YENİ BİR MESO-SUBSTİTÜE PORFİRİN TÜREVİNİN İN SİLİKO VE DFT ANALİZİ

Abstract

Bu çalışmada, yeni bir asimetrik meso-aril substitüe porfirin türevi sentezlenmiş ve karakterize edilmiştir. Yapısal özellikler, 1H ve 13C Nükleer Manyetik Rezonans (NMR), Fourier Dönüşümlü Kızılötesi (FT-IR) spektroskopisi ve Ultraviyole-Görünür (UV-Vis) spektroskopisi dahil olmak üzere bir dizi spektroskopik teknik kullanılarak kapsamlı bir şekilde ortaya konmuştur. Bileşiğin potansiyel terapötik uygulamalarını araştırmak amacıyla, meme kanseri ile ilişkili hedef reseptörler olan epidermal büyüme faktörü reseptörü (EGFR) ve insülin benzeri büyüme faktörü reseptörü (IGFR) ile etkileşimlerini incelemek için moleküler yerleştirme simülasyonları kullanılarak in silico çalışmalar gerçekleştirilmiştir. Ayrıca, bileşiğin biyolojik aktivite özellikleri absorpsiyon, dağılım, metabolizma ve atılım (ADME) analizi ile değerlendirilmiştir. Deneysel çalışmalara ek olarak, B3LYP/6-311G+(d,p) seviyesinde Yoğunluk Fonksiyonel Teorisi (DFT) hesaplamaları gerçekleştirilmiş ve moleküler yapının optimize edilmesi ve en yüksek dolu moleküler orbital (HOMO) ile en düşük boş moleküler orbital (LUMO) dağılımları gibi temel kuantum kimyasal parametrelerin belirlenmesi sağlanmıştır. Bu hesaplamalı veriler, sentezlenen bileşiğin elektronik özelliklerini ve reaktivitesini daha iyi anlamamıza katkıda bulunarak, kanser terapötik ajanı olarak geliştirilmesi için potansiyelini vurgulamaktadır.

Keywords

• Porfirin
• DFT analizi
• Moleküler docking
• ADME analizi

Project Number

21/131/03/1/4

IN SILICO AND DFT ANALYSIS OF A NEW MESO-SUBSTITUTED PORPHYRIN DERIVATIVE

Abstract

In this study, we synthesized and characterized a novel unsymmetrical meso-aryl substituted porphyrin derivative. Comprehensive structural elucidation was achieved using a suite of spectroscopic techniques, including 1H and 13C Nuclear Magnetic Resonance (NMR), Fourier-Transform Infrared (FT-IR) spectroscopy, and Ultraviolet-Visible (UV-Vis) spectroscopy. To further investigate the compound's potential therapeutic applications, in silico studies were performed, focusing on its interactions with breast cancer-associated target receptors, specifically the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor (IGFR), through molecular docking simulations. Additionally, bioactivity properties were evaluated via absorption, distribution, metabolism, and excretion (ADME) analysis. Complementary to the experimental work, Density Functional Theory (DFT) calculations at the B3LYP/6-311G+(d,p) level were conducted to optimize the molecular structure and determine key quantum chemical parameters, such as the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) distributions. These computational insights provide a deeper understanding of the electronic characteristics and reactivity of the synthesized compound, highlighting its potential for further development as a cancer therapeutic agent.

Keywords

• Porphyrin
• DFT analysis
• Molecular docking
• ADME analysis

Project Number

21/131/03/1/4

Thanks

The synthesis study was supported by the Scientific Research Projects Coordination Unit (BAP) of Mugla Sıtkı Koçman University with project number 21/131/03/1/4. The authors extend their appreciation to the Muğla Sıtkı Koçman University Scientific Research Foundation for their financial assistance.

