Synthesis and characterization of hydrophilic hydroxypyridinones and their complexes with molybdenum(VI)

Article abstract of DOI:10.1071/CH00093

We have prepared four N-substituted hydroxypyridinones containing alcohol and morpholine groups. Complexes of the type cis-MoO₂L₂, where L represents the hydroxypyridinonato ligands have also been synthesized. The ethanolamine derivative, cis-MoO₂(hep)₂ (5), has been characterized by an X-ray diffraction study whereby the pyridinone ligands are bound to molybdenum in a cis bidentate fashion via the deprotonated hydroxy groups and the ketone moieties. Crystals of (5) are triclinic, with a 9.1930(7), b 14.2718(8), c 14.6219(9) A, α 106.816(5), β 95.902(5), γ 96.350(5)°, Z 4, space group P1. CSIRO 2000.

Full text of DOI:10.1071/CH00093

C S I R O P U B L I S H I N G
Australian Journal
of Chemistry
Volume 53, 2000
© CSIRO 2000
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Aust. J. Chem., 2000, 53, 687–691
Synthesis and Characterization of Hydrophilic Hydroxy-
pyridinones and Their Complexes with Molybdenum(VI)
Noah A. Epstein,A Jennifer L. Horton,A Christopher M. Vogels,A
Nicholas J. TaylorB and Stephen A. Westcott A,C
A Department of Chemistry, Mount Allison University, Sackville, New Brunswick E4L 1G8, Canada.
B Department of Chemistry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
To whom correspondence should be addressed about X-ray crystallography.
C To whom correspondence should be addressed. Telephone: (506) 364-2372.
Fax: (506) 364-2313. E-mail: swestcott@mta.ca
We have prepared four N-substituted hydroxypyridinones containing alcohol and morpholine groups. Complexes
of the type cis-MoO2L2, where L represents the hydroxypyridinonato ligands have also been synthesized. The
ethanolamine derivative, cis-MoO2(hep)2 (5), has been characterized by an X-ray diffraction study whereby the
pyridinone ligands are bound to molybdenum in a cis bidentate fashion via the deprotonated hydroxy groups and
the ketone moieties. Crystals of (5) are triclinic, with a 9.1930(7), b 14.2718(8), c 14.6219(9) Å, 106.816(5),
–
95.902(5), 96.350(5)o, Z 4, space group P1. .
Keywords. Molybdenum; pyridinones; hydrophilicity; heart dysfunction.
Introduction
cacy of these drugs is usually limited by poor gastrointesti-
nal absorption. As a result, a number of N-substituted pyridi-
nones with various physical properties have been prepared in
order to improve the pharmacological activities of these
chelating agents.13 Vanadium compounds containing pyridi-
none,14,15 and related pyrone, ligands have found recent
utility as insulin mimics. For example, VO(ma)2 (ma =
deprotonated 3-hydroxy-2-methyl-4-pyrone) displays potent
insulinomimetic properties and has been the subject of
numerous chemical and physiological studies.16,17
Our interest in this area lies in developing molybdenum
complexes for the treatment of cardiac dysfunction associ-
ated with diabetes.18 We have recently found that sodium
molybdate prevents depression in cardiac function from
occurring in diabetic hearts. In order to ascertain the effects
molybdenum complexes have on heart function we have
begun to synthesize numerous complexes containing pyridi-
none ligands with different physical and chemical properties.
In this paper we report our initial efforts in generating novel
hydrophilic hydroxypyridinones along with the correspond-
ing molybdenum(VI) complexes.
2-Alkyl-3-hydroxypyridin-4-ones are a family of biden-
tate chelating ligands that are of interest in medicinal chem-
istry for a number of different applications.1–17 For instance,
L-mimosine (Fig. 1), a naturally occurring amino acid con-
taining the hydroxypyridinone unit, is the principal compo-
nent in Leucaena leucocephala believed to be responsible for
chemical defleecing in sheep.1 In the search for improved
chemical defleecing agents, several analogues of mimosine
have been generated and tested for their inhibitory activities
on wool growth.2–4
-Hydroxypyridinones have also been used to form com-
plexes with aluminium(III), gallium(III), and indium(III) for
the radioisotopic imaging of tumours.5–8 Their chemical sta-
bility and high affinity for iron9 also make these compounds
powerful therapeutic agents for the treatment of physiologi-
cal iron overload in humans.10–13 However, the overall effi-
Experimental
Chemicals used were of reagent grade. Maltol and amines were
obtained from Aldrich Chemicals and molybdic acid was purchased
from Strem. Tetrahydrofuran, hexane, and diethyl ether were distilled
from sodium benzophenone ketyl. Methylene chloride and chloroform
were distilled from CaH2. N.m.r. spectra were recorded on a JEOL
Manuscript received 17 July 2000
© CSIRO 2000
10.1071/CH00093
0004-9425/00/080687

