Interactions of metal ions with the intermediate of thiamine catalysis: Crystal structures of Cd(II), Hg(II) and Pt(II) complexes of 2-(α-hydroxybenzyl)thiamine

Article abstract of DOI:10.1016/S0277-5387(99)00215-6

Five complexes of formulae Cd(HBT)X₃·H₂O, Hg₂X₅(HBT) (X=Cl, Br), and Pt(HBT)(NO₂)₃ were prepared by reacting CdX₂, HgX₂ and K₂Pt(NO₂)₄ with 2-(α-hydroxybenzyl)thiamine (HBT), an active intermediate of thiamine catalysis, and their crystal structures were determined by X-ray diffraction. The metal ion binds to the N(1′) site of the pyrimidine ring in each case, despite the different shapes and sizes of metal coordination units; a tetrahedral unit in the cadmium complexes, a double-metal unit consisting of two tetrahedral Hg(II) ions in the mercury complexes and a square-planar unit in the platinum complex. The HBT ligands in these complexes adopt the S conformation, as usually observed in C(2)-substituted derivatives of thiamine, with average torsion angles φ_T being ±99° and φ_P being ±175°. A 'two-point' anion-bridge between the amino group of the pyrimidine ring and the cationic thiazolium ring of the same molecule is found in all the structures, being of the form N(4′α)-H...X₁-M-X₂...thiazolium-ring (M=metal ion), which is one of the factors that affect the S conformation. Stacking interactions between the pyrimidine and phenyl rings play an important role in the molecular conformation and crystal packing. The intramolecular close contact between the oxygen of the C(2)-substituent and the sulfur of the thiazolium ring is also a common feature to these complexes, which gives the mechanistic implications. Elsevier Science Ltd.

Full text of DOI:10.1016/S0277-5387(99)00215-6

Polyhedron 18 (1999) 2987–2994
www.elsevier.nl/locate/poly
Interactions of metal ions with the intermediate of thiamine catalysis
Crystal structures of Cd(II), Hg(II) and Pt(II) complexes of
2-(a-hydroxybenzyl)thiamine
1
*
Ning-Hai Hu , Toshio Norifusa, Katsuyuki Aoki
Department of Materials Science, Toyohashi University of Technology, Tempaku-cho, Toyohashi 441, Japan
Received 22 April 1999; accepted 19 July 1999
Abstract
Five complexes of formulae Cd(HBT)X3?H2O, Hg2X5(HBT) (X5Cl, Br), and Pt(HBT)(NO2)3 were prepared by reacting CdX2,
HgX2 and K2Pt(NO2)4 with 2-(a-hydroxybenzyl)thiamine (HBT), an active intermediate of thiamine catalysis, and their crystal structures
were determined by X-ray diffraction. The metal ion binds to the N(19) site of the pyrimidine ring in each case, despite the different
shapes and sizes of metal coordination units; a tetrahedral unit in the cadmium complexes, a double-metal unit consisting of two
tetrahedral Hg(II) ions in the mercury complexes and a square-planar unit in the platinum complex. The HBT ligands in these complexes
adopt the S conformation, as usually observed in C(2)-substituted derivatives of thiamine, with average torsion angles wT being 6998 and
wP being 61758. A ‘two-point’ anion-bridge between the amino group of the pyrimidine ring and the cationic thiazolium ring of the same
molecule is found in all the structures, being of the form N(49a)–H . . . X1 –M–X2 . . . thiazolium-ring (M5metal ion), which is one of the
factors that affect the S conformation. Stacking interactions between the pyrimidine and phenyl rings play an important role in the
molecular conformation and crystal packing. The intramolecular close contact between the oxygen of the C(2)-substituent and the sulfur
of the thiazolium ring is also a common feature to these complexes, which gives the mechanistic implications.
Ltd. All rights reserved.
1999 Elsevier Science
Keywords: C(2)-substituted derivative of thiamine; Complex; Crystal structure
1. Introduction
Thiamine (vitamin B1) has a physiological function in
the form of its pyrophosphate (TPP) (I), which acts as a
coenzyme for a number of enzymes involved in catalyzing
the decarboxylation of a-keto acids or the transfer of
aldehyde or acyl groups [1]. According to Breslow [2,3],
the catalytic function depends on the dissociation of a
proton from the C(2) position of the thiazolium ring,
leading to the formation of a carbanion of TPP that could
be added to the carbonyl group of the substrate such as
pyruvate. Upon decarboxylation, the so-called ‘active
aldehyde’ intermediate (II) is formed, which reacts sub-
sequently with an acceptor to give the product.
