Monohydroxamic acids and bridging dihydroxamic acids as chelators to ruthenium(iii) and as nitric oxide donors: Syntheses, speciation studies and nitric oxide releasing investigation

Article abstract of DOI:10.1039/b711863e

The synthesis and spectroscopic characterisation of novel mononuclear Ru^III(edta)(hydroxamato) complexes of general formula [Ru(H ₂edta)(monoha)] (where monoha = 3- or 4-NH₂, 2-, 3- or 4-Cl and 3-Me-phenylhydroxamato), as well as the first example of a Ru ^III-N-aryl aromatic hydroxamate, [Ru(H₂edta)(N-Me-bha)] ·H₂O (N-Me-bha = N-methylbenzohydroxamato) are reported. Three dinuclear Ru^III complexes with bridging dihydroxamato ligands of general formula [{Ru(H₂edta)}₂(μ-diha)] where diha = 2,6-pyridinedihydroxamato and 1,3- or 1,4-benzodihydroxamato, the first of their kind with Ru^III, are also described. The speciation of all of these systems (with the exception of the Ru-1,4-benzodihydroxamic acid and Ru-N-methylbenzohydroxamic systems) in aqueous solution was investigated. We previously proposed that nitrosyl abstraction from hydroxamic acids by Ru ^III involves initial formation of Ru^III-hydroxamates. Yet, until now, no data on the rate of nitric oxide (NO) release from hydroxamic acids has been published. We now describe a UV-VIS spectroscopic study, where we monitored the decrease in the ligand-to-metal charge-transfer band of a series of Ru^III-monohydroxamates with time, with a view to gaining an insight into the NO-releasing properties of hydroxamic acids. The Royal Society of Chemistry.

Full text of DOI:10.1039/b711863e

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/dalton | Dalton Transactions
Monohydroxamic acids and bridging dihydroxamic acids as chelators to
ruthenium(III) and as nitric oxide donors: syntheses, speciation studies and
nitric oxide releasing investigation†
Darren Griffith, Krystyna Krot, Jedd Comiskey, Kevin B. Nolan and Celine J. Marmion*
Received 3rd August 2007, Accepted 21st September 2007
First published as an Advance Article on the web 11th October 2007
DOI: 10.1039/b711863e
III
The synthesis and spectroscopic characterisation of novel mononuclear Ru (edta)(hydroxamato)
complexes of general formula [Ru(H
2
edta)(monoha)] (where monoha = 3- or 4-NH
2
, 2-, 3- or 4-Cl and
III
3
-Me-phenylhydroxamato), as well as the first example of a Ru -N-aryl aromatic hydroxamate,
[
Ru(H
2
edta)(N-Me-bha)]·H O (N-Me-bha = N-methylbenzohydroxamato) are reported. Three
2
III
dinuclear Ru complexes with bridging dihydroxamato ligands of general formula
[
1
{Ru(H
2
edta)}
2
(l-diha)] where diha = 2,6-pyridinedihydroxamato and 1,3- or
III
,4-benzodihydroxamato, the first of their kind with Ru , are also described. The speciation of all of
these systems (with the exception of the Ru–1,4-benzodihydroxamic acid and
Ru–N-methylbenzohydroxamic systems) in aqueous solution was investigated. We previously proposed
III
that nitrosyl abstraction from hydroxamic acids by Ru involves initial formation of
III
Ru -hydroxamates. Yet, until now, no data on the rate of nitric oxide (NO) release from hydroxamic
acids has been published. We now describe a UV-VIS spectroscopic study, where we monitored the
III
decrease in the ligand-to-metal charge-transfer band of a series of Ru -monohydroxamates with time,
with a view to gaining an insight into the NO-releasing properties of hydroxamic acids.
ꢀ
Introduction
an O,O -bidentate manner to form stable metal chelates with
characteristically high formation constants. Desferal, for example,
a trihydroxamic acid used clinically as an Fe scavenger, coordinates
to Fe via its three hydroxamato moieties, forming an Fe -
Hydroxamic acids RC(O)NHOH have emerged in recent years
as a class of compounds that can fulfil a variety of roles in
biology and medicine, many of which are as a result of their
enzyme-inhibitory properties. The versatile biological activity
of hydroxamic acids is undoubtedly due to their ability to
III
III
1
trishydroxamate with log b ∼30.
1
,2
Despite such an active interest in hydroxamato complexes of
III
Fe , surprisingly there is only one literature report to date on their
complexes with Ru . In this, the first structurally characterised
Ru hydroxamato complex, [Ru(H edta)(2-MeO-pha)] (where 2-
MeO-pha is 2-methoxyphenylhydroxamato) (Fig. 1 ), and the
synthesis and spectroscopic characterisation of several others are
1
,2
form stable metal chelates, and possibly their NO-releasing
III
3
properties. In addition, when deprotonated, the hydroxamate
III
2
−
anion (RCOHNO ) can form salt linkages in their complexes
with proteins, and when neutral (RCOHNOH) may engage in
important hydrogen-bonding interactions.
The powerful metal-chelating ability of hydroxamic acids has
also been utilised to construct a diverse host of fascinating
metal complexes including hydroxamates,
examples in supramolecular chemistry such as metallacrowns,
coordination polymers and tetrahedral cluster complexes.
1
14
reported.
1
,4–8
1,4,9
hydroximates and
1
,10,11
12
13
One of the first physiological roles of hydroxamic acids was
associated with their use as siderophores, a class of low molec-
ular weight iron (Fe)-sequestering agents involved in microbial
III
iron transport. As a result, the chemistry of Fe -hydroxamato
complexes has been extensively studied, with numerous X-ray
structural reports of and determination of stability constants
2
Fig. 1 Structure of [Ru(H edta)(2-OMe-pha)].
III
for Fe complexes with synthetic and naturally occurring hy-
III
droxamic acids. Typically, hydroxamic acids coordinate Fe in
The speciation and stability constants for several mononuclear
III
Ru -hydroxamato complexes were also reported in addition to
III
III 14
Centre for Synthesis & Chemical Biology, Department of Pharmaceutical &
Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephens
Green, Dublin 2, Ireland. E-mail: cmarmion@rcsi.ie; Fax: +353 1 402 2168;
Tel: +353 1 402 2161
their relative affinity for Ru over Fe . We now report the
syntheses and spectroscopic characterisation of three dinuclear
III
Ru -complexes with bridging dihydroxamato ligands, the first of
III
their kind with Ru to be reported as well as a series of novel
†
Electronic supplementary information (ESI) available: Titration curves.
III
See DOI: 10.1039/b711863e
mononuclear Ru -hydroxamato complexes, including the first
This journal is © The Royal Society of Chemistry 2008
Dalton Trans., 2008, 137–147 | 137

View Article Online
III
example of a Ru -N-aryl aromatic hydroxamato derivative. The
with magnesium sulfate and then removed in vacuo affording a tan-
coloured oil, which was purified by column chromatography on
silica using ethyl acetate–n-heptane as eluent to give N-Me-bhaH
speciation of all of these systems (with the exception of the Ru–1,4-
benzodihydroxamic acid and the Ru–N-methylbenzohydroxamic
acid systems) in aqueous solution was investigated and is also
herein reported.
(0.95 g, 23%) as a colourless oil: d
(5H, m, ar H), 2.94 (s, 3H, CH ).
H
(400 MHz; CDCl ) 7.31–7.43
3
3
We previously proposed that nitrosyl abstraction from hy-
droxamic acids by K[Ru(Hedta)Cl] involves initial formation of
Syntheses of mono- and dihydroxamic acids
III
Ru -hydroxamato complexes with the subsequent formation of
II
II
−
the Ru -nitrosyl [Ru (Hedta)(NO)Cl] and the corresponding
A series of mono- and dihydroxamic acids, listed in Table 1, were
synthesised by reaction of hydroxylamine with the corresponding
methyl or ethyl esters according to the method described for 1,4-
3
carboxylic acid. Yet, until now, no data on the rate of NO release
from hydroxamic acids have been published. We have carried out
a UV-VIS spectroscopic investigation in which we monitored the
decrease in the hydroxamato ligand-to-Ru metal charge-transfer
1
benzodihydroxamic acid below. H NMR and selected IR data and
elemental analyses for each of the hydroxamic acids synthesised
may also be found in Table 1.
