"Click" chemistry-mediated phenylene-cored carborane dendrimers

Article abstract of DOI:10.1021/om201255b

Phenylene-cored small dendrimers containing three to nine peripheral o-carborane clusters were synthesized via Cu(I)-catalyzed Huisgen-type azide alkyne cycloaddition reactions. The resulting dendrimers have been characterized by IR and NMR spectroscopy a

Full text of DOI:10.1021/om201255b

Article
pubs.acs.org/Organometallics
“Click” Chemistry-Mediated Phenylene-Cored Carborane
Dendrimers∥
Barada Prasanna Dash,† Rashmirekha Satapathy,†,⊥ Barrie P. Bode,‡ Cory T. Reidl,† James W. Sawicki,†
Allen J. Mason,† John A. Maguire,§ and Narayan S. Hosmane*,†
†Department of Chemistry & Biochemistry, Northern Illinois University, DeKalb, Illinois 60115-2862, United States
‡Department of Biological Sciences, Northern Illinois University, DeKalb, Illinois 60115-2857, United States
§Department of Chemistry, Southern Methodist University, Dallas, Texas 75275-0314, United States
S
* Supporting Information
ABSTRACT: Phenylene-cored small dendrimers containing
three to nine peripheral o-carborane clusters were synthesized
via Cu(I)-catalyzed Huisgen-type azide alkyne cycloaddition
reactions. The resulting dendrimers have been characterized by
IR and NMR spectroscopy and MALDI-TOF mass spectral
analysis. The biological evaluation of branched dendrimer 16
containing nine carborane cages has been carried out using
human liver cancer cells (SK-Hep1). Dendrimer 16 was
accumulated in the SK-Hep1 cancer cells in a concentration-
dependent manner. The highest boron accumulation up to 2540 ng of boron/5 × 105 cells was observed at a 50 μM
concentration of 16 over a period of 20 h. The high accumulation of 16 into the tumor cell lines indicates that such dendritic
boron drug delivery platforms could be possible for application in boron neutron capture therapy in cancer treatment.
containing three to nine o-carborane clusters. The biological
uptake of the branched dendrimer 16 that contains the highest
boron content with nine o-carborane clusters has also been
carried out using human hepatocellular carcinoma cells (SK-
Hep1).
INTRODUCTION
■
Dendrimers and dendritic macromolecules often find applica-
tions as drug delivery platforms.1 Because of the dendrimer’s
unique branching architecture and high number of surface
functional groups, it can carry large payloads of therapeutic
molecules. Enhanced cellular uptake of dendrimer-based drug
delivery systems has been observed.2 Because of the leaky
vasculature of tumor tissues, macromolecular and dendrimer-
based drug delivery systems are preferentially transported to
the tumor tissues and accumulate in them in a process known
as the enhanced permeability and retention (EPR) effect.3
Therefore, incorporation of carboranes into dendritic macro-
molecules could be a viable approach for the delivery of boron
to the tumor tissues for successful treatment of cancer via
boron neutron capture therapy (BNCT). It has been estimated
that a concentration of 30 μg of 10B per gram of tissue is
necessary for effective BNCT; this is a relatively high
concentration that can be achieved using dendritic molecules
containing multiple carborane clusters.4 Carboranes are
relatively easy to functionalize, resistant to biodegradation,
and boron-rich in nature.5,6 Therefore, carboranes are useful in
medicinal chemistry as a source of boron and as pharmaco-
phores.6 Dendritic structures containing multiple carborane
clusters have been synthesized by employing various synthetic
approaches.4a,7 In an attempt to employ a new synthetic
strategy for the synthesis of carborane-appended dendritic
molecules in the present study, we have used a Cu(I)-catalyzed
Huisgen-type azide−alkyne “click” cycloaddition reaction8 for
the syntheses of phenylene-cored carborane dendrimers9
RESULTS AND DISCUSSION
■
Synthesis. When commercially available methyl-3,5-dihy-
droxybenzoate 1 was treated with propargyl bromide in the
presence of K2CO3, bis(ether) 2 was obtained in quantitative
yield. The bromide 4 was obtained in almost quantitative yield
by reduction of 2 with LiAlH4, followed by bromination with
PBr3 in CH2Cl2 at room temperature (see Scheme 1). The
bromide 8 was obtained from methyl-3,4,5-trihydroxybenzoate,
5, following the same sequence, that is, reacting 5 with
propargyl bromide in the presence of K2CO3, and further
reduction of ester 6 with LiAlH4, followed by bromination with
PBr3 in CH2Cl2 at room temperature, as shown in Scheme 1.10
After the preparation of alkynyl dendrons, the central cores
containing multiple peripheral alkyne moieties from 1,3,5-
tris(4-hydroxyphenyl)benzene 9 were synthesized.11 Whereas
the carboranyl azide 13 was prepared according to the literature
procedure,11 the alkyne−azide “click” cycloaddition strategy
was employed for the synthesis of carborane-appended
dendritic macromolecules.8 On the other hand, the alkynyl
Special Issue: F. Gordon A. Stone Commemorative Issue
Received: December 19, 2011
Published: January 20, 2012
© 2012 American Chemical Society
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manner over 20 h. At 10 μM, dendrimer 16 yielded 690 59
ng of B per 5 × 105 cells, whereas at 20 and 50 μM, it yielded
Scheme 1. Synthesis of Alkynyl Dendrons
1370
244 and 2540
142 ng of B per 5 × 105 cells,
respectively. Further studies will be required to determine
whether compound 16 is taken up into the cell or bound to the
cell surface. The detailed description of the growth of the cell
culture and preparation of the biodistribution assay and
measurements are given in the Experimental Section.