*Corresponding author. Present address: Changchun Institute of Ap-
plied Chemistry, Chinese Academy of Sciences, Changchun 130022,
China. Tel.: 186-431-568-2828 ext. 5542; fax: 186-431-568-5653.
E-mail address: hunh@ns.ciac.jl.cn (N.-H. Hu)
1Corresponding co-author. This author is also a corresponding author.
0277-5387/99/$ – see front matter
PII: S0277-5387(99)00215-6
1999 Elsevier Science Ltd. All rights reserved.

2988
N.-H. Hu et al. / Polyhedron 18 (1999) 2987–2994
It is well known that a divalent metal ion Mg(II) is
aqueous and methanolic aqueous solutions. We report here
five crystal structures, of which Cd(HBT)Cl3?H2O (1) and
Cd(HBT)Br3?H2O (2) are isomorphous to the reported
required as a cofactor for thiamine catalysis [4,5]. Other
divalent metal ions such as Mn(II), Co(II), Zn(II) and
Cd(II) also show activity but with less efficiency [6,7].
Attempts to establish the role of the metal ion led to a
large body of crystal structures of thiamine–metal com-
pounds [8]. These compounds exist in two forms: ionic
salts with a metal-containing anion [9–16] and metal
complexes where direct metal bonding to thiamine is
observed [17–30]. The latter shows metal ion bonding to
N(19) of the pyrimidine ring in the major cases [17–
25,27–29] and to the hydroxyethyl oxygen of thiamine
[26–29] or the pyrophosphate group of TPP [30] in the
minor cases. In spite of the importance of C(2)-substituted
derivatives as intermediates in thiamine reactions, research
on the metal complexes with such derivatives is relatively
rare. Hadjiliadis et al. [31,32] recently reported crystal
structures of Hg(II) complexes of 2-(a-hydroxy-
benzyl)thiamine (HBT) [31] and 2-(a-hydroxy-
benzyl)thiamine monophosphate (HBTMP) [32], both of
which show metal bonding to the N(19) site.
HBT–Hg(II)
complex,
Hg2Cl5(HBT)
(3)
and
Hg2Br5(HBT) (4) are the first example showing a double-
metal unit bonding to the pyrimidine N(19), and
Pt(HBT)(NO2)3 (5) provides evidence that a metal ion not
belonging to group IIB binds to HBT through N(19) and is
therefore the first of its type.
2. Experimental
2.1. Preparation of the complexes
2-(a-Hydroxybenzyl)thiamine chloride hydrochloride
(HBTCl?HCl) was synthesized by using the method
described in the literature [33]. The resulting light-yellow
product was recrystallized from water by the addition of
acetone.
Cd(HBT)Cl3?H2O (1), Hg2Cl5(HBT) (3) and
Hg2Br5(HBT) (4) were prepared by reacting equimolar
(0.1 mmol) amounts of HBTCl?HCl and metal halide,
CdCl2 for 1, HgCl2 for 3 and HgBr2 for 4, respectively,
In order to ascertain the general aspect of the interac-
tions between metal ions and the thiamine intermediates,
we tried to prepare the metal complexes with HBT in
Table 1
Crystal data and details of data collection and structure refinement for the five complexes
Complex
1
2
3
4
5
Formula
C19H25CdCl3N4O3S C19H25Br3CdN4O3S
C19H23Cl5Hg2N4O2S C19H23Br5Hg2N4O2S C19H23N7O8PtS
Formula weight
Space group
608.26
P21 /n
9.6077(8)
7.677(3)
31.554(2)
741.61
P21 /n
9.762(1)
7.740(2)
31.952(5)
949.92
P1
1172.18
P1
704.59
P21 /n
8.116(2)
16.207(3)
19.337(4)
¯
¯
˚
a (A)
10.068(1)
17.286(2)
7.646(1)
91.99(1)
94.79(1)
83.16(1)
1316.2(3)
2
2.397
0.1530.2530.3
122.6
v22u
5–55
6496
10.260(1)
17.531(4)
7.730(2)
91.52(2)
94.70(1)
83.40(1)
1376.3(5)
2
2.829
0.0230.1530.18
185.0
v22u
5–55
5843
˚
b (A)
˚
c (A)
a (8)
b (8)
g (8)
90.170(7)
90.39(1)
96.18(3)
3
˚
V (A )
2327.5(9)
4
1.736
0.130.230.6
13.1
2414.2(8)
4
2.040
0.130.230.25
59.8
v
2528.7(9)
4
1.851
0.1630.1830.32
56.9
v
Z
Dcalc (g cm23
)
Crystal size (mm)
m(Mo Ka) (cm21
Scan technique
2u Range (8)
)
v
5–55
6191
4196
4196
3
281
1
0.035
0.036
1.72
5–55
6432
5542
2986
4
284
3–45
4645
3312
1696
Reflections measured
Reflections used (M)
Observed reflections
with Fo .ns(Fo)
Variables (N)
Weighting schemea (w)
Rb
4075
4075
3
308
2632
2632
3
4
351
299
[s2(F2o)1(0.17P)211.88P]21
0.075
0.217
0.99
1
1/s2(Fo)
0.058
[s2(Fo2)1(0.1P)2]21
0.044
0.043
2.62
0.054
0.122
0.84
Rwc
0.045
3.19
Sd
Max. shift/error
0.008
0.026
0.099
0.031
0.229
Max. and min.