III
band of a series of Ru -hydroxamato complexes with time, with
a view to gaining an insight into the NO-releasing properties of
hydroxamic acids.
1,4-Benzodihydroxamic acid, terephthalohydroxamic acid
(
1,4-bhaH
2
)
Experimental
Hydroxylamine hydrochloride (6.3 g, 90 mmol) was mixed with
sodium hydroxide (7.2 g, 180 mmol) in deionised water (45 cm ).
3
Materials and instrumentation
The solution was then added to dimethyl terephthalate (5.8 g,
Benzohydroxamic acid (bhaH), acetohydroxamic acid (achaH),
benzoyl chloride, the ester reagents and deuterated solvents were
all purchased from Aldrich and used without further purification.
3
3
0 mmol) in methanol (50 cm ). The resulting solution was stirred
◦
for 72 hours at 40 C and was acidified to pH 5.5 using 5% HCl. The
solvent was removed in vacuo yielding a yellow solid. Methanol
RuCl
3
·xH
2
O was kindly donated by Johnson Matthey. IR spectra
3
(
60 cm ) was added and sodium chloride filtered. The solvent was
−
1
were recorded as KBr discs (4000–400 cm ) on a Mattson Genesis
II CSI FTIR spectrometer and the spectra analysed using WinFirst
software. H NMR spectra were recorded on a Bruker Avance
removed in vacuo yielding a white solid, which was recrystallised
from water to give 1,4-bhaH (3.4 g, 58%) as a white crystalline
solid (Found: C, 48.7; H, 4.1; N, 14.1%. Calc. for C : C,
2
1
8
H
8
N
2
O
4
4
00 MHz NMR spectrometer and the spectra analysed using
TopSpin 1 software. The residual undeuterated DMSO signal at
.505 ppm or the Me Si signal were used as internal references.
4
9.0; H, 4.0; N, 14.3%); d
H
(400 MHz, DMSO): 11.33 (2H, br s,
−1
OH), 9.14 (2H, br s, NH) and 7.81 (4H, s, aromatic H); mmax/cm
2
4
3288vs (NH), 2730b (OH), 1649vs, 1612vs (CO) and 1562s (CN).
UV-VIS spectra were performed on a Helios a Thermo Spectronic
Spectrophotometer in a quartz cell. Liquid chromatography-mass
spectrometry experiments were performed on a Quattro Micro
quadrupole electrospray mass spectrometer (Micromass, Waters
Corp., USA); 10 lL of the samples were injected in 300 lL of
acetonitrile–water (60 : 40, v/v). The mass spectrometry data
were acquired both in positive and negative ion modes. Magnetic
measurements were carried out on polycrystalline samples using
a Sherwood Scientific Magnetic Susceptibility Balance. Elemental
analysis (C, H, N, Cl & K) were performed at the Microanalytical
Laboratory, School of Chemistry and Chemical Biology, Univer-
sity College Dublin.
III
Syntheses of Ru complexes
K[Ru(Hedta)Cl]·2H
2
O (1)
K[Ru(Hedta)Cl]·2H O (4.6 g, 63%) was prepared by modification
2
16
of a literature method (Found: C, 23.8; H, 3.3; N, 5.4; Cl, 7.0; K,
7.6%. Calc. for RuC H N O ClK: C, 24.0; H, 3.4; N, 5.6; Cl, 7.1;
1
0
17
2
11
−
1
K, 7.8%); mmax/cm 3410s (OH), 2992s, 2942s (CH, CH ), 1726s
(CO, free glycine arm), and 1632s (CO, bound glycinato arms).
2
[
Ru(H
2
edta)(N-Me-bha)]·H
2
O (2)
3
Syntheses
An ethanolic solution (10 cm ) of N-methylbenzohydroxamic
acid (N-Me-bha) (0.22 g, 1.45 mmol) was added to an aqueous
Synthesis of N-aryl aromatic hydroxamic acid
3
solution (25 cm ) of K[Ru(Hedta)Cl]·2H
2
O (0.56 g, 1.12 mmol).
15
The reaction was stirred for 2 hours. A red precipitate 2 (0.56 g,
3%) was filtered and dried over P (Found: C, 38.5; H, 4.3;
N, 7.4%. Calc. for RuC18 11: C, 38.6; H, 4.3; N, 7.5%);
), 1722vs (CO, free glycine arms), 1640vs
(CO, glycinato) and 1611vs (CO, hydroxamato); ESI-MS m/z: 543
N-Methylbenzohydroxamic acid (N-Me-bhaH)
8
2
O
5
N-Methylhydroxylamine hydrochloride (2.36 g, 28 mmol) was
H
24
3
N O
−
1
added to sodium carbonate (3.65 g, 34 mmol) in deionised water
m
max/cm 3494vs (NCH
3
3
(
50 cm ) under nitrogen. The solution was covered with diethyl
3
3
+
ether (20 cm ). Benzoyl chloride (4.06 cm , 35 mmol) in diethyl
ether (30 cm ) was added dropwise over 10 minutes to the stirring
([M + H] ); leff = 1.89 l
Complexes 4–14 were synthesised according to the method
O below. In all cases
B
.
3
heterogeneous mixture in an ice–salt bath. The mixture was stirred
and then cooled for a further 30 minutes, after which 20% sodium
described for [{Ru(H
2
edta)}
2
(l-1,4-bha)]·2H
2
the reaction solutions were concentrated in vacuo before being
left overnight in a refrigerator whereupon solids precipitated over
time. Numerous attempts were made to isolate crystals suitable for
an X-ray crystallographic study but to no avail.
3
hydroxide (12 cm ) was added. The aqueous layer was neutralised
to pH 7 with 6 M HCl, saturated with sodium chloride and
extracted five times with chloroform. The chloroform was dried
1
38 | Dalton Trans., 2008, 137–147
This journal is © The Royal Society of Chemistry 2008

View Article Online
This journal is © The Royal Society of Chemistry 2008
Dalton Trans., 2008, 137–147 | 139

View Article Online
[
{Ru(H
2
edta)}
2
(l-1,4-bha)]·2H
2
O (3)
[Ru(H
2
edta)(4-Cl-pha)]·2H
2
O (11)
3
An aqueous solution (20 cm ) of 1,4-benzodihydroxamic acid (0.15
g, 0.75 mmol) was added to an aqueous solution (15 cm ) of
Yield: 0.32 g, 55%. (Found: C, 34.4; H, 3.6; N, 6.8%. Calc. for
3
−1
RuC17
H
23
N
3
ClO12: C, 34.15; H, 3.9; N, 7.0%); mmax/cm 3297vs
K[Ru(Hedta)Cl]·2H
2
O (0.75 g, 1.50 mmol) in deionised water (15
cm ). The reaction was stirred for 3 hours, concentrated in vacuo
and left to stand in a refrigerator overnight. A red precipitate 3
(NH), 1731s (CO, free glycine arms), 1648vs (CO, glycinato) and
1610s (CO, hydroxamato).
3
(
0.70 g, 46%) was filtered and dried over P
2
O (Found: C, 33.1;
5
[
Ru(H
2
edta)(2-Me-pha)]·2H
2
O (12)
H, 4.0; N, 8.5%. Calc. for Ru 22: C, 33.2; H, 3.8; N,
8
1
m/z: 977 ([M–H] ); leff = 2.16 l
2
C
28
H
38
N O
6
−
1
Yield: 0.045 g, 20%. (Found: C, 37.1; H, 4.3; N, 6.8%. Calc. for
.3%); mmax/cm 3288vs (NH), 1724vs (CO, free glycine arms),
−
1
RuC18
H
26
N
3
O
12: C, 37.4; H, 4.5; N, 7.3%); mmax/cm 3228vs (NH),
730s (CO, free glycine arms) and 1630vs (CO, glycinato and
hydroxamato).
