Synthesis of macrocyclization cyclophanes and their metal complexes, characterization and antimicrobial activity

Siklofan tipi bileşikler, kimyasal özelliklerinden dolayı ilginç bir organik kimya sınıfı oluşturmaktadır. Tüm siklik bileşiklerin yapısında yüksek verimli sentez için makrosiklizasyon en kritik konudur. Özellikle küçük bir siklofan yapısı ile deneysel adımlar büyük bir siklofan yapısına göre daha zordur. Bu yazıda, akıllı ilaç özellikleri için gümüş siklofan bileşiklerini sentezlemek üzere üç farklı malzeme grubu uygulanmıştır. Birinci malzeme grubunda 5,6-dimetil-1H-benzo[d]imidazol (1) ve 2,6-bis(klorometil)piridin (2) reaksiyona girerek 5,6-dimetil-1-((6) oluşturdu. -((5,6-dimetil-1H-benzo[d]imidazol-1-il)metil)piridin-2-il)metil)-1H-benzo[d]imidazol bileşik (3). İkinci malzeme grubunda etil 2-bromoasetat (4), suda çözünür (5) olan simetrik bir karben bileşiği oluşturmak üzere siklofan bileşiğinin farklı nitrojen atomları ile reaksiyona sokulmuştur. Üçüncü malzeme grubunda gümüş(I) oksit (6) ve paladyum (II) klorür (7) ile reaksiyona girerek gümüş (I) ve paladyum (II) metal kompleksleri sentezlendi. Karben bileşikleri ile gümüş ve paladyum komplekslerinin (5, 6 ve 7) bakteri ve mantarlara karşı antimikrobiyal aktiviteleri daha detaylı olarak incelenmiştir. Gümüş (I) kompleksi (6), Gram-pozitif, Gram-negatif ve mantar gibi mikroorganizmalar ile karıştırıldığında antimikrobiyal madde gösterirken, bu özellik paladyum (II)-karben kompleksinde (7) gözlenmemiştir.

Anahtar Kelimeler:

carbene, cyclophane, metal complexe

Synthesis of macrocyclization cyclophanes and their metal complexes, characterization and antimicrobial activity

Due to their chemical properties, cyclophane-type compounds constitute an interesting organic chemistry class. In the structure of all cyclic compounds, macrocyclization is the most critical issue for high-efficiency synthesis. Especially with a small cyclophane structure, the experimental steps are more complicated than with a prominent cyclophane structure. In this manuscript, three different material groups were applied to synthesize silver cyclophane compounds for smart drug properties. In the first material group, 5,6-dimetil-1H-benzo[d] imidazole (1) and 2,6-bis(chloromethyl)pyridine (2) were reacted to form 5,6-dimethyl-1- ((6-((5,6-dimethyl-1H-benzo[d]imidazole-1-il)methyl)pyridine-2-il)methyl)-1H-benzo[d] imidazole compound (3). In the second material group, ethyl 2-bromoacetate (4) reacted to different nitrogen atoms of the cyclophane compound to form a symmetric carbene compound, which is water-soluble (5). In the third material group, the silver (I) and palladium (II) metal complexes were synthesized due to the reaction with silver(I) oxide (6) and palladium (II) chloride (7). Antimicrobial activities of the carbene compounds and silver and palladium complexes (5, 6, and 7) were investigated against bacteria and fungal in more detail. Silver (I) complex (6) shows an antimicrobial agent when mixed with microorganisms, such as Gram-positive, Gram-negative, and fungal, but this property has not been observed in the palladium (II)-carbene complex (7).

Keywords:

