Teofilin Grubu İçeren s-Triazin Türevlerinin ve Bazı Geçiş Metal Komplekslerinin Sentezi ve Karakterizasyonu

Abstract

Bu çalışmada, iki yeni teofilin sübstitüe s-triazin ligandı ve bunların trinükleer kompleksleri sentezlendi. Teofilin-7-asetik asit (I), tiyonil klorür ile reaksiyona sokularak asidik kısmın klorlanmasıyla 2-(1,3-dimetil-2,6-diokso-2,3-dihidro-1H-purin-7(6H)-il)asetil klorür (II) elde edildi. Bu bileşik, AlCl3 katalizörlüğünde diklorometan içinde -10°C'de 24 saat boyunca ayrı ayrı o-fenilendiamin ve p-fenilendiamin ile reaksiyona sokuldu. Bu reaksiyonlar sonucunda III ve IV bileşikleri elde edildi. Daha sonra III ve IV bileşikleri, etanol içinde ayrı ayrı 2,4,6-tri(p-formilfenoksi)-1,3,5-triazin (TRIPOD) ile reaksiyona sokularak s-triazin çekirdekli üç ayaklı ligandlar ACL1 ve ACL2 elde edildi. Tripodal geçiş metal kompleksleri (ACC1-ACC8), ACL1 ve ACL2'nin çeşitli geçiş metal tuzları (MCl2.nH2O, M=Mn2+, Co2+, Ni2+ ve Cu2+) ile reaksiyonu sonucu elde edildi. Elde edilen tüm ligandların yapıları 1H ve 13C NMR, FTIR ve elementel analiz yöntemleriyle aydınlatıldı. Komplekslerin yapıları ise FTIR, manyetik duyarlılık, ICP-OES ve TGA yöntemleri kullanılarak karakterize edildi.

Keywords

• Teofilin
• teofilin-7-asetik asit
• s-triazin
• metal kompleksleri

Synthesis and Characterization of s-Triazine Derivatives Containing Theophylline Group, and Some Transition Metal Complexes

Abstract

In this paper, two novel theophylline-substituted s-triazine ligands and their trinuclear complexes were synthesized. Theophylline-7-acetic acid (I) was reacted with thionyl chloride, resulting in chlorination of the acidic moiety to afford 2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)acetyl chloride (II). This compound was reacted separately with o-phenylenediamine and p-phenylenediamine in the presence of AlCl₃ as a catalyst in dichloromethane at -10°C for 24 h. As a result of these reactions, compounds III and IV were obtained. Compounds III and IV were then separately reacted with 2,4,6-tri(p-formylphenoxy)-1,3,5-triazine (TRIPOD) in ethanol, yielding the s-triazine-cored tripodal ligands ACL1 and ACL2. Tripodal transition metal complexes (ACC1-ACC8) were obtained by reacting ACL1 and ACL2 with various transition metal salts (MCl2.nH2O, M=Mn2+, Co2+, Ni2+, and Cu2+). The structures of all obtained ligands were elucidated by 1H and 13C NMR, FTIR, and elemental analysis methods. The structures of the complexes were characterized using FTIR, magnetic susceptibility, ICP-OES, and TGA methods.

Keywords

• Theophylline
• Teophylline-7-acetic acid
• s-Triazine
• Metal complexes

References

1. E.M. Smolin, L. Rapoport, S-Triazines and Derivatives, Vol. 13, John Wiley & Sons, 2009.
2. A. Schwarzer, T. Saplinova, E. Kroke, Tri-s-triazines (s-heptazines)—From a “mystery molecule” to industrially relevant carbon nitride materials, Coord. Chem. Rev., 257 (2013) 2032-2062.
3. N. Kushwaha, C. Sharma, The chemistry of triazine isomers: Structures, reactions, synthesis and applications, Mini-Rev. Med. Chem., 20 (2020) 2104-2122.
4. B. Salaković, S. Kovačević, M. Karadžić Banjac, S. Podunavac-Kuzmanović, L. Jevrić, I. Pajčin, J. Grahovac, New perspective on comparative chemometric and molecular modeling of antifungal activity and herbicidal potential of alkyl and cycloalkyl s-triazine derivatives, Processes, 11 (2023) 358.
5. F.G. Zhang, Z. Chen, X. Tang, J.A. Ma, Triazines: Syntheses and inverse electron-demand Diels–Alder reactions, Chem. Rev., 121 (2021) 14555-14593.
6. E.T. Parker, Scope and Influence of Enhanced Triazine Degradation in US Soils, 2017.
7. S. Klementova, L. Keltnerova, Triazine herbicides in the environment, in: Herbicides, Physiology of Action, and Safety, 2015, pp. 71-96.
8. T.W. Baumann, Some thoughts on the physiology of caffeine in coffee: and a glimpse of metabolite profiling, Braz. J. Plant Physiol., 18 (2006) 243-251.

