Thiol-ene synthesis of cationic carbosilane dendrons: A new family of synthons

Article abstract of DOI:10.1021/om301217g

A variety of neutral and cationic carbosilane dendrons containing a wide range of active groups, such as -N₃, -OH, -NH₂, and -SH, at the focal points were synthesized from carbosilane vinyl dendrons BrG _nV_m from generations 1-3 by substitution of the bromine atom at the focal point and functionalization of the vinyl groups via thiol-ene click chemistry with HS(CH₂)₂NMe₂·HCl. These dendritic wedges were characterized by NMR, MS, and elemental analysis.

Full text of DOI:10.1021/om301217g

Article
pubs.acs.org/Organometallics
Thiol-Ene Synthesis of Cationic Carbosilane Dendrons: a New Family
of Synthons
Elena Fuentes-Paniagua,†,‡ Cornelia E. Pena-Gonzalez,† Marta Galan,† Rafael Gomez,*,†,‡
́
́
́
̃
F. Javier de la Mata,*,†,‡ and Javier Sanchez-Nieves*,†,‡
́
†
ica and ‡Networking Research Center for Bioengineering, Biomaterials and
de Henares (Madrid), Spain
́
́
Departamento de Quımica Organ
́
ica y Quımica Inorgan
Campus Universitario, E-28871 Alcala
́
́
Nanomedicine (CIBER-BBN), Universidad de Alcala,
́
S
* Supporting Information
ABSTRACT: A variety of neutral and cationic carbosilane
dendrons containing a wide range of active groups, such as −N3,
−OH, −NH2, and −SH, at the focal points were synthesized
from carbosilane vinyl dendrons BrGnVm from generations 1−3
by substitution of the bromine atom at the focal point and
functionalization of the vinyl groups via thiol-ene click chemistry
with HS(CH2)2NMe2·HCl. These dendritic wedges were
characterized by NMR, MS, and elemental analysis.
with click chemistry coupling, or primary amines and carboxylic
acids related with amide bond formation, as these functions are
present in a wide range of biomolecules and are also important
coordinative groups for transition metals. On the other hand,
proper functionalization of the dendron periphery would
provide the properties required for the use their development
calls for.37−39
Our group is interested in biomedical applications of
dendritic molecules. For this use, these molecules should not
only show low cytotoxicity but also be preferably soluble in
aqueous media.40 However, in the particular case of carbosilane
dendrimers, the macromolecule is endowed with high hydro-
phobicity due to the low polarity of the C−C and C−Si bonds
in its scaffold. To enable them to be water-soluble, the
periphery has to be modified with polar moieties, anionic or
cationic, or neutral, such as carbohydrates, thus making them
suitable for biomedical applications.17,31,41−58 Carbosilane
dendrimers bearing cationic groups have already been tested
for gene therapy,17,31,41−43,46,48 bactericides,44,45,47 and immune
response inhibitors49,50 and have also been shown to interact
with drugs.51
These promising results of carbosilane dendrimers in
biomedical applications have triggered our search for new
systems, in which we aim to cut down the synthetic steps and
also look for new properties. In this sense, only a few
carbosilane dendrons have been described so far,59−61 some of
which were designed for biomedical applications, such as sialic
acid terminated dendrons against influenza viruses58 or as guest
molecules with amino acids at the focal point.62 The growth of
carbosilane dendrons requires the presence of terminal olefins;
thus the thiol-ene approach is very interesting for the
1. INTRODUCTION
Dendritic molecules have been studied for several applications
such as catalysis, material sciences, and nanobiotechnology for
their well-defined and uniform branching structure, multi-
valency, and variety of typologies.1−17 Two main topologies
define these macromolecules: spherical dendrimers, which
usually show a symmetric distribution around a core, and
dendritic wedges or dendrons, which are cone-shaped
molecules with two different functions, one in the periphery
and another at the focal point. The presence of these two
potentially different moieties gives dendrons an entity by
themselves, thus giving the design of dendrons its own place in
macromolecular chemistry, as it allows the precise combination
of several properties in a single molecule. Dendrons have been
used to modify properties of polymers,18 stabilize nano-
particles,19−23 and improve biological activity of functional
molecules,24−27 as well as other purposes.4,28
The synthesis of dendrimers follows an iterative procedure of
at least two different types of reactions, which should have high
yields, be regioselective, be reproducible, and, if possible,
produce the minimum number of byproducts in order to be
useful for higher generations. Click chemistry refers to a type of
reaction characterized by easy initiation, high yields, minimal
product purification, and high tolerance to a variety of solvents
and functional groups. For that reason the number of
dendrimers synthesized using this kind of reaction has
increased over the last few years.29−34 One of these reactions
is the addition of thiols to olefins, known as thiol-ene click
chemistry.35,36
Heterofunctionalization of dendrons would require, on one
hand, the presence of adequate focal points that bind to the
target molecule. In this sense, several moieties are widely
deserving of being candidates for their selectivity shown toward
a particular fragment, such as alkyne, azide, and thiol, related
Received: December 17, 2012
Published: March 12, 2013
© 2013 American Chemical Society
1789
dx.doi.org/10.1021/om301217g | Organometallics 2013, 32, 1789−1796

Organometallics
Article
a
Scheme 1. Synthesis of Neutral and Cationic Dendrons
a
Conditions: (i) ClMg(C2H3); (ii) MX (M = Na, X = N3; M = K, X = Pht, MeC(O)S) or 1,4-C6H4(OH)2, K2CO3; (iii) HS(CH2)2NMe2·HCl, hν,
DMPA; (iv) H2NNH2; (v) HCl.
functionalization of these molecules, as previously shown for
spherical dendrimers.63,64 However, no carbosilane dendrons
have yet been synthesized by this methodology. Hence, in this
work we report the application of this procedure to the
synthesis of carbosilane dendrons bearing amine or ammonium
functions in the periphery and versatile focal points that show
the orthogonality of this approach. The thiol-ene addition also
saves the final hydrosilylation steps, which carbosilane
dendrimers usually undergo during growth, diminishing
undesirable side reactions.65 Finally, the aim of decorating the
dendron periphery with ammonium moieties is to provide
water solubility to these wedges, as required for biomedical
Figure 1. Dendron skeletons (G1−G3) described in this work.
applications, and also to offer the same features as other related
spectra. Furthermore, the 29Si NMR gave rise to one resonance
carbosilane dendrimers that are being applied in biomedicine
at δ ca. −13.5 due to the outer Si atom.
(vide supra).
Our next goal was to substitute the focal point of dendrons
1−3 with active groups that play an important role in different
areas of chemistry, such as −N3, −OH, −NH2, and −SH. The
2. RESULTS AND DISCUSSION
azide moiety was introduced by a direct method, as this group
did not interfere with the subsequent thiol-ene reaction.
Dendrons 1−3 reacted with NaN3 upon heating in acetone
to afford the dendrons N3GnVm (n = 1, m = 2 (4); n = 2, m = 4
(5); n = 3, m = 8 (6)) in high yields as colorless oils (Scheme
1). NMR spectroscopy clearly confirmed modification of the
focal point (Figure 2), as the resonances of the initial CH2Br
group were not observed. The presence of the new CH21N3
fragment was identified as one triplet at δ ca. 3.20 in the H
NMR spectra and at δ ca. 51.0 in the 13C NMR spectra.
