The Synthesis, characterization and antimicrobial activity of organometallic Ru(II) complex containing phenylthiourea ligand

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Nararak Leesakul
Rachna Neang
Parichad Chuklin
Saowanit Saithong
Luksamee Vittaya


A novel organometallic ruthenium(II)-p-cymene complex, [Ru(η6-p-cymene)(ptu)2Cl]SH, where ptu= N-phenylthiourea, was synthesized. Its structure was characterized by single crystal x-ray diffraction, elemental analysis and spectroscopic techniques (1H-NMR and FTIR). The geometrical structure of the complex was tetrahedral, distorted by η6 π-bonding to the p-cymene ring, with one chloro ligand and two molecules of ptu ligand.  Antibacterial and antifungal activities were investigated. The [Ru(η6-p-cymene)(ptu)2Cl]SH complex produced  MIC/MBC values of 32/32 µg/mL against methicillin resistant Staphylococcus aureus (MRSA), Staphylococcus aureus ATCC25923 (SA) and flucytosine-resistant Cryptococcus neoformans ATCC90113 flucytosine – resistant, CN90113 but apparently exhibited no antifungal against Microsporum gypseum clinical isolate.  

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[1] Enright MC, Robinson DA, Randle G, Feil EJ, Grundmann H, Spratt BG. The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). PNAS USA 2002; 99(11):7687-92.

[2] Elizaquivel P, Aznar R. Comparison of four commercial DNA extraction kits for PCR detection of Listeria monocytogenes, Salmonella, Escherichia coli O157:H7, and Staphylococcus aureus in fresh, minimally processed vegetables. J Food Protect 2008; 71(10):2110-4.

[3] Kabbani AT, Hammud HH, Ghannoum AM. Preparation and antibacterial activity of copper and cobalt complexes of 4-chloro-3-nitrobenzoate with a nitrogen donor ligand. Chem Pharm Bull 2007; 55(3):446-50.

[4] Beckford F, Dourth D, Shaloski M, Didion J, Thessing J, Woods J, Crowell V, Gerasimchuk N, Gonzalez-Sarrías A, Seeram NP. Half-sandwich ruthenium–arene complexes with thiosemicarbazones: Synthesis and biological evaluation of [(η6-p-cymene) Ru (piperonalthiosemicarbazones) Cl] Cl complexes. J Inorg Biochem 2011; 105(8):1019-29.

[5] Sun D, Zhang W, Yang E, Li N, Liu H, Wang W. Investigation of antibacterial activity and related mechanism of a ruthenium(II) polypyridyl complex. Inorg Chem Commun 2015; 56:17-21.

[6] Zhang P, Sadler PJ. Advances in the design of organometallic anticancer complexes. J Organomet Chem 2017; 839:5-14.

[7] Pastuszko A, Majchrzak K, Czyz M, Kupcewicz B, Budzisz E. The synthesis, lipophilicity and cytotoxic effects of new Ruthenium(II) arene complexes with chromone derivatives. J Inorg Biochem. 2016; 159:133-41.

[8] Chuklin P, Chalermpanaphan V, Nhukeaw T, Saithong S, Chainok K, Phongpaichit S, Ratanaphan A, Leesakul N. Synthesis, x-ray structure of organometallic Ruthenium (II) p-cymene complexes based on P- and N- donor ligands and their in vitro antibacterial and anticancer studies. J Organomet Chem 2017; 846:242-50.

[9] Pantić DN, Aranđelović S, Radulović S, Roller A, Arion VB, Grgurić-Šipka S. Synthesis, characterisation and cytotoxic activity of organoruthenium (II)-halido complexes with 1H-benzimidazole-2-carboxylic acid. J Organomet Chem 2016; 819:61-8.

[10] Allardyce CS, Dyson PJ. Ruthenium in medicine: current clinical uses and future prospects. Platin Met Rev 2001;45(2): 62-9.

[11] Chen J, Peng F, Zhang Y, Li B, She J, Jie X, Zou Z, Chen M, Chen L. Synthesis, characterization, cellular uptake and apoptosis-inducing properties of two highly cytotoxic cyclometalated ruthenium(II) beta-carboline complexes. Eur J Med Chem 2017; 140:104-17.

[12] Raj KR, Ramesh R, Małecki J. Synthesis and structure of arene Ruthenium (II) benzhydrazone complexes: antiproliferative activity, apoptosis induction and cell cycle analysis. J Organomet Chem 2018; 862:95-104.