CONCLUSIONS
■
The Cu(I)-catalyzed azide−alkyne cycloaddition reaction
(CuAAC) has been found to be a facile approach for the
synthesis of phenylene-cored small dendrimers containing three
to nine carborane clusters at the periphery. All three carborane-
appended dendrimers were synthesized from the single starting
compound 1,3,5-tris(4-hydroxyphenyl)benzene 9 in very good
yields. The biological evaluation of dendrimer 16 containing
nine carborane cages has shown that the boron has been
accumulated in the human liver cancer cells in a concentration-
dependent manner. It was found that up to 2540 ng of boron
per 5 × 105 cells was accumulated over a period of 20 h. The
high accumulation of the macromolecular compound into the
cancer cells indicates that the dendritic molecules could be the
potential boron delivery platforms for BNCT applications.
EXPERIMENTAL SECTION
■
General Methods. All reactions were generally performed under
argon in oven-dried flasks using Schlenk lines. Solvents and reagents
were added by syringes. Solvents were dried using standard
procedures. Reagents were used as purchased without further
purification unless indicated otherwise. Products were all purified by
column chromatography on silica gel (70−230 mesh), and yields refer
to analytically pure samples. While the 1H NMR spectra were recorded
on a Fourier-Transform multinuclear NMR spectrometer at 500 and
300 MHz, the 13C NMR spectra were recorded at 125 and 75 MHz.
The chemical shifts are reported relative to tetramethylsilane (TMS)
(1H: δ = 0.00 ppm) and CDCl3 (13C: δ = 77.0 ppm). The integrals are
in accordance with the assignments, the coupling constants (J's) are all
given in hertz, and all of the 13C NMR spectra were proton-decoupled.
The 11B NMR spectra were recorded at 160.5 MHz, and the chemical
shifts are relative to the BF3·Et2O standard. The infrared (IR) spectra
of all compounds were recorded on an FT-IR spectrophotometer.
Melting points of the solids were measured using a standard apparatus,
and the data were uncorrected. Mass spectral analyses were carried out
using ES and MALDI-TOF mass spectrometers.
Cell Culture. Human hepatocellular carcinoma cells (SK-Hep1)
were chosen because of their well-characterized aggressive growth and
accelerated nutrient uptake rates, reflective of highly malignant
cancer,12a and the emerging interest in pursuing BNCT for
hepatocellular carcinoma (HCC).12b SK-Hep1 were grown in
Dulbecco’s Modified Essential Medium (DMEM) supplemented
with 2 mM L-glutamine and 10% (v/v) fetal bovine serum (FBS)
and were maintained in a humidified atmosphere of 5% CO2/95% air
at 37 °C, as previously described.12a Cells were seeded into 12-well
culture plates at a concentration of 4 × 104 cells per well and allowed
to attach and grow to 90% confluence prior to initiation of
experiments.
core 10 was obtained from 9 by reacting with propargyl
bromide and K2CO3 and was then reacted with carboranyl
azide 13 under “click” reaction conditions, leading to 14 in 85%
yield. Compound 14 contains three carborane cages appended
to the central phenylene core, as shown in Scheme 2.
