Phosphonioalkylthiosulfate zwitterions - New masked thiol ligands for the formation of cationic functionalised gold nanoparticles

Article abstract of DOI:10.1039/b610480k

We report the synthesis and structural characterisation of a new family of stable phosphonioalkylthiosulfate zwitterions, R₃P ⁺(CH₂)_nS₂O₃^- (R = Ph or Bu, n = 3,4,6, 8 or 10) which behave as cationic masked thiolate ligands with applications in the functionalisation of gold nanoparticles, having potential as new diagnostic biorecognition systems. The ligands were prepared by treatment of ω-bromoalkylphosphonium salts with sodium thiosulfate. The crystal and molecular structures of the zwitterions (R = Ph, n = 3) and (R = Bu, n = 3) were determined. A series of phosphonioalkanethiolate-capped gold nanoparticles dispersed in water was prepared by borohydride reduction of potassium tetrachloroaurate in the presence of the zwitterions in a dichloromethane-water system. UV-visible spectroscopy and scanning transmission electron-microscopy indicated that capped nanoparticles of ca. 5 nm diameter were present. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b610480k

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Phosphonioalkylthiosulfate zwitterions—new masked thiol ligands for the
formation of cationic functionalised gold nanoparticles
Yon Ju-Nam,a Neil Bricklebank,*a David W. Allen,a Philip H. E. Gardiner,a Mark E. Lightb and
Michael B. Hursthouseb
Received 20th July 2006, Accepted 10th October 2006
First published as an Advance Article on the web 27th October 2006
DOI: 10.1039/b610480k
We report the synthesis and structural characterisation of a new family of stable
phosphonioalkylthiosulfate zwitterions, R3P+(CH2)nS2O3 (R = Ph or Bu, n = 3,4,6, 8 or 10) which
−
behave as cationic masked thiolate ligands with applications in the functionalisation of gold
nanoparticles, having potential as new diagnostic biorecognition systems. The ligands were prepared by
treatment of x-bromoalkylphosphonium salts with sodium thiosulfate. The crystal and molecular
structures of the zwitterions (R = Ph, n = 3) and (R = Bu, n = 3) were determined. A series of
phosphonioalkanethiolate-capped gold nanoparticles dispersed in water was prepared by borohydride
reduction of potassium tetrachloroaurate in the presence of the zwitterions in a dichloromethane–water
system. UV-visible spectroscopy and scanning transmission electron-microscopy indicated that capped
nanoparticles of ca. 5 nm diameter were present.
Introduction
There is much current interest in the development of receptor-
functionalised metal and semiconductor nanoparticles which
are able to recognise and interact with specific biomolecules.
Such systems are expected to form the basis of new diagnostic
biosensor technologies and novel therapeutic agents. The most
widely studied systems are based on gold. The modification of the
surface of gold nanoparticles with various functionalised thiols
containing reporter groups makes them versatile systems and
opens a range of possibilities for the specific recognition of other
molecules, and in the design of optical sensor systems based on
the consequent modifications to the surface plasmon resonance
properties of the gold nanoparticle.1,2 However, comparatively few
such reported thiols involve a cationic head group which offers
the ability to bind negatively charged analytes. The fluorescent
ethidium thiolate (1) has been employed in the design of a gold
cluster system used to bind DNA.3 Gold nanoparticles bearing
the imidazoliumalkane thiol (2) have been shown to act as
simple colourimetric anion sensors.4 Gold nanoparticles modified
with simple alkylammonium alkanethiols have also been shown
to bind to DNA.5,6 Rotello and co-workers7 synthesised gold
nanoparticles functionalised with a mixture of octanethiol and 11-
trimethylammonium-undecanethiol, so-called mixed monolayer
protected gold clusters (MMPCs), and showed that these MMPCs
with trimethylammonium cationic head groups on the surface
can interact electrostatically and bind with the negatively charged
phosphate backbone of 37mer duplex DNA. They also studied the
ability of these MMPCs to inhibit DNA transcription in vitro, their
utilisation in gene delivery into cells and as transfection vectors.8
Our own interest in the chemistry of phosphonium systems
has led us to design and synthesise a family of novel phospho-
nioalkylthiosulfate ligands which can be used to functionalise
the surface of gold nanoparticles. The phosphonium moiety
offers a number of advantages including biocompatibility and
the relative ease of preparing a wide range of derivatives, e.g.,
phosphonium analogues having a fluorescent reporter head group
or phosphine oxide derivatives having the ability to form hydrogen-
bonded complexes with biomolecules. The cationic phospho-
nioalkanethiol (3) has been shown to have a remarkable ability to
pass through mitochondrial membranes and to accumulate inside
the mitochondrion, with consequent influence on the chemistry of
the host cell.9 Thiobutyltriphenylphosphonium bromide was used
successfully by Murphy et al.10 to identify changes in the redox
state of mitocondrial thiol compounds during oxidative stress.