Carbosilane dendrons with a Br atom at the focal point and
vinyl functions in the periphery were synthesized following the
procedure described for analogous dendrons decorated with
allyl groups66 from BrGn(SiCl2)m (n = 1, m = 1; n = 2, m = 2; n
= 3, m = 4) and ClMg(C2H3), thus giving the corresponding
vinyl dendrons BrGnVm (n = 1, m = 2 (1); n = 2, m = 4 (2); n =
3, m = 8 (3)) as colorless oils in high yields (Scheme 1). In
general, dendrons are named in this work according to the
XGn(Y)m nomenclature, where X indicates the nature of the
focal point, Gn the dendron generation, and (Y)m the peripheral
function and its number (Figure 1). The reason for synthesizing
these vinyl-terminated dendrons was the fact that the related
allyl compounds showed very little reactivity toward the thiol-
ammonium derivative used in this work. The most important
NMR data of these compounds showed resonances arising
from the CH2Br group at the focal point, one triplet at δ ca.
3.40 in the 1H NMR spectra and one signal at δ ca. 33.0 in the
13C NMR spectra and from the peripheral vinyl groups two
1
Furthermore, H−15N NMR spectroscopy showed two cross
peaks belonging to the nitrogen atoms NCH2 and NNCH2
at δ ca. −308 and −131, respectively, whereas the external N
atom could not be detected.
With respect to the introduction of a hydroxyl group at the
focal point, mixtures of dendrons 1−3 were directly heated in
the presence of an excess of hydroquinone and K2CO3. Thus,
the compounds HOGnVm (n = 1, m = 2 (7); n = 2, m = 4 (8); n
= 3, m = 8 (9)) were obtained as colorless oils in moderate
yields (Scheme 1). The change at the focal point (Figure 2) was
confirmed by means of 1H NMR spectroscopy, giving
1
multiplets at δ ca. 5.70 and 6.05 in the H NMR spectra and
two resonances at δ ca. 133.0 and 137.0 in the 13C NMR
1790
dx.doi.org/10.1021/om301217g | Organometallics 2013, 32, 1789−1796

Organometallics
Article
Figure 2. NMR spectra of first-generation vinyl dendrons showing the XC4H8Si chain.
Figure 3. Representative dendrons of the third generation synthesized in this work.
resonances at δ ca. 3.90 due to the new CH2O group and a
broad singlet at δ ca. 4.75 for the OH terminal, and also by the
resonances of the two different aromatic CH groups, which
were observed as a multiplet at δ ca. 6.75. The 13C NMR
spectra showed a peak for the CH2O group at δ ca. 68.3 and in
the case of the four different aromatic C atoms peaks for the
CH groups at δ ca. 132.9 and 136.8 and for the Cipso atoms at δ
ca. 149.3 and 153.2.
However, in the case of the −NH2 and −SH groups,
precursors acting as protective groups, such as phthalimide
(Pht) for primary amines −NH2 and thioacetate (MeCOS) for
terminal thiols −SH, had to be used. In this sense, addition of
KPht to solutions of dendrons BrGnVm (1−3) led to the
corresponding modified dendrons PhtGnVm (n = 1, m = 2 (10);
n = 2, m = 4 (11); n = 3, m = 8 (12)) in high yields upon
heating in DMF (Scheme 1). As above, the introduction of the
phthalimide group at the focal point was confirmed by NMR
1791
dx.doi.org/10.1021/om301217g | Organometallics 2013, 32, 1789−1796

Organometallics
Article
spectroscopy (Figure 2), showing one triplet at δ ca. 3.65 for
the CH2N group in the 1H NMR spectra and one resonance at
δ ca. 37.5 for the carbon atom of this group in the 13C NMR
spectra. Furthermore, 15N NMR spectroscopy proved the
presence of the phthalimide group, showing one resonance at δ
ca. −216.
The thioacetate group was introduced by reaction of
dendrons 1−3 with HSC(O)Me and K2CO3 in acetone at 55
°C, to give the new dendrons MeC(O)SGnVm (n = 1, m = 2
(13); n = 2, m = 4 (14); n = 3, m = 8 (15)) as orange oils in
high yields (Scheme 1). NMR spectroscopy showed the
exchange of the Br atom for the MeC(O)S function at the
focal point (Figure 2) by means of the 1H NMR resonances at
δ ca. 2.82 and 2.30 for the CH2S and the MeC(O) groups,
respectively, and the 13C NMR resonances at δ ca. 28.7 for the
CH2S group and at δ ca. 30.6 and 196.0 for the Me and CO
groups of the MeC(O) moiety, respectively.
Once vinyl dendrons with adequate focal points were
obtained, we proceeded to modify their periphery via thiol-
ene addition. Thus, solutions of dendrons XGnVm (X = N3 (4−
6), HO (7−9), Pht (10−12), MeC(O)S (13−15)) and 2-
dimethylethylenethiol hydrochloride, HS(CH2)2NMe2·HCl, in
THF/MeOH stirred under UV irradiation (see the Exper-
imental Section) afforded the new wedges XGn(S-
(CH2)2NMe2·HCl)m (X = N3, n = 1, m = 2 (16), n = 2, m =
4 (17), n = 3, m = 8 (18); X = OH, n = 1, m = 2 (19), n = 2, m
= 4 (20), n = 3, m = 8 (21); X = Pht; n = 1, m = 2 (22), n = 2,
m = 4 (23), n = 3, m = 8 (24); X = MeC(O)S; n = 1, m = 2
(25), n = 2, m = 4 (26), n = 3, m = 8 (27)) (Scheme 1 and
Figure 3), which were obtained as white solids in high yields.
These reactions required the presence of a photoinitiator,
which in our case was 2,2′-dimethoxy-2-phenylacetophenone
(DMPA). The addition of the thiol to the vinyl groups was
regioselective at the β-position (vide infra). These compounds
were thus soluble in water and other polar solvents, such as
alcohols and DMSO.
neutral dendrons NH2Gn(S(CH2)2NMe2)m (n = 1, m = 2 (28);
n = 2, m = 4 (29); n = 3, m = 8 (30) in good yields. In this
process, deprotonation of the ammonium groups was also
produced by basic hydrazine. This change led to the isolation of
these wedges as oils, which were soluble in organic solvents but
not in water. The presence of the new focal point NH2CH2− in
dendrons 28−30 was clearly identified by NMR spectroscopy,
1
showing a new triplet at δ ca. 2.65 in the H NMR for the
CH2N at the focal point and a resonance at δ ca. 41.9 in the 13C
NMR spectra for the carbon atom of this group. Furthermore, a
shifting to lower frequency was observed for the resonances
corresponding to the CH2NMe2 groups, as a consequence of
charge neutralization of the nitrogen atoms.
For the synthesis of dendrons with −SH functions at the
focal point, excess HCl in dioxane was added to solutions of
dendrons 25−27 to give the compounds HSGn(S-
(CH2)2NMe2·HCl)m (n = 1, m = 2 (31); n = 2, m = 4 (32);
n = 3, m = 8 (33)) as pale yellow solids in moderate yields (ca.
70%) which were soluble in polar organic solvents and in water.
