[en] Five cationic ruthenium-arene complexes with the generic formula [Ru(SAc)(S2C·NHC)(p-cymene)](PF6) (5a-e) were prepared in almost quantitative yields using a straightforward one-pot, two-step experimental procedure starting from [RuCl2(p-cymene)]2, an imidazol(in)ium-2-dithiocarboxylate (NHC·CS2) zwitterion, KSAc, and KPF6. These half-sandwich compounds were fully characterized by various analytical techniques and the molecular structures of two of them were solved by X-ray diffraction analysis, which revealed the existence of an intramolecular chalcogen bond between the oxygen atom of the thioacetate ligand and a proximal sulfur atom of the dithiocarboxylate unit. DFT calculations showed that the C=S…O charge transfer amounted to 2.4 kcal mol-1. The dissolution of [Ru(SAc)(S2C·IMes)(p-cymene)](PF6) (5a) in moist DMSO-d6 at room temperature did not cause the dissociation of its sulfur ligands. Instead, p-cymene was slowly released to afford the 12-electron [Ru(SAc)(S2C·IMes)]+ cation that could be detected by mass spectrometry. Monitoring the solvolysis process by 1H NMR spectroscopy showed that more than 22 days were needed to fully decompose the starting ruthenium-arene complex. Compounds 5a-e exhibited a high antiproliferative activity against human glioma Hs683 and human lung carcinoma A549 cancer cells. In particular, the IMes derivative (5a) was the most potent compound of the series, achieving toxicities similar to those displayed by marketed platinum drugs.
Disciplines :
Chemistry
Author, co-author :
Zain Aldin, Mohammed ; Université de Liège - ULiège > Faculté des Sciences > Doct. scienc. (chimie)
Zaragoza, Guillermo; Unidade de Difracción de Raios X, RIAIDT, Universidade de Santiago de Compostela, Campus Vida, 15782, Santiago de Compostela, Spain
Choquenet, Eva; Microbiology, Bioorganic and Macromolecular Chemistry, Faculté de Pharmacie, Université Libre de Bruxelles, 1050, Brussels, Belgium
Blampain, Guillaume; Microbiology, Bioorganic and Macromolecular Chemistry, Faculté de Pharmacie, Université Libre de Bruxelles, 1050, Brussels, Belgium
Berger, Gilles; Microbiology, Bioorganic and Macromolecular Chemistry, Faculté de Pharmacie, Université Libre de Bruxelles, 1050, Brussels, Belgium
Delaude, Lionel ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie organométallique et catalyse homogène
Language :
English
Title :
Synthesis, characterization, and biological activity of cationic ruthenium-arene complexes with sulfur ligands.
Publication date :
June 2024
Journal title :
Journal of Biological Inorganic Chemistry
ISSN :
0949-8257
eISSN :
1432-1327
Publisher :
Springer Science and Business Media Deutschland GmbH, Germany
G. Süss-Fink Arene ruthenium complexes as anticancer agents Dalton Trans 2010 39 1673 1688 1:CAS:528:DC%2BC3cXhtlCqtr4%3D 10.1039/b916860p
W.H. Ang A. Casini G. Sava P.J. Dyson Organometallic ruthenium-based antitumor compounds with novel modes of action J Organomet Chem 2011 696 989 998 1:CAS:528:DC%2BC3MXisFKnsbg%3D 10.1016/j.jorganchem.2010.11.009
A.L. Noffke A. Habtemariam A.M. Pizarro P.J. Sadler Designing organometallic compounds for catalysis and therapy Chem Commun 2012 48 5219 5246 1:CAS:528:DC%2BC38XmtlOqtLs%3D 10.1039/c2cc30678f