residual (e A
23
˚
)
0.47, 20.73
1.98, 22.32
1.21, 21.79
2.07, 21.70
1.04, 20.52
a P 5 (F2o 1 2F2c )/3 for 2 and 5.
b R 5 o iFou; 2 uFci/o uFou using observed reflections with Fo .ns(Fo).
c Rw 5 [o w(uFou 2 uFcu)2 /o wuFou2]1 / 2 for 1, 3 and 4 and Rw 5 [o w(Fo2 2 Fc2)2 /o w(F2o)2]1 / 2 for 2 and 5.
d S 5 [o w(uFou 2 uFcu)2 /(M 2 N)]1 / 2 for 1, 3 and 4 and S 5 [o w(Fo2 2 F2c )2 /(M 2 N)]1 / 2 for 2 and 5.

N.-H. Hu et al. / Polyhedron 18 (1999) 2987–2994
2989
Table 2
each dissolved in a mixed solution of water and methanol
a
˚
Bond lengths (A) and angles (8) for the metal coordination units
(v/v 1:1) and adjusting the pH value to 5 by using 0.1 N
KOH solution. Colourless crystals formed after a few days.
The colourless crystals of Cd(HBT)Br3?H2O (2) were
obtained by employing a similar method to the above but
using HBTCl?HCl (0.1 mmol), Cd(CH3CO2) (0.1 mmol)
and NaBr (0.4 mmol) as starting materials.
1
2
Cd–N(19)
Cd–X(1)
Cd–X(2)
Cd–X(3)
2.251(3)
2.506(1)
2.416(1)
2.472(1)
2.257(9)
2.579(2)
2.533(2)
2.582(2)
Pt(HBT)(NO2)3 (5) was prepared by reacting HBTCl?
HCl (0.1 mmol) with Ag(NO3) (0.2 mmol) in water. Then
the AgCl formed was filtered off and to the filtrate was
added an aqueous solution of K2Pt(NO2)4 (0.1 mmol).
Light-yellow crystals were obtained from the resulting
solution after 2 weeks.
N(19)–Cd–X(1)
N(19)–Cd–X(2)
N(19)–Cd–X(3)
X(1)–Cd–X(2)
X(1)–Cd–X(3)
X(2)–Cd–X(3)
100.34(9)
115.61(8)
122.58(8)
107.94(4)
101.36(4)
106.87(4)
100.7(2)
113.6(2)
123.2(2)
109.51(6)
101.46(6)
106.87(6)
3b
4
Hg(1)–N(19)
Hg(1)–X(1)
Hg(1)–X(2)
Hg(1)–X(3)
Hg(2)–X(1)
Hg(2)–X(2)
Hg(2)–X(4)
Hg(2)–X(5)
Hg(2)9–Cl(1)
Hg(2)9–Cl(2)
Hg(2)9–Cl(4)
Hg(2)9–Cl(5)
2.250(6)
2.572(3)
2.544(3)
2.360(4)
2.882(3)
2.931(3)
2.321(3)
2.286(3)
2.512(8)
2.444(9)
2.422(6)
2.612(8)
2.289(12)
2.653(3)
2.651(3)
2.480(3)
2.984(3)
2.962(3)
2.433(2)
2.422(3)
2.2. X-ray structure determination
A crystal for each compound was mounted on a glass
fiber for X-ray measurement. Reflection data were col-
lected on a Rigaku AFC7R diffractometer for 1, 2, 3 and 4,
and on a Siemens R3m/E diffractometer for 5 with
graphite-monochromated Mo Ka radiation (l50.71073
˚
A) at 293 K. The details of crystal data, data collection and
structure refinement are summarized in Table 1. Intensity
data were corrected for absorption effects. The programs
used for structure calculations are UNICSIII [34] for 1, 3
and 4, SHELXL [35] for 2 and 5. All structures were
solved by heavy-atom methods and refined by block-
diagonal least-squares on F for 1, 3 and 4 and full-matrix
least-squares on F2 for 2 and 5. The Hg(2) atom in 3 and
the four oxygen atoms of the NO22 groups in 5 are
disordered, each in two possible positions. The occupancy
factors were estimated according to their electron densities.
