An alternate route to disulfanido complexes by nucleophilic attack of thiolates on ruthenium-bound thiosulfonato ligands

Article abstract of DOI:10.1021/ic101795s

The reaction of the thiosulfonato complexes [(p-cym)Ru(bipy)(S-SO ₂R)]⁺ (R = Ph, ρ-Tol) with the thiolates R'S ^- (R' = alkyl or aryl) leads to S-S bond cleavage and to the quantitative formation of the corresponding disulf

Full text of DOI:10.1021/ic101795s

Inorg. Chem. 2010, 49, 9119–9121 9119
DOI: 10.1021/ic101795s
An Alternate Route to Disulfanido Complexes by Nucleophilic Attack
of Thiolates on Ruthenium-Bound Thiosulfonato Ligands
Erwan Galardon,*,† Patrick Deschamps,‡ Alain Tomas,‡ Pascal Roussel,§ and Isabelle Artaud*,†
†
ꢀ
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR 8601 CNRS, Universite Paris
‡
ꢁ
Descartes, 45 rue des Saints Peres, 75270 Paris Cedex 06, France, Laboratoire de Cristallographie et RMN
ꢀ
Biologiques, UMR 8015 CNRS, Universite Paris Descartes, 4 avenue de l’Observatoire, 75270 Paris Cedex 06,
§
ꢀ
ꢀ
ꢀ
France, and Unite de Catalyse et Chimie du Solide (UCCS), UMR 8012 CNRS, Ecole Nationale Superieure de
Chimie de Lille, BP 90108, 59652 Villeneuve d’Ascq Cedex, France
Received September 2, 2010
The reaction of the thiosulfonato complexes [(p-cym)Ru(bipy)(S-
SO2R)]þ (R = Ph, p-Tol) with the thiolates R0S- (R0 = alkyl or aryl)
leads to S-S bond cleavage and to the quantitative formation of the
corresponding disulfanido derivatives [(p-cym)Ru(bipy)(S-SR0)]þ.
The aryldisulfanido complexes also react with benzyl thiolate by
S-S bond cleavage to give [(p-cym)Ru(bipy)(SSCH2Ph)]þ.
nucleophilicity of sulfur ligands like hydrogen (sulfido)3 (HS-)
or disulfido4 (S22-) and their subsequent reaction with electro-
philic sulfur or carbon centers, respectively. Herein, we propose
an alternate route toward disulfanido complexes, resulting
from the nucleophilic attack of a thiolate on a metal-bound
thiosulfonate moiety. Interestingly, the thiolate does not react
at the metal center by ligand exchange but selectively on the
thiosulfonate ligand itself, leading to cleavage of the S-S(O)2
bond and to the formation of a new S-S bond.
The new complexes [(p-cym)Ru(bipy)(S-SO2(p-Tol)]þ (1a)
and [(p-cym)Ru(bipy)(S-SO2(Ph)]þ (1b) were synthesized
and isolated as their PF6 salts by first reacting the complex
[(p-cym)Ru(bipy)(Cl)](PF6) with AgNO3 in methanol, fol-
lowed by the addition of the thiosulfonate salt p-TolSO2SK
or PhSO2SNa. Thiosulfonato complexes of ruthenium, based
on the Cp ligand, have already been reported, but they were
obtained either by oxygen transfer from the thiosulfinato
derivatives CpRu(PPh3)(CO)(SS(O)R)5 or by reaction be-
tween the hydrogen (sulfido) compounds CpRu(dppe)(SH)
or CpRu(dppm)(SH) and sulfonyl chlorides.6 The X-ray
The recent report of crystal structures that reveal persulfides
directly ligated to a transition-metal center in biological
systems1 has opened a new field of investigation for coordina-
tion chemists. To provide a rational synthesis of disulfanido
complexes and to study their chemical reactivity, however, still
remain challenges. With three potential reactive centers,
namely, the metal cation and the two sulfurs of the S-S bond,
these species are indeed highly reactive. We have recently
reported the first direct synthesis of alkyldisulfanido complexes
by the simple reaction between a hydroxo zinc complex and a
synthetic persulfide.2 However, this strategy requires a stable
persulfide and is therefore limited to bulky and electron-rich
derivatives. It also absolutely requires the presence of a base in
the metal coordination sphere of the starting complex, to avoid
the known degradation of hydrodisulfides in a basic solu-
tion. Other rational strategies found in the literature use the
crystal structure of 1b PF6 is displayed in Figure 1, and it
3
shows bond lengths and angles in the range observed in
related derivatives of ruthenium5,6 or other metals.7
Upon the addition of a methanolic solution of sodium benzyl
thiolate to a solution of 1a or 1b in methanol or dimethyl
sulfoxide (DMSO), the color of the mixture immediately
turned from yellow to orange. Careful analysis of the 1H NMR
spectrum of the crude reaction mixture (Figure 2) of 1a
*To whom correspondence should be addressed. E-mail: erwan.galardon@
parisdescartes.fr (E.G.), isabelle.artaud@parisdescartes.fr (I.A.).
