Metal Complexes of the trans-Influencing Ligand Thiomaltol

Article abstract of DOI:10.1021/ic0347135

The wide use of the ligand 3-hydroxy-2-methyl-4-pyrone (maltol) in bioinorganic chemistry has prompted an effort to further exploit this ligand class by achieving an efficient, one-step synthesis of the chelator 3-hydroxy-2-methyl-4-thiopyrone (thiomaltol). Complexes of thiomaltol with nickel(II) and iron(III) have been prepared and studied by using UV-visible spectroscopy and electrochemical methods. In addition, both complexes as well as the free thiomaltol ligand have been structurally characterized by using single-crystal X-ray diffraction methods. The ligand is found to exert a strong trans influence on the structure of the complexes in the solid state with the nickel(II) and iron(III) complexes demonstrating a cis and fac geometry, respectively. The compounds described here should significantly expand the scope and utility of O,S-donor ligands derived from maltol and related precursors.

Full text of DOI:10.1021/ic0347135

Inorg. Chem. 2003, 42, 7455−7459
Metal Complexes of the trans-Influencing Ligand Thiomaltol
Jana A. Lewis, David T. Puerta, and Seth M. Cohen*
Department of Chemistry and Biochemistry, UniVersity of California,
San Diego, La Jolla, California 92093-0358
Received June 21, 2003
The wide use of the ligand 3-hydroxy-2-methyl-4-pyrone (maltol) in bioinorganic chemistry has prompted an effort
to further exploit this ligand class by achieving an efficient, one-step synthesis of the chelator 3-hydroxy-2-methyl-
4-thiopyrone (thiomaltol). Complexes of thiomaltol with nickel(II) and iron(III) have been prepared and studied by
using UV−visible spectroscopy and electrochemical methods. In addition, both complexes as well as the free
thiomaltol ligand have been structurally characterized by using single-crystal X-ray diffraction methods. The ligand
is found to exert a strong trans influence on the structure of the complexes in the solid state with the nickel(II) and
iron(III) complexes demonstrating a cis and fac geometry, respectively. The compounds described here should
significantly expand the scope and utility of O,S-donor ligands derived from maltol and related precursors.
Introduction
has been extensively examined as an orally active insulin
mimetic for the treatment of diabetes;10-13 bis(ethylmalto-
lato)oxovanadium(IV) (BEOV), a derivative of BMOV, is
currently being evaluated in clinical trials.14,15
Despite the wide-ranging interest in metal complexes of
maltol, surprisingly few complexes based on heteroatom
derivatives of maltol have been described. Most notably, the
detailed coordination chemistry of the thio derivative of
maltol, 3-hydroxy-2-methyl-4-thiopyrone (thiomaltol), and
related compounds has been largely unexplored. Various
reports of the synthesis of thiomaltol exist,16,17 along with a
few reports of its use as an extractant for transition
metals;18-21 however, these studies report little detailed
3-Hydroxy-2-methyl-4-pyrone (maltol) is a natural product
and a common food additive,1 which has also been exten-
sively used as a monoanionic, bidentate metal chelator. Metal
complexes of maltol with a wide variety of transition and
group 13/14 metals have been of significant interest,
particularly in the bioinorganic community.2-6 Neutral,
water-soluble complexes of maltol with aluminum(III) have
been used to examine the role that this metal plays in
neurodegenerative diseases such as Alzheimer’s.7 Complexes
with gallium(III) have been studied for use as potential
radiopharamaceuticals,8 and the iron(III) complex was in-
vestigated as a water-soluble ferric iron source for the
treatment of iron-deficiency anemia.9 Perhaps of greatest
interest, the complex bis(maltolato)oxovanadium(IV) (BMOV)
(10) Melchior, M.; Rettig, S. J.; Liboiron, B. D.; Thompson, K. H.; Yuen,
V. G.; McNeill, J. H.; Orvig, C. Inorg. Chem. 2001, 40, 4686-4690.
(11) Thompson, K. H.; McNeill, J. H.; Orvig, C. Chem. ReV. 1999, 99,
2561-2571.