NMR spectroscopy confirmed that the thioacetate group had
disappeared and that the thiol HSCH2− moiety had been
1
formed. The H NMR spectra showed one triplet at δ ca. 2.46
for the CH2 group, and the resonance for the SH proton
appeared at δ ca. 1.33, as detected by COSY, since it is
overlapped with the resonances of the carbosilane fragment,
while in the 13C NMR spectra a resonance for the CH2SH
carbon atom at δ ca. 25.0 was observed.
3. CONCLUSIONS
A versatile and simple procedure has been developed for the
synthesis of a library of carbosilane dendrons containing
ammonium or amine groups in the periphery and reactive
groups, such as −N3, −OH, −NH2, and −SH, at the focal
point, which are attractive for a variety of applications. The new
dendritic wedges were obtained in good to high yields from
carbosilane dendrons with a C−Br bond at the focal point and
vinyl groups in the peripheral dendrons by modification of the
focal point followed by thiol-ene addition. For the preparation
of the −NH2 and −SH derivatives protective groups had to be
introduced prior to the thiol-ene reaction. The cationic
carbosilane wedges thus obtained were water-soluble, which is
an important requirement for biomedical applications. Hence,
these new families of synthons displaying focal points to which
different biomolecules such as drugs, peptides, antibodies, or
also chromophores may be conjugated and a cationic
ammonium periphery are promising building blocks for
biomedical applications.
The NMR spectroscopic and analytical data for derivatives
16−27 were consistent with their proposed structures. The
presence of the new chain Si(CH2)2S was confirmed by
1
TOCSY H NMR, which showed two multiplets at δ ca. 0.88
and 2.60 for the protons of the SiCH2 and the CH2S groups,
respectively, whereas the outer chain S(CH2)2N gave rise to
two multiplets at δ ca. 3.00 and 3.30 for the protons of the
SCH2 and the CH2N groups, respectively. Furthermore, a
singlet at δ ca. 3.30 confirmed the presence of the NMe2H
fragment. The carbon atoms of the CH2 groups of the
Si(CH2)2S chain were observed in the 13C NMR spectra at δ ca.
13.5 for the SiCH2 group and at δ ca. 26.0 for the CH2S group,
whereas those belonging to the S(CH2)2N chain arose at δ ca.
24.5 for the SCH2 group and at δ ca. 55.5 for the CH2S group.
The NMe2H group was also detected at δ ca. 41.4 by 13C NMR
spectroscopy. 29Si NMR spectra showed one resonance for the
Si atom of this outer group at δ ca. 2.4. Finally, 15N NMR
spectra resolved one resonance at about δ −338.3 for the
NMe2·HCl group. The α addition was only observed in first-
generation dendrons, by means of a doublet at about 1.20 ppm
4. EXPERIMENTAL SECTION
4.1. General Considerations. All reactions were carried out
under an inert atmosphere, and solvents were purified from
appropriate drying agents when necessary. Thiol-ene reactions were
carried out employing a HPK 125 W mercury lamp from Heraeus
Noblelight with maximum energy at 365 nm, in normal glassware
under an inert atmosphere. NMR spectra were recorded on a Varian
Unity VXR-300 (300.13 (1H), 75.47 MHz (13C)) or on a Bruker
AV400 instrument (400.13 (1H), 100.60 (13C), 40.56 MHz (15N), and
1
in the H NMR spectra; this signal was overlapped with the
1
79.49 MHz (29Si)). Chemical shifts (δ) are given in ppm. H and 13
C
resonances of the intermediate alkyl chains in higher
generations. The integration of this resonance indicated ca.
2.5% formation of this function.
Removal of the protecting Pht group of dendrons to generate
others with a −NH2 function at the focal point was achieved by
addition of hydrazine to dendrons 22−24, which gave the
resonances were measured relative to solvent peaks considering TMS
at 0 ppm; meanwhile 15N and 29Si resonances were measured relative
to external MeNO and TMS, respectively. When necessary, assign-
ment of resonances was done from HSQC, HMBC, COSY, TOCSY,
and NOESY NMR experiments. Elemental analyses were performed
on a LECO CHNS-932 instrument. Mass spectra were obtained from
1792
dx.doi.org/10.1021/om301217g | Organometallics 2013, 32, 1789−1796

Organometallics
Article
a Bruker Ultraflex III instrument for MALDI-TOF in dithranol, an
Agilent 6210 TOF LC/MS instrument for ESI-TOF in MeOH/H2O
with (NH4)(HCO2), and an AB Sciex QSTAR instrument for ESI-
POS in H2O/MeOH. The compounds ClMg(C2H3), NaN3,
(HO)2C6H4, KPht, MeC(O)SH, HS(CH2)2NMe2·HCl, 2,2′-dime-
thoxy-2-phenylacetophenone (DMPA), H2NNH2, and HCl (4 M in
dioxane) (Aldrich) and K2CO3 (Panreac) were obtained from
commercial sources. The compounds BrGn(SiCl2)m (n = 1, m = 1; n
= 2, m = 2; n = 3, m = 4)66 were synthesized as reported.
4.2.4. PhtG1V2 (10). To a DMF solution (25 mL) of wedge 1 (0.270
g, 1.16 mmol) were added the commercial reagent KPht (0.875 g,
98.00 mmol) and 10% NaI. The reaction mixture was heated to 80 °C
for 16 h in a Teflon-valved ampule. Then a Et2O/H2O extraction was
performed, and after the organic phase was dried over MgSO4 and the
volatiles were evaporated, compound 10 was obtained as a yellowish
oil (0.21 g, 61%). Data for 10 are as follows. NMR (CDCl3): 1H NMR
δ 0.11 (s, 3 H, SiMe), 0.67 (t, J = 8.8 Hz, 2 H, NCH2CH2CH2CH2Si),
1.36 (m,
2 H, NCH2CH2CH2CH2Si), 1.68 (m, 2 H,
NCH2CH2CH2CH2Si), 3.64 (t, J = 7.3 Hz, 2 H, NCH2), 5.69 and
4.2. Synthesis of Compounds. 4.2.1. BrG1V2 (1). An Et2O
solution of ClMg(C2H3) (33.3 mL, 53.28 mmol) was added drop by
drop to a BrG1(SiCl2) solution (5.550 g, 22.20 mmol) in Et2O cooled
to 0 °C, and then the mixture was stirred overnight at room
temperature. Afterward a water solution of NH4Cl was added (12%, 40
mL), organic phase was separated, and the aqueous phase was
extracted twice with Et2O. Finally the organic phase was washed with
brine and dried over MgSO4 and SiO2. The solution was filtered, and
the volatiles were removed under vacuum, yielding 1 as a colorless
6.05 (m, 6 H, SiCHCH2), 7.68 and 7.81 (m, 4 H, C6H4); 13C{1H}
NMR
δ −5.5 (SiMe), 13.4 (NCH2CH2CH2CH2Si), 21.0
(NCH2CH2CH2CH2Si), 32.0 (NCH2CH2CH2CH2Si), 37.6 (NCH2),
123.0 (C6H4, CH), 132.1 (C6H4, Cipso), 132.9 (SiCHCH2), 133.7
(C6H4, CH), 136.6 (SiCHCH2), 168.3 (CO); 15N NMR δ −216.7;
29Si NMR δ −12.8 (G1−SiMe). MS: [M + H]+ 300.15 amu (calcd
300.14 amu). Anal. Calcd for C17H21NO2Si (299.44 g/mol): C, 68.19;
H, 7.07; N, 4.68. Found: C, 68.67; H, 7.16; N, 4.67.