688
N. A. Epstein et al.
JNM-GSX270 Fourier-transform n.m.r. spectrometer. 1H n.m.r. chemi-
cal shifts are reported in ppm and referenced to residual protons in
CDCl3, D2O and (CD3)2SO at 270 MHz. 13C{1H} n.m.r. chemical shifts
are referenced to internal solvent peaks at 68 MHz. Infrared spectra
were obtained with Nujol on KBr/NaCl plates by using a Perkin–Elmer
710B and a Mattson Polaris spectrophotometer and are reported in
cm–1. Melting points were measured uncorrected with a Mel-Temp
apparatus. Microanalyses for C, N, and H were carried out at Desert
Analytics (Tucson, Arizona).
Synthesis of cis-Bis(3-hydroxy-1-(2-hydroxyethyl)-2-methylpyridin-
4(1H)-onato)dioxomolybdenum(VI) (MoO2(hep)2) (5)
Molybdic acid (0.16 g, 0.46 mmol) was dissolved in water (10 cm3)
and then cooled in an ice-water bath for 5 min before solid pyridinone
Hhep (1) (0.35 g, 2.05 mmol) was added slowly. The reaction mixture
was stirred at 0°C and was filtered cold after 2 h to afford a bright
yellow solid. This precipitate was recrystallized from hot water (5 cm3)
to give orange-yellow crystals. Yield: 0.23 g (56%); m.p. 278°C (dec.)
(Found: C, 41.2; H, 4.5; N, 6.0. C16H20MoN2O8 requires C, 41.4; H, 4.4;
N 6.0%). 1H n.m.r. (in (CD3)2SO): 7.85, d, J 5 Hz, CH; 6.55, d, J 5 Hz,
CH; 5.20, br s; 4.27, br m, CH2; 3.78, br m, CH2; 2.49, s, CH3. 13C{1H}
n.m.r. (in (CD3)2SO): 169.9, 154.4, 138.7, 133.7, 108.3, 60.1, 56.2,
12.2. I.r. (Nujol): 2934, 2869, 1612, 1552, 1461, 1377, 1269, 1075, 931,
887, 823, 703, 637.
Synthesis of 3-Hydroxy-1-(2-hydroxyethyl)-2-methylpyridin-4(1H)-
one (Hhep) (1)
Maltol (3.14 g, 24.93 mmol) and ethanolamine (4.67 g, 76.40 mmol)
were combined in water (15 cm3) and heated to reflux for 67 h. Solvent
was removed under vacuum to give a dark brown oil which was tritu-
rated with propan-1-ol (10 cm3) and suction-filtered. The resultant solid
was recrystallized from water (5 cm3) to afford light brown crystals.
Yield: 2.21 g (53%); m.p. 199oC. 1H n.m.r. (in D2O): 7.49, d, J 5 Hz,
CH; 6.36, d, J 5 Hz, CH; 4.06, t, J 5 Hz, CH2; 3.74, t, J 5 Hz, CH2; 2.26,
s, CH3. 13C{1H} n.m.r. (in D2O): 171.5, 147.2, 141.6, 137.4, 114.7,
62.8, 58.4, 14.3. I.r. (Nujol): 3298, 2936, 2864, 1622, 1562, 1500, 1462,
1377, 1339, 1230, 1083, 1064.