(12) Caravan, P.; Gelmini, L.; Glover, N.; Herring, F. G.; Li, H.; McNeill,
J. H.; Rettig, S. J.; Setyawati, I. A.; Shuter, E.; Sun, Y.; Tracey, A.
S.; Yuen, V. G.; Orvig, C. J. Am. Chem. Soc. 1995, 117, 12759-
12770.
(13) Sun, Y.; James, B. R.; Rettig, S. J.; Orvig, C. Inorg. Chem. 1996, 35,
1667-1673.
(14) Storr, T.; Mitchell, D.; Buglyo´, P.; Thompson, K. H.; Yuen, V. G.;
McNeill, J. H.; Orvig, C. Bioconjugate Chem. 2003, 14, 212-221.
(15) Dikanov, S. A.; Liboiron, B. D.; Orvig, C. J. Am. Chem. Soc. 2002,
124, 2969-2978.
(16) Blazevic, K.; Jakopcic, K.; Hahn, V. Bull. Sci. Cons. Acad. Sci. (RSF
Yugosl.) 1969, 14, 1-2.
(17) Tilbrook, G. S.; Hider, R. C.; Moridani, M. Y. International Patent
PCT/GB97/03306, Great Britain, 1998.
(18) Uhlemann, E.; Bechmann, W.; Ludwig, E. Anal. Chim. Acta 1978,
100, 635-642.
(19) Uhlemann, E.; Petzold, W.; Raab, M. Z. Anorg. Allg. Chem. 1984,
508, 191-196.
* Author to whom correspondence should be addressed. Tel: (858) 822-
5596. Fax: (858) 822-5598. E-mail: scohen@ucsd.edu.
(1) Schenck, J. R.; Spielman, M. A. J. Am. Chem. Soc. 1945, 67, 2276-
2277.
(2) Ellis, B. L.; Duhme, A. K.; Hider, R. C.; Hossain, M. B.; Rizvi, S.;
van der Helm, D. J. Med. Chem. 1996, 39, 3659-3670.
(3) Barret, M. C.; Mahon, M. F.; Molloy, K. C.; Steed, J. W.; Wright, P.
Inorg. Chem. 2001, 40, 4384-4388.
(4) Lord, S. J.; Epstein, N. A.; Paddock, R. L.; Vogels, C. M.; Hennigar,
T. L.; Zaworotko, M. J.; Taylor, N. J.; Driedzic, W. R.; Broderick, T.
L.; Westcott, S. A. Can. J. Chem. 1999, 77, 1249-1261.
(5) Luo, H.; Rettig, S. J.; Orvig, C. Inorg. Chem. 1993, 32, 4491-4497.
(6) Ge´rard, C.; Hugel, R. P. J. Chem. Res., Synop. 1978, 10, 404-405.
(7) Finnegan, M. M.; Rettig, S. J.; Orvig, C. J. Am. Chem. Soc. 1986,
108, 5033-5035.
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10.1021/ic0347135 CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/15/2003
Inorganic Chemistry, Vol. 42, No. 23, 2003 7455

Lewis et al.
characterization of the resulting coordination complexes.22-24
Herein, we report a single-step, high-yield synthesis of
thiomaltol and the preparation of the iron(III) and nickel(II)
coordination complexes of this intriguing ligand. The struc-
tures, spectroscopy, and electrochemical properties of these
complexes are also described. The ligand is found to have a
strong trans influence on the stereochemistry of the resulting
metal complexes.25,26 Mixed O,S-donor ligands of this sort
are expected to find utility in a variety of potential bioinor-
ganic applications including use as medical chelators or in
heavy metal waste remediation.