1
4.2.5. MeCOSG1V2 (13). MeCOSH (0.627 mL, 8.776 mmol) and
K2CO3 (2.049 g, 8.98 mmol) were stirred in acetone (60 mL) at room
temperature for 1 h. Afterward, BrG1V2 (1; 2.000 g, 8.58 mmol) was
added and the mixture was stirred at 55 °C for 22 h. Volatiles were
removed under vacuum, and the residue was dissolved in Et2O.
Subsequently brine was added, the organic phase was separated, and
the aqueous phase was extracted twice with Et2O. The organic phase
was washed with brine and dried over MgSO4. The solution was
filtered through Celite, and the volatiles were removed under vacuum,
yielding 13 as an orange oil (1.85 g, 95%). Data for 13 are as follows.
liquid (4.66 g, 90%). Data for 1 are as follows. NMR (CDCl3): H
NMR δ 0.13 (s, 3 H, SiMeC2H3), 0.63 (m, 2 H, CH2SiC2H3), 1.46 (m,
2 H, BrCH2CH2CH2CH2Si), 1.85 (m, 2 H, BrCH2CH2CH2CH2Si),
3.39 (t, J = 6.6 Hz, 2 H, BrCH2CH2CH2CH2Si), 5.71 (m, 2 H,
SiCHCH2), 6.03 (m, 4 H, SiCHCH2; 13C{1H} NMR δ −5.4 (SiMe),
13.1 (BrCH2CH2CH2CH2Si), 22.3 (BrCH2CH2CH2CH2Si), 33.6
(BrCH2CH2CH2CH2Si), 36.2 (BrCH2CH2CH2CH2Si), 133.1
(SiCHCH2), 136.6 (SiCHCH2); 29Si NMR δ −13.5 (SiCHCH2).
Anal. Calcd for C9H17BrSi (233.22 g/mol): C, 46.35; H, 7.35. Found:
C, 46.83; H, 7.65.
4.2.2. N3G1V2 (4). A solution of 1 (0.500 g, 2.15 mmol) in acetone
(60 mL) was heated to 60 °C in the presence of an excess of NaN3
(0.965 g, 4.30 mmol) and 18-crown-6 (0.061 g, 0.24 mmol) for 16 h.
After this time, volatiles were removed and the mixture was extracted
with H2O/Et2O. The organic phase was dried over Na2SO4 and dried
under vacuum to give 4 as a colorless oil (0.39 g, 93%). Data for 4 are
as follows. NMR (CDCl3): 1H NMR δ 0.13 (s, 3 H, SiMeC2H3), 0.64
1
NMR (CDCl3): H NMR δ 0.11 (s, 3 H, SiCH3), 0.62 (m, 2 H,
SCH2CH2CH2CH2Si), 1.37 (m, 2 H, SCH2CH2CH2CH2Si), 1.57 (m,
2 H, SCH2CH2CH2CH2Si), 2.29 (s, 3 H, CH3COS), 2.83 (t, J = 7.2
Hz, 2 H, SCH2CH2CH2CH2Si), 5.67 (m, 2 H, SiCHCH2), 6.01 (m, 4
H, SiCHCH2); 13C{1H} NMR
δ −5.4 (SiCH3), 13.5
(SCH2CH2CH2CH2Si), 22.9 (SCH2CH2CH2CH2Si), 28.7
( S C H 2 C H 2 C H 2 C H 2 S i ) , 3 0 . 6 ( C H 3 C O S ) , 3 3 . 0
(SCH2CH2CH2CH2Si), 132.9 (SiCHCH2), 136.7 (SiCHCH2), 195.9
(CH3COS); 29Si NMR δ −13.0 (CH3Si). Anal. Calcd for for
C11H20OSSi (228.43): C, 57.84; H, 8.88; S, 14.04. Found: C, 58.20;
H, 8.81; S, 14.17.
(t,
J = 8.2 Hz, 2 H, CH2SiC2H3), 1.40 (m, 2 H,
N3CH2CH2CH2CH2Si), 1.61 (m, 2 H, N3CH2CH2CH2CH2Si), 3.32
(t, J = 6.9 Hz, 2 H, N3CH2CH2CH2CH2Si), 5.70 and 6.06 (m, 6 H,
S i C H C H 2 ) ; 1 3 C { 1 H } N M R
δ − 5 . 4 ( S iM e ) , 1 3 . 6
4.2.6. N3G1(SNMe2HCl)2 (16). Compound 4 (0.089 g, 0.46 mmol),
2-(dimethylamino)ethanethiol hydrochloride (0.136 g, 0.91 mmol), 5
mol % of DMPA (0.020 g, 0.08 mmol), and a 1/2 THF/methanol
solution (5 mL) were combined. The reaction mixture was
deoxygenated and irradiated for 1.5 h. Another 5 mol % of DMPA
was added, and the reaction mixture was irradiated for another 1.5 h
and monitored by 1H NMR. The initial reaction mixture was
concentrated by rotary evaporation and redissolved in methanol.
Afterward, it was precipitated in Et2O, and after the solvent was
separated, the solid was dried under vacuum to afford 16 as a white
(N3CH2CH2CH2CH2Si), 20.9 (N3CH2CH2CH2CH2Si), 32.4
(N3CH2CH2CH2CH2Si), 51.0 (N3CH2CH2CH2CH2Si), 133.1
(SiCHCH2), 136.6 (SiCHCH2). 15N NMR : δ −308.7 (NN
NCH2), −131.9 (NNNCH2); 29Si NMR δ −12.9 (SiCHCH2).
MS: [M + H]+ 196.12 amu (calcd 196.12 amu). Anal. Calcd for
C9H17N3Si (195.34 g/mol): C, 55.34; H, 8.77; N, 21.51. Found: C,
55.63; H, 8.49; N, 21.89.
4.2.3. HOArG1V2 (7). 1,4-(HO)2C6H4 (2.860 g, 25.68 mmol), 1
(0.600 g, 2.57 mmol), K2CO3 (0.710 g, 5.14 mmol), and crown ether
18-C-6 (0.070 g, 0.26 mmol) were stirred in acetone (70 mL) at 90 °C
in a sealed ampule for 2 days under vacuum. Afterward, the volatiles
were removed under vacuum and a water solution of NH4Cl (12%, 50
mL) and CH2Cl2 were added. The organic phase was separated, and
the aqueous phase was extracted twice with Et2O. The organic phase
was dried over MgSO4 and for an extra 10 min also with SiO2. The
solution was filtered, and the volatiles were removed under vacuum.