Synthesis of cis-Bis(3-hydroxy-1-(3-hydroxypropyl)-2-methylpyridin-
4(1H)-onato)dioxomolybdenum(VI) (MoO2(hmp)2) (6)
Molybdic acid (0.04 g, 0.12 mmol) was stirred in water (1 cm3) for
0.5 h, until completely dissolved. This solution was stirred in an ice-
water bath for 5 min upon which solid pyridinone Hhmp (2) (0.09 g,
0.49 mmol) was added slowly. After 24 h, a yellow precipitate was col-
lected by suction filtration and washed with acetone (5 cm3). The solid
was recrystallized from hot water (2 cm3) to afford orange-yellow crys-
tals. Yield: 0.09 g (78%); m.p. 228°C (dec.) (Found: C, 41.4; H, 4.4; N
5.3. C18H24MoN2O8·1.5H2O requires C, 41.6; H, 5.3; N, 5.4%). 1H (in
(CD3)2SO): 7.90, d, J 5 Hz, CH; 6.54, d, J 5 Hz, CH; 4.83, br s; 4.28,
t, J 8 Hz, CH2; 3.55, ov m, CH2; 2.57, s, CH3; 1.95, m, CH2. 13C{1H}
n.m.r. (in (CD3)2SO): 169.7, 154.6, 137.9, 133.2, 108.6, 57.2, 51.5,
33.0, 11.7. I.r. (Nujol): 3434, 2944, 1612, 1550, 1494, 1467, 1357,
1265, 1054, 917, 883, 716, 642.
Synthesis of 3-Hydroxy-1-(3-hydroxypropyl)-2-methylpyridin-4(1H)-
one (Hhmp) (2)
Maltol (0.99 g, 7.82 mmol) and 3-aminopropan-1-ol (0.59 g, 7.87
mmol) were combined in water (5 cm3) and heated to reflux for 66 h.
An organic extraction was performed with chloroform (3×10 cm3) to
remove impurities and the aqueous layer was collected. Removal of
water under vacuum afforded a dark brown oil which was dissolved in
propan-2-ol (2 cm3) to which acetone (1 cm3) was added. After 18 h at
5°C, a light beige powder precipitated and was collected by suction fil-
tration and was washed with ice-cold acetone (20 cm3). Yield: 0.25 g
(18%); m.p. 122–124°C. 1H n.m.r. (in D2O): 7.58, d, J 8 Hz, CH; 6.44,
d, J 5 Hz, CH; 4.12, t, J 8 Hz, CH2; 3.57, t, J 5 Hz, CH2; 2.36, s, CH3;
1.93, m, J 5 Hz, CH2. 13C{1H} n.m.r. (in D2O): 171.4, 147.8, 140.7,
137.1, 114.9, 60.6, 54.0, 34.7, 14.0. I.r. (Nujol): 3361, 3157, 2893,
1626, 1566, 1504, 1350, 1237, 1078, 1034, 919, 824.
Synthesis of cis-Bis(3-hydroxy-2-methyl-1-morpholinopyridin-4(1H)-
onato)dioxomolybdenum(VI) (MoO2(mmp)2) (7)
The pyridinone Hmmp (3) (0.10 g, 0.48 mmol) was mixed with
molybdic acid (0.04 g, 0.10 mmol) in water (5 cm3) and the reaction
was allowed to proceed for 20 h. The bright yellow precipitate that
formed was collected by suction filtration and washed with water (2×7
cm3) and diethyl ether (2×10 cm3). Yield: 0.09 g (82%); m.p.
266–269°C (dec.) (Found: C, 42.5; H, 5.0; N, 9.9. C20H26MoN4O8·H2O
requires C, 42.6; H, 5.0; N, 9.9%). 1H n.m.r. (in (CD3)2SO): 8.44, d, J
5 Hz, CH; 6.66, d, J 8 Hz, CH; 4.01, d, J 11 Hz, CH2; 3.76, t, J 11Hz,
CH2; 3.29, d, J 11 Hz, CH2; 3.13, t, J 8 Hz, CH2; 2.49, s, CH3. 13C{1H}
n.m.r. (in (CD3)2SO): 169.8, 153.5, 135.2, 133.6, 108.5, 66.1, 53.9,
11.4. I.r. (Nujol): 3542, 2976, 2976, 2881, 2838, 1608, 1553, 1516,
1453, 1376, 1296, 1111, 920, 894, 819, 734.
Synthesis of 3-Hydroxy-2-methyl-1-morpholinopyridin-4(1H)-one
(Hmmp) (3)
Maltol (1.00 g, 7.87 mmol) and 4-aminomorpholine (1.05 g, 10.30
mmol) were combined in water (10 cm3). The reaction mixture was
heated to reflux for 42 h and cooled to 5°C, upon which light brown
crystals precipitated. After 24 h, the solid was collected by suction fil-
tration and washed with cold propan-2-ol (3×5 cm3). The filtrate
volume was reduced to 5 cm3 under vacuum and the solution cooled
again to 5°C. More of the light brown solid precipitated and was col-
lected by suction filtration and washed with propan-2-ol (3×5 cm3).