The phenyl group in 5 was refined as a regular hexagon.
The non-hydrogen atoms were refined anisotropically. All
hydrogen atoms were calculated at their ideal positions
except for 1, in which all hydrogen atoms were located on
difference Fourier maps. Hydrogen atoms were fixed in the
final refinements for all the structures. The final positional
parameters and anisotropic displacement parameters are
given in Supplementary data.
N(19)–Hg(1)–X(1)
N(19)–Hg(1)–X(2)
N(19)–Hg(1)–X(3)
X(1)–Hg(1)–X(2)
X(1)–Hg(1)–X(3)
X(2)–Hg(1)–X(3)
X(1)–Hg(2)–X(2)
X(1)–Hg(2)–X(4)
X(1)–Hg(2)–X(5)
X(2)–Hg(2)–X(4)
X(2)–Hg(2)–X(5)
X(4)–Hg(2)–X(5)
Cl(1)–Hg(2)9–Cl(2)
Cl(1)–Hg(2)9–Cl(4)
Cl(1)–Hg(2)9–Cl(5)
Cl(2)–Hg(2)9–Cl(4)
Cl(2)–Hg(2)9–Cl(5)
Cl(4)–Hg(2)9–Cl(5)
108.7(2)
97.2(2)
126.6(2)
97.1(1)
105.4(1)
117.9(1)
82.5(1)
99.7(1)
105.5(1)
93.8(1)
102.4(1)
151.5(1)
101.4(3)
108.0(2)
107.4(3)
104.8(3)
107.8(2)
124.9(3)
108.6(4)
97.6(4)
120.8(4)
99.3(1)
109.7(1)
118.2(1)
85.7(1)
100.6(1)
105.9(1)
95.8(1)
105.1(1)
147.1(1)
5
Pt–N(19)
Pt–N(11)
Pt–N(12)
Pt–N(13)
2.02(1)
1.965(8)
1.971(8)
1.96(2)
3. Results
Bond lengths and angles of the metal coordination units
for the five complexes are listed in Table 2. The molecular
dimensions of HBT ligands (given in Supplementary data)
agree well among these complexes. Compared with the
N(19)-protonated HBT [36], a major difference is in the
C(29)–N(19)–C(69) bond angles and the C(49)–N(49a)
bond lengths (average 1168 for the bond angles and 1.33 A
for the bond lengths for the five complexes). The protona-
tion at N(19) has more effect on increasing the bond angle
(121.18) and decreasing the bond length (1.310 A) than
N(19)–Pt–N(11)
N(19)–Pt–N(12)
N(19)–Pt–N(13)
N(11)–Pt–N(12)
N(11)–Pt–N(13)
N(12)–Pt–N(13)
89.7(7)
93.9(7)
176.1(7)
176.3(8)
87.4(8)
89.0(8)
˚
a X5Cl for 1 and 3 and Br for 2 and 4.
b The occupancy factors are 0.90 for Hg(2) and 0.10 for Hg(2)9 in 3.
˚
does the metallation.

2990
N.-H. Hu et al. / Polyhedron 18 (1999) 2987–2994
Fig. 1. Molecular structure of 1, showing that a Cd(II)-coordination unit
translated one unit along a axis forms the ‘two-point’ bridge, N(49a)–
H . . . Cl(1)–Cd–Cl(3) . . . thiazolium-ring and that a water molecule is
held by the complex molecule through three hydrogen bonds and an
O(W) . . . thiazolium-ring close contact. Broken lines denote hydrogen
bonds and grating lines denote close contacts.
Fig. 2. Intra- and intermolecular ring stacking between the pyrimidine
and phenyl rings with average contact distances for 1 (top number) and 2
(bottom number).
oriented in such a way that the phenyl ring is parallel to
the pyrimidine ring forming a close intramolecular stack-
ing. The average separation between the two aromatic
˚
˚
3.1. Cadmium complexes Cd(HBT)Cl3?H2O (1) and
Cd(HBT)Br3?H2O (2)
rings is 3.44 A in 1 and 3.49 A in 2. The complex
molecules are further involved in intermolecular stacking
between the pyrimidine and phenyl rings along the b
˚
The structure of 1 is shown in Fig. 1; that of 2 is similar
and not shown. Although HBT coordinates to a tetrahedral
[CdX3]21 unit through N(19), some structural features
similar to the uncomplexed HBT are observed. The ligand
adopts the S conformation in terms of the torsion angles
defined by Pletcher et al. [36]: wT 5C(59)–C(359)–N(3)–
C(2) and wP 5N(3)–C(359)–C(59)–C(49) are 97.4(4) and
2173.5(3)8 for 1 and 297.5(2) and 173.3(9)8 for 2,
respectively. This conformation is characterized by H(69)
directing over the thiazolium ring. The C(2) substituent is
direction with an average contact distance of 3.67 A in 1
and 3.71 A in 2 (Fig. 2). Another significant intramolecu-
˚
lar close contact [37] exists between O(2b) of the sub-
stituent and the electropositive S(1) of the thiazolium ring
(Table 3).