They demonstrated that the lipophilic triphenylphosphonium
cation interacts with the negatively charged mitochondrial matrix
causing its accumulation inside the isolated mitochondria and in
mitochondria from living cells.11 These workers also detected the
formation of disulfide bonds due to reaction of the thiol groups
in the matrix with the mitochondrial protein and low-molecular
weight thiols during the oxidative stress. This showed that such
salts containing lipophilic cations can be used to determine
mitochondrial dysfunction.10–12 Thiol (3) has been prepared from
the hydrolysis of the related thioacetate salt (4) and shown to
undergo gradual oxidation in air to form the disulfide-bridged
aBiomedical Research Centre, Sheffield Hallam University, Howard St.,
Sheffield, UK S1 1WB
bDepartment of Chemistry, The University of Southampton, Highfield,
Southampton, UK SO17 1BJ. E-mail: N.Bricklebank@shu.ac.uk
This journal is
The Royal Society of Chemistry 2006
Org. Biomol. Chem., 2006, 4, 4345–4351 | 4345
©

View Article Online
system (5).13 As gold-containing drugs, such as auranofin and
triethylphosphine gold(I) chloride, have demonstrated their an-
titumour effects,14 there is also an interest in the possibility of
studying the extent to which phosphonioalkanethiol-capped gold
nanoparticles might be incorporated into cells and exert new
biological effects. Here we report our studies of the synthesis
and characterisation of a family of phosphonioalkylthiosulfate
zwitterions and their in situ reaction with reduced gold salts to
form cationic-functionalised gold nanoparticles.
being sources of the phosphonioalkanethiolates in the synthesis
of the functionalised gold nanoparticles.
The shorter alkyl chain compounds are crystalline solids and
are soluble in polar organic solvents. In addition, the tributylphos-
phoniopropylthiosulfate (9F, R = Bu, n = 3) is also water-soluble,
making it attractive for studies in biological media.
Analytical data and electrospray mass spectrometry support the
formulation of these compounds as phosphonioalkylthiosulfate
zwitterions. When studied by ESMS in negative ion mode, all
compounds exhibited a well-defined molecular ion, whereas in
positive ion mode, an ion corresponding to M + Na was observed.
The synthesis of a trimethylphosphonium analogue of the triph-
enylphosphoniopropylthiosulfate zwitterion was also attempted
by following the same synthetic route. However, the step in-
volving treatment of the intermediate 3-bromoalkylphosphonium
salt with sodium thiosulfate resulted in the cleavage of the
trimethylphosphonium group.
Structural characterisation of phosphonioalkylthiosulfate
zwitterions
Results and discussion
We have carried out an X-ray structural study of the triph-
enylphosphoniopropylthiosulfate (9A, R = Ph, n = 3) which
confirms the expected structure (Fig. 1). Crystal data and structure
refinement details are presented in Table 1. Selected bond lengths
and bond angles are presented in Table 2(a). There are no
intramolecular interactions between the cationic head group and
the thiosulfato group which could lead to the formation of a
quasi-7-membered cyclic structure from the electrostatic attraction
of P+ with O−. Similarly, intermolecular electrostatic effects do
not appear to dominate the way in which the dipolar units
pack in the crystal, which is rather unusual. Along the [101]
direction the individual units pack in a head to head manner
in which ‘supramolecular edge to face’ interactions17 between the
triphenylphosphonio units and possible weak C–H · · · O hydrogen
Synthesis of phosphonioalkylthiosulfate zwitterions
The synthesis of the series of triphenyl- and tributyl-phos-
phonioalkylthiosulfate zwitterions is shown in Scheme 1. The
design of our ligands has been influenced by the work of Lukkari
et al.15 and Murray et al.16 who described the generation of
alkanethiolate-protected gold surfaces and clusters from Bunte
salts such as the sodium S-dodecylthiosulfate (6), which were
identical to those obtained directly from the use of the free thiols.