Thiopyromeconic Acid (2). 3-Hydroxy-4-pyrone (pyromeconic
acid, 0.5 g, 4.5 mmol) was suspended in 50 mL of CH2Cl2 and
dissolved upon heating of the solution to ∼50 °C. Hexamethyl-
disiloxane (HMDO, 1.2 g, 7.5 mmol) and P4S10 (0.4 g, 0.8 mmol)
were added to the stirring solution. The reaction flask was protected
from light with aluminum foil, fitted with a condenser, and heated
to reflux under nitrogen for ∼18 h. The bright orange solution was
evaporated to dryness on a rotary evaporator to get an orange oil.
The product was purified by silica flash column chromatography
eluting with 1:1 hexanes:CH2Cl2, as a bright yellow fraction. After
removal of solvent on a rotary evaporator the product was obtained
1
as a yellow, crystalline solid. Yield: 70%. Mp 53 °C. H NMR
(CDCl3, 400 MHz, 25 °C): δ 7.37 (d, J ) 4.8 Hz, 1H, Ar-H),
7.60 (d, J ) 5.2 Hz, 1H, Ar-H), 7.68 (s, 1H, -OH), 7.85 (s, 1H,
Ar-H). 13C NMR (CDCl3, 100 MHz, 25 °C): δ 124.7 (Ar-C),
133.4 (Ar-C), 147.6 (Ar-C), 152.7 (Ar-C), 187.8 (CdS). GC-
EIMS: m/z 127.8 [M•]+. Anal. Calcd for C5H4O2S: C, 46.86; H,
3.15. Found: C, 46.61; H, 3.40.
[Fe(thiomaltolato)3] (3). Thiomaltol (60 mg, 0.42 mmol) was
suspended in 5 mL of water. The ligand was dissolved by the
addition of 42 µL of 10 M NaOH (1 equiv) producing a bright
yellow solution. FeCl3‚6H2O (38 mg, 0.14 mmol) was added to
the reaction mixture, resulting in the formation of a black precipitate.
The solution was placed under a nitrogen atmosphere and heated
to reflux for ∼0.5 h. Upon cooling, the solution was filtered through
a fine glass frit and washed with ∼20 mL of water to obtain a
black powder. Yield: 71%. Mp 235 °C (dec). ESI-MS: m/z 337.8
[M - L]+, 143.0 [L + H]+; Anal. Calcd for C18H15O6S3Fe: C,
45.10; H, 3.15. Found: C, 45.17; H, 3.08.
[Ni(thiomaltolato)2] (4). [Ni(thiomaltolato)2] was synthesized
by the same procedure used for [Fe(thiomaltolato)3] starting from
thiomaltol (50 mg, 0.35 mmol) and Ni(OAc)2‚2H2O (43 mg, 0.17
mmol). The product was obtained as a maroon powder. Yield: 68%.
Mp 230 °C (dec); 1H NMR (CDCl3, 400 MHz, 25 °C): δ 2.47 (s,
6H, -CH3), 7.13 (d, J ) 4.8 Hz, 2H, Ar-H), 7.51 (d, J ) 4.8 Hz,
2H, Ar-H). 13C NMR (CDCl3, 100 MHz, 25 °C): δ 15.4 (-CH3),
119.6 (Ar-C), 143.6 (Ar-C), 152.4 (Ar-C), 164.2 (Ar-C), 178.8
(CdS). ESI-MS: m/z 341.0 [M + H]+. Anal. Calcd for C12H10O4S2-
Ni: C, 42.26; H, 2.96. Found: C, 41.96; H, 2.83.
X-ray Crystallographic Analysis. Single crystals of each
compound suitable for X-ray diffraction structural determination
were mounted on quartz capillaries by using Paratone oil and were
cooled in a nitrogen stream on the diffractometer (-173 °C). Data
were collected on a Bruker AXS area detector diffractometer. Peak
integrations were performed with the Siemens SAINT software
package. Absorption corrections were applied using the program
SADABS. Space group determinations were performed by the
program XPREP. The structures were solved by direct methods
and refined with the SHELXTL software package.28 All hydrogen
atoms were fixed at calculated positions with isotropic thermal
parameters unless otherwise noted; all non-hydrogen atoms were
refined anisotropically.