Combined yield: 0.68 g (41%); m.p. 277–278°C. 1H n.m.r. (in CDCl3):
7.53, d, J 5 Hz, CH; 6.47, d, J 8 Hz, CH; 4.02, d, J 11 Hz, CH2; 3.81,
t, J 11 Hz, CH2; 3.19, t, J 8 Hz, CH2; 2.94, ov m; 2.42, s, CH3. 13C{1H}
n.m.r. (in (CD3)2SO): 168.9, 144.3, 132.8, 130.7, 110.8, 66.2, 53.6,
11.0. I.r. (Nujol): 3174, 3085, 2891, 1619, 1581, 1524, 1499, 1455,
1376, 1217, 1111, 919, 820.
Synthesis of cis-Bis(3-hydroxy-2-methyl-1-(3-
morpholinopropyl)pyridin-4(1H)-onato)dioxomolybdenum(VI)
(MoO2(mpp)2) (8)
cis-MoO2(ma)2 (ma = maltolato)18 (1.00 g, 2.65 mmol) was com-
bined with 4-(3-aminopropyl)morpholine (0.77 g, 5.30 mmol) in water
(8 cm3) and ethanol (4 cm3). The mixture was heated to reflux for 8.5 h
and, after cooling to room temperature, solvent was removed under
vacuum to afford a dark brown oil. Trituration with tetrahydrofuran
(10×10 cm3) afforded an orange-yellow solid. Yield: 0.59 g (39%); m.p.
166°C (dec.) (Found: C, 48.9; H, 5.9; N, 8.6. C26H38MoN4O8·H2O
requires C, 48.1; H, 6.2; N, 8.6%). 1H n.m.r. (in CDCl3): 7.41, d, J 5
Hz, CH; 6.51, d, J 5 Hz, CH; 4.13, t, J 8 Hz, CH2; 3.72, br m; 2.51, s,
CH3; 2.42, br m; 2.35, t, J 5 Hz, CH2; 1.92, br t, J 5 Hz, CH2. 13C{1H}
n.m.r. (in CDCl3): 170.7, 155.7, 136.8, 133.4, 109.7, 66.6, 54.2, 53.3,
52.3, 26.7, 12.4. I.r. (Nujol): 3535, 3416, 2891, 1608, 1553, 1516, 1485,
1464, 1365, 1295, 1263, 1229, 1062, 920, 895.
Synthesis of 3-Hydroxy-2-methyl-1-(3-
morpholinopropyl)pyridin-4(1H)-one (Hmpp) (4)
Maltol (1.00 g, 7.87 mmol) and 4-(3-aminopropyl)morpholine
(1.15 g, 7.97 mmol) were combined in water (12 cm3) and heated to
reflux for 6 h. Solvent was removed under vacuum to afford a brown oil
which was dissolved in tetrahydrofuran (6 cm3) and stored at 5°C. After
several weeks a light brown solid precipitated and was collected by
Crystallography
Crystal Data
1
suction filtration. Yield: 0.13 g (7%); m.p. 178°C. H (in CDCl3):
7.33, d, J 8 Hz, CH; 6.39, d, J 8Hz, CH; 4.48, br s; 4.02, t, J 8 Hz, CH2;
3.72, ov m; 2.41, ov m; 2.34, t, J 5 Hz, CH2; 1.91, t, J 5 Hz, CH2.
13C{1H} n.m.r. (in CDCl3): 169.7, 146.5, 137.4, 128.0, 111.1, 67.1,
54.4, 53.7, 51.3, 27.3, 12.0. I.r. (Nujol): 3159, 2971, 2882, 1627, 1566,
1535, 1507, 1460, 1376, 1232, 1111, 1021, 958, 837.
Complex (5). C16H20MoN2O8, mol. wt 464.3, triclinic, space group
–
P 1, a 9.1930(7), b 14.2718(8), c 14.6219(9) Å,
106.816(5),
95.902(5)°, 96.350(5)°, V 1806.7(3) Å3, F(000) 944, Z 4, Dc 1.707 g
cm–3, (Mo K ) 7.74 cm–1, temperature 180 K.