668vs (CO, glycinato) and 1609vs (CO, hydroxamato); ESI-MS
−
1
B
.
[{Ru(H
2
edta)}
2
(l-1,3-bha)]·4H
2
O (4)
[
Ru(H
2
edta)(3-Me-pha)]·2H
2
O (13)
Yield: 0.48 g, 80%. (Found: C, 31.8; H, 3.7; N, 8.0%. Calc. for
−
1
Ru
2
C
28
H
42
6
N O24: C, 31.5; H, 3.4; N, 7.8%); mmax/cm 3213s (NH),
Yield: 0.053 g, 24%. (Found: C, 37.2; H, 4.4; N, 7.0%. Calc. for
RuC18
1730 s (CO, free glycine arms) and 1632vs (CO, glycinato and
hydroxamato); ESI-MS m/z: 543 ([M + H] ).
−
1
1
732vs (CO, free glycine arms) and 1639vs (CO, glycinato and
H
26
N O12: C, 37.4; H, 4.5; N, 7.3%); mmax/cm 3221vs (NH),
3
−
hydroxamato); ESI-MS m/z: 977 ([M–H] ).
+
[{Ru(H
2
edta)}
2
(l-2,6-pyha)]·4H
2
O (5)
[
Ru(H
2
edta)(4-Me-pha)]·2H
2
O (14)
Yield: 0.29 g, 28%. (Found: C, 30.6; H, 3.5; N, 9.0%. Calc. for
−
1
Ru
2
C
27
H
41
7
N O24: C, 30.9; H, 3.9; N, 9.3%); mmax/cm 3265vs (NH),
Yield: 0.096 g, 40%. (Found: C, 37.3; H, 4.2; N, 7.0%. Calc. for
RuC H N O : C, 37.4; H, 4.5; N, 7.3%); mmax/cm 3228vs (NH),
1730s (CO, free glycine arms) and 1630vs (CO, glycinato and
hydroxamato).
−
1
1
731vs (CO, free glycine arms) and 1641vs (CO, glycinato and
1
8
26
3
12
−
hydroxamato); ESI-MS m/z: 978 ([M–H] ).
[
Ru(H
2
edta)(bha)]·2H
2
O (6)
II
Syntheses of Ru -nitrosyl complexes
Yield: 0.55 g, 68%. (Found: C, 36.4; H, 4.1; N, 7.3%. Calc. for
−
1
RuC17
H
24
N
3
O
12: C, 36.2; H, 4.3; N, 7.5%); mmax/cm 3195s (NH),
731s (CO, free glycine arms) and 1634vs (CO, glycinato and
hydroxamato); leff = 1.76 l
Reaction of K[Ru(Hedta)Cl]·2H
NH -phaH, 2-, 3- or 4-Cl-phaH and 2-, 3- or 4-Me-phaH and 2,6-
pyhaH under reflux, resulted in the facile formation of the brown
2
O with achaH, bhaH, 2-, 3- or 4-
1
2
B
.
2
II
Ru -nitrosyl adduct of formula K[Ru(Hedta)(NO)Cl] regardless
[
Ru(H
2
edta)(3-NH
2
-pha)]·2H
2
O (7)
of hydroxamic acid used. In contrast, 1,3- and 1,4-bhaH , when
2
reacted with K[Ru(Hedta)Cl] under reflux, gave the corresponding
Yield: 0.12 g, 53%. (Found: C, 35.2; H, 4.2; N, 10.0%. Calc.
for RuC17
(
III
red Ru -dihydroxamates in high yield and the nitrosyl adduct
−
1
H
25
N
4
O12: C, 35.3; H, 4.4; N, 9.7%); mmax/cm 3264b
could only be isolated as a minor product upon purification of
the filtrates using a sephadex LH20 column. A typical synthesis is
NH), 1729s (CO, free glycine arms) and 1624vs (CO, glycinato
+
and hydroxamato); ESI-MS m/z: 544 ([M + H] ).
described below. Reaction of K[Ru(Hedta)Cl]·2H
phaH did not produce a nitrosyl product, rather it resulted in the
formation of [Ru(H O 2 only.
edta)(N-Me-bha)]·H
2
O with N-Me-
[
Ru(H
2
edta)(4-NH
2
-pha)]·4H
2
O (8)
2
2
Yield: 0.54 g, 61%. (Found: C, 32.9; H, 4.5; N, 9.0%. Calc. for
−
1
RuC17
H
29
N
4
O
14: C, 33.2; H, 4.8; N, 9.1%); mmax/cm 3442vs,
380vs, 3233s (NH), 1730s (CO, free glycine arms) and 1629vs
CO, glycinato and hydroxamato).
K[Ru(Hedta)(NO)Cl]·H
2
O (15)
3
(
3
An aqueous solution (20 cm ) of benzohydroxamic acid (bhaH)
3
(0.41 g, 3.0 mmol) was added to an aqueous solution (15 cm )
of K[Ru(Hedta)Cl]·2H
2
O (0.5 g, 1.0 mmol), resulting in a red
solution. Upon heating, the reaction solution turned brown in
[
Ru(H
2
edta)(2-Cl-pha)]·H
2
O (9)
colour. It was refluxed for ∼30 min and then concentrated in vacuo
Yield: 0.084 g, 38%. (Found: C, 35.5; H, 3.7; N, 7.2%. Calc. for
3
−
1
(10 cm ). After overnight refrigeration a white precipitate was
RuC17
H
21
N
3
ClO11: C, 35.2; H, 3.65; N, 7.25%); mmax/cm 3211s
NH), 1730s (CO, free glycine arms) and 1635vs (CO, glycinato
and hydroxamato).
filtered and dried. The brown filtrate was taken to dryness on a
rotary evaporator. The resulting brown precipitate was stirred in a
(
1
: 1 diethyl ether–ethyl acetate suspension overnight. The brown
product was filtered, purified on a sephadex column LH20 using
water as eluent to give 15 (0.29 g, 58%) as a brown solid (Found: C,
[
Ru(H
2
edta)(3-Cl-pha)]·2H
2
O (10)
Yield: 0.26 g, 43%. (Found: C, 34.3; H, 3.4; N, 6.8%. Calc. for
23.4; H, 2.9; N, 8.5; Cl, 6.9; K, 7.4%. Calc. for RuC10
C, 23.4; H, 2.95; N, 8.2; Cl, 6.9; K, 7.6%); d (400 MHz; D
glycine), 4.34 (s, 2H, CH
H
15
N
3
ClKO10
:
−
1
RuC17
H
23
N
3
ClO12: C, 34.15; H, 3.9; N, 7.0%); mmax/cm 3167s
H
2
O;
(
NH), 1732s (CO, free glycine arms) and 1650vs (CO, glycinato
Me
4
Si) 4.43 (d, 2H, CH
2
2
glycine), 4.09
glycine) 3.61 (4H, m,
+
and hydroxamato); ESI-MS m/z: 563 ([M + H] ).
(2H, s, CH
2
glycine), 3.84 (2H, s, CH
2
1
40 | Dalton Trans., 2008, 137–147
This journal is © The Royal Society of Chemistry 2008

View Article Online
CH
2
ethylenediamine); d
C
(400 MHz; D
2
O; Me
4
Si) 181.8, 178.5
Results and discussion
(CO, glycinato), 177.7, 168.8 (CO, free glycine), 65.45, 65.4, 64.7,
−
1
Synthesis and spectroscopic characterisation of hydroxamic acids
64.3 (CH
2
glycinato), 62.8, 60.4 (CH
2
ethylenediamine); mmax/cm
edta), 1894vs (NO), 1726s
III
and their Ru -hydroxamato complexes
3
345 s (OH), 2986 s, 2947 s (CH, H
2
(
4
CO, free glycine arms) and 1649b (CO, glycinato); ESI-MS m/z:
56 ([M–H] ).
