazenes. Organophosphorus Chem. 2015 Apr; 44: 397–430, Royal Sciety of Chemistry (RSC Publishing).
2. Referans2. Chandrasekhar V, Narayanan RS. Phosphazenes. Organophosphorus Chem. 2016 Mar; 45: 375-437, Royal Sciety of Chemistry (RSC Publishing).
3. Referans3. Egemen G, Hayvalı M, Kılıç Z, Solak AO, Üstündağ Z. Phosphorus-Nitrogen Compounds. Part 17. The Synthesis, Spectral and Electrochemical Investigations of Porphyrinophosphazenes. J. Porphyrins Phthalocyanines. 2010; 14: 1-8.
4. Referans4. Okumuş A, Bilge S, Kılıç Z, Öztürk A, Hökelek T, Yılmaz F. Phosphorus–nitrogen compounds. part 20: fully substituted spiro-cyclotriphosphazenic lariat (PNP-pivot) ether derivatives. Spectrochimica Acta Part A. 2010 Apr; 76: 401-9.
5. Referans5. İlter EE, Asmafiliz N, Kılıç Z, Işıklan M, Hökelek T, Çaylak N, Şahin E. Phosphorus−nitrogen compounds. 14. synthesis, stereogenism, and structural ınvestigations of novel N/O spirocyclic phosphazene derivatives. Inorg. Chem. 2007 Oct; 46: 9931-44.
6. Referans6. Işıklan M, Asmafiliz N, Özalp EE, İlter EE, Kılıç Z, Çoşut B, Yeşilot S, Kılıç A, Öztürk A, Hökelek T, Koç LY, Açık L, Akyüz E. 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. Inorg. Chem. 2010 Jun; 49: 7057-71.
7. Referans7. Işıklan M, Sonkaya Ö, Çoşut B, Yeşilot S, Hökelek T. Microwave-assisted and conventional synthesis and stereogenic properties of monospirocyclotriphosphazene derivatives. Polyhedron. 2010 Apr; 29 (6): 1612-18.
8. Referans8. Asmafiliz N, Kılıç Z, Hayvalı Z, Açık L, Hökelek T, Dal H, Öner Y. Phosphorus-nitrogen compounds. Part 23: syntheses, structural investigations, biological activities, and DNA interactions of new N/O spirocyclotriphosphazenes. Spectrochimica Acta Part A. 2012 Feb; 86: 214-23.

9. Referans9. Omotowa BA, Phillips BS, Zabinski JS, Shreeve JM. Phosphazene- based ionic liquids: synthesis, temperature-dependent viscosity, and effect as additives in water lubrication of silicon nitride ceramics. Inorg. Chem. 2004 July; 43: 5466-71.
10. Referans10. Jimenez J, Laguna A, Gascon E, Sanz JA, Serrano JL, Barbera J, Oriol L. New liquid crystalline materials based on two generations of dendronised cyclophosphazenes. Chem. Eur. J. 2012 Nov; 18: 16801-14.
11. Referans11. Harrup MK, Gering KL, Rollins HW, Sazhin SV, Benson MT, Jamison DK, Michelbacher CJ, Luther TA. Phosphazene based additives for improvement of safety and battery lifetimes in lithium-ion batteries. ESC Trans. 2012 May; 41 (39): 13-25.
12. Referans12. Nishimoto T, Yasuda T, Lee SY, Kondo R, Adachi C. A six-carbazole-decorated cyclophosphazene as a host with high triplet energy to realize efficient delayed-fluorescence OLEDs. Mater. Horiz. 2014 Sep; 1: 264-69.
13. Referans13. Coşut B, Hacıvelioğlu F, Durmuş M, Kılıç A, Yeşilot S. The synthesis, thermal and photophysical properties of phenoxycyclotriphosphazenenyl-substituted cyclic and polymeric phosphazenes. Polyhedron. 2009 Aug; 28: 2510-16.
14. Referans14. Yenilmez Çiftçi G, Şenkuytu E, Durmuş M, Yüksel F, Kılıç A. Fluorenylidene bridged cyclotriphosphazenes: ‘turnoff’ fluorescence probe for Cu2+ and Fe3+ ions. Dalton Trans. 2013 Aug; 42: 14916-26. Referans15. Kağıt R, Yıldırım M, Ozay O, Yeşilot S, Ozay H. Phosphazene based multicentered naked-eye fluorescent sensor with high selectivity for Fe3+ ions. Inorg. Chem. 2014 Feb; 53: 2144-51.
15. Referans16. Al kubaisi AH, Deutsche WF, Hursthouse MB, Parkesa HG, Shaw LY, Shaw RA. The Reactions of N3P3Cl6 and related compounds wıth difunctıonal reagents. comparisons and contrasts. Phosphorus and Sulfur and the Related Elements. 1986 Dec; 28 (1-2): 229-37.