As seen previously in the thiamine compounds in which
the molecules assume the S conformation, there is a
‘two-point’ anion-bridge [23] between the pyrimidine and
thiazolium rings in 1 and 2, that is, a halide atom X(1)
forms a hydrogen bond with N(49a) and another halide
Table 3
Hydrogen bonds and short contacts in 1 and 2a,b
˚
˚
Donor-H
Acceptor
D . . . A (A)
H . . . A (A)
D–H . . . A (8)
Hydrogen bonds
N(49a)–H(491)
N(49a)–H(492)
O(2b)–H(2b)
O(5g)–H(5g)
C(69)–H(69)
1
2
1
2
1
2
N(39)i
X(1)ii
X(1)iii
O(W)
O(W)
X(3)
3.136(4)
3.362(3)
3.046(3)
2.706(4)
3.439(5)
3.104(3)
2.769(5)
3.15(1)
3.490(9)
3.126(9)
2.71(1)
3.50(1)
3.24(1)
2.73(1)
2.23
2.47
2.06
1.75
2.44
2.11
1.86
2.29
2.72
2.31
1.91
2.58
171
154
173
179
176
170
168
176
151
171
162
171
O(W)–H(W1)
O(W)–H(W2)
O(5g)iv
˚
Close contacts (A)
1
2
1
2
S(1)
O(2b)
X(3)ii
X(3)ii
C(4)
2.782(3)
3.527(4)
3.449(3)
3.371(5)
2.78(1)
3.63(1)
3.560(8)
3.33(1)
O(W)
C(59)
C(59)
C(69)
C(5)
3.327(5)
3.444(5)
3.382(6)
3.452(5)
3.28(1)
3.48(2)
3.43(2)
3.51(2)
C(2)
N(3)
O(W)
C(2b1)
C(2b6)
C(2b1)
a Symmetry code: for 1, (none) x, y, z; (i) 22x, 12y, 2z; (ii) 11x, y, z; (iii) 11x, y21, z; (iv) 1.52x, y20.5, 0.52z; for 2, (none) x, y, z; (i) 2x,
12y, 2z; (ii) x21, y, z; (iii) x21, y21, z; (iv) 0.52x, y20.5, 0.52z.
b X5Cl for 1 and Br for 2.

N.-H. Hu et al. / Polyhedron 18 (1999) 2987–2994
2991
Fig. 3. Polymeric chain structure in 1. Note that the dimers are formed through N(49a)–H . . . N(39) hydrogen bonds, which are further connected by
hydrogen bonds into a chain. Broken lines denote hydrogen bonds.
X(3) of the same metal coordination unit stacks on the
thiazolium ring, as shown in Table 3. Interestingly, we
note that the complex molecule captures a water molecule
through three hydrogen bonds, O(5g)–H . . . O(W), C(69)–
this weak bonding is supported by the tetrahedral O(5g)
with two lone pairs, one aligned with Hg(2) and the other
with the proton of O(2b). If the Hg(2) . . . O(5g) inter-
action is considered, we can describe the complex as a
cyclic dimer [Hg2X5(HBT)]2 with two HBT ligands
bridged by two [Hg2X5]21 units across a centre of
symmetry, very similar to the situations of
[Mn(thiamine)Cl2(H2O)]221 [28] and [Cd(thiamine)Cl3]2
[29] complexes.
The following structural features are found in 3 and 4.
(i) The ligand assumes the S conformation with the torsion
angles: wT 596.5(9)8 in 3 and 99(2)8 in 4; wP 52171.7(7)8
in 3 and 2176(2)8 in 4. (ii) The C(2a)–O(2b) bond points
to the direction of the C(2)–S(1) bond resulting in a close
contact between O(2b) and S(1). (iii) The ‘two-point’
H . . . O(W)
and
Cl(3) . . . H–O(W),
and
an
O(W) . . . thiazolium-ring close contact. These interactions,
together with those mentioned above stabilize the molecu-
lar conformation.