References

1. Merhi, A., “Synthesis of new organic and organometallic Porphyrin Assemblies for Optics”. Other [cond-mat.other]. INSA de Rennes, 2013. English. ⟨NNT: 2013ISAR0022⟩.
2. Rezazgui, O., “Towards a bio-inspired photoherbicide: Synthesis and studies of fluorescent tagged or water-soluble”, Doctoral dissertation, Université de Limoges, 2015.
3. Miao, W., Zhu, Z., Li, Z., Hao, E. and Jiao, L., “Novel expanded porphyrinoids with multiple-inner-ring-fusion and/or tunable aromaticity”, Chinese Chemical Letters, 30: 1895–1902, 2019.
4. Luna, M. A., Moyano, F., Sereno, L. and D’Eramo, F., “Spectroscopic and electrochemical studies of high-valent water soluble manganese porphyrine”, Electrocatalytic water oxidation, Electrochimica Acta, 135: 301–310, 2014.
5. Marques, H. M., “Corrins and porphyrins: two of nature’s pigments of life”, Journal of Coordination Chemistry, 77(11): 1161-1210, 2024.
6. Arambula, J. F. and Sessler, J. L.,” Porphyrinoid Drug Conjugates”, Chem Perspective, 6: 1634-1651, 2020.
7. Senge, M. O., Sergeeva, N. N. and Hale, K. J., “Classic highlights in porphyrin and porphyrinoid total synthesis and biosynthesis”, Chem. Soc. Rev, 50: 4730-4789, 2021.
8. Teixeira, R., Serra, V. V., Botequim, D., Paulo, P. M. R., Andrade and Costa, S. M. B., “Fluorescence Spectroscopy of Porphyrins and Phthalocyanines: Some Insights into Supramolecular Self-Assembly, Microencapsulation, and Imaging Microscopy”, Molecules, 26: 4264- 4289, 2021.