Hydroxamic acids
−
The hydroxamic acids were synthesised according to literature
20
methods, by reaction of hydroxylamine with the corresponding
carboxylic methyl or ethyl esters, with the exception of N-
methylbenzohydroxamic acid, which was synthesised from a
Potentiometric and spectrophotometric studies
The pH-metric titrations were carried out on a Molspin pH
meter and titration controller with Thermo Russell CMAW711
combined electrode and Hamilton syringe autoburette. All mea-
15
carboxylic acid chloride. They were obtained in good yields
(
∼50–80%) and high purity, and were characterised by elemental
1
−
3
analysis, IR and H NMR spectroscopy.
surements were carried out using solutions of 0.1 mol dm ionic
◦
Selected IR stretches are given in Table 1. Occasionally, two
sharp stretches corresponding to the symmetric and asymmetric
strength (KNO
3
) at 25 ± 0.1 C. Carbonate-free KOH solution
−
3
of known concentrations (ca. 0.2 mol dm ), standardised with
potassium hydrogen phthalate, were used as titrant. In the
Ru (edta) hydroxamic acid titrations readings were taken every
17
mCO are observed but typically only one broad band appears due
21
III
to intramolecular hydrogen bonding. The mNH of the hydroxamic
−
1
acid is generally observed between 3150 and 3350 cm . The broad
OH of the hydroxamic acid may be attributed to intermolecular
hydrogen bonding and is in the main observed in the range 2730 to
3
seconds to a precision of 0.001 pH units using the Molspin
m
titrator set on ‘slow reaction rate’. A minimum number of readings
is used to calculate the standard deviation and this is compared
to the required precision. This process is repeated between 9 and
−
1
2
930 cm . These values concur with previously reported literature
21
values.
9
00 times until the standard deviation is less than the required
1
6
H NMR spectra for the hydroxamic acids in d DMSO show
the hydroxamic acid NH and OH resonances at ca. 9 and 11 ppm,
respectively. The appearance of these resonances are very much
concentration-dependent due to intermolecular hydrogen bonding
at high concentrations.
precision. This ensures that pH data are collected for a fully
equilibrated system. Each titration curve was carried out in
triplicate and 120 points per titration were used to calculate the
experimental equilibrium constants.
The electrode system was calibrated by the method of Irving
1
8
et al. (pK
w
= 13.831) so that the pH-meter readings could
III
be converted into hydrogen ion concentration. For the Ru
systems sufficient time was allowed for equilibration prior to pH
measurements.
Ru complexes
K[Ru(Hedta)Cl]·2H
2
O
The pK
a
values of the hydroxamic acids and of the aqueous
O system were determined by titrating so-
III
Previous attempts to synthesise Ru -hydroxamato complexes
K[Ru(Hedta)Cl]·2H
2
3
using RuCl O were hampered by the formation of ill-defined
3
·xH
2
−
−3
−3
−3
lutions (∼2.0 × 10 mol dm ) in HNO (5.0 × 10 mol dm )
3
oligomeric products. Therefore with a view to synthesising and
−3
with a KOH solution of known concentration (0.19807 mol dm ).
This method was also used to determine the exact concentration
of the ligand and metal stock solutions. Stability constants of
III
characterising Ru -hydroxamato derivatives, a well-characterised
III
Ru complex K[Ru(Hedta)Cl]·2H
2
O was selected where the
3−
ligand Hedta is pentadentate with one uncoordinated and
protonated glycine moiety. It was prepared by modification of
a literature method and obtained in good yield (63%) and high
III
the Ru -edta-hydroxamato complexes were determined by pH-
−
3
metric methods using ligand concentrations in the range 1 × 10
to 4 × 10 mol dm . The resulting data were analysed using
HYPERQUAD2000.
16
−
3
−3
purity. Its IR spectrum exhibits two mCO stretches; the first, a broad
19
−1
band at 1632 cm , is attributed to the carbonyl groups of the Ru-
bound glycinato groups and the second, a very distinct sharp band
−
1
at 1726 cm , attributed to the carbonyl group of the protonated
free glycine arm of Hedta.
UV-VIS spectroscopic investigation
22
◦
A UV-VIS spectroscopic investigation was performed at 50
C
on a Thermo Spectronic Helios a UV-Vis spectrophotometer
III
Mononuclear Ru -hydroxamato complexes
equipped with a thermostatted cell. The reduction in absorbance
III
at kmax corresponding to the hydroxamato ligand-to-Ru metal
K[Ru(Hedta)Cl] rapidly forms the aqua species when dissolved
in water and exists predominantly in its most labile form
III
charge transfer (LMCT) band of the Ru -hydroxamato species
2
−
III
−
23
[
Ru(edta)(monoha)] (where monoha is acha, bha, 2-, 3- or 4-NH
2
-
[Ru (edta)(H
2
O)] between pH 5–6. Reaction of an excess of
III
−
pha, 3-Me-pha) was followed. Typical experimental conditions
were pH 4.50, ligand to metal ratio of 10 : 1, [Ru] = 2.00 mM
and I = 0.20 KCl thus ensuring good pseudo-first-order plots of
hydroxamic acid with [Ru (edta)(H
2
O)] in aqueous solution
afforded the corresponding Ru -monohydroxamato complexes
of general formula [Ru(H
edta)(monoha)] (monoha = bha, 3- or
4-NH -pha, 2-, 3- or 4-Cl-pha, 2-, 3- or 4-Me-pha, NMe-pha)
III
2
ln(A
t
− A
∞
) versus time where A
t
and A
∞
are the absorbances
2
at time t and infinity, respectively. The metal complex solutions
in varying yields but high purity, Scheme 1. All complexes were
characterised by IR spectroscopy, elemental analysis and in certain
instances by electrospray ionisation mass spectroscopy (ESI-MS)
and magnetic susceptibility measurements.
were freshly prepared before each experiment. The temperature
◦
(
± 0.5 C) of the cell housing was regulated by circulation of
thermostatted water.
This journal is © The Royal Society of Chemistry 2008
Dalton Trans., 2008, 137–147 | 141

View Article Online
Scheme 1
1
4
Although numerous attempts were made to isolate crystals
suitable for an X-ray crystallographic study, only crystals of
agreement with previously reported data. Selected mononuclear
III
Ru -hydroxamato complexes were further identified by ESI-MS
[
Ru(H
2
edta)(2-OMe-pha)]·2H
2
O ever materialised, the crystal
in the positive mode. Mass peaks at 543, 544, 563 and 543 amu are
14
structure of which was previously reported. Nevertheless, com-
parison of the IR spectra of our complexes with the IR spectrum
observed for [Ru(H
pha)] (543), [Ru(H
2
edta)(N-Me-bha)] (542), [Ru(H
edta)(3-Cl-pha)] (562) and [Ru(H
2
edta)(3-NH
2
-
2
2
edta)(3-Me-
of [Ru(H
2
edta)(2-OMe-pha)]·2H
2
O, assisted in the successful
pha)] (542), respectively, and all of which display the correct iso-
topic abundances. The room temperature leff of the mononuclear
III
characterisation of the Ru -hydroxamato complexes synthesised.
The coordination geometry of [Ru(H
is a slightly distorted octahedron as expected due to the presence
of different donor atoms. H edta is present as a 2N, trans-2O-
dicarboxylato) tetradentate ligand with two fully protonated
uncoordinated carboxylic acid moieties. The hydroxamato ligand,
2
edta)(2-OMe-pha)]·2H
2
O
[Ru(H
1.79 l
to 2.3 l
2
edta)(bha)]·2H
and 1.89 l , respectively, and fall within the range of 1.7
, typical of a low-spin paramagnetic Ru complex with
2
O and [Ru(H
2
edta)(N-Me-bha)]·H
2
O are
B
B
III
2
B
5
0
(
an electron configuration t2g
The Ru -hydroxamato complexes of bhaH and the monosub-
g
e at this temperature.