Crystal packing is dominated by three kinds of interac-
tions, the ‘two-point’ bridge in the a direction, the aro-
matic ring stacking along the b direction and a pair of
interbase hydrogen bonds, N(49a)–H . . . N(39), in the c
direction creating a dimer across an inversion centre. The
dimers are linked with the intervention of a water molecule
into a chain (Fig. 3).
3.2. Mercury complexes Hg2Cl5(HBT) (3) and
Hg2Br5(HBT) (4)
Compound 3 is isostructural with 4 except that Hg(2) in
3 is disordered at two sites. Fig. 4 shows the molecular
structure of 4. The metal coordination unit consists of two
distorted tetrahedra sharing two vertexes. Despite the
bulky double-metal unit [Hg2X5]21, the HBT ligand
remains to coordinate to the metal ion through N(19) of the
pyrimidine ring. There is a close contact between Hg(2)
˚
and O(5g) of a neighbouring molecule, 2.988(8) A in 3
˚
and 3.10(1) A in 4 (Table 4). This distance is longer than
˚
the normal bond length of Hg–O(5g) [2.60(2) A] in the
Hg–thiamine complex [26] but shorter than the sum of van
˚
der Waals radii (3.25 A) estimated by using van der Waals
˚
radii of 1.73 A for mercury, suggested by Canty and
˚
Deacon [38], and 1.52 A for oxygen [39]. Accordingly, the
O(5g) atom can be considered to be a weak secondary
coordination, which makes the Hg(2) distorted from a
tetrahedron to a triangular bipyramid. The feasibility of
Fig. 4. Molecular structure of 4, showing a double-metal unit binding to
the N(19) site.

2992
N.-H. Hu et al. / Polyhedron 18 (1999) 2987–2994
Table 4
Hydrogen bonds and short contacts in 3 and 4a,b
˚
˚
Donor-H
Acceptor
D . . . A (A)
H . . . A (A)
D–H . . . A (8)
Hydrogen bonds
N(49a)–H(491)
N(49a)–H(492)
O(2b)–H(2b)
O(5g)–H(5g)
3
4
3
4
3
4
N(39)i
X(1)ii
3.12(1)
3.546(8)
2.87(1)
3.325(7)
3.09(2)
3.74(2)
2.89(2)
3.46(1)
2.15
2.61
1.92
2.41
2.12
2.80
1.92
2.50
177
165
163
157
180
163
172
161
O(5g)iii
X(2)iv
˚
Close contacts (A)
S(1)
N(3)
C(4)
3
4
3
4
O(2b)
X(4)ii
X(4)ii
C(59)
2.919(7)
3.379(7)
3.299(9)
3.42(1)
2.89(1)
3.48(1)
3.37(2)
3.40(3)
C(2b5)
S(1)
Hg(2)
Hg(2)9
C(29)v
X(5)v
3.47(1)
3.419(4)
2.988(8)
3.37(1)
3.48(3)
3.487(5)
3.10(1)
O(5g)vi
O(5g)vi
C(2b2)
a Symmetry code: (none) x, y, z; (i) 12x, 12y, 2z; (ii) x21, y, z; (iii) 12x, 2y, 12z; (iv) 22x, 2y, 12z; (v) x, y, 11z; (vi) 22x, 2y, 2z.
b X5Cl for 3 and Br for 4.
bridge is of the form N(49a)–H . . . X(1)–Hg(2)–
X(4) . . . thiazolium-ring. (iv) The stacking interactions
between the pyrimidine and phenyl rings run along the c
3.3. Platinum complex Pt(HBT)(NO2 )3 (5)
As is shown in Fig. 5, the Pt(II) ion is coordinated by an
N(19) atom of the pyrimidine ring and three N atoms of the
NO22 groups in a square-planar geometry. The coordina-
tion plane is approximately perpendicular to the pyrimidine
ring with a dihedral angle of 72.2(5)8. The Pt–N(19)
˚
direction, with average intramolecular separations 3.51 A
˚
˚
in 3 and 3.55 A in 4 and intermolecular separations 3.56 A
˚
in 3 and 3.60 A in 4.
The dimers are formed through N(49a)–H . . . N(39)
hydrogen bonds and they are further associated into a
chain extending along the b direction. This occurs through
a pair of hydrogen bonds between O(2b) and O(5g) atoms.