[13] Allardyce CS, Dyson PJ, Ellis DJ, Salter PA, Scopelliti R. Synthesis and characterisation of some water soluble ruthenium (II)–arene complexes and an investigation of their antibiotic and antiviral properties. J Organomet Chem 2003; 668(1):35-42.

[14] Nikolić S, Opsenica DM, Filipović V, Dojčinović B, Aranđelović S, Radulović S. Strong in vitro cytotoxic potential of new ruthenium–cymene complexes. Organometallics. 2015; 34(14):3464-73.

[15] Mansour AM. Structural studies and biological activity evaluation of Pd(II), Pt(II) and Ru(II) complexes containing N-phenyl, N`-(3-triazolyl) thiourea. Appl Organomet Chem 2018; 32(1):3928.

[16] Saeed S, Rashid N, Jones PG, Ali M, Hussain R. Synthesis, characterization and biological evaluation of some thiourea derivatives bearing benzothiazole moiety as potential antimicrobial and anticancer agents. Eur J Med Chem 2010; 45(4):1323-31.

[17] Shakeel A, Altaf A. Thiourea derivatives in drug design and medicinal chemistry: A Short Rev 2016;10 p.

[18] Criado JJ, Rodrı́guez-Fernández E, Garcı́a E, Hermosa MR, Monte E. Thiourea derivatives of α-aminoacids. Synthesis and characterization of Ni(II), Cu(II) and Pt(II) complexes with l-valinate derivatives antifungal activity. J Inorg Biochem 1998; 69(1):113-9.

[19] Del CR, Criado JJ, Garcı́a E, Hermosa MR, Jiménez-Sánchez A, Manzano JL, Monte E, Rodrı́guez-Fernández E, Sanz F. Thiourea derivatives and their Nickel(II) and Platinum(II) complexes: Antifungal activity. J Inorg Biochem 2002; 89(1):74-82.

[20] Bruker, SMART, SAINT and SADABS, Bruker AXS Inc, Madison,Wisconsin, USA, 2013.

[21] Sheldrick GM. Crystal structure refinement with SHELXL. Acta Crystallogr C 2015; 71(Pt 1):3-8.

[22] Farrugia L. WinGX and ORTEP for windows: an update. J Appl Crystallogr 2012; 45(4):849-54.

[23] Clare F, Macrae IJB, James AC, Paul RE, Patrick M, Elna P, Lucia R, Robin T, Jacco van de S, Peter AW. Mercury CSD 2.0 – new features for the visualization and investigation of crystal structures. Appl Crystallogr 2008; 41: 466–70.

[24] Franklin RC llI, MD Matthew AW, MD, MBA, FIDSA Jeff A, PhD Michael ND, PharmD, FIDSA George ME, MD Mary JF, PhD, MPH Dwight JH, PhD David WH, MD Janet AH, MCLS, MT(ASCP) Jean BP, PhD, D(ABMM) Mair P, MD, FRCP, FRCPath Jana MS, MMSc Richard BT, Jr, PhD Maria MT, BS, MT(ASCP) John DT, MD Melvin PW, MD Barbara LZ, PhD. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard—ninth edition CLSI 2012;32.

[25] Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard-Third edition. 2008.

[26] Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; approved standard- Second edition. 2008.

[27] Akinchan NT, Drożdżewski PM, Battaglia LP. Crystal structure and spectroscopic characterization of bis(N-phenylthiourea). J Chem Crystallogr 2002; 32(3):91-7.

[28] Ralte L, Patrick JC, Rao KM. Study of reactivity of p-cymene ruthenium(II) dimer towards diphenyl-2-pyridylphosphine : Synthesis, characterization and molecular structures of [(η6-p-cymene)RuCl2(PPh2Py)] and [(η6-p-cymene)RuCl(PPh2Py)]BF4. J Chem Sci 2004; 116(1):21-7.

[29] Grgurić-Šipka S, Ivanović I, Rakić G, Todorović N, Gligorijević N, Radulović S, Arion VB, Keppler BK, Tešić ŽLj. Ruthenium(II)–arene complexes with functionalized pyridines: Synthesis, characterization and cytotoxic activity. Eur J Med Chem 2010; 45(3):1051-8.

[30] Hanif M, Nawaz MA, Babak MV, Iqbal J, Roller A, Keppler BK. RutheniumII(eta6-arene) complexes of thiourea derivatives: synthesis, characterization and urease inhibition. Molecules. 2014;19(6):8080-92.

[31] Henderson W, Kilpin TD, Nicholson BK. (p-cymene) thioglycollato ruthenium (II) dimer; a complex with an ambi-basic S, O-donor ligand. Struct Chem 2007;19(2):199-202.