The sulfur–sulfur bond of the Bunte salt undergoes cleavage
with loss of sulfite ion as a result of the interaction with the
gold surface. Such compounds are easily prepared by treatment
of a bromoalkane with sodium thiosulfate in aqueous ethanol.
Adapting this approach, we have converted readily accessible
x-bromoalkylphosphonium salts (8) into a series of phospho-
nioalkylthiosulfate zwitterions (9A–9E, R = phenyl, n = 3, 4,
6, 8, 10; 9F, R = butyl, n = 3), which act as cationic masked thiols,
˚
bonds (ca. 2.5 A) seem to dominate. Along the [10−1] direction an
intermolecular ‘head to tail’ arrangement is found, whereas along
the [010] direction, the individual units associate as ‘head to tail’
dimers.
Scheme 1
4346 | Org. Biomol. Chem., 2006, 4, 4345–4351
This journal is
The Royal Society of Chemistry 2006
©

View Article Online
Table 1 Crystal data and structure refinement for 3-triphenylphosphoniopropylthiosulfate and 3-tributylphosphoniopropylthiosulfate
Compound
9A
9F
Empirical formula
Formula weight
Crystal system
Space group
C21H21O3PS2
416.47
Monoclinic
P21/n
11.6475(3)
14.2692(3)
12.0730(3)
106.561(1)
1923.30(8)
4
1.438
0.380
872
Colourless block
0.15 × 0.08 × 0.08
3.39–25.02
6267
C15H33O3PS2
356.50
Monoclinic
P21/n
˚
a/A
9.0500(3)
˚
b/A
14.3012(4)
15.0732(6)
96.326(2)
1938.98(11)
4
1.221
0.364
776
Colourless block
0.10 × 0.10 × 0.03
3.07–25.02
23499
˚
c/A
b/◦
Volume/A
3
˚
Z
D
calc/Mg m−3
)
Absorption coefficient/mm−1
F(000)
Crystal
Crystal size/mm3
h range for data collection/◦
Reflections collected
Independent reflections
Completeness to h = 25.02◦
Max. and min. transmission
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [F2 > 2r(F2)]
R indices (all data)
3381 [Rint = 0.0434]
3406 [Rint = 0.0797]
99.7%
99.7%
0.9924 and 0.9630
3381/0/244
1.043
0.9892 and 0.9645
3406/39/194
1.042
R1 = 0.0416, wR2 = 0.0994
R1 = 0.0594, wR2 = 0.1487
R1 = 0.0565, wR2 = 0.1068
R1 = 0.0775, wR2 = 0.1589
−3
−3
˚
˚
Largest diff. peak and hole
0.311 and −0.444 e A
1.078 and −0.633 e A
Fig. 1 Molecular structure of 3-triphenylphosphoniopropylthiosulfate (9A)-an ORTEP drawing with 30% probability ellipsoids.
Similarly, an X-ray structural study of the 3-tributylphos-
phoniopropylthiosulfate (9F, R = Bu, n = 3) confirmed the
expected structure (Fig. 2). Crystal data and structure refinement
details are presented in Table 1. Selected bond lengths and bond
angles are presented in Table 2(b). Fig. 3 shows possible hydrogen
bonding between C–H bonds a to the phosphonium centre and
the thiosulfato oxygen atoms which influence the packing of the
molecules in the unit cell. The structural parameters for these
hydrogen bond interactions are presented in Table 3.
present in organic disulfides and alkylthiosulfates (6), yielding
organic thiolates which then bind to the surface of the particle.1,15,16
Consequently, we were confident that the S–S bond of the
phosphonioalkylthiosulfate zwitterions would be cleaved under
the reductive conditions used for the synthesis of the capped
nanoparticles, to form the related phosphonioalkylthiolates, e.g.,
(10), (Scheme 2). This was confirmed by sodium borohydride
reduction of the salt (9A), the resulting phosphonioalkylthiolate
being trapped with iodomethane to form the salt (11). NMR
spectroscopy and electrospray mass spectrometry supported the
formulation of this compound. When studied by MALDI TOFMS
in positive ion mode, (accurate mass analysis), an ion cor-
responding to the 3-methylthiopropylphosphonium cation was
observed.