Experimental Section
General. Unless otherwise noted, starting materials were ob-
tained from commercial suppliers (Aldrich) and used without further
purification. 3-Hydroxy-4-pyrone (pyromeconic acid) was synthe-
sized according to a literature procedure.27 Elemental analysis was
performed at the University of California, Berkeley Analytical
1
Facility or Numega Resonance Labs, Inc. (San Diego, CA). H/
13C NMR spectra were recorded on a Varian FT-NMR spectrometer
running at 300 or 400 MHz located in the Department of Chemistry
and Biochemistry, University of California, San Diego. Gas
chromatography electron impact mass spectrometry (GC-EIMS)
was performed on a ThermoFinnigan Trace GC-MS, and electro-
spray ionization mass spectrometry (ESI-MS) was performed on
either a ThermoFinnigan LCQ Advantage (quadrupole ion trap) or
a Hewlett-Packard 5989B single-quadrupole mass spectrometer
located in the Department of Chemistry and Biochemistry, Uni-
versity of California, San Diego. UV-visible spectra were recorded
in methanol using a Hewlett-Packard 8452A spectrophotometer
under PC control using the ChemStation software suite.
Thiomaltol (1). 3-Hydroxy-2-methyl-4-pyrone (maltol, 2.5 g,
19.9 mmol) was suspended in 125 mL of toluene and dissolved
upon heating of the solution to ∼100 °C. Hexamethyldisiloxane
(HMDO, 5.4 g, 33.2 mmol) and P4S10 (1.6 g, 3.6 mmol) were added
to the stirring solution. The reaction flask was protected from light
with aluminum foil, fitted with a condenser, and heated to reflux
under nitrogen for 7.5 h. A black precipitate was removed by
vacuum filtration, and the filtrate was concentrated to give a dark
brown solid. The product was purified by silica flash column
chromatography eluting with 0-4% MeOH in CH2Cl2, as a bright
yellow band. After removal of solvent on a rotary evaporator, an
orange oil was isolated, which gave thiomaltol as orange needles
upon storage at 4 °C. Yield: 70%. Mp 74-77 °C. 1H NMR (CDCl3,
300 MHz, 25 °C): δ 2.43 (s, 3H, -CH3), 7.29 (d, J ) 5.1 Hz, 1H,
Ar-H), 7.55 (d, J ) 5.1 Hz, 1H, Ar-H), 7.75 (br s, 1H, -OH).
13C NMR (CDCl3, 100 MHz, 25 °C): δ 15.1 (-CH3), 123.9
(Ar-C), 145.1 (Ar-C), 146.8 (Ar-C), 150.3 (Ar-C), 185.4
(CdS). GC-EIMS: m/z 141.9 [M•]+. Anal. Calcd for C6H6O2S:
C, 50.69; H, 4.25. Found: C, 50.32; H, 4.17.
(20) Bechmann, W.; Uhlemann, E.; Raab, M. Z. Anorg. Allg. Chem. 1985,
530, 213-221.
(21) Shuknecht, B.; Uhlemann, E.; Wilke, G. Z. Chem. 1975, 15, 285-
286.
Thiomaltol. Orange crystals of thiomaltol (1) suitable for X-ray
diffraction structural determination were grown from cooling an
oil of the compound containing small amounts of toluene, CH2Cl2,
and methanol to 4 °C. No cocrystallized solvent molecules were
found in the unit cell.
[Fe(thiomaltolato)3]. Black crystals of [Fe(thiomaltolato)3] (3)
suitable for X-ray diffraction structural determination were grown
from slow evaporation of a solution of the complex in acetone. No
solvent molecules were found in the unit cell.