Hydrophilic Hydroxypyridinones
689
–
–
Yellow tabular prism, 0.52{101} by 0.42{021} by 0.36{111}, 2
range 4.0–56.0°, 9111 collected reflections, 8584 independent (Rint
0.0147), 7712 observed (F 6 (F)), final R factor 0.0228, wR 0.0360,
goodness of fit 2.64, min./max. transmission 0.7180/0.8005.
Data Collection, Structure Resolution and Refinement
Data for (5) were collected on a Nicolet LT2 equipped Siemens P4
diffractometer using the
method (4
2
56°). The data were cor-
rected for absorption by a faced-indexed analytical method. Three stan-
dard reflections every 100 showed no significant decay. The structures
were solved by Patterson and Fourier methods, and refined by full matrix
least squares (SHELXTL IRIS).19 A weighting scheme of w–1
=
2(F)
+0.00005F2 was used in the last cycles of refinement. All non-hydrogen
atoms were refined anisotropically. Hydrogen atoms were located by a
difference Fourier but included by the riding model method with refined
isotropic thermal parameters. Hydroxy (OH) protons were fixed in found
positions. R = ||Fo|–|Fc||/ |Fo|; Rw = [ (w(|Fo|–|Fc|)2/ (w|Fo|)2]1/2
.
also makes the coordinated pyrone more susceptible to
nucleophilic attack by the amine.5,6
Although metal complexes containing N-substituted 3-
hydroxypyridin-4-ones are well known,11,14,15,20,24-28 the only
molybdenum complexes reported have simple alkyl or aryl
groups attached to the ring nitrogen.18,27 This work repre-
sents examples of molybdenum complexes containing
pyridinone ligands with alcohol and morpholine appendages.
The four-band infrared spectral pattern between 1400 and
1610 cm–1, characteristic of pyridinone ligands,29,30 is
observed upon complexation with molybdenum. These four
bands are assigned collectively as (C=C) and (C=O).
N.m.r. data are also consistent with complexes of the type
cis-MoO2L2 where L represents the hydroxypyridinonato
ligands. A single-crystal X-ray diffraction study was carried
out on MoO2(hep)2 (5) to confirm this assignment.
The molecular structure of one of the two independent
molecules of (5), found in the unit cell, is shown in Fig. 3,
atomic coordinates are given in Table 1, and bond distances
and angles are provided in Tables 2 and 3, respectively. The
conformationally different molecules both have a cis
arrangement of the oxo ligands, and the Mo=O bond lengths
(average 1.709 (2) Å) are comparable to those found in other
oxomolybdenum(VI) complexes.18 The two ketonic oxygen
atoms of the pyridinone moieties are trans to the oxo ligands
and the stronger-field hydroxy oxygens are trans to one
another. A slight lengthening of the ketone C=O bond is
observed upon complexation, with a mean distance of
1.298(3) Å, which results in the molybdenum–oxygen
(ketone) bond being somewhat longer (average 2.211(3) Å)
than the molybdenum–deprotonated oxygen distance, the
average being only 1.995(2) Å. This observation illustrates
the distinction between Lewis acid–base versus covalent
bonding for these two types of oxygen atoms.
Results and Discussion
Four hydroxypyridinones have been prepared (Fig. 2) by
the addition of the corresponding primary amine to aqueous
solutions of maltol (3-hydroxy-2-methyl-4-pyrone, Hma) at
elevated temperatures. Functionalization of the ring nitrogen
in the hydroxypyridinones allows for fine tuning of physical
properties such as water solubility and hydrolytic stability.20
Biological studies of maltol-based pyridinones (1) and (2),
respectively, derived from 2-aminoethan-1-ol and 3-amino-
propan-1-ol, have been conducted.21 Compounds (1) and (2)
were isolated in low to moderate yields (18–53%) with both
being water-soluble. The morpholine-derived pyridinones
(3) and (4) could also be prepared by a similar methodology
where the propylmorpholine derivative (4) has increased sol-
ubility in common organic solvents compared to (3). Similar
diarylpyridinones have been prepared recently.22
The molybdenum compounds (5)–(8) prepared in this
study (Scheme 1), could be generated by either direct addi-
tion of the hydroxypyridinone to molybdic acid or by addi-
tion of the precursor amine to aqueous solutions of
preformed maltolato complex cis-MoO2(ma)2.18,23 The
second methodology provides an easy route to making a
wide variety of N-substituted pyridinone molybdenum com-
plexes owing to the ease of isolation, increased yields, milder
conditions, and shorter reaction times. The molybdenum
centre not only acts as a protecting group for the hydroxy
group, thereby reducing the amount of hydrogen bonding
involved in these systems, but its electron-deficient nature
The bond distances within the pyridinone ring also
display similar trends to that described earlier for other
metal–pyridinone complexes.18 Apronounced localization of
the formal double bonds in the ring is clearly indicated by the
short C(2)–C(3), C(5)–C(6), and ketone C(1)–O(3) bonds.