Synthesis of phosphonium-monolayer protected gold clusters
Previous studies have indicated that gold nanoparticles and
colloidal gold solutions have the ability to cleave the S–S bonds
This journal is
The Royal Society of Chemistry 2006
Org. Biomol. Chem., 2006, 4, 4345–4351 | 4347
©

View Article Online
◦
˚
Table 2 Selected bond lengths [A] and angles [ ] in 3-phosphoniopro-
pylthiosulfates
(a) 3-Triphenylphosphoniopropylthiosulfate 9A
C1–P1
C7–P1
C13–P1
C19–P1
1.795(2)
1.792(2)
1.794(2)
O1–S2
O2–S2
O3–S2
S1–S2
1.4507(19)
1.4442(18)
1.4484(19)
2.1117(9)
1.805(2)
C21–S1
1.820(3)
C20–C19–P1
C20–C21–S1
C7–P1–C1
C7–P1–C13
C1–P1–C13
C7–P1–C19
C1–P1–C19
C13–P1–C19
115.39(17)
114.77(18)
107.97(11)
111.12(11)
110.13(11)
111.92(11)
108.79(11)
106.90(11)
C21–S1–S2
O2–S2–O3
O2–S2–O1
O3–S2–O1
O2–S2–S1
O3–S2–S1
O1–S2–S1
99.77(9)
115.11(12)
113.38(11)
113.15(12)
105.60(7)
101.20(8)
106.97(8)
(b) 3-Tributylphosphoniopropylthiosulfate 9F
P1–C9
P1–C5
P1–C13
P1–C1
1.796(4)
1.798(3)
1.799(4)
S1–S2
S2–O2
S2–O3
S2–O1
2.1030(14)
1.439(3)
1.440(3)
1.441(3)
Fig. 2 Molecular structure of 3-tributylphosphoniopropylthiosulfate
(9F).
1.805(3)
S1–C15
1.805(4)
C9–P1–C5
C9–P1–C13
C5–P1–C13
C9–P1–C1
C5–P1–C1
C13–P1–C1
C15–S1–S2
O2–S2–O3
O2–S2–O1
107.56(17)
108.13(18)
110.89(17)
110.16(16)
110.32(18)
109.73(18)
99.78(14)
114.45(18)
113.3(2)
O3–S2–O1
O2–S2–S1
O3–S2–S1
O1–S2–S1
113.90(18)
104.75(14)
102.34(13)
106.67(14)
The phosphonioalkanethiolate-capped gold nanoparticles were
synthesised in a two phase liquid–liquid system, following the
methods developed by Brust18 and Murray,16 via reduction of
potassium tetrachloroaurate in biphasic media with an excess
of sodium borohydride, with two variations based on the use of
dichloromethane–water instead of toluene–water as the biphasic
system, and without the use of tetraoctylammonium bromide to
−
aid transfer of the AuCl4 ions to the organic solvent, as it was
felt that this role would be fulfilled by the phosphoniothiosulfate
zwitterion. The preparation technique was the same for 3-
triphenylphosphoniopropylthiosulfate (9A), 6-triphenylphos-
phoniohexylthiosulfate
(9C),
8-triphenylphosphoniooctyl-
Fig. 3 Intermolecular contacts showing possible hydrogen bonding
between C–H bonds a to the phosphonium centre and thiosulfato oxygen
atoms in 3-tributylphosphoniopropylthiosulfate.
thiosulfate (9D), 10-triphenylphosphoniodecylthiosulfate (9E),
and tributylphosphoniopropylthiosulfate (9F) zwitterions and
was as follows. A solution of the zwitterion was prepared in
dichloromethane (DCM) and solid potassium tetrachloroaurate
(0.5 mol equiv.) was then added to the solution. This was
vigorously stirred for 10 minutes until the gold salt was totally
dissolved. The reduction was carried out by adding dropwise a
freshly prepared aqueous solution of sodium borohydride with
Table 3 Intermolecular contacts for hydrogen bonding between C–H bonds a to the phosphonium centre and thiosulfato oxygen atoms in 3-
tributylphosphoniopropylthiosulfate 9F
Donor
H
Acceptor
Symm
D–H
H · · · A
D · · · A
D–H · · · A
C(1)
C(5)
C(9)
C(9)
C(13)
H(1A)
H(5B)
H(9A)
H(9B)
H(13B
O(2)
O(1)
O(2)
O(3)
O(3)
$1
$2
$1
$2
$2
0.99
0.99
0.99
0.99
0.99
2.44
2.44
2.39
2.45
2.54
3.2657
3.4173
3.2529
3.2929
3.3672
140
171
146
142
141
$1 = 1 − x, −y, 1 − z, $2 = −1/2 + x, 1/2 − y, −1/2 + z, P1 · · · O2 = 3.744(13) $1, P1 · · · O3 = 3.541(12) $2, P1 · · · O1 = 4.730(16).