9. Temelli, B., “Addition reactions of aromatic compounds to multiple bonds in the presence of metal trifluoromethanesulfonates”, PhD Thesis, 2008.
10. Severance, S. and Hamza, I., “Trafficking of heme and porphyrins in metazoa”, Chemical Reviews, 109(10): 4596–4616, 2009.
11. Sawicki, K. T., Chang, H.-C. and Ardehali, H., “Role of heme in cardiovascular physiology and disease”, Journal of the American Heart Association, 4(1):1-14, 2015.
12. Tahoun, M., Gee, C. T., McCoy, V. E., Sander, P. M. and Muller, C. E., “Chemistry of porphyrins in fossil plants and animals”, RSC Advances, 11: 7552–7563, 2021.
13. Tian, Z., Li, H., Liu, Z., Yang, L., Zhang, C., He, J., Ai, W. and Liu, Y., Enhanced Photodynamic Therapy by Improved Light Energy Capture Effciency of Porphyrin Photosensitizers, Current Treatment Options in Oncology, 24: 1274- 1292, 2023.
14. Purtaş, S., Köse, M., Tümer, F., Tümer, M., Gölcü, A. and Ceyhan, G., “A novel porphyrin derivative and its metal complexes: Electrochemical, photoluminescence, thermal, DNA-binding, and superoxide dismutase activity studies”, Journal of Molecular Structure, 1105: 293–307, 2016.
15. Giovannetti, R., “The use of spectrophotometry UV-Vis for the study of porphyrins”, In Macro to Nano Spectroscopy, 87–108, 2012.
16. Lucantoni, L., Magaraggia, M., Lupidi, G., Ouedraogo, R. K., Coppellotti, O., Esposito, F., Fabris, C., Jori, G and Habluetzel, A., “Novel, meso-substituted cationic porphyrin molecule for photo-mediated larval control of the dengue vector Aedes aegypti”, PLoS ONE, 5(12: e1434, 2011.
17. Kurniawan, F., Miura, Y., Kartasasmita, R. E., Yoshioka, N., Mutalib, A. and Tjahjono, D. H., “In silico study, synthesis, and cytotoxic activities of porphyrin derivatives”, Pharmaceuticals, 11(8): 1-18, 2018.
18. Seyfried, T. N., Flores, R. E., Poff, A. M. and Agostino, D. P., “Cancer as a metabolic disease: Implications for novel therapeutics”, Carcinogenesis, 35: 515–527, 2014.
19. Siegel, R. L., Miller, K. D. and Jemal, A., “Cancer statistics”, CA: A Cancer Journal for Clinicians, 67(1): 7–30, 2017.
20. Sarikavakli, N., Genç, O., Çaliskan, Ş. G. and Erol, F., “Molecular docking, HOMO-LUMO, and quantum chemical computation analysis of anti-glyoximehydrazone derivatives containing pyrazolone moiety and their transition metal complexes”, Journal of the Indian Chemical Society, 100(5): 100981, 2023.
21. Hiroto, S., Miyake, Y. and Shinokubo, H., “Synthesis and functionalization of porphyrins through organometallic methodologies”, Chemical Reviews, 117: 2910–3043, 2017.
22. Urbani, M., Grätzel, M., Nazeeruddin, M. K. and Torres, T., “Meso-substituted porphyrins for dye-sensitized solar cells”, Chemical Reviews, 114: 12330–12396, 2014.
23. Wu, L. and Qu, X., “Cancer biomarker detection: Recent achievements and challenges”, Chemical Society Reviews, 44: 2963–2997, 2015.
24. Nishida, K., Tojo, T., Kondo, T. and Yuasa, M., “Evaluation of the correlation between porphyrin accumulation in cancer cells and functional positions for application as a drug carrier”, Scientific Reports, 11: 2046, 2021.
25. Charisiadis, A., Nikolaou, V., Karikis, N., Giatagana, C., Chalepli, K., Ladomenou, K., Biswas, S., Sharma, G. D. and Coutsolelos, A. G., “Two new bulky substituted Zn porphyrins bearing carboxylate anchoring groups as promising dyes for DSSCs”, New Journal of Chemistry, 40: 5930–5941, 2016.
26. Bera, R., Chakraborty, S., Nayak, S. K., Jana, B. and Patra, A., “Structural insight and ultrafast dynamics of 2D porphyrin nanostructures”, The Journal of Physical Chemistry C, 123: 15815–15826, 2019.
27. Fadda, A. A., El-Mekawy, R. E., El-Shafei, A., Freeman, H. S., Hinks, D. and El-Fedawy, M., “Design, Synthesis, and Pharmacological Screening ofNovel Porphyrin Derivatives” Journal of Chemistry, 2013.
28. Trott, O. and Olson, A. J., “AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading”, Journal of Computational Chemistry, 31(2): 455–461, 2010.”
29. Molinspiration. Retrieved from www.molinspiration.com
30. Frisch, M. J., et all. Gaussian 09, Revision A.02. Gaussian, Inc., Wallingford CT, 2016.
31. Gligori´c, E., Igi´c, R., Teofilovi´c, B. and Gruji´c-Leti´c, N., “Phytochemical Screening of Ultrasonic Extracts of Salix Species and Molecular Docking Study of Salix-Derived Bioactive Compounds Targeting Pro-Inflammatory Cytokines”. International Journal of Molecular Sciences. 24: 11848, 2023.
32. Verma, A., “Lead finding from Phyllanthus debelis with hepatoprotective potentials”, Asian Pacific Journal of Tropical Biomedicine, 1: 735–737, 2012.
33. Dhaheri, Y.A., Wali, A.F., Akbar, I., Rasool, S., Razmpoor, M., Jabnoun, S. and Rashid, S., Chapter 3 - Nigella sativa, a cure for every disease: Phytochemistry, biological activities, and clinical trials, Editor(s): Andleeb Khan, Muneeb Rehman, Black Seeds (Nigella Sativa), Elsevier, Pages 63-90, 2022.
34. Shtaiwi, A., Khan, S.U., Khedraoui, M. Alaraj, M., Samadi, A. and Chtita S., “A comprehensive computational study to explore promising natural bioactive compounds targeting glycosyltransferase MurG in Escherichia coli for potential drug development”. Scientific Reports, 14: 7098, 2024.
35. Becke, A., “Density-functional thermochemistry. III. The role of exact Exchange”, The Journal of Chemical Physics, 98: 5648–5652, 1993.
36. Lee, C., Yang, W. and Parr, R. G., “Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density”, Physical Review B, 37(2): 785–789, 1988.
37. Sukumaran, S., Zochedh, A., Chandran, K., Sultan, A. B. and Kathiresan, T., “Exploring the co-activity of FDA-approved drug gemcitabine and docetaxel for enhanced anti-breast cancer activity: DFT, docking, molecular dynamics simulation, and pharmacophore studies”, International Journal of Quantum Chemistry, 124(4): e27359, 2024.