A.A. Nazarov C.G. Hartinger P.J. Dyson Opening the lid on piano-stool complexes: an account of ruthenium(II)–arene complexes with medicinal applications J Organomet Chem 2014 751 251 260 1:CAS:528:DC%2BC3sXhs1Siur3E 10.1016/j.jorganchem.2013.09.016
B.M. Blunden M.H. Stenzel Incorporating ruthenium into advanced drug delivery carriers—an innovative generation of chemotherapeutics J Chem Technol Biotechnol 2015 90 1177 1195 1:CAS:528:DC%2BC2MXptlOqsrY%3D 10.1002/jctb.4507
C. Mari V. Pierroz S. Ferrari G. Gasser Combination of Ru(II) complexes and light: new frontiers in cancer therapy Chem Sci 2015 6 2660 2686 1:CAS:528:DC%2BC2MXntVGqsA%3D%3D 10.1039/c4sc03759f
B.S. Murray M.V. Babak C.G. Hartinger P.J. Dyson The development of RAPTA compounds for the treatment of tumors Coord Chem Rev 2016 306 86 114 1:CAS:528:DC%2BC2MXhtFCqtL7M 10.1016/j.ccr.2015.06.014
S.M. Meier-Menches C. Gerner W. Berger C.G. Hartinger B.K. Keppler Structure–activity relationships for ruthenium and osmium anticancer agents—towards clinical development Chem Soc Rev 2018 47 909 928 1:CAS:528:DC%2BC2sXhvVGmtb%2FE 10.1039/c7cs00332c
F. Marchetti R. Pettinari C. Di Nicola C. Pettinari J. Palmucci R. Scopelliti T. Riedel B. Therrien A. Galindo P.J. Dyson Synthesis, characterization and cytotoxicity of arene–ruthenium(II) complexes with acylpyrazolones functionalized with aromatic groups in the acyl moiety Dalton Trans 2018 47 868 878 1:CAS:528:DC%2BC2sXhvF2ns77F 10.1039/c7dt04249c
S. Swaminathan J. Haribabu N.K. Kalagatur R. Konakanchi N. Balakrishnan N. Bhuvanesh R. Karvembu Synthesis and anticancer activity of [RuCl2(η6-arene)(aroylthiourea)] complexes—high activity against the human neuroblastoma (IMR-32) cancer cell line ACS Omega 2019 4 6245 6256 1:CAS:528:DC%2BC1MXlslaqsb8%3D 10.1021/acsomega.9b00349
T.A. Khan K. Bhar R. Thirumoorthi T.K. Roy A.K. Sharma Design, synthesis, characterization and evaluation of the anticancer activity of water-soluble half-sandwich ruthenium(II) arene halido complexes New J Chem 2020 44 239 257 1:CAS:528:DC%2BC1MXitFOisL7K 10.1039/c9nj03663f
C. Chen C. Xu T. Li S. Lu F. Luo H. Wang Novel NHC-coordinated ruthenium(II) arene complexes achieve synergistic efficacy as safe and effective anticancer therapeutics Eur J Med Chem 2020 203 1:CAS:528:DC%2BB3cXhsVaktr3O 10.1016/j.ejmech.2020.112605
S. Harringer D. Wernitznig N. Gajic A. Diridl D. Wenisch M. Hejl M.A. Jakupec S. Theiner G. Koellensperger W. Kandioller B.K. Keppler Introducing N-, P-, and S-donor leaving groups: an investigation of the chemical and biological properties of ruthenium, rhodium and iridium thiopyridone piano stool complexes Dalton Trans 2020 49 15693 15711 1:CAS:528:DC%2BB3cXit1aksbnE 10.1039/d0dt03165h
M. Marloye H. Inam C.J. Moore V. Debaille J.R. Pritchard M. Gelbcke F. Meyer F. Dufrasne G. Berger Synthesis, structure and anticancer properties of new biotin- and morpholine-functionalized ruthenium and osmium half-sandwich complexes J Biol Inorg Chem 2021 26 535 549 1:CAS:528:DC%2BB3MXhsVagurbP 10.1007/s00775-021-01873-9
L. Rafols D. Josa D. Aguilà L. Barrios O. Roubeau J. Cirera V. Soto-Cerrato R. Pérez-Tomás M. Martínez A. Grabulosa P. Gamez Piano-stool ruthenium(II) complexes with delayed cytotoxic activity: origin of the lag time Inorg Chem 2021 60 7974 7990 1:CAS:528:DC%2BB3MXhtVyntr7J 10.1021/acs.inorgchem.1c00507