(22) Uhlemann, E.; Motzny, H.; Wilke, G. Z. Anorg. Allg. Chem. 1973,
401, 255-262.
(23) Rehorek, D.; Thomas, P.; Uhlemann, E. Z. Chem. 1973, 13, 23-24.
(24) Bechmann, W.; Uhlemann, E.; Kirmse, R.; Ko¨hler, K. Z. Anorg. Allg.
Chem. 1987, 544, 215-224.
(25) Enemark, E. J.; Stack, T. D. P. Angew. Chem., Int. Ed. Engl. 1995,
34, 996-998.
(26) Appleton, T. G.; Clark, H. C.; Manzer, L. E. Coord. Chem. ReV. 1973,
10, 335-422.
(27) Liu, Z. D.; Khodr, H. H.; Liu, D. Y.; Lu, S. L.; Hider, R. C. J. Med.
Chem. 1999, 42, 4814-4823.
(28) Sheldrick, G. M. In SHELXTL Vers. 5.1 Software Reference Manual;
Bruker AXS: Madison, WI, 1997.
7456 Inorganic Chemistry, Vol. 42, No. 23, 2003

Metal Complexes of the Ligand Thiomaltol
Table 1. Crystal Data for Thiomaltol, [Fe(thiomaltolato)3], and [Ni(thiomaltolato)2]
thiomaltol
[Fe(thiomaltolato)3]
C18H15O6S3Fe
[Ni(thiomaltolato)2]
C12H14O6S2Ni
empirical formula
temp, K
crystal system
space group
unit cell dimens
a, Å
C6H6O2S
100(2)
monoclinic
P21/c
100(2)
triclinic
P1h
100(2)
orthorhombic
Pbcn
5.3629(4)
8.5571(6)
22.928(15)
b, Å
8.6723(7)
12.8151(8)
6.6926(4)
c, Å
13.5524(11)
90
99.858(1)
90
17.6321(11)
83.965(1)
82.454(1)
81.990(1)
1890.7(2)
18.8132(13)
90
90
90
R, deg
â, deg
γ, deg
vol, Å3
621.00(8)
2886.9(3)
Z
4
4
8
density (calcd), mg/m3
crystal size, mm3
θ range for data collection, deg
reflns collected
indep reflns
1.521
1.684
1.735
0.49 × 0.33 × 0.15
0.34 × 0.19 × 0.13
1.17-27.51
12010
8356 [R(int) ) 0.0170]
8356/0/511
0.35 × 0.24 × 0.03
2.80-27.50
1.78-27.50
3780
23027
1398 [R(int) ) 0.0147]
1398/0/842
1.106
3309 [R(int) ) 0.0251]
3309/0/208
0.998
data/restraints/params
GOF on F2
0.950
final R indices [I > 2σ(I)]
R indices (all data)
largest peak/hole difference, e Å-3
R1 ) 0.0312, wR2 ) 0.0880
R1 ) 0.0323, wR2 ) 0.0887
0.389 and -0.357
R1 ) 0.0407, wR2 ) 0.0965
R1 ) 0.0538, wR2 ) 0.1005
0.800 and -0.268
R1 ) 0.0288, wR2 ) 0.0812
R1 ) 0.0351, wR2 ) 0.0835
0.426 and -0.618
Scheme 1. Synthesis of Thiomaltol from Maltol and
Thiopyromeconic Acid from Pyromeconic Acid
[Ni(thiomaltolato)2]. Wine-red crystals of [Ni(thiomaltolato)2]
(4) suitable for X-ray diffraction structural determination were
grown from slow evaporation of a solution of the complex in
acetone. Two water molecules were found in the asymmetric unit;
they are not coordinated to the nickel(II) ion. The water protons
were found in the difference map, and their positions were refined.