Then alumina column chromatography was performed using several
ethyl acetate/hexane mixtures with an increasing polarity gradient. At
60% acetate, compound 7 was obtained as a colorless oil (0.40 g,
60%). Data for 6 are as follows. NMR (CDCl3): 1H NMR δ 0.14 (s, 3
H, SiMe), 0.68 (t, Ja = 8.5 Hz, 2 H, CH2Si), 1.48 (m, 2 H, CH2CH2Si),
1.77 (m, 2 H, OCH2CH2), 3.88 (t, Jb = 6.4 Hz, 2 H, OCH2), 4.65 (bs,
1 H, HOAr−), 5.71 and 6.08 (m, 6 H, SiCHCH2), 6.75 (m, 4 H,
1
solid (0.19 g, 86%). Data for 16 are as follows. NMR (DMSO): H
NMR δ 0.00 (s, 3H, SiMe), 0.55 (t, Ja = 8.57 Hz, 2 H,
NCH2CH2CH2CH2Si), 0.93 (t, Jb = 7.2 Hz, 4H, SiCH2CH2S), 1.34
( m ,
2 H , N C H 2 C H 2 C H 2 C H 2 S i ) , 1 . 5 8 ( m , 2 H ,
NCH2CH2CH2CH2Si), 2.65 (t, Jb = 7.2 Hz, 4 H, SiCH2CH2S), 2.86
(s, 12 H, SCH2CH2NMe2HCl), 3.02 (t, Jc = 7.7 Hz, 4 H,
SCH2CH2NMe2HCl), 3.27 (m, 6 H, SCH2CH2NMe2HCl and
NCH2); 13C{1H} NMR δ −5.4 (SiMe), 12.4 (N3CH2CH2CH2CH2Si),
13.5 (SiCH2CH2S), 20.2 (N3CH2CH2CH2CH2Si), 24.3
(SCH2CH2N+), 26.0 (SiCH2CH2S), 31.5 (N3CH2CH2CH2CH2Si),
41.4 (−NMe2H+), 49.7 (N3CH2), 55.3 (CH2N+); 15N NMR δ −338.4
(−NMe2H+), −308.6 (NNNCH2), −131.7 (NNN−CH2);
29Si NMR δ 3.0 (G1-SiMe). MS: [M − Cl − HCl]+ 406.25 amu (calcd
406.25 amu), Anal. Calcd for C17H41Cl2N5S2Si (478.66 g/mol): C,
42.66; H, 8.63; N, 14.63; S, 13.40. Found: C, 41.96; H, 8.05; N, 13.59;
S, 14.30.
4.2.7. HOArG1(NMe2HCl)2 (19). This wedge was prepared from 7
(0.490 g, 1.87 mmol), 2-(dimethylamino)ethanethiol hydrochloride
(0.557 g, 3.74 mmol), DMPA (0.010 g, 0.37 mmol), and a 1/2 THF/
methanol solution (3 mL) using the preparative procedure for 16. The
product was dried in vacuo to afford 19 as a white solid (0.74 g, 73%).
C 6 H 4 O 2 ) ; 1 3 C { 1 H } N M R
δ
− 5 . 4 ( S i M e ) , 1 3 . 7
(OCH2CH2CH2CH2Si), 20.2 (OCH2CH2CH2CH2Si), 32.9
(OCH2CH2CH2CH2Si), 68.3 (OCH2), 115.6 and 115.9 (C6H4O2;
CH), 132.9 (SiCHCH2), 136.8 (SiCHCH2), 149.3 and 153.2
(C6H4O2; CO); 29Si NMR δ −12.8 (G1−SiMe). Anal. Calcd for
C15H22O2Si (262.42 g/mol): C, 68.65; H, 8.45. Found: C, 69.08; H,
8.53.
1793
dx.doi.org/10.1021/om301217g | Organometallics 2013, 32, 1789−1796

Organometallics
Article
1
Data for 19 are as follows. NMR (DMSO): H NMR δ 0.01 (s, 3 H,
SiMe), 0.56 (m, 2 H, OCH2CH2CH2CH2Si), 0.86 (t, Ja = 8.3 Hz, 4 H,
SiCH2CH2S), 1.31 (m, 2 H, OCH2CH2CH2CH2Si), 1.66 (m, 2 H,
OCH2CH2CH2CH2Si), 2.59 (t, Ja = 9.0 Hz, 4 H, SiCH2CH2S), 2.70
(s, 12 H, SCH2CH2NMe2H+), 2.86 (t, Jb = 8.0 Hz, 2 H,
SCH2CH2NMe2H+), 3.16 (t, Jb = 8.0 Hz, 2 H, SCH2CH2NMe2H+),
3.82 (t, Jc = 6.3 Hz, 2 H, OCH2), 6.68 (m, 4H, C6H4O2); 13C{1H}
obtained as a yellowish oil (0.10 g, 95%). Data for 20 are as follows.
NMR (CDCl3): 1H NMR δ −0.09 (s, 3 H, SiMe), 0.43 (t, Ja = 9.7 Hz,
2 H, NCH2CH2CH2CH2Si), 0.80 (t, Jb = 8.6 Hz, 4 H, SiCH2CH2S),
1.21 (m,
2 H, NCH2CH2CH2CH2Si), 1.38 (m, 2 H,
NCH2CH2CH2CH2Si), 2.14 (s, 12 H, SCH2CH2NMe2), 2.48 (m, 4
H, SCH2CH2NMe2), 2.52 (m, 4 H, SiCH2CH2S), 2.57 (m, 4 H,
SCH2CH2NMe2), 2.55 (m, 2 H, NH2CH2). 13C{1H} NMR δ −5.5
(SiMe), 13.2 (NCH2CH2CH2CH2Si), 14.3 (SiCH2CH2S), 20.9
(NCH2CH2CH2CH2Si), 27.4 (SCH2CH2NMe2), 29.6 (SiCH2CH2S),
36.8 (NCH2CH2CH2CH2Si), 45.2 (SiCH2CH2NMe2), 59.0
(SCH2CH2NMe2); 15N NMR δ −353.0 (−NMe2); 29Si NMR δ 2.5
(G1-SiMe). Anal. Calcd for C17H41N3S2Si (379.74 g/mol): C, 53.77;
H, 10.88; N, 11.07; S, 16.89. Found: C, 53.83; H, 10.20; N, 11.03; S,
16.13.
NMR
δ −5.4 (SiMe), 12.7 (OCH2CH2CH2CH2Si), 13.5
( S i C H 2 C H 2 S ) , 1 9 . 6 ( O C H 2 C H 2 C H 2 C H 2 S i ) , 2 4 . 3
( S C H 2 C H 2 N M e 2 H + ) , 2 6 . 0 ( S i C H 2 C H 2 S ) , 3 2 . 2
(OCH2CH2CH2CH2Si), 41.4 (SiCH2CH2NMe2H+), 55.3 (S-
CH2CH2NMe2H+), 67.0 (OCH2), 114.8 and 115.2 (C6H4O2; CH),
150.6 and 150.9 (C6H4O2; CO); 29Si NMR δ 3.0 (G1−SiMe); 15N
NMR δ −338.2 (SiCH2CH2NMe2H+). MS: [M − HCl − Cl]+
=
4.2.11. HSG1(SNMe2·HCl)2 (31). To an MeOH solution of 25
(1.000 g, 1.96 mmol) was added HCl in dioxane (4 M, 2.9 mL, 11.73
mmol), and the mixture was stirred at 55 °C overnight. Afterward,
volatiles were removed under vacuum, yielding 31 as a yellowish solid
476.27 amu (calcd 476.27 amu). Anal. Calcd for C23H46Cl2N2O2S2Si
(545.75 g/mol): C, 50.62; H, 8.50; N, 5.13; S, 11.75. Found: C, 50.78;
H, 8.37; N, 4.95; S, 12.02.