L. Delaude X. Sauvage A. Demonceau J. Wouters Synthesis and catalytic evaluation of ruthenium-arene complexes generated using imidazol(in)ium-2-carboxylates and -dithiocarboxylates Organometallics 2009 28 4056 4064 1:CAS:528:DC%2BD1MXotV2ltLc%3D 10.1021/om9002363
Q. Willem F. Nicks X. Sauvage L. Delaude A. Demonceau Ruthenium–arene complexes bearing imidazol(in)ium-2-dithiocarboxylate ligands: evaluation of their catalytic activity in the synthesis of enol esters J Organomet Chem 2009 694 4049 4055 1:CAS:528:DC%2BD1MXhtlWls73L 10.1016/j.jorganchem.2009.08.028
Delaude L (2009) Betaine adducts of N-heterocyclic carbenes: synthesis, properties, and reactivity. Eur J Inorg Chem. https://doi.org/10.1002/ejic.200801227
T.F. Beltrán L. Delaude Recent advances in small clusters and polymetallic assemblies based on transition metals and dithiocarboxylate zwitterions derived from N-heterocyclic carbenes J Cluster Sci 2017 28 667 678 1:CAS:528:DC%2BC2sXitFelu7s%3D 10.1007/s10876-017-1174-4
Delaude L, Demonceau A, Wouters J (2009) Assessing the potentials of zwitterionic NHC·CS2 adducts for probing the stereoelectronic parameters of N-heterocyclic carbenes. Eur J Inorg Chem. https://doi.org/10.1002/ejic.200801110
Mazars F, Hrubaru M, Tumanov N, Wouters J, Delaude L (2021) Synthesis of azolium-2-dithiocarboxylate zwitterions under mild, aerobic conditions. Eur J Org Chem. https://doi.org/10.1002/ejoc.202100274
M. Zain Aldin G. Zaragoza W. Deschamps J.-C.D. Tomani J. Souopgui L. Delaude Synthesis, characterization, and biological activity of water-soluble, dual anionic and cationic ruthenium-arene complexes bearing imidazol(in)ium-2-dithiocarboxylate ligands Inorg Chem 2021 60 16769 16781 1:CAS:528:DC%2BB3MXit1OgtL%2FJ 10.1021/acs.inorgchem.1c02648
F. Wang H. Chen S. Parsons I.D.H. Oswald J.E. Davidson P.J. Sadler Kinetics of aquation and anation of ruthenium(II) arene anticancer complexes, acidity and X-ray structures of aqua adducts Chem Eur J 2003 9 5810 5820 1:CAS:528:DC%2BD2cXhvVGk 10.1002/chem.200304724
F. Wang A. Habtemariam E.P.L. van der Geer R. Fernández M. Melchart R.J. Deeth R. Aird S. Guichard F.P.A. Fabbiani P. Lozano-Casal I.D.H. Oswald D.I. Jodrell S. Parsons P.J. Sadler Controlling ligand substitution reactions of organometallic complexes: tuning cancer cell cytotoxicity Proc Natl Acad Sci USA 2005 102 18269 1:CAS:528:DC%2BD28Xpt1aq 10.1073/pnas.0505798102
W.H. Ang E. Daldini C. Scolaro R. Scopelliti L. Juillerat-Jeannerat P.J. Dyson Development of organometallic ruthenium-arene anticancer drugs that resist hydrolysis Inorg Chem 2006 45 9006 9013 1:CAS:528:DC%2BD28XhtVWhs7fJ 10.1021/ic061008y
C. Scolaro C.G. Hartinger C.S. Allardyce B.K. Keppler P.J. Dyson Hydrolysis study of the bifunctional antitumour compound RAPTA-C, [Ru(η6-p-cymene)Cl2(pta)] J Inorg Biochem 2008 102 1743 1748 1:CAS:528:DC%2BD1cXhtVWit7rK 10.1016/j.jinorgbio.2008.05.004
Z. Futera J. Klenko J.E. Šponer J. Šponer J.V. Burda Interactions of the “piano-stool” [ruthenium(II)(η6-arene)(en)Cl]+ complexes with water and nucleobases; ab initio and DFT study J Comput Chem 2009 30 1758 1770 1:CAS:528:DC%2BD1MXnvV2ntbk%3D 10.1002/jcc.21179