690
N. A. Epstein et al.
An N(4)–C(7) bond distance of 1.479(3) Å is similar to that
reported for the free ligands L´* (cf. 1.474(1) Å)29 and L´´†
(cf. 1.482(4) Å).31 Of the four hydrogen bonds formed, three
(from H(9), H(29), and H(39)) are bonded to molybdenum
oxygens in neighbouring molecules. The fourth hydrogen
bond links molecule 1 to 2 in a head-to-tail fashion via
O(19)–H(19)···O(9B) (B = x, y, 1+z) and essentially results
in
a
three-dimensional polymeric sheet structure
[O(9)–H(9)···O(25A), 2.721(2) Å; O–H···O, 167°;
O(19)–H(19)···O(9B), 2.734(2) Å; O–H···O, 175°;
O(29)–H(29)···O(2C), 2.815(2) Å; O–H···O, 164°;
O(39)–H(39)···O(3D), 2.756(2) Å; O–H···O, 164°]. Atomic
coordinates, thermal parameters, bond lengths and angles,
and alternative views of complex (5) have been deposited as
Fig. 3. The molecular structure of MoO2(hep)2 (5).
Table 1. Fractional atomic coordinates and equivalent isotropic
displacement parameters (Å2) for (5)
104x
104y
104z
104Ueq
A
Molecule
1
Atom
Table 2. Bond distances (Å) for (5), together with hydrogen bonds
Mo(1)
O(1)
1019.5(2)
2671(2)
391(2)
4373.8(1)
4571(1)
5498(1)
3778(1)
4397(1)
2795(1)
3843(1)
3672(1)
4037(1)
4028(1)
3610(1)
3217(2)
3233(2)
3580(2)
2763(2)
1825(1)
4464(2)
2332(1)
2887(1)
2491(2)
1533(1)
994(2)
2846.3(1)
3568(1)
3183(1)
1616(1)
1683.4(9)
2447(1)
3546(1)
782(1)
160.3(6)
252(5)
245(5)
223(5)
187(4)
235(5)
192(4)
195(6)
170(6)
179(6)
194(5)
239(7)
244(7)
239(7)
263(7)
305(5)
259(7)
197(6)
170(6)
193(6)
232(6)
281(7)
257(7)
321(8)
331(8)
410(7)
285(7)
Bond distances
Molecule 1
Hydrogen bondsA
O(2)
O(3)
–781(2)
1975(1)
1170(2)
–456(2)
–341(2)
1170(2)
1761(2)
856(2)
–570(2)
–1199(2)
1417(2)
2323(2)
1438(2)
3322(2)
393(2)
O(4)
O(9)–H(9)
0.97
O(5)
H(9)···O(25A)
O(9)···O(25A)
O(19)–H(19)
H(19)···O(9B)
O(19)···O(9B)
O(29)–H(29)
H(29)···O(2C)
O(29)···O(2C)
O(39)–H(39)
H(39)···O(3D)
O(39)···O(3D)
1.77
O(6)
C(1)
Mo(1)–O(1)
1.703(1)
1.719(2)
2.211(1)
1.999(1)
2.182(1)
1.992(2)
2.721(2)
0.94
C(2)
803(1)
–28(1)
Mo(1)–O(2)
Mo(1)–O(3)
Mo(1)–O(4)
Mo(1)–O(5)
Mo(1)–O(6)
C(3)
1.80
N(4)
–894(1)
–932(2)
–119(2)
–1813(1)
–2155(2)
–2373(1)
7(2)
2917(1)
3519(1)
4057(1)
4044(1)
3483(2)
2910(2)
4688(2)
5719(2)
5746(1)
4625(2)
2.734(2)
0.91
C(5)
C(6)
C(7)
1.93
C(8)
2.815(2)
0.91
O(9)
Molecule 2
C(10)
C(11)
C(12)
C(13)
N(14)
C(15)
C(16)
C(17)
C(18)
O(19)
C(20)
1.87
–528(2)
–1409(2)
–1321(2)
–434(3)
401(2)
Mo(2)–O(21)
Mo(2)–O(22)
Mo(2)–O(23)
Mo(2)–O(24)
Mo(2)–O(25)
Mo(2)–O(26)
1.711(1)
1.702(2)
2.193(1)
2.005(2)
2.259(2)
1.984(1)
2.756(2)
1344(2)
1084(2)
1459(2)
1255(1)
3075(2)
–2100(3)
–1332(3)
136(2)
–2443(2)
A
Symmetry codes: A = x, y, –1+z; B = x, y, 1+z; C = –x, 1–y, 1–z;
D = 1+x, y, 1+z.