Cyclic Voltammetry of Iron Complexes. Cyclic voltammetry
experiments were performed by using a Bioanalytical Systems
(BAS) CV-50W voltammetric analyzer under PC control. Solutions
were prepared by dissolving ∼10 mg of metal complex in CH2Cl2
containing 0.1 M n-Bu4N(PF6). The auxiliary and reference
electrodes were a platinum wire and a silver electrode (Ag/AgClaq),
respectively. A platinum electrode (BAS) was used for the working
electrode. Samples were purged with N2(g) for ∼2 min before
experiments were performed. Sweep rates were varied from 0.050
to 1.500 V/s in order to check the reversibility of the couple. Both
[Fe(thiomaltolato)3] and [Fe(maltolato)3] showed reduced revers-
ibility with increasing sweep rate. Therefore, data are reported at a
sweep rate of 0.050 V/s at ambient temperature (∼25 °C). The
ferrocenium/ferrocene couple (Fc+/Fc0) was measured under identi-
cal conditions for use as a reference measurement (E1/2 ) +0.471
V, ∆Ep ) 0.127 V, 0.500 V/s); potentials are reported relative to
Fc+/Fc0.
thiopyromeconic acid (2) under similar conditions. In the
synthesis of 2, CH2Cl2 was used as the reaction solvent due
to the extreme volatility of the thione product, which proved
difficult to separate from higher boiling solvents such as
toluene. Thiopyromeconic acid was isolated as a yellow solid
in good yield. An earlier reported synthesis of thiomaltol
utilized a similar approach to that presented here, but relied
on multiple recrystallizations to obtain the pure product.16
An X-ray structure of the orange crystals of 1 unambigu-
ously demonstrated that the material was thiomaltol (Table
1). The C-C bonds in the six-membered ring are not
equivalent, with C1-C2 and C1-C6 bond lengths of ∼1.43
Å and C2-C3 and C4-C6 bond lengths of ∼1.35 Å,
indicating that the latter two bonds have significantly more
double-bond character (Figure 1). The C-S distance of 1.68
Å is indicative of the expected double bond.
Thiomaltol was complexed with iron(III) and nickel(II)
under ambient, aerobic conditions (Scheme 2) in order to
explore the coordination chemistry of this ligand with
transition metal ions possessing distinctive coordination
preferences. Addition of FeCl3‚6H2O to an aqueous solution
of thiomaltol instantly resulted in the formation of a black
precipitate. Similarly, reaction of thiomaltol with Ni(OAc)2‚
2H2O generated a maroon precipitate. These complexes were
stable to air and required no special handling. Single crystals
of both complexes were obtained, and their structures were
Results and Discussion
Several recent studies have demonstrated the utility of
P4S10 in combination with hexamethyldisiloxane (HMDO)
as an effective reagent for the thionation of esters, ketones,
amides, and lactones.29-31 On the basis of these reports maltol
was treated with P4S10 and HMDO in toluene and was heated
to reflux (Scheme 1); purification of the product by flash
silica column chromatography yielded an orange oil after
removal of solvent that upon cooling to 4 °C generated
thiomaltol (1) as analytically pure orange crystals in 70%
yield. The generality of this approach was demonstrated by
conversion of pyromeconic acid27 (3-hydroxy-4-pyrone) to
(29) Curphey, T. J. Tetrahedron Lett. 2000, 41, 9963-9966.
(30) Curphey, T. J. J. Org. Chem. 2002, 67, 6461-6473.
(31) Curphey, T. J. Tetrahedron Lett. 2002, 43, 371-373.
Inorganic Chemistry, Vol. 42, No. 23, 2003 7457

Lewis et al.
Figure 1. Structural diagram of thiomaltol (1) with atom-numbering
scheme (ORTEP, 50% probability ellipsoids).