4348 | Org. Biomol. Chem., 2006, 4, 4345–4351 This journal is The Royal Society of Chemistry 2006
©

View Article Online
Scheme 2
vigorous stirring. After 24 hours, the stirring was stopped, the
aqueous layer separated and purified by three DCM extractions
so as to remove the excess of capping agent. All the extracts
were monitored by TLC, using methanol (10%): dichloromethane
(90%) as mobile phase. A total removal of the excess organic
ligand was observed by TLC after the third DCM extraction.
When the tetrachloroaurate was added to the solution of the
zwitterion in DCM, the stirring organic solution turned yellow,
and then became dark purple–blue after the NaBH4 addition,
indicating that the reduction had taken place. In the case of the
triphenylphosphonioalkylthiosulfate (n = 3, 6, and 8), when the
stirring was stopped after 24 hours, the DCM layer was colourless
and the aqueous phase was dark purple–blue, indicating that
phosphonioalkylthiolate-capped nanoparticles were present in the
aqueous phase (Scheme 3).
nanoparticles reported in the literature.19 The solution of the gold
nanoparticles functionalised with triphenylphosphoniopropylth-
iosulfate zwitterion was also investigated by scanning transmission
electron microscopy (STEM). Highly uniform spherical nanopar-
ticles of ca. 5 nm can be observed in the STEM image (Fig. 5),
supporting the information given by the UV-visible spectrum.
The colloidal solutions presented good stability over 4 months
at room temperature. The solutions were monitored by UV-visible
spectroscopy and no changes were observed in their spectra during
this period.
When
10-triphenylphosphoniodecylthiosulfate
and
3-
tributylphosphoniopropylthiosulfate were used, dark blue
particles of aggregated colloidal gold were observed at the
interface between the aqueous and organic phases, showing no
affinity for either the dichloromethane or water. It would appear
that as the carbon chain length increases to more than 8 in the
triphenylphosphonium ligands, the formation of phosphonium
monolayer-protected gold colloids stable in an aqueous medium
becomes more difficult. Replacing the triphenylphosphonium
cationic group by tributylphosphonium group, also destabilises
the nanoparticles.
Evidence for the formation of gold nanoparticles was provided
by UV-visible spectroscopy. A broad band centred at 520 nm was
observed in the aqueous phase in the dark purple–blue solutions
containing gold nanoparticles functionalised with 9A, 9C and 9D
(Fig. 4), indicating that the particle size is between 5–10 nm in
diameter, according to the values for other thiolate-capped gold
Fig. 4 UV-visible absorption spectra of the aqueous phases obtained
in the syntheses of phosphonium-MPCs in a two-phase liquid–liquid
system in presence of the triphenylphosphoniopropylthiosulfate (Solution
A), triphenylphosphoniohexylthiosulfate (Solution B), and triphenylphos-
phoniooctylthiosulfate (Solution C) zwitterions as the precursors of the
protecting ligands.
Scheme 3
This journal is
The Royal Society of Chemistry 2006
Org. Biomol. Chem., 2006, 4, 4345–4351 | 4349
©

View Article Online
tems “QStar-Pulsar-i” hybrid quadrupole time of flight LCMS-
MS instrument. UV-visible spectra of aqueous colloidal solutions
were obtained on an ATI UNICAM UV2 spectrometer. Analytical
thin layer chromatography (TLC) was performed on Merck silica
gel 60F254 plates using 90 : 10 dichloromethane : methanol as eluent
system. Elemental analyses were carried out by MEDAC Ltd.
Synthesis of the series of triphenyl- and
tributyl-phosphonioalkylthiosulfate zwitterions
The synthesis of the series of triphenyl- and tributyl-
phosphonioalkylthiosulfate zwitterions is shown in Scheme 1.
All the compounds were generated by the reaction of triph-
enylphosphine or tributylphosphine (3.8 mmol) with the appro-
priate bromo-alcohol (15 mmol) in acetonitrile under reflux for
four hours, to obtain the corresponding hydroxyalkylphospho-
nium salts (7). The salts (7) were dissolved in HBr (48%) and heated
under reflux for five hours to obtain the bromoalkylphosphonium
salts (8). Finally, a series of phosphonioalkylthiosulfate zwitteri-
ons (9) was prepared by treatment of the salts (8) (1 mol) with
sodium thiosulfate (1.5 mol) in aqueous ethanol under reflux for
five hours. Progress of the reactions was monitored by TLC, using
20% methanol : 80% dichloromethane as mobile phase. All the
compounds (8) and (9) were obtained by dichloromethane extrac-
tion of the reaction mixtures and initially purified by trituration
with dry diethyl ether. Only the reaction of tributylphosphine with
the corresponding bromo-alcohols was performed under nitrogen.