9. S. Budavari, M.J. O’Neil, A. Smith, P.E. Heckelman, The Merck Index, Vol. 11, Merck, Rahway, NJ, USA, 1989.
10. S. Scheindlin, A new look at the xanthine alkaloids, Mol. Interv., 7 (2007) 236.
11. S.O. Kayaalp, Rasyonel Tedavi Yönünden Tıbbi Farmakoloji, 1. Cilt, Hacettepe-Taş Kitapçılık, 2000.
12. E. McFadden Jr., Methylxanthines in the treatment of asthma: The rise, the fall, and the possible rise again, Ann. Intern. Med., 115 (1991) 323-324.
13. C. Persson, A. Draco, Xanthines as airway anti-inflammatory drugs, J. Allergy Clin. Immunol., 81 (1988) 615-617.
14. P. Sullivan, Anti-inflammatory effect of low-dose oral theophylline in atopic asthma, Lancet, 343 (1994) 1512.
15. Y. Cevik, C. Kavalcı, M. Daş, S. İzdeş, Severe theophylline intoxication, rhabdomyolysis, disseminated intravascular coagulopathy and death, J. Emerg. Med. Case Rep., 1 (2010) 24-27.
16. M.W. Edmunds, M.S. Mayhew, Pharmacology for the Primary Care Provider, Elsevier Health Sciences, 2013.
17. M. Caraglia, M. Marra, G. Giuberti, A.M. D’Alessandro, S. Beninati, A. Lentini, S. Pepe, M. Boccellino, A. Abbruzzese, Theophylline-induced apoptosis is paralleled by protein kinase A-dependent tissue transglutaminase activation in cancer cells, J. Biochem., 132 (2002) 45-52.
18. M. Mabed, S. Aref, M. Fouda, S. El-Sharawy, Chlorambucil plus theophylline vs chlorambucil alone as a front line therapy for B-cell chronic lymphatic leukemia, Leuk. Lymphoma, 45 (2004) 2029-2035.
19. Ş. Uysal, Z.E. Koç, Synthesis and characterization of dopamine substitute tripodal trinuclear complexes capped s-triazine complexes: Investigation of their thermal and magnetic properties, J. Mol. Struct., 1109 (2016) 119-126.
20. Ş. Uysal, H.İ. Uçan, The synthesis and characterization of 2,4,6-tris(3,4-dihydroxybenzimino)-1,3,5-triazine and its complexes, J. Incl. Phenom. Macrocycl. Chem., 65 (2009) 403-409.
21. Ş. Uysal, A. Coşkun, The novel triazine cored tripodal and trinuclear Schiff base-oxime metal complexes: Their magnetic properties and thermal decompositions, J. Heterocycl. Chem., 48 (2011) 936-941.
22. Ş. Uysal, Synthesis and characterization of a new dioxime: Thermal and magnetic behavior of its complexes, J. Coord. Chem., 63 (2010) 2370-2378.
23. Ş. Uysal, A.N. Kurşunlu, The synthesis and characterization of star-shaped metal complexes of triazine cored Schiff bases, J. Inorg. Organomet. Polym. Mater., 21 (2011) 291-296.
24. M. Bevilacqua, V. Giuso, M. Rancan, L. Armelao, C. Graiff, W. Baratta, V. Di Marco, A. Biffis, Coordination chemistry of Ir with chelating ligands containing a xanthine-derived NHC moiety, Eur. J. Inorg. Chem., (2022) e202200484.
25. A.A. El-Habeeb, M.S. Refat, Synthesis, spectroscopic and biological characterizations of metal–theophylline complexes, Bull. Chem. Soc. Ethiop., 38 (2024) 725-738.
26. P. De Hoog, P. Gamez, W.L. Driessen, J. Reedijk, New polydentate ligands from triazine, Tetrahedron Lett., 43 (2002) 6783-6786.
27. D.C. Tahmassebi, T. Sasaki, Synthesis of a new trialdehyde template for molecular imprinting, J. Org. Chem., 59 (1994) 679-681.
28. B. İşçi, Ş. Uysal, The synthesis and characterization of trinuclear Schiff base complexes, J. Incl. Phenom. Macrocycl. Chem., 92 (2018) 281-299.
29. Z.E. Koç, Complexes of iron(III) and chromium(III) Schiff bases, J. Heterocycl. Chem., 48 (2011) 769-775.
30. Ş. Uysal, Z.E. Koç, Synthesis and characterization of dendrimeric melamine cored complexes, J. Hazard. Mater., 175 (2010) 532-539.
31. Ş. Uysal, H.İ. Uçan, The synthesis and characterization of melamine based Schiff bases, J. Incl. Phenom. Macrocycl. Chem., 65 (2009) 299-304.
32. I.M. Aouled, Ş. Uysal, Investigation of thermal and magnetic properties of dinuclear complexes, J. Mol. Struct., 1280 (2023) 135084.
33. I.M. Aouled, Ş. Uysal, Investigation of dinuclear complexes of triazine compounds, Synth. Commun., 51 (2021) 3642-3655.
34. K. Kiymaz, Ş. Uysal, Synthesis and characterization of dendrimeric s-triazine Schiff bases, J. Mol. Struct., 1271 (2023) 134029.
35. M. Erdogan, K. Kiymaz, H. Tahtaci, Ş. Uysal, Synthesis and characterization of Co(II) and Ni(II) complexes, J. Coord. Chem., 74 (2021) 2508-2533.
36. Ş. Uysal, M. Er, H. Tahtaci, Synthesis and characterization of thiosemicarbazone complexes, Synth. Commun., 46 (2016) 1820-1832.
37. Ş. Uysal, Z.E. Koç, The synthesis and characterization of heteromultinuclear complexes, J. Mol. Struct., 1165 (2018) 14-22.
38. Ş. Uysal, Z.E. Koç, Ş. Çelikbilek, H.İ. Uçan, Synthesis of star-shaped macromolecular Schiff base complexes, Synth. Commun., 42 (2012) 1033-1044.
39. A.A. Alothman, M.D. Albaqami, R.A. Alshgari, Synthesis and characterization of azo-dye metal complexes, J. Mol. Struct., 1223 (2021) 128984.
40. Z.E. Erdem Koç, Ş. Uysal, Synthesis and characterization of dendrimeric complexes, Helv. Chim. Acta, 93 (2010) 910-919.
41. I.M. Aouled, Ş. Uysal, The synthesis and characterization of s-triazine bridged Schiff base complexes, J. Mol. Struct., 1250 (2022) 131872.