Scheme 2. Synthesis of Iron(III) and Nickel(II) Complexes with
Thiomaltol
Figure 2. Structural diagram of [Fe(thiomaltolato)3] (3, top) and
[Ni(thiomaltolato)2] (4, bottom) with partial atom-numbering schemes
(ORTEP, 50% probability ellipsoids). Hydrogen atoms and solvent mol-
ecules have been omitted for clarity.
maltol chelators.12,32 The average Ni-O and Ni-S bond
distances in [Ni(thiomaltolato)2] are 1.88 and 2.16 Å,
respectively. The cis geometry causes a slight distortion in
the square planar conformation, “opening” the S1-Ni-S2
angle to 92.41° while making the O1-Ni-O3 angle more
acute at 86.83°.
determined by X-ray diffraction (Table 1). The iron(III)
complex 3 possesses the expected 6-coordinate, octahedral
coordination geometry for a tris(chelate) complex (Figure
2). The average Fe-O and Fe-S bond lengths are 1.97 and
2.50 Å, respectively. The twist angle of 3 is 48.2° (60° for
a perfect octahedron), slightly less than that reported for [Fe-
(maltolato)3].9 Unlike the structure of the [Fe(maltolato)3]
and [Al(maltolato)3] complexes,7,9 [Fe(thiomaltolato)3] has
a fac as opposed to mer geometry. Because the meridional
geometry is statistically favored,9 this suggests that the
thiomaltol ligand exhibits a substantial trans influence,
thereby enforcing a facial geometry that is enthalpically
favored. The trans influence is a thermodynamic trend
whereby a strong ligand will arrange itself trans to a weaker
ligand.25,26 The trans influence is distinct from the trans
effect, the latter of which is a kinetic phenomenon and refers
to rates of ligand substitution reactions.
The nickel(II) complex 4 has a 4-coordinate, cis square
planar geometry (Figure 2). The cis geometry is again
suggestive of a strong trans influence imposed by the
thiomaltol ligand; however, no structure of [Ni(maltolato)2]
was available in the CCDC for comparison. However, the
complexes [VdO(maltolato)2], [Zn(maltolato)2(H2O)], and
[Zn(maltolato)2(H2O)2], where the two maltol ligands make
up the square plane of either a square pyramidal or octahedral
coordination geometry, all display trans orientations of the
Figure 3 shows the electronic absorption spectra for
thiomaltol (1) and the metal complexes [Fe(thiomaltolato)3]
and [Ni(thiomaltolato)2] in methanol. Thiomaltol has two
major absorption bands at 276 and 358 nm, the latter of
which gives the compound its characteristic orange color.
Similarly, thiopyromeconic acid (2) has intense absorption
bands at 272 and 354 nm. In the [Fe(thiomaltolato)3] complex
(3) four major bands are observed. The high-energy band is
significantly more intense and is split into two transitions at
270 and 298 nm, with lower energy transitions at 368 and
510 nm. The broad transition at 510 nm is attributed to a
LMCT process consistent with tris(chelate) iron(III) com-
plexes of related ligands such as catecholates and hydroxy-
pyridinonates.33,34 The optical absorption spectrum of
[Ni(thiomaltolato)2] (4) is quite complicated with a broad
(split less definitively than the transition in the same part of
the iron(III) spectrum), intense absorption at 290 nm with a
(32) Ahmed, S. I.; Burgess, J.; Fawcett, J.; Parsons, S. A.; Russell, D. R.;
Laurie, S. H. Polyhedron 2000, 19, 129-135.
(33) Lever, A. B. P. Inorganic Electronic Spectroscopy, 2nd ed.; Elsevier:
Amsterdam, 1984.
(34) Cohen, S. M.; Petoud, S.; Raymond, K. N. Chem. Eur. J. 2001, 7,
272-279.
7458 Inorganic Chemistry, Vol. 42, No. 23, 2003

Metal Complexes of the Ligand Thiomaltol
Figure 4. Cyclic voltammogram of [Fe(thiomaltolato)3] in CH2Cl2
(I ) 0.1 M, scan rate ) 50 mV s-1, T ) 25 °C).