J. Zhao X. Zhang H. Liu Z. Xiong M. Li T. Chen Ruthenium arene complex induces cell cycle arrest and apoptosis through activation of P53-mediated signaling pathways J Organomet Chem 2019 898 1:CAS:528:DC%2BC1MXhsVGhtrjN 10.1016/j.jorganchem.2019.07.020
D. Lovison L. Allegri F. Baldan M. Ballico G. Damante C. Jandl W. Baratta Cationic carboxylate and thioacetate ruthenium(II) complexes: synthesis and cytotoxic activity against anaplastic thyroid cancer cells Dalton Trans 2020 49 8375 8388 1:CAS:528:DC%2BB3cXhtFagsrrI 10.1039/d0dt01390k
Al-Buthabhak HS, Falasca V, Yu Y, Sobolev AN, Skelton BW, Moggach SA, Ferro V, Al-Salami H, Baker MV (2022) Au-NHC complexes with thiocarboxylate ligands: synthesis, structure, stability, thiol exchange and in vitro anticancer activity. Appl Organomet Chem. https://doi.org/10.1002/aoc.6645
J. Furrer G. Süss-Fink Thiolato-bridged dinuclear arene ruthenium complexes and their potential as anticancer drugs Coord Chem Rev 2016 309 36 50 1:CAS:528:DC%2BC2MXhvVyqurrO 10.1016/j.ccr.2015.10.007
E. Păunescu G. Boubaker O. Desiatkina N. Anghel Y. Amdouni A. Hemphill J. Furrer The quest of the best—a SAR study of trithiolato-bridged dinuclear ruthenium(II)-arene compounds presenting antiparasitic properties Eur J Med Chem 2021 222 1:CAS:528:DC%2BB3MXhsVSitr3M 10.1016/j.ejmech.2021.113610
O. Desiatkina N. Anghel G. Boubaker Y. Amdouni A. Hemphill J. Furrer E. Păunescu Trithiolato-bridged dinuclear ruthenium(II)-arene conjugates tethered with lipophilic units: synthesis and Toxoplasma gondii antiparasitic activity J Organomet Chem 2023 986 1:CAS:528:DC%2BB3sXhvFels74%3D 10.1016/j.jorganchem.2023.122624
Bruker, APEX 3 2005 Madison Bruker AXS Inc.
R.C. Clark J.S. Reid The analytical calculation of absorption in multifaceted crystals Acta Crystallogr Sect A Fundam Crystallogr 1995 51 887 897 10.1107/s0108767395007367
M.C. Burla R. Caliandro M. Camalli B. Carrozzini G.L. Cascarano L. De Caro C. Giacovazzo G. Polidori R. Spagna SIR2004: an improved tool for crystal structure determination and refinement J Appl Crystallogr 2005 38 381 388 1:CAS:528:DC%2BD2MXitlSisrs%3D 10.1107/s002188980403225x
G. Sheldrick Crystal structure refinement with SHELXL Acta Crystallogr Sect C Struct Chem 2015 71 3 8 10.1107/s2053229614024218
G.M. Sheldrick SADABS, programs for scaling and correction of area detection data 1996 Göttingen University of Göttingen
F. Neese The ORCA program system Wiley Interdiscipl Rev Comput Mol Sci 2012 2 73 78 1:CAS:528:DC%2BC38XhvFGls7s%3D 10.1002/wcms.81
F. Neese Software update: the ORCA program system, version 4.0 Wiley Interdiscipl Rev Comput Mol Sci 2018 8 10.1002/wcms.1327
N. Mardirossian M. Head-Gordon ωB97M-V: a combinatorially optimized, range-separated hybrid, meta-GGA density functional with VV10 nonlocal correlation J Chem Phys 2016 144 1:CAS:528:DC%2BC28XpsF2lt78%3D 10.1063/1.4952647
N. Mardirossian L. Ruiz Pestana J.C. Womack C.-K. Skylaris T. Head-Gordon M. Head-Gordon Use of the rVV10 nonlocal correlation functional in the B97M-V density functional: defining B97M-rV and related functionals J Phys Chem Lett 2017 8 35 40 1:CAS:528:DC%2BC28XitVSrsLrO 10.1021/acs.jpclett.6b02527