2
Mo(2)
O(21)
O(22)
O(23)
O(24)
O(25)
O(26)
C(21)
C(22)
C(23)
N(24)
C(25)
C(26)
C(27)
C(28)
O(29)
C(30)
C(31)
C(32)
C(33)
N(34)
C(35)
C(36)
C(37)
C(38)
O(39)
C(40)
5596.5(2)
4650(2)
7352(2)
6178(2)
4729(2)
3563(2)
6092(2)
5729(2)
4913(2)
4318(2)
4534(2)
5338(2)
5974(2)
3766(2)
2263(2)
2480(2)
3459(2)
3821(2)
5215(2)
5657(2)
4683(2)
3295(2)
2823(2)
5174(3)
5377(2)
6232(2)
7148(2)
372.3(1)
–802(1)
231(1)
7586.8(1)
7125(1)
7361(1)
8002(1)
6441.6(9)
8219.1(9)
8996.2(9)
7337(1)
6472(1)
5729(1)
5848(1)
6655(2)
7386(2)
5156(2)
5417(2)
6342(1)
4825(1)
9159(1)
9596(1)
10575(1)
11129(1)
10739(2)
9768(2)
12137(1)
12182(2)
11489(1)
11034(2)
184.3(6)
274(5)
292(5)
223(5)
203(4)
226(5)
228(5)
189(6)
172(6)
174(6)
197(5)
251(7)
242(6)
255(7)
259(7)
371(6)
242(6)
204(6)
194(6)
194(6)
214(5)
254(7)
244(7)
253(7)
240(7)
289(5)
256(7)
Table 3. Selected bond angles (degrees) for (5)
1986(1)
733.0(9)
859(1)
Molecule 1
Molecule 2
614(1)
2363(1)
1691(1)
2006(1)
3012(1)
3657(2)
3366(2)
3434(2)
3647(2)
4335(1)
1290(2)
1182(1)
1086(1)
1477(1)
1953(1)
1992(2)
1611(2)
2594(2)
3677(2)
3880(1)
1382(2)
O(1)–Mo(1)–O(2) 103.9(1)
O(1)–Mo(1)–O(3) 162.4(1)
O(21)–Mo(2)–O(22) 103.5(1)
O(21)–Mo(2)–O(23) 162.6(1)
O(2)–Mo(1)–O(3)
O(1)–Mo(1)–O(4)
91.8(1)
93.1(1)
O(22)–Mo(2)–O(23)
O(21)–Mo(2)–O(24)
90.4(1)
90.9(1)
O(2)–Mo(1)–O(4) 103.6(1)
O(22)–Mo(2)–O(24) 102.6(1)
O(3)–Mo(1)–O(4)
O(1)–Mo(1)–O(5)
75.1(1)
87.8(1)
O(23)–Mo(2)–O(24)
O(21)–Mo(2)–O(25)
75.7(1)
88.6(1)
O(2)–Mo(1)–O(5) 163.7(1)
O(22)–Mo(2)–O(25) 165.6(1)
O(3)–Mo(1)–O(5)
O(4)–Mo(1)–O(5)
78.7(1)
86.9(1)
O(23)–Mo(2)–O(25)
O(24)–Mo(2)–O(25)
79.3(1)
84.7(1)
O(1)–Mo(1)–O(6) 105.2(1)
O(21)–Mo(2)–O(26) 106.5(1)
O(2)–Mo(1)–O(6)
O(3)–Mo(1)–O(6)
89.6(1)
82.7(1)
O(22)–Mo(2)–O(26)
O(23)–Mo(2)–O(26)
94.0(1)
82.4(1)
O(4)–Mo(1)–O(6) 154.3(1)
O(24)–Mo(2)–O(26) 152.4(1)
O(5)–Mo(1)–O(6)
Mo(1)–O(3)–C(1)
Mo(1)–O(4)–C(2)
76.2(1)
113.7(1)
119.4(1)
O(25)–Mo(2)–O(26)
74.8(1)
Mo(2)–O(23)–C(21) 113.6(1)
Mo(2)–O(24)–C(22) 118.7(1)
Mo(2)–O(25)–C(31) 111.2(1)
Mo(2)–O(26)–C(32) 119.5(1)
A Equivalent isotropic U defined as one-third of the trace of the orthogonalized Uij tensor.