4.2.8. PhtG1(NMe2HCl)2 (22). Compound 10 (0.303 g, 1.01 mmol),
2-(dimethylamino)ethanethiol hydrochloride (0.287 g, 2.02 mmol), 5
mol % of DMPA (0.052 g, 0.20 mmol), and a 1/2 THF/methanol
solution (5 mL) were combined. The reaction mixture was
deoxygenated and irradiated for 1.5 h. Another 5 mol % of DMPA
was added, and the reaction mixture was irradiated for another 1.5 h
1
(0.69 g, 75%). Data for 31 are as follows. NMR (D2O): H NMR δ
−0.05 (s, 3 H, SiCH3), 0.52 (m, 2 H, SCH2CH2CH2CH2Si), 0.84 (m,
4 H, SiCH2CH2S), 1.33 (m, 3 H, SCH2CH2CH2CH2Si, HS), 1.53 (m,
2 H, SCH2CH2CH2CH2Si), 2.46 (m, 2 H, SCH2CH2CH2CH2Si), 2.58
(t, J = 8.0 Hz, 4 H, SiCH2CH2S), 2.80 (m, 16 H, SCH2CH2N, NCH3),
3.26 (t, J = 7.0 Hz, 4 H, SCH2CH2N); 13C{1H} NMR δ −6.5 (SiCH3),
11.7 (SCH2 CH2 CH2 CH2 Si), 13.5 (SiCH2 CH2 S), 23.2
(SCH2CH2CH2CH2Si), 25.1 (SCH2CH2CH2CH2Si), 26.6
(SiCH2CH2S) 36.4 (SCH2CH2CH2CH2Si), 42.6 (SCH2CH2N), 42.7
(NCH3), 56.2 (SCH2CH2N); 15N NMR δ −338.3; 29Si NMR δ 2.9
(SiCH3). MS: [M − HCl − Cl]+ 397.22. Anal. Calcd for
C17H42Cl2N2S3Si (469.72): C, 43.47; H, 9.01; N, 5.96; S, 20.48.
Found: C, 42.99; H, 9.53; N, 5.97; S, 19.91.
1
and monitored by H NMR. After the reaction was completed, the
volatiles were removed under vacuum and then the residue was
dissolved in methanol. Afterward, it was precipitated in Et2O, and after
the solvent was separated, the solid was dried under vacuum to afford
22 as a white solid (0.46 g, 78%). Data for 20 are as follows. NMR
(DMSO): 1H NMR δ 0.00 (s, 3 H, SiMe), 0.60 (m, 2 H,
CH2SiC2H4S), 0.85 (m, 4 H, SiCH2CH2S). 1.28 (m, 2 H,
NCH2CH2CH2CH2Si), 1.60 (m, 2 H, NCH2CH2CH2CH2Si), 2.58
(m, 4 H, SiCH2CH2S), 2.73 (s, 12 H, NMe2H+), 2.86 (m, 4 H,
SCH2CH2N+), 3.16 (m, 4 H, SCH2CH2N+), 3.56 (m, 2 H, N−CH2),
7.84 (m, 4 H, C6H4), 10.79 (bs, 2 H, NMe2H+); 13C{1H} NMR δ −5.9
(SiMe), 11.9 (NCH2CH2CH2CH2Si), 13.4 (SiCH2CH2S), 20.2
(NCH2CH2CH2CH2Si), 24.0 (SCH2CH2N+), 25.9 (SiCH2CH2S),
31.0 (NCH2CH2CH2CH2Si), 36.5 (NCH2), 41.2 (NMe2H+), 55.2
(CH2N+), 122.5 and 133.9 (C6H4, CH), 131.1 (C6H4, Cipso), 167.5
ASSOCIATED CONTENT
* Supporting Information
■
S
Text giving the full experimental section and figures giving
selected NMR spectra. This material is available free of charge
via the Internet at http://pubs.acs.org.
(CO); 1 5 N NMR
δ
−338.9 (−NMe2 H+ ), −217.9
((CO)2NCH2).; 29Si NMR δ 3.0 (G1-SiMe). MS: [M − HCl − Cl]+
510.26 amu (calcd 510.26 amu). Anal. Calcd for C25H45Cl2N3O2S2Si
(582.77 g/mol): C, 51.52; H, 7.78; N, 7.21; S, 11.00. Found: C, 50.87;
H, 7.94; N, 6.69; S, 11.80.
AUTHOR INFORMATION
Corresponding Author
*Fax: 00 34 91 885 4683. Tel: 00 34 91 885 4685.
■
Notes
4.2.9. MeCOSG1(SNMe2·HCl)2 (25). A MeOH solution of HS-
(CH2)2NMe2·HCl (1.303 g, 9.20 mmol) was added to a THF solution
of 13 (1.000 g, 4.38 mmol) in the presence of DMPA (10%) as
catalyst and the mixture stirred under ultraviolet light (hν) for 4 h.
Volatiles were removed under vacuum, the residue was dissolved in
MeOH, excess Et2O was added, and the resulting precipitate was
washed with Et2O, yielding 25 as a yellow solid (1.57 g, 70%). Data for
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the grants CTQ2011-23245
(MINECO) and Consortium NANODENDMED ref S2011/
BMD-2351 (CAM) awarded to R.G. and UAH2011/EXP-037
1
25 are as follows. NMR (D2O): H NMR δ −0.02 (s, 3 H, SiCH3),
́
(University of Alcala) awarded to F.J.d.l.M. This study was also
0.53 (m, 2 H, SCH2CH2CH2CH2Si), 0.87 (m, 4 H, SiCH2CH2S), 1.30
(m, 2 H, SCH2CH2CH2CH2Si), 1.50 (m, 2 H, SCH2CH2CH2CH2Si),
2.28 (s, 3 H, CH3COS), 2.62 (m, 4 H, SiCH2CH2S), 2.85 (m, 18 H,
SCH2CH2CH2CH2Si, SCH2CH2N, NCH3), 3.33 (t, J = 7.5 Hz, 4 H,
supported by the CIBER-BBN financed by the Instituto de Salud
Carlos III, with assistance from the European Regional
Development Fund. E.F.-P. and M.G. acknowledge the
SCH2 CH2 N); 1 3 C{1 H} NMR
δ −5.6 (SiCH3 ), 12.7
Ministerio de Educacion
́
y Ciencia (Spain), and C.E.P.-G.
Superior, Ciencia y
( S C H 2 C H 2 C H 2 C H 2 S i ) , 1 3 . 9 ( S i C H 2 C H 2 S ) , 2 2 . 6
( S C H 2 C H 2 C H 2 C H 2 S i ) , 2 6 . 9 ( S i C H 2 C H 2 S ) , 2 8 . 7
( S C H 2 C H 2 C H 2 C H 2 S i ) , 3 0 . 6 ( C H 3 C O S ) , 3 2 . 7
(SCH2CH2CH2CH2Si), 42.7 (SCH2CH2N), 42.8 (NCH3), 56.4
(SCH2CH2N), 199.0 (CH3COS); 15N NMR δ −339.0; 29Si NMR δ
2.9 (SiCH3). MS [M − HCl − Cl]+ 439.23. Adequate analytical data
could not be obtained for this compound because the final product
showed a behavior very close to that of the starting HS-
(CH2)2NMe2·HCl.
acknowledges the Ministerio de Educacion
́
́
Tecnologia (Dominican Republic), for a fellowship.