The 4-triphenylphosphoniobutylthiosulfate (9B) was prepared
from the commercial (4-bromobutyl)triphenylphosphonium bro-
mide.
3-Triphenylphosphoniopropylthiosulfate (9A). Colourless crys-
tals, mp 240–243 ◦C. Found: C, 60.53; H, 5.11; C21H21O3PS2
requires: C, 60.56; H, 5.08%. ESMS 417 [M + H+], 439 [M +
Na+], 855 [2M + Na+]. d 31P NMR (CDCl3–DMSO) = 23.2 ppm;
d 1H NMR (CDCl3–DMSO) = 1.6 (2H, m), 2.6 (2H, m), 3.1 (2H,
m), 7.2–7.3 (15H, m) ppm.
4-Triphenylphosphoniobutylthiosulfate (9B). Colourless crys-
tals, mp 256–260 ◦C. Found: C, 61.24; H, 5.55; C22H23O3PS2
requires: C, 61.38; H, 5.38%. ESMS 431 [M + H+], 453 [M +
Na+], 883 [2M + Na+]. d 31P NMR (CDCl3–DMSO) = 23.6 ppm;
d 1H NMR (CDCl3–DMSO) = 1.6 (2H, m), 2.2 (2H, m), 2.7 (2H,
t), 3.05 (2H, m), 7.3–7.5 (15H, m) ppm.
Fig. 5 STEM micrograph of the gold nanoparticles functionalised with
triphenylphosphoniopropylthiosulfate zwitterion.
Conclusion
Functionalisation of the surface of metal nanoparticles is essential
for the development of these species for use in biomolecular
recognition or as novel therapeutic agents. In addition to providing
specific receptor sites, the functionalising ligand should also
impart the characteristics of organic molecules to the metal
nanoparticle; i.e. solubility in various solvents, which allows them
to be studied using conventional spectroscopic techniques.
Cationic-functionalised nanoparticles have demonstrated ver-
satility in a number of biomedical applications, including trans-
fection vectors and DNA surface recognition. To the best of
our knowledge, all the cationic-functionalising ligands currently
reported in the literature are based on ammonium species. Here we
have reported the synthesis and characterisation of the first alter-
native system, based on phosphonioalkylthiosulfate zwitterions.
Phosphonium groups offer a number of advantages, including
biocompatibility and the ease of synthesis of a wide range of
derivatives with different recognition capabilities. We have also
demonstrated that our phosphonioalkylthiosulfate zwitterions
readily disproportionate into phosphonioalkylthiolates in situ
during the synthesis of gold nanoparticles produced by the boro-
hydride reduction of gold(III) salts. UV spectroscopic and electron
microscopic studies have shown that the phosphoniothiolates bind
to the surface of the gold nanoparticles which are typically 5 nm in
diameter. The resulting cationic-functionalised gold nanoparticles
are dispersable in aqueous solution which augurs well for their
future use in biological applications.
6-Triphenylphosphoniohexylthiosulfate (9C). Colourless crys-
tals, mp 63–65 ◦C. Found: C, 62.12; H 5.95; C24H27O3PS2 requires:
C, 62.86; H, 5.93%. ESMS 459 [M + H+], 481 [M + Na+], 939 [2M +
1
Na+]. d 31P NMR (CDCl3) = 24.06 ppm; d H NMR (CDCl3) =
1.5 (2H, m), 1.6 (4H, m), 1.7 (2H, m), 3.05 (2H, t), 3.4 (2H, m),
7.6–7.8 (15H, m) ppm.
We are currently investigating the synthesis of related ligand sys-
tems and investigating the potential of phosphonioalkylthiolate-
functionalised gold nanoparticles and surfaces as biorecognition
systems using surface plasmon resonance techniques.