˚
distance, 2.02(1) A, is very close to that in
˚
Pt(thiamine)Cl3?H2O, 2.01(2)A [21], and slightly shorter
than that in trans-[Pt(dmso)(thiamine)Cl2][Ph4B], 2.06(1)
˚
A [24]. The torsion angles wT and wP are 2106(2) and
2179(2)8, corresponding to the S conformation. The ‘two-
point’ bridge is found here again. As is given in Table 5,
the pyrimidine and thiazolium moieties are bridged by the
Pt(II) coordination unit from a neighbouring molecule
through an N(49a)–H . . . O(5) [and O(6)] bifurcated hy-
drogen bond and an O(3) . . . thiazolium-ring close contact.
It can be seen from Fig. 5 that unlike the above structures,
the pyrimidine and phenyl rings are not fully but partially
stacked on each other, either intra- or intermolecularly.
Table 5 shows that the closest intramolecular contacts are
˚
C(59) . . . C(2b1) and C(69) . . . C(2b6) [both 3.50(2) A],
and the closest intermolecular contact is C(2b4) . . . N(39)
˚
(x11, y, z), 3.50(3) A. This partial stacking interaction is
probably due to the obstruction of the metal coordination
plane perpendicular to the pyrimidine ring.
The crystal packing mode is similar to that in 1 or 3.
The difference is only in that the thiamine dimers created
by interbase hydrogen bonds are connected in a tail-to-tail
fashion through hydrogen bonds of O(5g) . . . O(5g) (22x,
2y, 12z) across an inversion centre. This hydrogen bond
may be formed with a disordered hydrogen atom attached
to O(5g).
4. Discussion
There are many common structural features among the
five complexes though they are in three kinds of crystalline
forms. The present work indicates that the N(19) site is
Fig. 5. Molecular structure of 5 and partial ring stacking interactions. The
minor positions of disordered NO22 groups are not shown for clarity.
Broken lines denote the closest contacts.

N.-H. Hu et al. / Polyhedron 18 (1999) 2987–2994
2993
Table 5
Hydrogen bonds and short contacts in 5a
˚
˚
Donor-H
Acceptor
D . . . A (A)
H . . . A (A)
D–H . . . A (8)
Hydrogen bonds
N(49a)–H(491)
N(49a)–H(492)b
N(39)i
O(5)ii
O(6)ii
O(5g)iii
3.08(2)
3.50(2)
2.98(2)
2.96(6)
2.23
2.65
2.28
175
168
139
O(5g)
˚
Close contacts (A)
S(1)
C(2)
N(3)
O(2b)
O(3)ii
O(3)ii
2.75(2)
3.11(3)
3.09(4)
C(59)
C(69)
C(2b4)
C(2b1)
C(2b6)
N(39)iv
3.50(2)
3.50(2)
3.50(3)
a Symmetry code: (none) x, y, z; (i) 12x, 12y, 12z; (ii) x20.5, 0.52y, z20.5; (iii) 22x, 2y, 12z; (iv) x11, y, z.
b Bifurcated hydrogen bond.
favoured by metal bonding in the case of HBT. This may
be rationalizable from an electronic effect, namely the high
basicity of this site. The Cd–N(19) bond length of 2.251(3)
molecular conformation. On the other hand, Aoki et al.
[22,23] proposed that the S conformation is associated
with the ‘two-point’ bridge as described above while the F
conformation is accompanied by a ‘one-point’ bridge like
N(49a)–H . . . X . . . thiazolium-ring. Not only the ‘two-
point’ bridge exists in the HBT–metal complexes but also
it was found in the metal complexes and metal–anion salts
of C(2) free thiamine in the S-form (see Table 8 in Ref.
[23]). This implies that the crystal packing force also
imposes an effect on the conformation. Moreover, we
noticed that the V conformation has never been reported for
the crystal structure of thiamine or TPP but it was recently
found in the crystal structures of thiamine-dependent
enzymes [42–44], indicating that the V conformation may
result from an environment influence imposed by the
enzymes. Therefore, the conformation favoured by
thiamine should be a combined result of intra- and
intermolecular forces.
Besides the aromatic ring stacking, an important struc-
tural feature common to the HBT compounds is the close
contact of O(2b) . . . S(1). This interaction not only affects
the molecular conformation but has mechanistic implica-
tions. The possible functions are, for example, (i) to
provide a specific electrostatic substrate–coenzyme recog-
nition, (ii) to stabilize the C(2) substituent in the position
of catalytic reaction, and/or (iii) to facilitate the deproto-
nation from O(2b), which is required by the mechanism of
Breslow [2,3].