Mo(1)–O(5)–C(11) 113.0(1)
Mo(1)–O(6)–C(12) 118.3(1)
* L´ = 3-hydroxy-1-p-methoxyphenyl-2-methylpyridin-4(1H)-one.
† L´´ = 3-hydroxy-1,2-dimethylpyridin-4(1H)-one.

Hydrophilic Hydroxypyridinones
691
8
9
an Accessory Publication, copies of which are available
(until 31 December 2005) from the Australian Journal of
Chemistry, P.O. Box 1139, Collingwood, Vic. 3066.
Scarrow, R. C., and Raymond, K. N., Inorg. Chem., 1988, 27, 4140.
Clarke, E. T., and Martell, A. E., Inorg. Chim. Acta, 1992, 191, 57.
Kontoghiorghes, G. J., Biochim. Biophys. Acta, 1986, 882, 267.
Hider, R. C., and Hall, A. D., Prog. Med. Chem., 1991, 28, 41.
Shi, Y., Eyring, E. M., van Eldik, R., Liu, G., Bruenger, F. W., and
Miller, S. C., J. Biol. Inorg. Chem., 1997, 2, 728.
Liu, G., Miller, S. C., and Bruenger, F. W., Synth. Commun., 1996,
26, 2681.
10
11
12
Conclusions
13
Aseries of hydrophilic hydroxypyridinones, and their cor-
responding dioxomolybdenum(VI) complexes, have been
prepared and characterized by a number of physical
methods, including X-ray diffraction studies for the case of
cis-MoO2(hep)2 (5). The resulting metal complexes, like the
hydroxypyridinone ligands, have appreciable solubility in
aqueous solvents. We are currently investigating the biolog-
ical activities of these molybdenum complexes for their
ability to control heart dysfunction in diabetics and will
report our results in due course.
14
15
Taylor, P. D., Chem. Commun., 1996, 405.
Burgess, J., De Castro, B., Oliveira, C., Rangel, M., and
Schlindwein, W., Polyhedron, 1997, 16, 798.
16
17
Yuen, V. G., Orvig, C., and McNeill, J. H., Am. J. Physiol., 1997,
272, E30.
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., and Orvig, C., J. Am. Chem. Soc., 1995, 117, 12759, and
references therein.
18
Lord, S. J., Epstein, N. E., Paddock, R. L., Vogels, C. M., Hennigar,
T. L., Zaworotko, M. J., Taylor, N. J., Driedzic, W. R., Broderick, T.
L., and Westcott, S. A., Can. J. Chem., 1999, 77, 1249.
Sheldrick, G. M., SHELXTL-Plus, Version 4.21/v, Siemens Analytical
X-Ray Instruments, Inc., Madison, Wisconsin, U.S.A., 1990.
Clevette, D. J., Lyster, D. M., Nelson, W. O., Rihela, T., Webb, G. A.,
and Orvig, C., Inorg. Chem., 1990, 29, 667, and references therein.
Hider, R. C., and Hall, A. D., Perspect. Bioinorg. Chem., 1991, 1,
209.
Acknowledgments
19
20
21
22
Thanks are gratefully extended to the Heart and Stroke
Foundation of New Brunswick, the University of Waterloo,
and Mount Allison University for financial support. We also
thank Dan Durant, Roger Smith and Jacqueline Jacob (Mount
Allison University) for their expert technical assistance.
Anonymous reviewers are thanked for helpful comments.
Johnson, M. G., and Foglesong, R. J., Tetrahedron Lett., 1997, 38,
7003.
23
24
Greaves, S. J., and Griffith, W. P., Polyhedron, 1988, 7, 1973.
Feng, M.-H., van der Does, L., and Bantjes, A., J. Med. Chem.,
1993, 36, 2822.
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