Structural, Spectroscopic and Anti-cancer Properties of Hydroxy- and Sulfonamide-Azobenzene Platinum (II) Complexes: DFT and Molecular Docking Studies

Sultan Erkan

doi:10.17776/csj.421027

TR EN

Hidroksi- ve Sülfonamid- Azobenzen Platin (II) Komplekslerinin Yapısal, Spektroskopik ve Anti-Kanser Özellikleri: DFT ve Moleküler Yerleştirme Çalışmaları

Öz

Bidentat ligandlar olan sülfonamid-((E)-2-(4-metilfenilsülfonamido)-2',6'-diizoazobenzen, HL1) ve hidroksi-azo-2,6-diflorobenzen ((E)-2-((2,6-diflorofenil)diazenil)fenol, HL2) taşıyan üç platin (II) kompleksi ([Pt(L1)(DMSO)Cl], [Pt(L2)(DMSO)Cl] ve [Pt(L2)₂]) en uygun seviye olarak belirlenen B3LYP/6-31+G(d) ve B3LYP/LANL2DZ/6-31+G(d) seviyesi ile optimize edildi. Optimize yapılardan elde edilen yapısal parametreler (bağ uzunluklar ve bağ açıları), IR ve ¹H, ¹³C ve ¹⁹F-NMR kimyasal kaymaları deneysel veriler ile kıyaslandı ve sonuçlar deneysel sonuçlar ile uyumlu olduğu görüldü. A2780 ve A2780CP70 kanser hüclerine karşı deneysel inhibisyon etkinlikleri HOMO enerjisi (E_HOMO), LUMO enerjisi (E_LUMO), LUMO-HOMO enerji boşluğu (DE), sertlik (h), yumuşaklık (s), elektronegativite (c) ve kimyasal potansiyel (m) gibi kuantum kimyasal parametreler ile kıyaslandı. Aktivite yapı arasındaki ilişki incelendi ve E_LUMO deneysel inhibisyon etkinlik sıralaması ile bire bir uyumlu bulundu. Anti-kanser özellik gösteren ligand ve komplekslerin moleküler elektrostatik potansiyel (MEP) haritaları incelendi ve HL1 ve HL2 ligandları ve Comp. (1)-(3) için kanser hücrelerine bağlanma bölgeleri belirlendi. Ayrıca MEP haritalarından elde edilen elektrostatik potansiyel (ESP) yükleri ile ligandlar ve komplekslerin kanser hücresine bağlanma kolaylıklarına göre sıralamaları yapıldı. Elde edilen sıralama deneysel inhibisyon etkinlik sıralaması uyumlu bulundu. Çalışılan ligand ve kompleksler için Hex.8.0.0 programı ile moleküler yerleştirme çalışmaları yapıldı. A2780 ve A2780CP70 hücre çizgisine karşılık gelen hedef proteinler (PDB ID:4M5W ve 5FI4, sırasıyla) literatürde seçildi. 4M5W ve 5FI4 hedef proteinleri ile HL1 ve HL2 ligandaların etkileşim enerjileri sırasıyla -300.02, -240.80 ve -336.64, -247.04 kJ/mol olarak hesaplandı. Kompleksler ile 4M5W ve 5FI4 hedef proteinleri arasındaki bağlanma enerjileri -387.52, -285.44, -364.88 ve -399.63, -297.8, -385.323 kJ/mol olarak hesaplandı. Bu sonuçlara göre deneysel ve hesaplanan inhibisyon etkinlik sıralaması uyumlu bulundu.

Anahtar Kelimeler

Platinum (II) kompleksleri,DFT ve Moleküler Yerleştirme Çalışmaları

Structural, Spectroscopic and Anti-cancer Properties of Hydroxy- and Sulfonamide-Azobenzene Platinum (II) Complexes: DFT and Molecular Docking Studies

Abstract

The three platinum (II) complexes ([Pt(L1)(DMSO)Cl], [Pt(L2)(DMSO)Cl] and [Pt(L2)₂]) bearing the bidentate ligands sulphonamide-((E)-2-(4-methylphenylsulfonamido)-2′,6′-diﬂuoroazobenzene, HL1) and hydroxy-azo-2,6-diﬂuorobenzene ((E)-2-((2,6-diﬂuorophenyl)diazenyl)phenol, HL2) were optimized with the optimum levels of B3LYP/6-31+G(d) and B3LYP/LANL2DZ/6-31+G(d) level. The structural parameters (bond lengths and ligand angles), IR and ¹H, ¹³C and ¹⁹F-NMR spectra obtained from the optimized structures were compared with the experimental data and the results were found to be consistent with the experimental results. Experimental inhibition activities against A2780 and A2780CP70 cancer cells were compared with quantum chemical parameters such as HOMO energy (E_HOMO), LUMO energy (E_LUMO), LUMO-HOMO energy vacancy (DE), hardness (h), softness (s), electronegativity (c) and chemical potential (m). The relationship between the molecular structure with the biological activity was examined and E_LUMO order was found to be compatible with the experimental inhibition efficiency ranking. Molecular electrostatic potential (MEP) maps were studied of ligands and complexes exhibiting anti-cancer properties and for ligands and complexes, regions of attachment to cancer cells were determined. In addition, electrostatic potential (ESP) charges obtained from MEP maps of ligands and complexes were ranked according to their ease of binding to the cancer cell. The obtained ranking was found to be in accordance with the experimental inhibition efficiency order. For studied ligands and complexes, molecular docking studies were carried out with the Hex.8.0.0 program. The target proteins (PDB ID: 4M5W and 5FI4, respectively) corresponding to the A2780 and A2780CP70 cell lines were selected in the literature. The interaction energies of 4M5W and 5FI4 target proteins with HL1 and HL2 ligands were calculated to be -300.02, -240.80 and -336.64, -247.04 kJ/mol, respectively. The binding energies between the complexes and 4M5W and 5FI4 target proteins were calculated to be -387.52, -285.44, -364.88 and -399.63, -297.8, -385.323 kJ/mol. According to these results, the experimental and calculated inhibition efficiency order was found to be compatible.

Keywords

Platinum (II) complexes,DFT and Molecular Docking Studies

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Details

Primary Language

English

Subjects

-

Journal Section

Research Article

Authors

Sultan Erkan ^*
Türkiye

Publication Date

December 24, 2018

Submission Date

May 4, 2018

Acceptance Date

November 2, 2018

Published in Issue

Year 1970 Volume: 39 Number: 4

DOI

https://doi.org/10.17776/csj.421027

IZ

https://izlik.org/JA55YK66CB

Cite

RIS / Bibtex

APA

Erkan, S. (2018). Structural, Spectroscopic and Anti-cancer Properties of Hydroxy- and Sulfonamide-Azobenzene Platinum (II) Complexes: DFT and Molecular Docking Studies. Cumhuriyet Science Journal, 39(4), 1036-1051. https://doi.org/10.17776/csj.421027