(1) (a) Arendsen, A. F.; Hadden, J.; Card, G.; McAlpine, A. S.; Bailey, S.;
Zaitsev, V.; Duke, E. H. M.; Lindley, P. F.; Krockel, M.; Trautwein, A. X.;
Feiters, M. C.; Charnock, J. M.; Garner, C. D.; Marritt, S. J.; Thomson, A. J.;
Kooter, I. M.;Johnson, M. K.;VanDenBerg, W. A. M.;VanDongen, W. M. A.
M.; Hagen, W. R. J. Inorg. Biochem. 1998, 3(1), 81–95. (b) Bamford, V. A.; Bruno,
S.; Rasmussen, T.; Appia-Ayme, C.; Cheesman, M. R.; Berks, B. C.; Hemmings, A. M.
EMBO J. 2002, 21(21), 5599–5610. (c) Aragao, D.; Macedo, S.; Mitchell, E. P.;
Romao, C. V.; Liu, M. Y.; Frazao, C.; Saraiva, L. M.; Xavier, A. V.; LeGall, J.; van
Dongen, W. M. A. M.; Hagen, W. R.; Teixeira, M.; Carrondo, M. A.; Lindley, P.
J. Inorg. Biochem. 2003, 8(5), 540–548. (d) Kim, E. J.; Feng, J.; Bramlett, M. R.;
Lindahl, P. A. Biochemistry 2004, 43(19), 5728–5734.
(3) (a) Shaver, A.; Hartgerink, J.; Lai, R. D.; Bird, P.; Ansari, N.
Organometallics 1983, 2(7), 938–40. (b) Shaver, A.; Hartgerink, J. Can. J.
Chem. 1987, 65(6), 1190–1194. (c) Shaver, A.; Plouffe, P.-Y. Inorg. Chem. 1994,
33(19), 4327–4333.
(4) Lobana, T. S.; Isobe, K.; Kitayama, H.; Nishioka, T.; Doe, M.;
Kinoshita, I. Organometallics 2004, 23(22), 5347–5352.
(5) Shaver, A.; Plouffe, P. Y. J. Am. Chem. Soc. 1991, 113(20), 7780–7782.
(6) El-Khateeb, M.; Wolfsberger, B.; Schenk, W. A. J. Organomet. Chem.
2000, 612(1-2), 14–17.
(7) (a) El-khateeb, M.; Shaver, A.; Lebuis, A. M. J. Organomet. Chem.
2001, 622(1-2), 293–296. (b) El-khateeb, M.; Gorls, H.; Weigand, W.
J. Organomet. Chem. 2006, 691(26), 5804–5808. (c) Fischmann, A. J.; Forsyth,
C. M.; Spiccia, L. Inorg. Chem. 2008, 47(22), 10565–10574.
(2) Galardon, E.; Tomas, A.; Selkti, M.; Roussel, P.; Artaud, I. Inorg.
Chem. 2009, 48(13), 5921–5927.
r
2010 American Chemical Society
Published on Web 09/23/2010
pubs.acs.org/IC

9120 Inorganic Chemistry, Vol. 49, No. 20, 2010
Galardon et al.
