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

References

[1] Hu Y., Tabor R.F., Wilkinson B.L., Sweetness and light: design and applications of photo-responsive glycoconjugates, Org. Biomol. Chem., 13-8 (2015) 2216−2225.
[2] Velema W.A., Szymanski W., Feringa B.L., Photopharmacology: beyond proof of principle, J. Am. Chem. Soc., 136-6 (2014) 2178−2191.
[3] Li J., Wang X.¸ Liang X., Modification of Nucleic Acids by Azobenzene Derivatives and Their Applications in Biotechnology and Nanotechnology, Chem. Asian J., 9-12 (2014) 3344−3358.
[4] Kundu P.K., Klajn R., Watching single molecules move in response to light, ACS Nano, 8-12 (2014) 11913−11916.
[5] García-Iriepa C., Marazzi M., Frutos L.M., Sampedro D., E/Z Photochemical switches: syntheses, properties and applications, RSC Adv., 3-18 (2013) 6241−6266.
[6] Wegner H.A., Azobenzenes in a new light—Switching in vivo, Angew. Chem., Int. Ed., 51-20 (2012) 4787−4788.
[7] Bandara H.M.D., Burdette S.C., Photoisomerization in different classes of azobenzene, Chem. Soc. Rev., 41-5 (2012) 1809−1825.
[8] Merino E., Synthesis of azobenzenes: the coloured pieces of molecular materials, Chem. Soc. Rev., 40-7 (2011) 3835−3853.