III
III
ꢀ
2
-MeO-pha, is coordinated to the Ru centre in typical (O,O )-
stituted aromatic derivatives 3- and 4-NH
phaH, 2-, 3- and 4-Me-phaH, are schematically represented by the
general formula [Ru(H edta)(monoha)], shown in Scheme 1.
Of the red Ru -hydroxamato complexes synthesised, all but
one yielded products of general formula [Ru(H edta)(monoha)]
(where monoha = bha, 3- or 4-NH -pha, 2-, 3- or 4-Cl-pha, 2-,
3- or 4-Me-pha) and the % yields follow the substitution order
2
-phaH, 2-, 3- and 4-Cl-
14
bidentate fashion.
III
The IR spectra of the Ru -hydroxamato complexes display
three distinctive mCO bands. Using [Ru(H
edta)(4-Cl-pha)]·2H
as a representative example, the band at 1610 cm is attributed
to the hydroxamato carbonyl and is approximately 40 cm less
than that observed in the spectrum of the free ligand, indicative
2
III
2
2
O
−
1
2
−
1
2
−
1
of hydroxamato coordination. The mCO at 1648 cm and at
2- < 3- < 4-. Reaction of K[Ru(Hedta)Cl]·2H
2
O with 2-NH
edta)(2-NH
2
-
-
−
1
1731 cm can be assigned to the carbonyl groups of the metal-
phaH failed to yield the desired product, [Ru(H
2
2
bound glycinato and glycine arms of edta, respectively. In most
cases the mCO of the hydroxamato ligand and bound glycinato
arms of edta are merged and appear as one broad band instead
of the expected two sharp, distinct bands. A hydroxamato mNH
pha)], rather a blue solution resulted, which rapidly changed
to brown, from which a brown solid was subsequently isolated
II
and characterised as the Ru -nitrosyl, K[Ru(Hedta)(NO)Cl].
III
Blue Ru -edta-catecholamine complexes have previously been
−
1
24
is also observed at 3297 cm . In general the spectra of the
reported. The N-methyl-substituted derivative, [Ru(H
2
edta)(N-
III
Ru -hydroxamato complexes display mNH from ca. 3200 to 3350
Me-bha)], obtained in high yield and high purity, is the first of its
−
1
III
cm while [Ru(H
2
edta)(N-Me-bha)] displays a strong mCH of the
kind with Ru to be reported.
−
1
hydroxamato N–CH
3
group at 3494 cm . The IR spectra of
the Ru -hydroxamato complexes exhibit the same overall pattern
as was evidenced for [Ru(H O, indicating
III
III
Dinuclear Ru -hydroxamato complexes
2
edta)(2-OMe-pha)]·2H
2
III
that they all have similar structures, particularly with respect to
denticity and protonation state of the edta ligand, hydroxamato
binding mode and geometry of the complexes. They are also in
To date, there have been no reports in the literature on Ru -
II
dihydroxamato complexes. A Ni (2,6-pyha) complex has been
II
reported where the dihydroxamato ligand chelates the Ni ion
1
42 | Dalton Trans., 2008, 137–147
This journal is © The Royal Society of Chemistry 2008

View Article Online
via the {N,Npy,N} donor set to give a discrete mononuclear
PPh [Ni(2,6-pyha) O complex. Another report describes
]·7H
the use of 1,3-benzodihydroxamic acid (L) in the construction of
an Fe pyramid and consequently a three-dimensional porous
metal–organic framework. Herein, we report reaction of the
dihydroxamic acids, 1,3-bhaH , 1,4-bhaH and 2,6-pyhaH with
equivalents of K[Ru(Hedta)Cl], which affords novel dinu-
2,6-pyha)] (979), and all of which display the characteristic
25
[
4
]
2
2
2
Ru isotopic abundances. [{Ru(H
2
edta)}
2
(l-1,4-bha)]·2H
2
O was
at room
also found to have a magnetic moment of 2.16 l
B
III
4
L
6
temperature, typical of a low-spin paramagnetic Ru complex
and indicative of no magnetic exchange between the Ru centres
26
III
at this temperature. In the IR spectra of both [{Ru(H
2
edta)}
2
(l-
2
2
2
2
1,3-bha)]·4H
2
O and [{Ru(H
2
edta)}
2
(l-2,6-pyha)]·4H
2
O, the mCO of
III
clear Ru -dihydroxamato complexes [{Ru(H
2
edta)}
2
(l-1,3-bha)],
(l-2,6-pyha)], re-
the hydroxamato and edta glycinato arms are merged and appear
as one broad band.
[{Ru(H
2
edta)}
2
(l-1,4-bha)] and [{Ru(H
2
edta)}
2
spectively (Fig. 2), where the dihydroxamic acids coordinate
in a bridging fashion via two independent O,O donor head
ꢀ
Formation constants and species-distribution curves
III
groups. Elemental analyses and ESI-MS for the dinuclear Ru -
dihydroxamato complexes, together with the potentiometric study
Speciation and spectroscopic studies were carried out on ligands
(
discussed later) and a comparison of their IR spectra versus
L where L is 3- and 4-NH
2
-phaH, 4-NMe -phaH, 2-, 3- and
2
those of the free dihydroxamic acids, unambiguously confirm the
formation of the bridging dihydroxamato complexes. In the IR
4-Cl-phaH, 3-Me-phaH and their complexes with the binary
III
Ru -edta system and the results support the presence of the
III
spectrum of [{Ru(H
2
edta)}
2
(l-1,4-bha)]·2H
2
O, for example, a mCO
ternary Ru -edta-hydroxamato complexes of general formula
−
1
−1
2−
at 1668 cm and at 1724 cm can be assigned to the stretching
frequencies of the carbonyl groups of the glycinato and free glycine
[Ru(edta)(monoha)] , similar to those found in the solid state (3–
11 and 13). The 2-Me-pha and 4-Me-pha systems were previously
−
1
14
arms of edta, respectively. The mCO at 1609 cm is that of the
reported.
−
1
hydroxamato carbonyl groups and is approximately 40 cm less
than that observed in the spectrum of the free ligand, indicative of
III
The ternary Ru -edta-monohydroxamic acid systems
ꢀ
hydroxamato (O,O ) coordination.
The pK
are given in Table 2, are as one would expect with 4-NMe
having the highest pK value (9.47) and 2-Cl-phaH having the
lowest (8.27). The stability constants of the aromatic hydroxamato
a
values for the ligands synthesised, the details of which
2
-phaH
a
2
−
complexes of general formula [Ru(edta)(monoha)] or ML, (where
monoha or L = bha or its monosubstituted derivatives 3-NH
pha, 4-NH -pha, 2-Cl-pha, 3-Cl-pha, 4-Cl-pha, 3-Me-pha and
-pha), were obtained pH-metrically and lie in the range
2
-
2
4
6
-NMe
.15(4)–7.05(1), Table 2.
2
With the exception of the 4-NMe -pha derivative,
2
2
−
[
Ru(edta)(NMe
2
-pha)] (log b = 7.32(3)), all the complexes
III
studied (in which the ratio of Ru : monohydroxamic acid ligand
was 1 : 1), having log b values ranging from 6.15(4) to 7.05(1),
are less stable than the previously reported benzohydroxamato
Ru(edta) complex, [Ru(edta)(bha)] (log b = 7.28(1)), despite
the variance in basicity of ligands studied relative to the
benzohydroxamato ligand. Interestingly also is the fact that,
2
−
14
although the order of basicity of the amino derivatives is 4-NMe
phaH >2-NH -phaH >3-NH -phaH >4-NH -phaH, the order
of complex stability is [Ru(edta)(NMe
2
-
2
2
2
2
−
2
-pha)] > [Ru(edta)(4-
2
−
2−
NH
formation constants for the 2-NH
as 2-NH -phaH reacted quickly and irreversibly with the Ru(edta)
2
-pha)] > [Ru(edta)(3-NH
2
-pha)] . Species distribution and
2
-pha system were not obtained
2
system to form the nitrosyl adduct. Therefore competing nitrosyl
formation hampered the speciation studies for ternary systems
involving 2-NH -phaH. It is also noteworthy that para-substituted
2
Ru(phenylhydroxamato) complexes were more stable than the
corresponding meta-substituted phenylhydroxamato complexes,
which were in turn more stable than the ortho-substituted
derivatives despite the different electronic properties associated
with the different substituents where the order of stability of
Fig. 2 Structures of [{Ru(H
2
edta)}
2
(l-1,4-bha)] 3, [{Ru(H
2
edta)}
2
-
(
l-1,3-bha)] 4 and [{Ru(H edta)}
2
2
(l-2,6-pyha)] 5.
the ML species was: 4-NMe
2
-pha > bha > 4-NH
2
-pha > 4-Cl-
ESI-MS in the negative mode was used to unequivocally identify
phaH > 3-Me-phaH > 3-NH
Table 2.