REFERENCES
(1) Cuadrado, I.; Moran
Alonso, B.; Lobete, F. In Advances in Dendritic Macromolecules;
Newkome, G. R., Ed.; Jai Press: Greenwich, CT, 1999; Vol. 3, pp 151−
191.
■
́
, M.; Losada, J.; Casado, C. M.; Pascual, C.;
(2) Newkome, G. R.; Moorefield, C. N.; Vogtle, F. Dendrimers and
4.2.10. NH2G1(NMe2)2 (28). An excess of N2H4 (0.03 mL, 0.96
mmol) was added to a solution of 22 (0.141 g, 0.24 mmol) in MeOH
(10 mL). The reaction mixture was heated overnight at 80 °C in a
sealed ampule. Afterward solvent and excess N2H4 were removed and
the product was extracted into CH2Cl2. After evaporation 28 was
̈
Dendrons: Concepts, Syntheses, Applications; Wiley-VCH: Weinheim,
Germany, 2001.
(3) Twyman, L. J.; King, A. S. H.; Martin, I. K. Chem. Soc. Rev. 2002,
31, 69−82.
1794
dx.doi.org/10.1021/om301217g | Organometallics 2013, 32, 1789−1796

Organometallics
Article
(4) Yokoyama, S.; Otomo, A.; Nakahama, T.; Okuno, Y.; Mashiko, S.
Top. Curr. Chem. 2003, 228, 205−226.
(40) Duncan, R.; Izzo, L. Adv. Drug Delivery Rev. 2005, 57, 2215−
2237.
(5) Paleos, C. M.; Tsiourvas, D.; Sideratou, Z.; Tziveleka, L. Curr.
Top. Med. Chem. 2008, 8, 1204−1224.
(41) Ortega, P.; Bermejo, J. F.; Chonco, L.; de Jesus, E.; de la Mata,
́
F. J.; Fernan
́
dez, G.; Flores, J. C.; Gom
́
ez, R.; Serramía, M. J.; Munoz-
̃
(6) Cheng, Y. Y.; Xu, Z. H.; Ma, M. L.; Xu, T. W. J. Pharm. Sci. 2008,
97, 123−143.
(7) Smith, D. K. Curr. Top. Med. Chem. 2008, 8, 1187−1203.
(8) Joshi, N.; Grinstaff, M. Curr. Top. Med. Chem. 2008, 8, 1225−
1236.
Fernandez, M. A. Eur. J. Inorg. Chem. 2006, 1388−1396.
́
(42) Bermejo, J. F.; Ortega, P.; Chonco, L.; Eritja, R.; Samaniego, R.;
Mullner, M.; de Jesus, E.; de la Mata, F. J.; Flores, J. C.; Gom
́
ez, R.;
́
Munoz-Fernandez, A. Chem. Eur. J. 2007, 13, 483−495.
́
̃
(43) Weber, N.; Ortega, P.; Clemente, M. I.; Shcharbin, D.;
(9) Shcharbin, D. G.; Klajnert, B.; Bryszewska, M. Biochemistry 2009,
Bryszewska, M.; de la Mata, F. J.; Gomez, R.; Munoz-Fernandez, M. A.
́
́
̃
74, 1070−1079.
J. Controlled Release 2008, 132, 55−64.
(10) Rolland, O.; Turrin, C. O.; Caminade, A. M.; Majoral, J. P. New
J. Chem. 2009, 33, 1809−1824.
́
(44) Ortega, P.; Copa-Patino, J. L.; Munoz-Fernandez, M. A.;
̃ ̃
Soliveri, J.; Gom
3264−3269.
(45) Rasines, B.; Hernan
Patino, J. L.; Soliveri, J.; Munoz-Fernandez, M. A.; Gomez, R.; de la
́
ez, R.; de la Mata, F. J. Org. Biomol. Chem. 2008, 6,
(11) Mintzer, M. A.; Simanek, E. E. Chem. Rev. 2009, 109, 259−302.
(12) Medina, S. H.; El-Sayed, M. E. H. Chem. Rev. 2009, 109, 3141−
3157.
́
dez-Ros, J. M.; de las Cuevas, N.; Copa-
́
́
̃
̃
(13) Astruc, D.; Boisselier, E.; Ornelas, C. Chem. Rev. 2010, 110,
Mata, F. J. Dalton Trans. 2009, 8704−8713.
(46) Gonzalo, T.; Clemente, M. I.; Chonco, L.; Weber, N. D.; Díaz,
L.; Serramía, M. J.; Gras, R.; Ortega, P.; de la Mata, F. J.; Gomez, R.;
Lopez-Fernandez, L. A.; Munoz-Fernandez, M. A.; Jimenez, J. L. Chem.
Med. Chem. 2010, 5, 921−929.
(47) Ortega, P.; Fuentes-Paniagua, E.; Sanchez-Nieves, J.;
1857−1959.
(14) Villaraza, A. J. L.; Bumb, A.; Brechbiel, M. W. Chem. Rev. 2010,
110, 2921−2959.
́
́
́
́
́
̃
(15) Dutta, T.; Jain, N. K.; McMillan, N. A. J.; Parekh, H. S.
Nanomed. Nanotechnol. Biol. Med. 2010, 6, 25−34.
(16) Heegaard, P. M. H.; Boas, U.; Sorensen, N. S. Bioconjugate
Chem. 2010, 21, 405−418.
́
Hernan
Fernandez, M. A.; Gom
2011, 9, 5238−5248.
(48) Jimenez, J. L.; Gom
de la Mata, F. J.; Munoz-Fernan
́
dez-Ros, J. M.; Copa-Patino, J. L.; Soliveri, J.; Munoz-
̃
̃
́
́
ez, R.; de la Mata, F. J. Org. Biomol. Chem.
(17) Jimen
Leal, M.; Munoz-Fernan
́
ez, J. L.; Pion, M.; de la Mata, F. J.; Gom
dez, M. A. New J. Chem. 2012, 36, 299−309.
(18) Schluter, A. D.; Rabe, J. P. Angew. Chem., Int. Ed. 2000, 39, 864−
883.
́
ez, R.; Munoz, E.;
̃
́
ez, R.; Briz, V.; Madrid, R.; Bryszewsk, M.;
dez, M. A. J. Drug Deliv. Sci. Technol.
̃
́
́
́
̃
2012, 22, 75−82.
(49) Gras, R.; Relloso, M.; Garcıa, M. I.; de la Mata, F. J.; Gom
Lopez-Fernandez, L. A.; Munoz-Fernandez, M. A. Biomaterials 2012,
33, 4002−4009.
(50) Gras, R.; Garcıa, M. I.; Gom
Fernandez, M. A. Mol. Pharm. 2012, 9, 102−110.
(51) Rasines, B.; Sanchez-Nieves, J.; Molina, I. T.; Guzman
Munoz-Fernandez, M. A.; Gomez, R.; de la Mata, F. J. New J. Chem.
2012, 36, 360−370.
(52) Rasines, B.; San
L.; Jimen
(19) Daniel, M.-C.; Ruiz, J.; Nlate, S.; Palumbo, J.; Blais, J.-C.; Astruc,
D. Chem. Commun. 2001, 2000−2001.
(20) Kim, M. K.; Jeon, Y. M.; Jeon, W. S.; Kim, H. J.; Hong, S. G.;
Park, C. G.; Kim, K. Chem. Commun. 2001, 667−668.