Figure 3. Titration of complex 2b PF6 in DMSO (4 ꢀ 10-5 M) by
3
sodium benzyl thiolate (inset: variation of the absorbance at 434 nm with
the amount of added thiolate).
observed by 1H NMR. Again, the Ru-S distance is similar to
that observed in the CpRu(PPh3)(CO)(SSR) complexes.5
The reaction is general, and aromatic as well as aliphatic
thiolates can be successfully used (Scheme 1), with the only
complexes detected at the end of the reaction being the
disulfanido derivatives 2a-2d.
Figure 1. ORTEP views of complexes 1b PF6 (a) and 2c BPh4
3
3
(b) showing thermal ellipsoids at 50% probability and atom labeling.
The hydrogen atoms and the anions have been omitted for clarity.
Selected bonds lengths for 1b PF6 (2c BPh4): Ru1-S1, 2.401 (2.384);
3
3
Ru1-N1, 2.082 (2.078); Ru1-N2, 2.075 (2.084); S1-S2, 2.040 (2.042).
A similar reaction takes place between the aryldisulfanido
complexes 2a and 2b and sodium benzyl thiolate. The reac-
1
tion, in DMSO, can easily be monitored by H NMR. The
addition of 1 equiv of benzyl thiolate to either 2a or 2b leads
to the immediate and complete formation of 2c as a single
complex (see Figure S1 in the Supporting Information). With
2b, which bears a coumarin chromophore, the reaction can
conveniently be monitored by UV-visible spectroscopy.
While 2b (λmax = 367 nm) is stable for hours in solution, it
immediately reacts with benzyl thiolate with concomitant
release of 4-methyl-2-oxo-2H-chromene-7-thiolate (λmax
=
434 nm). In both cases, the reactions are not equilibrated,
showing that the released aryl thiolate is not able to attack the
alkyldisulfanido ligand by UV-visible spectroscopy (Figure 3).
The conversion of complex 1 into complex 2 is related to
the reaction of organic thiosulfonates RSO2SR0 with thiols
R00SH, which is known to yield the disulfides R0SSR00 along
with the release of the sulfinic acid RSO2H.8 More interestingly,
this conversion shares some similarities with the reaction cata-
lyzed by rhodanese-like enzymes9 or thiosulfate reductase,10
which assist cleavage of the S-S bond of thiosulfate (S2O32-) or
thiosulfonate (RSO2S-) anions by a thiolate. The active sites of
these enzymes are characterized by an intense electrostatic field
generated by basic amino acid residues such as arginines and
histidines, which provide a strong anion binding site for the
substrate.11 When the electron density is reduced from the
terminal sulfur of the thiosulfate or thiosulfonates, this field
favors the nucleophilic attack of the thiolate and the formation
of a persulfide, which can subsequently react with a sulfur
acceptor, such as cyanide or thiols.
Figure 2. Aromatic regionofthe 1H NMRspectra recorded at500 MHz
of 1a PF6 (0.02 M in DMSO-d6) before (a, top) and after (b, bottom)
the addition of 1 equiv of sodium benzyl thiolate (*, p-TolSO2Na;
O, PhCH2SS-Ru).
3
Scheme 1. Synthesis and Notation of the Disulfanido Complexes
-
indicates the release of p-TolSO2 in solution, along with the
replacement of the initial signals of the thiolate anion by a new
set of more shielded peaks (Δδ = 1.35 ppm for the benzylic
protons), attributed to the introduction of the benzyl group
within the coordination sphere of the metal.
This is in agreement with the reaction proposed in Scheme 1,
in which the S-S(O)2 bond is cleaved by a nucleophilic attack
of the thiolate on the internal sulfur atom of the metal
thiosulfonate ligand. Further evidence for the formation of
the disulfanido species, Ru-S-SCH2Ph, comes from analysis
of the mass spectrometry spectrum (ESIþ mode) of the crude
reaction mixture, which displays a peak at m/z 547 (2c, 100%),
and from X-ray structure analysis of 2c crystallized as the BPh4
salt, shown in Figure 1. The Ru-S bond length in 2c is slightly
From the few precedents found in the literature,12 it
appears that sulfur-containing nucleophiles do not promote
(8) (a) Boduszek, B.; Kice, J. L. J. Org. Chem. 1982, 47, 2055–2060.