The titration curve for the ternary Ru-3-NH -phaH system, as
a representative example, and typical of the Ru-monohydroxamic
2
-pha > 3-Cl-phaH > 2-Cl-pha,
III
the dinuclear Ru -dihydroxamato complexes; mass peaks at 977,
77 and 978 amu were observed for [{Ru(H edta)} (l-1,3-bha)]
978), [{Ru(H edta)} (l-1,4-bha)] (978) and [{Ru(H edta)} (l-
9
(
2
2
2
2
2
2
2
This journal is © The Royal Society of Chemistry 2008
Dalton Trans., 2008, 137–147 | 143

View Article Online
acid systems studied, is shown in Fig. S1 (see ESI†) and is
compared to those for the free ligand 3-NH
2
-phaH and the
−
binary [Ru(Hedta)Cl] . In the ternary system there are three
dissociable protons below pH 10; the first two correspond to
deprotonation of the Hedta ligand and the hydroxamic acid
2
−
leading to [Ru(edta)(3-NH -pha)] and the third ionisation, in
2
weakly alkaline solution, is due to deprotonation of the NH group
of the coordinated hydroxamato giving the dianionic hydroximato
3
−
complex [Ru(edta)(3-NH
The concentration-distribution curves for the ternary Ru-3-
NH -phaH system, again described here as a representative ex-
ample, are shown in Fig. 3 and Fig. 4. The yellow-coloured binary
Ru(edta) complex reacts with 3-NH -phaH from ca. pH 3.3 to give
-pha)] complex, which is the dominant
2
-phaH−1)] .
2
2
2
−
the red [Ru(edta)(3-NH
species between ca. pH 5.3–7.2. [Ru(edta)(3-NH
2
2
−
2
-pha)] has a
maximum concentration at pH 6.4 whereupon deprotonation
of the hydroxamato NH group commences, resulting in the
formation of the purple doubly deprotonated hydroximato com-
3
−
plex [Ru(edta)(3-NH
2
-phaH−1)] , the major species in solution
between ca. pH 7.0–10.0. Above ca. pH 7.5, the hydroxo complex
4
−
[
Ru(edta)(3-NH
2
-phaH−1)(OH)] is observed.
III
III
Fig. 3 Species distribution for Ru -3-NH
2
-phaH, [Ru ] = 2 mM,
III
Ru –3-NH
2
-phaH = 1 : 1.
III
III
Fig. 4 Species distribution for Ru -1,3-bhaH
2
, [Ru ] = 2 mM,
III
Ru –1,3-bhaH
2
= 2 : 1.
Although several examples involving hydroximato coordination
have been cited in the literature, these mainly involve oligonuclear
1
metallacrowns. In addition to our previous report detailing the
1
44 | Dalton Trans., 2008, 137–147
This journal is © The Royal Society of Chemistry 2008

View Article Online
III
14
4−
only examples of Ru hydroxamato and hydroximato complexes,
[{Ru(edta)} (l-1,3-bha)] complex has a slightly higher log b
2
4
−
there are only a handful of reports on deprotonation of hy-
droxamato to hydroximato ligands in mononuclear complexes.
Hydroximato complexes of Cu and V at high pH were identified
by EPR spectroscopy and those of Mo by O and H NMR
spectroscopy. Benzo- and anthranilo-hydroximato manganate
value relative to the [{Ru(edta)} (l-2,6-pyha)] complex, Table 2.
2
The concentration distribution curves for the Ru-1,3-bhaH
2
27
28
system, again as a representative example, are shown in Fig. 4 and
are the first of their kind to be reported in the literature. The yellow-
coloured binary Ru(edta) complex reacts with 1,3-bhaH from
1
7
1
29
2
30
4−
(
IV and III respectively) complexes have also been reported.
ca. pH 4 to give the reddish–brown [{Ru(edta)} (l-1,3-bha)]
2
A more recent report by Hambley and co-workers details an
elegant study whereby, upon manipulation of pH, they were
successful in isolating either the hydroxamato or hydroximato
Co -tpa (tpa is tris(2-methylpyridyl)amine) complexes in the
solid state including the mononuclear hydroximato complexes
complex, which is the dominant species between ca. pH 5.2–8.2.
This species has a maximum concentration at ca. pH 7 whereupon
deprotonation of only one of the two hydroxamato NH groups
2
III
commences. This results in the formation of [{Ru(edta)} (l-
5
−
−
1,3-bhaH )] , with one hydroxamic acid function coordinated
1
III
ꢀ
[
Co(achaH−1)tpa]ClO
and [Co(bhaH−1)tpa]Cl·6H
4
·0.5H
2
O, [Co(pphaH−1)tpa](ClO
4
)
0.5·4H
2
O
to Ru via (O,O ) hydroxamato where the NH remains intact
while the other is coordinated to the second Ru in the doubly
deprotonated (O,O ) hydroximato form with deprotonated N. This
is the major species in solution above ca. pH 8.2.
III
2
O where achaH−1, pphaH−1 and
ꢀ
bhaH−1 are acetohydroximato, propionhydroximato and benzo-
hydroximato, respectively, and the crystal structures of which
they reported. They also report a crystal structure in which
the asymmetric unit consists of two independent molecules,
with one each of the hydroxamato, [Co(acha)(tpa)] and hydrox-
imato, [Co(achaH−1)(tpa)] forms of the acetohydroxamic acid
5
−
The formation of [{Ru(edta)} (l-1,3-bhaH )] , where one of
2
−1
the two hydroxamato NH groups is deprotonated, was confirmed
by a UV-VIS spectrophotometric study. As can be seen from
Fig. 5, upon increasing pH from 7.5 to 9.3, the colour of the
solution changes from red to purple and the LMCT band corre-
9
ligand.
III
sponding to the hydroxamato O–Ru transition shifts to longer
III
wavelength due to the formation of the new hydroximato com-
The ternary Ru -edta-dihydroxamato systems
5
−
plex [{Ru(edta)}
2
(l-1,3-bhaH−1)] and consistent with previously
The pK
.20) and 2,6-pyhaH
former values of which have not previously been reported, Table 2.
The titration curve for the ternary Ru-1,3-bhaH system, as
a
values for the dihydroxamic acids, 1,3-bhaH
2
(8.04 and
reported metal hydroxamato to hydroximato conversion. This
2
−
9
2
(2.34, 7.81 and 9.09) were calculated, the
shift was not observed for [Ru(edta)(N-Me-acha)] , as previously
reported, where such a deprotonation could not occur. Beyond
14
2
pH 8.5, there is no further shift in kmax, indicative of the presence of
5
−
a representative example, and typical of the dihydroxamic acids
studied, is shown in Fig. S2 (see ESI†) and is compared to that
of the free ligand 1,3-bhaH
these studies, there was a 4 : 1 excess of Ru to dihydroxamic
only one species i.e. [{Ru(edta)} (l-1,3-bhaH )] . The presence
2
−1
of this species was further supported by our speciation studies,
Fig. 5.
−
2
and the binary [Ru(Hedta)Cl] . In
III
III
acid used to ensure that all ligand present reacted with the Ru .