16. Referans17. Akbaş H, Okumuş A, Karadağ A, Kılıç Z, Hökelek T, Süzen Y, Koç LY, Açık L, Aydın B, Türk M. Phosphorus–nitrogen compounds: part 32. structural and thermal characterizations, antimicrobial and cytotoxic activities, and in vitro DNA binding of the phosphazenium salts. J. Therm. Anal. Calorim. 2016 Sep; 123: 1627-41.
17. Referans18. Elmas G, Okumuş A, Kılıç Z, Gönder LY, Açık L, Hökelek T. The Syntheses and Structural Characterizations, Antimicrobial Activity and in vitro DNA Binding of 4-Fluorobenzylspiro(N/O)cyclotriphosphazenes and their Phosphazenium Salts. JOTCSA, 2016 Aug; 3 (3): 25-46.
18. Referans19. Akbaş H, Karadağ A, Aydın A, Destegül A, Kılıç Z. Synthesis, structural and thermal properties of hexapyrrolidinocyclotriphosphazenes-based protic molten salts: antiproliferative effects against HT29, HeLa, and C6 cancer cell lines. J. Mol. Liq. 2017 Jan; 230: 482-95.
19. Referans20. Bruker program 1D WIN-NMR (release 6.0) and 2D WIN-NMR (release 6.1).
20. Referans21. Seto S, Tanioka A, Ikeda M, Izawa S. European Patent Office, Bulletin, 2004.
21. Referans22. Okumuş A, Elmas G, Kılıç Z, Ramazanoğlu N, Açık L, Türk M, Akça G. The reactions of N3P3Cl6 with monodentate and bidentate ligands: The syntheses and structural characterizations, in vitro antimicrobial activities and DNA interactions of 4-fluorobenzyl(N/O)spirocyclotriphosphazenes. Turk. J. Chem. 2017 March; DOI: 10.3906/kim-1612-80.
22. Referans23. Tümer Y, Koç L.Y, Asmafliz N, Kılıç Z, Hökelek T, Soltanzade H, Açık L, Yola ML, Solak AO. Phosphorus–nitrogen compounds: part 30. syntheses and structural investigations, antimicrobial and cytotoxic activities and DNA interactions of vanillinato-substituted NN or NO spirocyclic monoferrocenyl cyclotriphosphazenes. J. Biol. Inorg. Chem. 2015 Dec; 20: 165-78.
23. Referans24. Mutlu G, Elmas G, Kılıç Z, Hökelek T, Koç LY, Türk M, Açık L, Aydın B, Dal H. Phosphorus-nitrogen compounds: part 31. syntheses, structural and stereogenic properties, in vitro cytotoxic and antimicrobial activities, DNA interactions of novel bicyclotetraphosphazenes containing bulky side group. Inorganica Chimica Acta. 2015 July; 436: 69-81.
24. Referans25. Akbaş H, Okumuş A, Kılıç Z, Hökelek T, Süzen Y, Koç LY, Açık L, Çelik ZB. Phosphorus-nitrogen compounds: part 27. syntheses, structural characterizations, antimicrobial and cytotoxic activities, and DNA interactions of new phosphazenes bearing secondary amino and pendant (4-fluorobenzyl)spiro groups. European Journal of Medicinal Chemistry. 2013 Dec; 70: 294-307.
25. Referans26. Başterzi NS, Bilge Koçak S, Okumuş A, Kılıç Z, Hökelek T, Çelik Ö, Türk M, Koç L. Y, Açık L, Aydın B, Dal H. Syntheses, structural characterization and biological activities of spiro-ansa-spiro-cyclotriphosphazenes. New J. Chem. 2015 Sep; 39: 8825-39.
26. Referans27. Haapasalo M, Ranta H, Ranta KT. Facultative gram-negative enteric rods in persistent periapical infections. Acta Odontol Scand. 1983; 41: 19-22.
27. Referans28. Okumuş A, Elmas G, Cemaloğlu R, Aydın B, Binici A, Şimşek H, Açık L, Türk M, Güzel R, Kılıç Z, Hökelek T. Phosphorus-nitrogen compounds. part 35. syntheses, spectroscopic and electrochemical properties, antituberculosis, antimicrobial and cytotoxic activities of mono-ferrocenyl-spirocyclotetraphosphazenes. New J. Chem. 2016 Apr; 40: 5588-603.
28. Referans29. Elmas G, Okumuş A, Sevinç P, Kılıç Z, Açık L, Atalan M, Türk M, Deniz G, Hökelek T. Phosphorus-nitrogen compounds. Part 37. Syntheses and structural characterizations, biological activities of mono and bis(4-fluorobenzyl)spirocyclotetraphosphazenes. New J. Chem. 2017; DOI: 10.1039/C7NJ00478H.