(21) Daniel, M.-C.; Ruiz, J.; Nlate, S.; Blais, J.-C.; Astruc, D. J. Am.
Chem. Soc. 2003, 125, 2617−2628.
́
́
ez, R.;
́
́
́
̃
́
́
ez, R.; de la Mata, F. J.; Munoz-
̃
́
́
́
, M.;
(22) Jiang, G.; Wang, L.; Chen, W. Mater. Lett. 2007, 61, 278−283.
(23) Cho, T. J.; Zangmeister, R. A.; MacCuspie, R. I.; Patri, A. K.;
Hackley, V. A. Chem. Mater. 2011, 23, 2665−2676.
(24) Hardy, J. G.; Love, C. S.; Gabrielson, N. P.; Pack, D. W.; Smith,
D. K. Org. Biomol. Chem. 2009, 7, 789−793.
́
́
̃
́
chez-Nieves, J.; Maiolo, M.; Maly, M.; Chonco,
́
́
ez, J. L.; Munoz-Fernan
R. Dalton Trans. 2012, 41, 12733−12748.
(53) Chonco, L.; Pion, M.; Vacas, E.; Rasines, B.; Maly, M.; Serramía,
́
dez, M. A.; de la Mata, F. J.; Gom
́
ez,
̃
(25) Takahashi, T.; Hirose, J.; Kojima, C.; Harada, A.; Kono, K.
Bioconjugate Chem. 2007, 18, 1163−1169.
́
M. J.; Lop
Munoz-Fernan
́
ez-Fernan
́
dez, L.; de la Mata, F. J.; Alvarez, S.; Gom
dez, M. A. J. Controlled Release 2012, 161, 949−958.
́
ez, R.;
(26) Berna, M.; Dalzoppo, D.; Pasut, G.; Manunta, M.; Izzo, L.;
Jones, A. T.; Duncan, R.; Veronese, F. M. Biomacromolecules 2006, 7,
146−153.
́
̃
(54) Oka, H.; Onaga, T.; Koyama, T.; Guo, C.-T.; Suzuki, Y.; Esumi,
Y.; Hatano, K.; Terunuma, D.; Matsuoka, K. Bioorg. Med. Chem. Lett.
2008, 18, 4405−4408.
(55) Mori, T.; Hatano, K.; Matsuoka, K.; Esumi, Y.; Toone, E. J.;
Terunuma, D. Tetrahedron 2005, 61, 2751−2760.
(27) Pan, J.; Wen, M.; Yin, D.; Jiang, B.; He, D.; Guo, L. Tetrahedron
2012, 68, 2943−2949.
(28) Caminade, A. M.; Maraval, A.; Majoral, J. P. Eur. J. Inorg. Chem.
2006, 887−901.
(56) Nishikawa, K.; Matsuoka, K.; Watanabe, M.; Igai, K.; Hino, K.;
Hatano, K.; Yamada, A.; Abe, N.; Terunuma, D.; Kuzuhara, H.; Natori,
Y. J. Infect. Dis. 2005, 191, 2097−2105.
(57) Yamada, A.; Hatano, K.; Matsuoka, K.; Koyama, T.; Esumi, Y.;
Koshino, H.; Hino, K.; Nishikawa, K.; Natori, Y.; Terunuma, D.
Tetrahedron 2006, 62, 5074−5083.
(29) Uliniuc, A.; Popa, M.; Hamaide, T.; Dobromir, M. Cellulose
Chem. Technol. 2012, 46, 1−11.
(30) Finn, M. G.; Fokin, V. V. Chem. Soc. Rev. 2010, 39, 1231−1232.
́
(31) Arnaiz, E.; Doucede, L. I.; Garcia-Gallego, S.; Urbiola, K.;
Gomez, R.; de Ilarduya, C. T.; de la Mata, F. J. Mol. Pharm. 2012, 9,
433−447.
(58) Sakamoto, J.-I.; Koyama, T.; Miyamoto, D.; Yingsakmongkon,
S.; Hidari, K. I. P. J.; Jampangern, W.; Suzuki, T.; Suzuki, Y.; Esumi, Y.;
Nakamura, T.; Hatano, K.; Terunuma, D.; Matsuoka, K. Bioorg. Med.
Chem. 2009, 17, 5451−5464.
(32) Carlmark, A.; Hawker, C. J.; Hult, A.; Malkoch, M. Chem. Soc.
Rev. 2009, 38, 352−362.
(33) Nwe, K.; Brechbiel, M. W. Cancer Biother. Radiopharm. 2009,
24, 289−302.
(59) Vigo, S.; Andres
Organomet. Chem. 2012, 717, 88−98.
(60) Nunez, R.; Gonzalez-Campo, A.; Laromaine, A.; Teixidor, F.;
Sillanpaa, R.; Kivekas, R.; Vinas, C. Org. Lett. 2006, 8, 4549−4552.
́ ́
́
, R.; Gomez-Sal, P.; Mata, J. d. l.; Jesus, E. d. J.
(34) Liang, L.; Astruc, D. Coord. Chem. Rev. 2011, 255, 2933−2945.
(35) Love, A. B. Polym. Chem. 2010, 1, 17−36.
(36) Kang, T.; Amir, R. J.; Khan, A.; Ohshimizu, K.; Hunt, J. N.;
́
́
̃
̈
̈
̈
̃
́
Sivanandan, K.; Montanez, M. I.; Malkoch, M.; Ueda, M.; Hawker, C.
̃
J. Chem. Commun. 2010, 46, 1556−1558.
(61) Andres
R. Eur. J. Inorg. Chem. 2005, 3742−3749.
́
́ ́
, R.; de Jesus, E.; de la Mata, F. J.; Flores, J. C.; Gomez,
(37) Grayson, S. M.; Frec
3867.
(38) Hecht, S.; Frec
91.
́
het, J. M. J. Chem. Rev. 2001, 101, 3819−
(62) van Heerbeek, R.; Kamer, P. C. J.; van Leeuwen, P. N. M. W.;
Reek, J. N. H. Org. Biomol. Chem. 2006, 4, 211−223.
́
het, J. M. J. Angew. Chem., Int. Ed. 2001, 40, 74−
(63) Rissing, C.; Son, D. Y. Organometallics 2008, 27, 5394−5397.
(64) Rissing, C.; Son, D. Y. Organometallics 2009, 28, 3167−3172.
̌
́ ́ ́
́
A.; Cermak, J.; Walterova, Z.; Horsky, J. Macro-
(39) Newkome, G. R.; Shreiner, C. Chem. Rev. 2010, 110, 6338−
6442.
(65) Krupkova,
molecules 2010, 43, 4511−4519.
1795
dx.doi.org/10.1021/om301217g | Organometallics 2013, 32, 1789−1796

Organometallics
Article
(66) San
́ ́
chez-Nieves, J.; Ortega, P.; Munoz-Fernandez, M. A.;
̃
Gomez, R.; de la Mata, F. J. Tetrahedron 2010, 9203−9213.
́
1796
dx.doi.org/10.1021/om301217g | Organometallics 2013, 32, 1789−1796