metal complex carbene, cyclophane, antimikrobiyal aktivite,

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[1] Odemir, I., Yasar, S., & Cetinkaya, B. (2005). Ruthe nium(II) N-heterocyclic carbene complexes in the transfer hydrogenation of ketones. Transition Metal Chemistry, 30, 831–835. [CrossRef]
[2] Hopkinson, M. N., Richter, C., Schedler, M., & Glo rius, F. (2014). An overview of N-heterocyclic car benes. Nature, 510, 485–496. [CrossRef]
[3] Bellotti, P., Koy, M., Hopkinson, M. N., & Glorius, F. (2021). Recent advances in the chemistry and appli cations of N-heterocyclic carbenes. Nature Reviews Chemistry, 5(10), 711–725. [CrossRef]
[4] Gong, W., Zhang, G., Liu, T., Giri, R., & Yu, J. Q. (2014). Site-selective C (sp3)–H functionalization of di-, tri-, and tetrapeptides at the N-terminus. Journal of the American Chemical Society, 136(48), 16940–16946. [CrossRef]
[5] Gago, S., Gonzalez, J., Blasco, S., Parola, A. J., Al belda, M. T., Garcia-Espana, E., & Pina, F. (2014). Protonation, coordination chemistry, cyanometal late “supercomplex” formation and fluorescence chemosensing properties of a bis (2, 2′-bipyridino) cyclophane receptor. Dalton Transactions, 43(6), 2437–2447. [CrossRef]
[6] Li, C. (2014). Pillararene-based supramolecular polymers: from molecular recognition to polymer ic aggregates. Chemical Communications, 50(83), 12420–12433. [CrossRef]
[7] Brown, C. J., & Farthing, A. C. (1949). Preparation and structure of di-p-xylylene. Nature, 164, 915– 916. [CrossRef]
[8] Gulder, T., & Baran, P. S. (2012). Strained cyclophane natural products: Macrocyclization at its limits. Nat ural Product Reports, 29(8), 899–934. [CrossRef]
[9] Bruns, C. J., Frasconi, M., Iehl, J., Hartlieb, K. J., Schneebeli, S. T., Cheng, C., ... & Stoddart, J. F. (2014). Redox switchable daisy chain rotaxanes driven by radical–radical interactions. Journal of the American Chemical Society, 136(12), 4714–4723. [CrossRef]
[10] Yamaguchi, J., Yamaguchi, A. D., & Itami, K. (2012). C-H Bond functionalization: Emerging synthet ic tools for natural products and pharmaceuticals. Angewandte Chemie International Edition, 51(36), 8960–9009. [CrossRef]
[11] Peng, B., Ma, J., Guo, J., Gong, Y., Zhang, R.W.Y., Zeng, J., Chen, W.W., Ding, K., & Zhao, B. (2022). A powerful chiral super brønsted C–H acid for asym metric catalysis. Journal American Chemical Society, 144(7), 2853–2860. [CrossRef]
[12] Raad, D., & Assaad, J. J. (2022). Structural proper ties of fiber-reinforced concrete containing thermo setting polymer plastic wastes. Journal of Sustainable Cement-Based Materials, 11(2), 137–147. [CrossRef]
[13] Park, H., Kim, Y., Kim, D., Lee, S., Kim, F. S., & Kim, B. J. (2022). Disintegrable n‐type Electroactive Ter polymers for high‐performance, transient organic electronics. Advanced Functional Materials, 32(2), Article 2106977. [CrossRef]
[14] Chu, D., Gong, W., Jiang, H., Tang, X., Cui, Y., & Liu, Y. (2022). Boosting enantioselectivity of chiral mo lecular catalysts with supramolecular metal–organic cages. CCS Chemistry, 4(4), 1180–1189. [CrossRef]
[15] Kaloglu, M., Kaloglu, N., Ozdemir, I., Günal, S., & Ozdemir, I. (2016). Novel benzimidazol-2-ylidene carbene precursors and their silver (I) complexes: Potential antimicrobial agents. Bioorganic & Medici nal Chemistry, 24(16), 3649–3656. [CrossRef]
[16] Gunal, S., Kaloglu, N., Ozdemir, I., Demir, S., & Oz demir, I. (2012). Novel benzimidazolium salts and their silver complexes: Synthesis and antibacterial properties. Inorganic Chemistry Communications, 21, 142–146. [CrossRef]
[17] Altmann, P. J., Jandl, C., & Pothig, A. (2015). In troducing a pyrazole/imidazole based hybrid cy clophane: a hydrogen bond sensor and binucleat ing ligand precursor. Dalton Transactions, 44(25), 11278–11281. [CrossRef]
[18] Samani, Z. R., Mehranpour, A., & Hasaninejad, A. (2020). Preparation of 2, 5‐disubstituted pyrim idines from vinamidinium salts and synthesis of novel disulfane derivatives. Journal of Heterocyclic Chemistry, 57(5), 2150–2156. [CrossRef]
[19] Chen, Z. L., Empel, C., Wang, K., Wu, P. P., Cai, B. G., Li, L., ... & Xuan, J. (2022). Enabling cyclopro panation reactions of imidazole heterocycles via chemoselective photochemical carbene transfer re actions of NHC-boranes. Organic Letters, 24(11), 2232–2237. [CrossRef]
[20] Tsuchiya, K., Kurohara, T., Fukuhara, K., Misawa, T., & Demizu, Y. (2022). Helical foldamers and stapled peptides as new modalities in drug discovery: Mod ulators of protein-protein interactions. Processes, 10(5), Article 924. [CrossRef]
[21] Smalley, C. J. H., Hoskyns, H. E., Hughes, C. E., Johnstone, D. N., Willhammar, T., Young, M. T., Pickard, C. J., Logsdail, A. J., Midgley, P. A., & Har ris, K. D. M. (2022). A structure determination protocol based on combined analysis of 3D-ED data, powder XRD data, solid-state NMR data and DFT-D calculations reveal the structure of a new polymorph of L-tyrosine. Chemical Science, 13(18), 5277–5288. [CrossRef]
[22] Turkyilmaz, M., Dönmez, M., & Ates, M. (2022). Synthesis of pincer type carbene and their Ag(I)- NHC complexes, and their antimicrobial activities. Journal of Sustainable Construction Materials and Technologies, 7(2), 53–61. [CrossRef]
[23] Hussaini, S. Y., Haque, R. A., & Razali, M. R. (2019). Recent progress in Silver(I)-, gold (I)/(III)- and pholeadium(II)-N-heterocyclic carbene complexes: A review towards biological perspectives. Journal Organometalic Chemistry. 882, 96–111. [CrossRef]
[24] Khalil, E.A.M., & Mohamed, G.G. (2022). Prepa ration, spectroscopic characterization and anti tumor-antimicrobial studies of some Schiff base transition and inner transition mixed ligand com plexes. Journal of Molecular Structure, 1249, Article 131612. [CrossRef]
[25] McFarland, A. W., Elumalai, A., Miller, C. C., Hu mayun, A., & Mills, D. K. (2022) Effectiveness and applications of a metal-coated HNT/Polylactic acid antimicrobial filtration system. Polymers, 14(8), Ar ticle 1603. [CrossRef]
[26] Becenen, N. Ulucam, G. & Altun, O. (2017). Syn thesis and antimicrobial activity of iron cyclo hexanedicarboxylic acid and examination of pH effect on extraction in water and organic phases. Trakya University Journal of Natural Sciences, 18(1), 1–7.
[27] Tran, T. N. T., Nguyen, T. D. P., Dinh, H. T., Bui, T. T., Ho, L. H., Nguyen-Phan, T. X., Khoo, K. S., Chew, K. W., Show, P. L. (2021). Characterization of bacteria type strain Bacillus. spp isolated from extracellular polymeric substance harvested in seafood wastewa ter. Journal of Chemical Technology & Biotechnology, 97(2), 501–508. [CrossRef]