Two deprotonation processes were observed for the ligand; upon
titration with KOH, two protons are released, one from each of
the hydroxamato OH groups, Table 2. Four dissociable protons are
observed in the ternary Ru-edta-1,3-bhaH system below pH 7, the
2
first two of which correspond to deprotonation of the Hedta ligand
followed by deprotonation of the two hydroxamato moieties of
4
−
1
,3-bhaH
2
leading to the formation of [{Ru(edta)}
2
(l-1,3-bha)] ,
the major species present in solution between pH 5.2–8.2, Fig. 4.
Under weakly alkaline conditions, deprotonation of one of the two
NH’s of the coordinated 1,3-bha is observed giving the novel triply
deprotonated trianionic hydroximato complex [{Ru(edta)}
2
(l-1,3-
5
−
III
III
bhaH−1)] .
Fig. 5 UV-VIS spectra of K[Ru (Hedta)Cl]·2H
2
O + 1,3-bhaH
2
, [Ru ] =
III
The pK
{Ru(edta)}
a
values for the Ru dihydroxamato complexes,
2 lM, [1,3-bhaH
2
] = 1 mM, initial volume 5 mL, titrated with 0.5 M
4
−
4−
KOH; spectra 1: pH 7.5; spectra 2: 7.9; spectra 3: pH 8.5; spectra 4: 9.3.
[
2
(l-1,3-bha)] and [{Ru(edta)}
2
(l-2,6-pyha)] , cor-
4−
5−
[
k
{Ru(edta)}
2
(l-1,3-bha)] , kmax = 534 nm; [{Ru(edta)}
2
(l-1,3-bhaH−1)] ,
responding to deprotonation of hydroxamato NH protons were
found to be 8.21 and 7.76, respectively, Table 2. These values are
higher compared to the Ru monohydroxamato complexes due to
the increased overall negative charge of their conjugate acids i.e.
max = 554 nm.
II
Ru -nitrosyl complexes
4
- in the case of the dihydroxamato complexes, [{Ru(edta)}
2
(l-
4
−
diha)] compared to 2- for the monohydroxamato complexes,
Reaction of K[Ru(Hedta)Cl]·2H
2
O with achaH, bhaH, 2-, 3-
2
−
[
Ru(edta)(monoha)] . With the exception of [{Ru(edta)}
bha)] (which could not be investigated potentiometrically due to
poor aqueous solubility although the complex [{Ru(H edta)} (l-
,4-bha)]·4H O was isolated in the solid state) the stability
constants of the dihydroxamato complexes of general formula
2
(l-1,4-
or 4-NH -phaH, 2-, 3- or 4-Cl-phaH and 2-, 3- or 4-Me-phaH
2
4
−
and 2,6-pyhaH on heating, resulted in the facile formation of
the brown Ru -nitrosyl adduct of formula K[Ru(Hedta)(NO)Cl]
regardless of the hydroxamic acid used. Elemental analysis, IR,
2
II
2
2
1
2
1
13
H and C NMR spectrum are consistent with the formulation
4
−
II
[{Ru(edta)}
2
(l-diha)] or M
2
L were obtained pH-metrically. The
K[Ru (Hedta)(NO)Cl]·H
2
O, and concur with previously reported
This journal is © The Royal Society of Chemistry 2008
Dalton Trans., 2008, 137–147 | 145

View Article Online
II
22
obs and kmax for [Ru(edta)(monoha)]2− where monoha = 2-, 3-,
examples of Ru -edta-NO complexes in the literature. The IR
spectra of K[Ru(Hedta)(NO)Cl]·H O contains a distinctive mNO at
894 cm . ESI-MS in the negative mode was used to unequivo-
Table 3
k
4
-NH -pha, acha, bha and 3-Mepha
2
2
−
1
1
−
1
k
max/nm
kobs/min
II
II
−
cally identify the Ru -NO complex, [Ru (Hedta)(NO)Cl] ; a mass
peak at 456 amu with the characteristic Ru isotopic abundance
was observed. Interestingly, we found that the N-substituted
hydroxamic acid, N-Me-bhaH, lacking the NH hydroxamato
proton, regardless of the reaction conditions, did not release NO.
In contrast, 1,3- and 1,4-bhaH
K[Ru(Hedta)Cl] under reflux, predominately gave the corre-
sponding dinuclear Ru -dihydroxamato complexes and while the
2
2
2
−
−
−
[Ru(edta)(2-NH -pha)]
Ru(edta)(4-NH
Ru(edta)(3-NH
Ru(edta)(acha)]
Ru(edta)(bha)]
2
525
516
485
455
481
483
0.1381
−3
−3
−3
−3
−3
[
[
[
[
2
-pha)]
-pha)]
7.7 × 10
7.2 × 10
2.3 × 10
1.6 × 10
1.3 × 10
2
2
−
2−
2
−
,
when reacted with
[Ru(edta)(3-Me-pha)]
2
III
III
NH
2
-pha) and Ru (edta)(4-NH -pha) complexes with a view
2
nitrosyl adduct could be isolated, it was obtained as the minor
product.
to examining the effect of substituent position on the rate. A
summary of the results is given in Table 3.
The UV-VIS spectra corresponding to the Ru(edta)(3-NH -pha)
2
system and described here as a representative example, Fig. 6,
exhibits a decrease in the LMCT band at 485 nm with time
Nitrosyl abstraction from hydroxamic acids
As previously reported by us, K[Ru(Hedta)Cl] abstracts NO from
III
2−
and is indicative of conversion of [Ru (edta)(3-NH
[
2
-pha)] to
Ru (edta)(NO)Cl] . Spectra were recorded at 15 min intervals
until such time as there was no further spectral change i.e. at time
II
hydroxamic acids on heating to form the stable Ru -nitrosyl
II
−
II
complex K
2
[Ru (edta)(NO)Cl] and the corresponding carboxylic
acid. We proposed that this reaction involves initial formation of a
t = 435 min in this case. A plot of ln(Abs
t
−Abs
∞
) versus time gives
III
2−
[
Ru (edta)(hydroxamato)] complex that undergoes nucleophilic
−3
−1
a straight line with a kobs = 7.2 × 10 min , where kobs represents
a combination of keq and k shown in Scheme 2. Of the hydroxamic
acids studied, the decrease in the LMCT band of [Ru(edta)(2-
attack by hydroxide on the hydroxamato carbonyl carbon, to give
a tetrahedral intermediate from which hydroxylamine (a known
source of NO) is eliminated with subsequent formation of the
2−
−1
NH
2
-pha)] was fastest with a kobs = 0.1381 min , most probably
II
II
2−
Ru -nitrosyl complex [Ru (edta)(NO)Cl] . We found that the
due to the presence of the amino group at the 2-position relative to
the hydroxamato moiety, which can partake in hydrogen bonding
thereby stabilising the proposed tetrahedral intermediate in the
mechanism described earlier.
optimum pH for nitrosyl formation was at ca. pH 4.5. Above
III
this pH, the Ru hydroximato complex (via deprotonation of
the hydroxamato N) starts to form and, as previously reported
by us, this species cannot release NO under these experimental
14
conditions. However, it is noteworthy that, under physiological
conditions, hydroxamic acids have been shown to release NO via
3
a NO-mediated Fe-haem containing guanylate cyclase pathway.
UV-VIS spectroscopic investigation
We decided to carry out a UV-VIS spectroscopic investigation
to determine the rate of NO release from the aliphatic aceto-
hydroxamic acid, the aromatic benzohydroxamic acid and from
substituted benzohydroxamic acids where the substituents were
either electron-withdrawing (–Cl) or electron-releasing (–NH
2
and/or –Me). Of the hydroxamic acids reported in this paper,
all but the chloro derivatives could be investigated for NO release.
Whilst they were sufficiently soluble for speciation studies, this was
not the case for our kinetic investigation where the required ratio
of ligand to Ru was 10 : 1. In any case, the rate of NO release
from a total of 6 hydroxamic acids was investigated.
Fig. 6 UV-VIS spectra of the Ru(edta)-3-NH
2
-phaH system where
III
III
III
[
Ru ] = 2 mM and [Ru ]–[3-NH
2
-phaH] = 1 : 10. Spectra recorded
◦
at 15 min intervals, pH 4.50, 50 C.