(b) Boduszek, B.; Kice, J. L. J. Org. Chem. 1982, 47, 3199–3207.
(9) (a) Mintel, R.; Westley, J. J. Biol. Chem. 1966, 241(14), 3381–3385.
(b) Mintel, R.; Westley, J. J. Biol. Chem. 1966, 241(14), 3386–3389.
(10) Chauncey, T. R.; Westley, J. J. Biol. Chem. 1983, 258(24), 15037–
15045.
(11) Bordo, D.; Deriu, D.; Colnaghi, R.; Carpen, A.; Pagani, S.; Bolognesi,
M. J. Mol. Biol. 2000, 298, 691–704.
(12) (a) Song, L. C.; Yan, C. G.; Hu, Q. M.; Wang, R. J.; Mak, T. C. W.;
Huang, X. Y. Organometallics 1996, 15(6), 1535–1544. (b) Song, L. C.; Qin,
X. D.; Hu, Q. M.; Huang, X. Y. Organometallics 1998, 17(24), 5437–5440.
˚
shorter (Δ = 0.017 A) than that in 1a, and this correlates with
˚
an increase of the average Ru-N distance (Δ = 0.023 A). The
structure also clearly shows that the benzylic protons of the
disulfanido moiety lie above one of the aromatic rings of the
bipy ligand, accounting for the strong shielding of these protons

Communication
Inorganic Chemistry, Vol. 49, No. 20, 2010 9121
the S-S(O)2 bond cleavage of thiosulfonato metal complexes
but lead to ligand exchange.12 Similarly, very recently,
we reported that the reaction between alkyldisulfanido
tris(pyrazolyl)borate zinc complexes and thiols in the pre-
sence of a base results in a metal-based reaction rather than in
sulfur attack of the S-S bond.2 In the case of octahedral RuII
d6complexes, ligand-exchange reactions are usually slow
compared with those of other divalent metal complexes,13
and this results in an unprecedented reaction leading to
2a-2d and to the specific conversion of 2a or 2b into 2c.
Indeed, we can expect a slow exchange of the thiosulfonato or
disulfanido ligands in 1 and 2 because in similar derivatives
thiolate substitution is slow14 and the Ru-S bond strength is
rather insensitive to the sulfur oxidation state.15 This drives
the reaction with the nucleophilic thiolates toward cleavage
of the S-S bonds, although the reaction is only feasible in the
presence of good leaving groups such as sulfinates or aryl
thiolates.
In conclusion, we successfully controlled the heterolytic
cleavage of the S-S bond of a metal-coordinated thiosulfo-
nate. The versatile chemoselective nucleophilic attack at the
internal sulfur of Ru-S-S(O2)R by thiolates gives access to
alkyl- or aryldisulfanido complexes, Ru-S-S-R0, with
release of the sulfinate anion RS(O2)-. This reaction is highly
reminiscent of the thiolate cleavage of organic thiosulfonates
R1-S-S(O2)R2 by a selective attack at the sulfenyl sulfur to
give a disulfide R1-S-S-R0.
(13) (a) Taube, H. Comments Inorg. Chem. 1981, 1(1), 1. (b) Reedijk, J.
Platinum Met. Rev. 2008, 52(1), 2–11.
(14) Wang, F. Y.; Habtemariam, A.; van der Geer, E. P. L.; Fernandez,
R.; Melchart, M.; Deeth, R. J.; Aird, R.; Guichard, S.; Fabbiani, F. P. A.;
Lozano-Casal, P.; Oswald, I. D. H.; Jodrell, D. I.; Parsons, S.; Sadler, P. J.
Proc. Natl. Acad. Sci. U.S.A. 2005, 102(51), 18269–18274.
(15) Sriskandakumar, T.; Petzold, H.; Bruijnincx, P. C. A.; Habtemariam,
A.; Sadler, P. J.; Kennepohl, P. J. Am. Chem. Soc. 2009, 131(37), 13355–
13361.
Supporting Information Available: Synthetic procedures for
all of the complexes described, Figure S1, and crystallographic
data of complexes 1b PF6 and 2c BPh4 in CIF format. This
3
3
material is available free of charge via the Internet at http://
pubs.acs.org.