F. Weigend R. Ahlrichs Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn: design and assessment of accuracy Phys Chem Chem Phys 2005 7 3297 3305 1:CAS:528:DC%2BD2MXpsFWgu7o%3D 10.1039/b508541a
F. Weigend Accurate Coulomb-fitting basis sets for H to Rn Phys Chem Chem Phys 2006 8 1057 1065 1:CAS:528:DC%2BD28Xhs12ntrc%3D 10.1039/b515623h
E.D. Glendening J.K. Badenhoop A.E. Reed J.E. Carpenter J.A. Bohmann C.M. Morales P. Karafiloglou C.R. Landis F. Weinhold NBO 70 2018 Madison Theoretical Chemistry Institute, University of Wisconsin
K. Syed Mohamed D.K. Padma Spectral studies on pyridinium hexafluorophosphate Spectrochim Acta Part A 1985 41 725 728 10.1016/0584-8539(85)80181-1
Mayfield HG, Bull WE (1971) Co-ordinating tendencies of the hexafluorophosphate ion. J Chem Soc A. https://doi.org/10.1039/j19710002279
Only data for complexes 3a–e are displayed in Table 2, see Ref. 26 for complexes 4a–e
A. Bauzá D. Quiñonero P.M. Deyà A. Frontera Halogen bonding versus chalcogen and pnicogen bonding: a combined Cambridge structural database and theoretical study CrystEngComm 2013 15 3137 3144 1:CAS:528:DC%2BC3sXks1GhtL8%3D 10.1039/c2ce26741a
D.J. Pascoe K.B. Ling S.L. Cockroft The origin of chalcogen-bonding interactions J Am Chem Soc 2017 139 15160 15167 1:CAS:528:DC%2BC2sXhs1amt7%2FM 10.1021/jacs.7b08511
P. Scilabra G. Terraneo G. Resnati The chalcogen bond in crystalline solids: a world parallel to halogen bond Acc Chem Res 2019 52 1313 1324 1:CAS:528:DC%2BC1MXpt1WjsL0%3D 10.1021/acs.accounts.9b00037
L. Vogel P. Wonner S.M. Huber Chalcogen bonding: an overview Angew Chem Int Ed 2019 58 1880 1891 1:CAS:528:DC%2BC1cXisVWks77O 10.1002/anie.201809432
B.R. Beno K.-S. Yeung M.D. Bartberger L.D. Pennington N.A. Meanwell A survey of the role of noncovalent sulfur interactions in drug design J Med Chem 2015 58 4383 4438 1:CAS:528:DC%2BC2MXjs1Giu7g%3D 10.1021/jm501853m
K.T. Mahmudov V.A. Aliyeva M.F.C. Guedes da Silva A.J.L. Pombeiro S.M. Huber The chalcogen bond in solution: synthesis, catalysis and molecular recognition Halogen bonding in solution 2021 Weinheim Wiley-VCH 363 382 10.1002/9783527825738.ch11
O.A. Vydrov T. Van Voorhis Nonlocal van der Waals density functional: the simpler the better J Chem Phys 2010 133 1:CAS:528:DC%2BC3cXhsF2rt7fN 10.1063/1.3521275
M.A. Iron T. Janes Evaluating transition metal barrier heights with the latest density functional theory exchange-correlation functionals: the MOBH35 benchmark database J Phys Chem A 2019 123 3761 3781 1:CAS:528:DC%2BC1MXovVKmtrY%3D 10.1021/acs.jpca.9b01546
M.A. Iron T. Janes Correction to “Evaluating transition metal barrier heights with the latest density functional theory exchange-correlation functionals: the MOBH35 benchmark database” J Phys Chem A 2019 123 6379 6380 1:CAS:528:DC%2BC1MXhtlKjt7vJ 10.1021/acs.jpca.9b06135
G. Berger H. Leclercqz A. Derenne M. Gelbcke E. Goormaghtigh J. Nève V. Mathieu F. Dufrasne Synthesis and in vitro characterization of platinum(II) anticancer coordinates using FTIR spectroscopy and NCI COMPARE: a fast method for new compound discovery Bioorg Med Chem 2014 22 3527 3536 1:CAS:528:DC%2BC2cXnvFWitbo%3D 10.1016/j.bmc.2014.04.017