8-Triphenylphosphoniooctylthiosulfate (9D). Pale cream pow-
der, mp 40–45 ◦C. Found: C, 62.14; H, 6.37; C26H31O3PS2·H2O
requires C, 61.88; H, 6.59%. ESMS 485 [M+], 510 [M + Na+]. d 31
NMR (CDCl3) = 23.8 ppm; d H NMR (CDCl3) = 1.2 (5H, m),
1.5 (7H, m), 2.4 (1H, m), 2.9 (1H, t), 3.3 (2H, m), 7.6–7.7 (15H,
m) ppm.
P
1
Experimental
10-Triphenylphosphoniodecylthiosulfate (9E). Pale cream pow-
General
der, mp 60–65 ◦C. Found: C, 63.69; H, 6.75; C28H35O3PS2·H2O
1H and 31P NMR spectra were obtained in CDCl3 and in CDCl3–
DMSO mixture on a Bruker DMX 250 (250 MHz) spectrometer.
Electrospray mass spectra were recorded using an Applied Biosys-
requires C, 63.13; H, 7.00%. ESMS 513 [M+], 538 [M + Na+]. d 31
NMR (CDCl3) = 23.6 ppm; d H NMR (CDCl3) = 1.0 (8H, m),
P
1
1.4 (6H, m), 3.2 (2H, m), 3.9 (4H, m), 7.5–7.7 (15H, m) ppm.
4350 | Org. Biomol. Chem., 2006, 4, 4345–4351
This journal is
The Royal Society of Chemistry 2006
©

View Article Online
3-Tributylphosphoniopropylthiosulfate (9F). Colourless crys-
tals, mp 133–136 ◦C. Found: C, 50.27; H, 9.69; C15H33O3PS2
requires C, 50.53; H, 9.33%. ESMS 357 [M + H+], 379 [M +
Na+], 735 [2M + Na+], 1091 [3M + Na+]. d 31P NMR (CDCl3) =
until the gold salt was totally dissolved. The reduction was carried
out by adding dropwise a freshly prepared aqueous solution of
sodium borohydride (3 mL, 400 mmol L−1) with vigorous stirring,
and 15 mL of deionised water was then added to the mixture. After
24 hours, the stirring was stopped. And three DCM extractions
were then carried out for the purification of the aqueous phase.
1
33.7 ppm; d H NMR (CDCl3) = 0.9 (9H, t), 1.5 (12H, m), 2.1
(8H, m), 2.5 (2H, m), 3.1 (2H, t) ppm.
TEM
Synthesis of 3-(methylthio)propyl-triphenylphosphonium iodide
(11)
One drop of a dispersion of the phosphoniopropylthiolate-capped
gold nanoparticle sample in methanol was placed onto a 300-mesh
copper grid, the solvent allowed to evaporate, and then the grid was
carbon coated. A Carl Zeiss STM SUPRATM 40VP GEMINITM
FE-SEM with a Multi-Mode STEM (30.00 kV) detection system
was used to determine the average particle size for the sample
studied.
The alkylation of (10) was carried out using the following
method: triphenylphosphoniopropylthiosulfate (0.5 mmol) was
dissolved in 3 mL of methanol. A freshly prepared aqueous
solution of sodium borohydride (5 mmol) was then added drop
by drop to the reaction flask, in order to allow formation of the
zwitterion Ph3P+(CH2)3S−. The mixture was stirred for 3 hour
at room temperature. The formation of 3-(methylthio)propyl-
triphenylphosphonium iodide was achieved by the reaction of (10)
and iodomethane (5 mmol) under nitrogen and the mixture was
stirred overnight at room temperature. Progress of the reaction was
monitored by TLC, using 10% methanol : 90% dichloromethane
as a mobile phase. The resulting mixture was extracted with
dichloromethane, the organic phase was collected and after
removing the solvent, the resulting compound (11) was initially
purified by trituration with dry diethyl ether.
Acknowledgements
We thank Sheffield Hallam University for funding this work,
Stuart Creasy and Leon Bowen (Materials Research Institute
of Sheffield Hallam University) and Carl Zeiss SMT-Nano
Technology Systems Division for the STEM images.
References
3-(Methylthio)propyl-triphenylphosphonium iodide (11). Pale
cream solid, 68% yield; mp 136–138 ◦C. Accurate MALDI
TOFMS analysis: found 351.1307 [M +]; C22H24PS requires
351.1336 [M+]; d 31P NMR (CDCl3) = 24.3 ppm, d 1H NMR
(CDCl3) = 1.9 (3H, s), 2.8 (2H, t), 3.3 (2H, m), 3.8 (2H, m),
7.6–7.8 (15H, m) ppm.