[9] Beharry A.A., Woolley G.A., Azobenzene photoswitches for biomolecules, Chem. Soc. Rev., 40-8 (2011) 4422− 4437.
[10] Hamon F., Djedaini-Pilard F., Barbot F., Len C., Azobenzenes—synthesis and carbohydrate applications, Tetrahedron, 65-49 (2009) 10105−10123.
[11] Samanta S., Ghosh P., Goswami S., Recent advances on the chemistry of transition metal complexes of 2-(arylazo) pyridines and its arylamino derivatives, Dalton Trans., 41-8 (2012) 2213−2226.
[12] Muggia F.M., Recent updates in the clinical use of platinum compounds for the treatment of gynecologic cancers., In Semin. Oncol., WB Saunders, 31 (2004) 17–24.
[13] Belani C.P., Recent updates in the clinical use of platinum compounds for the treatment of lung, breast, and genitourinary tumors and myeloma, In Semin.Oncol., WB Saunders, 31 (2004) 25–33.
[14] Cleare M.J., Hoeschele J.D., Antilt umour Platinum Compounds, Platin. Met. Rev., 17 (1973) 2–13.
[15] Cleare M.J., Hoeschele J.D., Studies on the antitumor activity of group VIII transition metal complexes, Bioinorg. Chem., 2-3 (1973) 187–210.
[16] Endresi, H., 1985. A hydrogen-bridged dimeric stacked structure in a dioximato complex: (oxamide oximato)(oxamide oxime) platinum (II) iodide dihydrate, [Pt(C2H5N4O2)(C2H5N4O2)]I.2H2O. Acta Cryst. C41, 1047-1049.
[17] Guedes da Silva, M. F. C., Izotova, Y. A., Pombeiro, A. J. L., Kukushkin, V. Y., 1998. Manifestation of redox duality of 2-propanone oxime: Pt(II)-assisted reduction versus Pt (IV) - mediated oxidation of Me2O= NOH species. Inorg. Chim. Acta. 277, 83-88.
[18] Makarycheva-Mikhailova, A. V., Haukka, M., Bokach, N. A., Garnovskii, D. A., Galanski, M., Keppler, B. K., Pomberio, A. J. L., Kukushkin, V. Y., 2002. Platinum(IV)-mediated coupling of dione monoximes and nitriles: a novel reactivity pattern of the classic oxime-based chelating ligands. New J. Chem. 26, 1085-1091.
[19] Köcher, S., Lutz, M., Spek, A. L., Walfort, B., Rüffer, T., van Klink, G. P. M., van Koten, G., Lang, H., 2008. Oxime-substituted NCN-pincer palladium and platinum halide polymers through non-covalent hydrogen bonding (NCN=[C6H2(CH2NMe2)2-2,6]−). Journal of Organometallic Chemistry. 693, 2244-2250.
[20] Grabmann, G., Meier, S. M., Scaffidi-Domianello, Y. Y., Galanski, M., Keppler, B. K., Hartinger, C. G., 2012. Capillary zone electrophoresis and capillary zone electrophoresis– electrospray ionization mass spectrometry studies on the behavior of anticancer cis- and trans- [dihalidobis(2-propanone oxime)platinum(II)] complexes in aqueous solutions. Journal of Chromatography A. 1267, 156-161.
[21] Deo C., Bogliotti N., Métivier R., Retailleau P., Xie J., Photoswitchable arene ruthenium complexes containing o-sulfonamide azobenzene ligands, Organometallics, 34-24 (2015) 5775−5784.
[22] Samper K.G., Marker S.C., Bayón P., MacMillan S.N., Keresztes I., Palacios Ò., Wilson J.J., Anticancer activity of hydroxy-and sulfonamide-azobenzene platinum (II) complexes in cisplatin-resistant ovarian cancer cells, Journal of Inorganic Biochemistry, 174 (2017) 102–110.
[23] Dennington II R. D.; Keith T.A.; Millam J.M. GaussView 5.0, Wallingford, CT, 2009.
[24] Frisch M J, Trucks G W, Schlegel H B, Scuseria G E, Robb M A, Cheeseman J R, Scalmani G, Barone V, Mennucci B & Petersson G A, et al. Gaussian, Inc., Wallingford CT, 2010.
[25] Zhurko G.A., Zhurko D.A., ChemCraft, version 1.6, 2009. (http://www. chemcraftprog.com)
[26] Roothaan C. C. J., New developments in molecular orbital theory, Rev. Mod. Phys., 23-2 (1951) 69.
[27] Awad M.K., Mustafa M.R., Computational simulation of the molecular structure of some triazoles as inhibitors for the corrosion of metal surface, Journal of Molecular Structure: THEOCHEM., 959 (2010) 66–74.
[28] Becke A.D., Density‐functional thermochemistry. III. The role of exact Exchange, The Journal of Chemical Physics, 98-7 (1993) 5648–5652.
[29] Tüzün B., Kaya C., Investigation of DNA–RNA Molecules for the Efficiency and Activity of Corrosion Inhibition by DFT and Molecular Docking, Journal of Bio- and Tribo-Corrosion 4-69 (2018) 2-11.
[30] Üngördü A., Tezer N., Effect on frontier molecular orbitals of substituents in 5-position of uracil base pairs in vacuum and water, Journal of Theoretical and Computational Chemistry, 16-07 (2017) 1750066.
[31] Sayin, K., Üngördü, A., Investigation of anticancer properties of caffeinated complexes via computational chemistry methods, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 193 (2018) 147-155.
[32] Sarigul M., Erkan S.K., Deveci P., Atabey H., KarakasbD., Kurtoglu M., Multi-properties of a new azo-Schiff base and its binuclear copper (II) chelate: Preparation, spectral characterization, electrochemical, potentiometric and modeling studies. Journal of Molecular Structure, 1149 (2017) 520-529.
[33] Karakaş D., Erkan S.K., Theoretical investigation on the vibrational and electronic spectra of three isomeric forms of dicobalt octacarbonyl, Journal of Molecular Structure, 1062 (2014) 77-81.
[34] Erkan S.K, Sayın K., Karakaş D., Theoretical Studies on Eight Oxovanadium (IV) Complexes with Salicylaldehyde and Aniline Ligands, Hacettepe J Biol Chem, 42 (2014) 337-342.
[35] Drací̌nsky M., Bour P., Hodgkinson P., Temperature dependence of NMR parameters calculated from path integral molecular dynamics simulations, J. Chem. Theory Comput., 12-3 (2016) 968−973.
[36] Pearson R. G., Absolute electronegativity and hardness: application to inorganic chemistry, Inorg. Chem., 27-4 (1988) 734-740.
[37] Koopmans T., Über die Zuordnung von Wellenfunktionen und Eigenwerten zu den einzelnen Elektronen eines Atoms, Physica, 1 (1934) 104.
[38] Muscia G.C., Cazorla S.I., Frank F.M., Borosky G.L., Buldain G.Y., Asís S.E., Malchiodi E.L., Synthesis, trypanocidal activity and molecular modeling studies of 2-alkylaminomethylquinoline derivatives, Eur. J. Med. Chem., 46-9 (2011) 3696-3703.
[39] Kushwaha P.S., Mishra P.C., Relationship of hydrogen bonding energy with electrostatic and polarization energies and molecular electrostatic potentials for amino acids: an evaluation of the lock and key model, Int. J. Quant. Chem., 76-6 (2000) 700-713.
[40] Wagener M., Sadowysky J., Gasteiger J., Autocorrelation of molecular surface properties for modeling corticosteroid binding globulin and cytosolic Ah receptor activity by neural networks, J. Am. Chem. Soc., 117-29 (1995) 7769– 7775.
[41] Sayin K., Karakaş D., Erkan S.K., Alagöz Sayin T., Computational study of some fluoroquinolones: Structural, spectral and docking investigations, Journal of Molecular Structure, 1156 (2018) 172-181
[42] Qin D., Wang W., Lei H., Luo H., Cai H., Tang C., Wang T., CDDO-Me reveals USP7 as a novel target in ovarian cancer cells, Oncotarget, 7-47 (2016) 77096.
[43] Han W., Menezes D.L., Xu Y., Knapp M.S., Elling R., Burger M.T., Ni Z.J., Smith A., Lan J., Williams T.E., Verhagen J., Huh K., Merritt H., Chan J., Kaufman S., Voliva C.F., Pecchi S., Discovery of imidazo [1, 2-a]-pyridine inhibitors of pan-PI3 kinases that are efficacious in a mouse xenograft model. Bioorganic & medicinal chemistry letters, 26-3 (2016) 742-746.

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 2018 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