Figure 3. Absorbance spectra of thiomaltol (s), [Fe(thiomaltolato)3]
(- -), and [Ni(thiomaltolato)2] (‚‚‚) in methanol.
influence on the stereochemistry of these compounds. In
addition, the spectroscopic and electrochemical properties
of these metal complexes have been investigated. Earlier
studies have examined mixed O,S-donor ligands as metal
chelators for use as sequestering agents for heavy metals such
as lead(II).35-37 It is anticipated that thiomaltol, thiopyrome-
conic acid, and derivatives of these compounds may find
potential utility as environmentally and medicinally useful
heavy metal chelators.18,21 Investigations to test this hypoth-
esis are presently underway.
shoulder at 332 nm and several weaker transitions at 408,
478, and 546 nm. The complexity of the [Ni(thiomaltolato)2]
electronic spectra is expected on the basis of studies of other
square planar nickel(II) thiolate compounds where a number
of bands are commonly observed due to d-d, LMCT,
MLCT, and ligand-centered transitions.33 Characteristic
ligand-field transitions for square planar nickel(II) complexes
are typically found between 400 and 555 nm (ꢀ ) 50-500
M-1 cm-1); although [Ni(thiomaltolato)2] has an appropriate
transition at 546 nm, the large extinction coefficient (ꢀ )
∼5000 M-1 cm-1) suggests that this band must be mixed
with a substantial charge transfer component.33 The electronic
absorption spectra of thiomaltol and [Ni(thiomaltolato)2]
measured here are consistent with earlier descriptions of these
compounds.22
The electrochemistry of [Fe(thiomaltolato)3] (3) was
examined and compared with that of [Fe(maltolato)3].
Relative to ferrocene under the same conditions,
[Fe(thiomaltolato)3] showed a quasireversible redox couple
(Figure 4) centered at -1.24 V (∆Ep ) 0.11 V) while that
of [Fe(maltolato)3] was -1.36 V (∆Ep ) 0.20 V). As
anticipated, the softer O,S donor set of thiomaltol signifi-
cantly stabilizes the ferrous ion relative to the harder maltol
ligand.
Acknowledgment. We thank Dr. Lev N. Zakharov, Dr.
Peter K. Gantzel, and Prof. Arnold L. Rheingold (U.C. San
Diego) for assistance with the crystallography and Ms. Alexis
Kaushansky for synthetic assistance. This work was sup-
ported by the University of California, San Diego, a Chris
and Warren Hellman Faculty Scholar award (S.M.C.), a
Hellman Fellows award (S.M.C.), American Cancer Society
Grant IRG-70-002-29 (S.M.C.), NIH Grant No. GM-60202-
03 (D.T.P.), and GAANN Fellowship No. GM-60202-03
(J.A.L.). J.A.L. is the recipient of an Achievement Rewards
for College Scientists (ARCS) Fellowship.
Supporting Information Available: X-ray crystallographic data
in CIF format. This material is available free of charge via the
Internet at http://pubs.acs.org. X-ray crystallographic data is also
available from the Cambridge Crystallographic Data Centre. Refer
to CCDC reference numbers 210943, 210944, and 210945.
Conclusions
In summary, the facile, high-yield syntheses of the
interesting metal chelators thiomaltol and thiopyromeconic
acid have been described. The crystal structures of thiomaltol
and its iron(III) and nickel(II) metal complexes have been
determined in order to probe the coordination chemistry of
this ligand. These are the first structures of any thiomaltol
metal complex, and the ligand is found to exert a strong trans
IC0347135
(35) Abu-Dari, K.; Hahn, F. E.; Raymond, K. N. J. Am. Chem. Soc. 1990,
112, 1519-1524.
(36) Abu-Dari, K.; Karpishin, T. B.; Raymond, K. N. Inorg. Chem. 1993,
32, 3052-3055.
(37) Rupprecht, S.; Franklin, S. J.; Raymond, K. N. Inorg. Chim. Acta 1995,
235, 185-194.
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