We reacted K[Ru(Hedta)Cl] with achaH, bhaH, 3-NH
and 3-Me-phaH in ten-fold excess at pH 4.50 and at 50
2
-phaH
◦
C
in acetic acid–sodium acetate buffer and followed the reaction
by UV-VIS spectroscopy. The formation of the ternary complex
2
−
[
Ru(edta)(monoha)] is marked by a colour change from yellow to
III
red and the appearance of a hydroxamato ligand to Ru charge-
transfer band. As the reaction proceeds at this pH, this LMCT
band diminishes with time with a marked colour change from red
to brown indicative of conversion of the Ru -hydroxamato com-
plex to the Ru -nitrosyl adduct, [Ru (edta)(NO)Cl] , Scheme 2,
Scheme 2
III
II
II
−
III
Under the stated conditions, NO release from the Ru -
acetohydroxamato complex is faster than that of the benzo-
hydroxamato derivative, not surprising given the fact that the
phenyl ring of the benzohydroxamato is electron withdrawing. The
and consistent with our solid-state study. Because NO release from
III
the Ru (edta)(3-NH -pha) complex proved fastest, we decided to
2
III
further investigate the rate of NO release from the Ru (edta)(2-
1
46 | Dalton Trans., 2008, 137–147
This journal is © The Royal Society of Chemistry 2008

View Article Online
2
−
[
Ru(edta)(3-NH
2
pha)] complex releases NO over 5 times faster
6 E. Farkas, D. Batka, E. Edit Csap o´ , P. Bugly o´ , W. Haase and D. Sanna,
2
−
Polyhedron, 2007, 26, 543–554.
D. A. Brown, N. J. Fitzpatrick, H. Muller-Bunz and A. T. Ryan, Inorg.
Chem., 2006, 45, 4497–4507.
than the 3-Me-substituted derivative [Ru(edta)(3-Mepha)] , sug-
gesting that mesomeric in addition to inductive effects have a role
to play.
7
8 T. W. Failes and T. W. Hambley, J. Inorg. Biochem., 2007, 101, 396–403.
T. W. Failes and T. W. Hambley, Dalton Trans., 2006, 1895–1901.
9
1
1
1
0 V. L. Pecoraro, A. J. Stemmler, B. R. Gibney, J. J. Bodwin, H. Wang, J.
W. Kampt, and A. Barinski, Metallocrowns: A New Class of Molecular
Recognition Agents, Wiley-Interscience, New York, 1996.
1 T. N. Parac-Vogt, A. Pacco, P. Nockemann, S. Laurent, R. N. Muller,
M. Wickleder, G. Meyer, L. Vander Elst and K. Binnemans, Chem.–
Eur. J., 2005, 12, 204–210.
Conclusions
III
In this paper we report the first examples of dinuclear Ru com-
plexes with bridging dihydroxamato and dihydroximato ligands of
general formula [{Ru(H
2
edta)}
2
(l-diha)] and [{Ru(H
2
edta)}
2
(l-
2 C. Mulcahy, F. M. Dolgushin, K. A. Krot, D. Griffith and C. J.
Marmion, Dalton Trans., 2005, 1993–1998.
−
1
III
dihaH−1)] , respectively. A series of mononuclear Ru hy-
droxamato and hydroximato complexes of general formula
13 T. Beissel, R. E. Powers, T. N. Parac and K. N. Raymond, J. Am. Chem.
Soc., 1999, 121, 4200–4206.
14 J. Comiskey, E. Farkas, K. A. Krot-Lacina, R. Pritchard, C. A.
McAuliffe and K. B. Nolan, J. Chem. Soc., Dalton Trans., 2002, 4243–
−
1
[
Ru(H
2
edta)(monoha)] and [Ru(H
2
edta)(monohaH−1)] , respec-
III
tively, as well as the first example of a Ru -N-aryl aromatic
hydroxamato derivative are reported. We also detail a UV-VIS
spectroscopic investigation where we monitored the decrease
in LMCT absorbance of a series of Ru -monohydroxamato
complexes with time, gaining a better insight into the NO-releasing
properties of aliphatic and aromatic hydroxamic acids.
4
249.
15 R. M. Coates and S. J. Firsan, J. Org. Chem., 1986, 51, 5198–5209.
16 J. Jolley, C. J. Campbell, A. Casteneiras, A. I. Yanovsky and K. B.
Nolan, Polyhedron, 1999, 18, 49–55.
1
1
III
7 G. Gran, Acta Chem. Scand., 1950, 4, 559–577.
8 H. Irving, M. G. Miles and L. D. Pettit, Anal. Chim. Acta, 1967, 38,
4
75–488.
1
2
9 A. Sabatini, A. Vacca and P. Gans, Coord. Chem. Rev., 1992, 120,
89–405.
0 B. Riet, G. L. Wampler and H. L. Elford, J. Med. Chem., 1979, 22,
89–592.
Acknowledgements
3
We gratefully acknowledge Enterprise Ireland, EU COST D20,
EU COST D39 and the Programme for Research in Third Level
Institutions (PRTLI), administered by the HEA for funding. We
thank Dr Dilip Rai (School of Chemistry & Chemical Biology,
Science Education & Research Centre, UCD, Belfield, Dublin 4,
Ireland) for MS analysis. We sincerely thank Johnson Matthey for
5
21 D. A. Brown, R. A. Coogan, N. J. Fitzpatrick, W. K. Glass, D. E.
Abukshima, L. Shiels, M. Ahlgren, K. Smolander, T. T. Pakkanen, T.
A. Pakkanen and M. Perakyla, J. Chem. Soc., Perkin Trans. 2, 1996,
(
12), 2673–2679.
2
2 A. A. Diamantis and J. V. Dubrawski, Inorg. Chem., 1981, 20, 1142–
1150.
III
23 T. Matsubara and C. Creutz, Inorg. Chem., 1979, 18, 1956–1966.
2
a generous loan of Ru salts.
4 F. N. Rein, R. C. Rocha and H. E. Toma, J. Inorg. Biochem., 2001, 85,
1
55–166.
´
References
25 J. Switek-Kozłowska, E. Gumienna-Kontecka, A. Dobosz, I. A.
Golenya and I. O. Fritsky, J. Chem. Soc., Dalton Trans., 2002, 24,
4639–4643.
26 Y. Bai, D. Guo, C.-Y. Duan, D.-B. Dang, K.-L. Pang and Q.-J. Meng,
Chem. Commun., 2004, 186–187.
27 E. Farkas, E. Kozma, M. Petho, K. M. Herlihy and G. Micera,
Polyhedron, 1998, 17, 3331–3342.
1
C. J. Marmion, D. Griffith and K. B. Nolan, Eur. J. Inorg. Chem., 2004,
5, 3003–3016.
1
2
3
R. Codd, Coord. Chem. Rev., 2007, DOI: 10.1016/j.ccr.2007.08.001.
C. J. Marmion, T. Murphy, J. R. Docherty and K. B. Nolan, Chem.
Commun., 2000, 1153–1154.
4
5
D. Griffith, K. Lyssenko, P. Jensen, P. E. Kruger and C. J. Marmion,
Dalton Trans., 2005, 956–961.
28 A. Dessi, G. Micera, D. Sanna and L. S. Erre, J. Inorg. Biochem., 1992,
48, 279–287.
29 E. Farkas, H. Cs o´ ka and I. T o´ th, Dalton Trans., 2003, 1645–1652.
30 R. Mukhopadhyay, Ashim B. Chatterjee and R. Bhattacharyya,
Polyhedron, 1992, 11, 1353–1358.
S. K. Maiti, K. M. Abdul Malik, S. Gupta, S. Chakraborty, A. K.
Ganguli, A. K. Mukherjee and R. Bhattacharyya, Inorg. Chem., 2006,
4
5, 9843–9857.
This journal is © The Royal Society of Chemistry 2008
Dalton Trans., 2008, 137–147 | 147