1 M.-C. Daniel and D. Astruc, Chem. Rev., 2004, 104, 293.
2 K. G. Thomas and P. V. Kamat, Acc. Chem. Res., 2003, 36, 888.
3 G. Wang, J. Zhang and R. W. Murray, Anal. Chem., 2002, 74, 4320.
4 H. Itoh, K. Naka and Y. Chujo, J. Am. Chem. Soc., 2004, 126,
3026.
5 H. Nakao, H. Shiigi, Y. Yamamoto, T. Nagaoka, S. Sugiyama and T.
Ohtani, Nano Lett., 2003, 3, 1391.
6 G. Wang and R. W. Murray, Nano Lett., 2004, 4, 95.
7 C. M. McIntosh, E. A. Esposito, III, A. K. Boal, J. M. Simard, C. T.
Martin and V. M. Rotello, J. Am. Chem. Soc., 2001, 123, 7626.
8 A. Verma and V. M. Rotello, Chem. Commun., 2005, 303.
9 M. F. Ross, G. F. Kelso, F. H. Blackie, A. M. James, H. M. Cocheme, A.
Filipovska, T. Da Ros, T. R. Hurdy, R. A. J. Smith and M. P. Murphy,
Biochemistry (Moscow), 2005, 70(2), 222.
10 R. J. Burns, R. A. J. Smith and M. P. Murphy, Arch. Biochem. Biophys.,
1995, 322, 60.
11 R. J. Burns and M. P. Murphy, Arch. Biochem. Biophys., 1997, 339, 33.
12 T.-K. Lin, G. Hughes, A. Muratoska, F. H. Blaikie, P. S. Brookes, V.
Darley-Usmar, R. A. J. Smith and M. P. Murphy, J. Biol. Chem., 2002,
19, 17048.
13 A. Filipovska, M. R. Eccles, R. A. J. Smith and M. P. Murphy, FEBS
Lett., 2004, 556, 1890.
14 M. J. McKeage, L. Maharaj and S. J. Berners-Price, Coord. Chem. Rev.,
2002, 232, 127.
15 J. Lukkari, M. Meretoja, I. Kartio, K. Laajalehto, M. Rajama¨ki, M.
Lindstro¨m and J. Kankare, Langmuir, 1999, 15, 3529.
16 Y.-S. Shon, S. M. Gross, B. Dawson, M. Porter and R. W. Murray,
Langmuir, 2000, 16, 6555.
X-Ray crystallography study of the
triphenylphosphoniopropylthiosulfate and
tributylphosphoniopropylthiosulfate zwitterions
All single crystal X-ray diffraction data were collected on a Bruker
Nonius KappaCCD mounted at the window of a Mo FR591
˚
rotating anode (k = 0.71073 A). The crystals were kept at a
temperature of 120 K, and the data were corrected for absorption
by the empirical multi-scan method employed in SORTAV.20 The
structures were solved via direct methods and refined by full matrix
least squares on F2 (SHELX97).21 Non-hydrogen atoms were
refined anisotropically and hydrogen atoms were treated using
a riding model.†
Synthesis of phosphonium-monolayer protected gold clusters
A solution of the zwitterions corresponding to the protecting
ligand was prepared in DCM (0.25 mmol, 14 mmol L−1) and
potassium tetrachloroaurate (0.12 mmol, 7 mmol L−1) was then
added to the solution. This was vigorously stirred for 10 minutes
17 M. Scudder and I. Dance, J. Chem. Soc., Dalton Trans., 2000, 2909.
18 M. Brust, M. Walker, D. Bethell, D. J. Schiffrin and R. Whyman,
J. Chem. Soc., Chem. Commun., 1994, 801.
19 R. Elghanian, J. J. Storhoff, R. C. Mucic, R. L. Letsinger and C. A.
Mirkin, Science, 1997, 277, 1078.
20 R. H. Blessing, Acta Crystallogr., Sect. A, 1995, 51, 33.
21 SHELX97: Programs for Crystal Structure Analysis (Release 97–2),
G. M. Sheldrick, Institu¨t fu¨r Anorganische Chemie der Universita¨t:
Tammanstrasse 4, D-3400 Go¨ttingen, Germany, 1998.
† CCDC reference numbers 243256 and 620796. For crystallographic data
in CIF or other electronic format see DOI: 10.1039/b610480k
This journal is
The Royal Society of Chemistry 2006
Org. Biomol. Chem., 2006, 4, 4345–4351 | 4351
©