It is of interest to note that all the HBT–metal complex-
es manifest a very similar packing mode. The molecular
packing is controlled by three factors. (i) A polymeric
chain structure is formed with hydrogen-bonded [N(49a)–
H . . . N(39)] dimers connected by hydrogen bonds involv-
ing the water molecule and the O(5g) atom in 1 and 2, a
pair of O(2b)–H . . . O(5g) hydrogen bonds in 3 and 4 and
hydrogen bonds between the symmetry-related O(5g)
atoms in 5. (ii) The molecular chains are associated with
each other by the ‘two-point’ bridge interactions. (iii)
Interestingly, all the HBT compounds including free HBT
show one of the axes having a similar length, that is the b
axis for 1 and 2, c axis for 3 and 4, a axis for 5 (which is
˚
A in 1 is comparable with that in Cd(thiamine)Cl3?
˚
0.6H2O, 2.239(2) A [17]. This bond length increases with
the decrease of electronegativity of anionic ligands, indi-
cated by the values in 2 and 4 containing Br2 ligands
being larger than those in 1 and 3 containing Cl2 ligands,
while the C(29)–N(19)–C(69) bond angle increases with
increasing electronegativity. Somewhat surprisingly, the
crystal structures of metal complexes of C(2)-substituted
derivatives reported so far, including this work, are exclu-
sively those of HBT and HBTMP. Attempts to prepare
metal complexes of other C(2)-adducts only led to the
salt-type compounds in our laboratory. A distinct structural
aspect of HBT different from other C(2)-adducts is
aromatic ring stacking between the pyrimidine and phenyl
rings. Thus, the structure of the HBT complex could be
stabilized by such a stacking interaction. The intramolecu-
lar stacking distances are in the order of free HBT (3.41
˚
˚
˚
˚
˚
A),1 (3.44 A),2 (3.49 A),3 (3.51 A),4 (3.55 A),
indicative of an influence of the shape and size of the
metal coordination unit on the aromatic stacking.
Pletcher et al. [36] defined the conformations of
thiamine and its derivatives in three forms: F (wT ¯0,
wP ¯6908), S (wT ¯6100, wP ¯61508) and V (wT ¯690,
wP ¯7908). The crystal structure data show that the F
conformation is common to C(2) free thiamine and the S
conformation is characteristic of C(2)-substituted deriva-
tives. The factors affecting the conformation of thiamine
have been an interesting point. Shin et al. [40,41] argued
that the conformation of thiamine is largely influenced by
intramolecular properties. It is obvious that the conforma-
tion of HBT depends on the intrinsic property of the
molecule since all the HBT compounds are in the S-form
in spite of different space groups and metal coordination
units. This intrinsic property may arise from the tendency
to form the O(2b) . . . S(1) close contact and ring stacking
interaction. In view of that these two interactions are
observed in all of the HBT compounds, it seems possible
that both of these factors are important in stabilizing the

2994
N.-H. Hu et al. / Polyhedron 18 (1999) 2987–2994
[16] J.S. Casas, A. Castineiras, M.D. Couce, G. Martinez, J. Sordo, J.M.
Varela, J. Organomet. Chem. 517 (1996) 165.
[17] R.E. Cramer, R.B. Maynard, J.A. Ibers, J. Am. Chem. Soc. 103
(1981) 76.
slightly longer because of the partial stacking) and b axis
for the free HBT. This axis is the direction of aromatic ring
stacking.
[18] R.E. Cramer, R.B. Maynard, R.S. Evangelista, J. Am. Chem. Soc.
106 (1984) 111.
Supplementary data
[19] K. Aoki, H. Yamazaki, J. Am. Chem. Soc. 107 (1985) 6242.
[20] A. Bencini, E. Borghi, Inorg. Chim. Acta 135 (1987) 85.
[21] R.E. Cramer, R.E. Kirkup, M.J.J. Carrie, Inorg. Chem. 27 (1988)
123.
Supplementary data are available from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK on request, quoting the deposition numbers
CCDC118802–CCDC118806.
[22] E. Archibong, A. Adeyemo, K. Aoki, H. Yamazaki, Inorg. Chim.
Acta 156 (1989) 77.
[23] K. Aoki, N.-H. Hu, H. Yamazaki, A. Adeyemo, Inorg. Chim. Acta
175 (1990) 247.
[24] R.E. Cramer, M.J.J. Carrie, Inorg. Chem. 32 (1993) 3509.
[25] J.S. Casas, A. Castineiras, M.D. Couce, A. Sanchez, J. Sordo, J.M.
Varela, Polyhedron 14 (1995) 1825.
Acknowledgements
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(1990) 383.
NHH is indebted to the Japan Society for the Promotion
of Science for financial support under the RONPAKU
Program.
[27] K. Aoki, H. Yamazaki, A. Adeyemo, Inorg. Chim. Acta 180 (1991)
117.
[28] N.-H. Hu, Inorg. Chim. Acta 186 (1991) 209.
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