In a similar methodology, the alkynyl core 11 containing six
alkynyl moieties in the periphery was obtained in 88% yield by
the reaction between 9 and 4 in the presence of K2CO3. The
dendrimer 15 was obtained via the “click” cycloaddition
reaction between core 11 and carboranyl azide 13, in 78%
yield. As can be seen in Scheme 2, six carborane cages are
appended to the central phenylene core. A further branched
dendrimer species 16, appended with nine carborane cages to
the central phenylene core, was isolated in 76% yield following
the same reaction procedure (see Scheme 2). Because of the
presence of nine o-carborane clusters, 16 possesses the highest
boron content in the series, which is up to 30% of the weight of
the molecule. Therefore, the biological evaluation of 16 was
warranted.
All compounds were characterized by 1H, 13C, and 11B NMR
spectra; IR spectra; and mass spectral analysis where possible.
The IR spectra of compounds containing carborane clusters
showed strong bands between 2580 and 2586 cm−1
corresponding to ν(B−H). The presence of carborane clusters
1
was also evident from the H, 13C, and 11B NMR spectra.
Confirmatory mass spectral analyses of the compounds were
also carried out, in addition to melting point measurements for
all solid compounds. Finally, the mass spectral data of all
compounds confirmed their identifications. The MALDI-TOF
mass spectral data for the carborane-appended dendrimers 14,
15, and 16 showed prominent peaks at m/z 1192.13 (M+,
100%), 2397.58 (M+, 100%), and 3345.05 (M++ 2Na),
respectively (see the Supporting Information).
Biological Evaluation of Dendrimer 16. The carborane-
appended dendrimer 16 was dissolved in dimethylsulfoxide
(DMSO) as a 10 mM stock solution and added to the growth
medium to final concentrations of 10, 20, and 50 μM. Control cells
received vehicle (DMSO) alone (0.5% final [DMSO]). The medium
was aspirated from the cells and replaced with medium containing the
compound at 10, 20, and 50 μM, and cells were placed at 37 °C for 20
h. All assays were performed in triplicate for each time point and
temperature. After each time period, the medium was aspirated and
the cell monolayers were rinsed twice with 1 mL of phosphate-
Biological Evaluation of Dendrimer 16. As shown in
Figure 1, dendrimer 16 accumulated in the SK-Hep1 human
hepatocellular carcinoma cells in a concentration-dependent
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Scheme 2. Synthesis of Dendrimers Containing Three to Nine Carborane Clusters via “Click” Chemistry
buffered saline (PBS). The cells were scraped into 500 μL of PBS with
a plastic spatula and triturated 10−15 times with a pipet to yield a
single cell suspension. Cell pellets were obtained by centrifugation of
the cell suspension at 500g for 2 min, followed by aspiration of the
supernatant. Cell pellets were stored at −80 °C until assayed for boron
content by ICP-MS. Quantitative measurements were performed on a
PerkinElmer Sciex Elan 6000 inductively coupled plasma mass
spectrometer. Results are reported as nanograms of boron per 5 ×
105 cells.
Preparation and Analytical Data of Compounds 4 and 8.
Methyl-3,5-dihydroxybenzoate 1 (10.0 g, 59.471 mmol) was dissolved
in dry acetone (200 mL). Potassium carbonate (36.11 g, 261.67
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mg, 2.37 mmol). Purification: Silicagel column chromatography using
20−30% EtOAc in hexane. Pure product: 300 mg. Yield: 80%.
1
Colorless solid. mp: 55−56 °C. H NMR (CDCl3, 500 MHz): δ 7.67
(s, 3H), 7.63 (d, 6H, J = 8.65 Hz), 7.08 (d, 6H, J = 8.65 Hz), 6.76 (d,
6H, J = 1.75 Hz), 6.62 (d, 3H, J = 1.85 Hz), 5.10 (s, 6H), 4.71 (d,
12H, J = 2.20 Hz), 2.55 (t, 6H, J = 2.10 Hz). 13C NMR (CDCl3, 125
MHz): δ 158.9, 158.3, 141.7, 139.6, 134.1, 128.4, 123.9, 115.2, 106.8,
101.7, 78.3, 75.7, 69.8, 55.9. IR (KBr): 3286, 2920, 2867, 2121, 1595,
1510, 1449, 1385, 1292, 1151, 1061, 818 cm−1. MALDI-TOF-MS (m/
z): calcd, 949.05; found, 948.87 (M+, 100%).
12: 1,3,5-Tris(4-hydroxyphenyl)benzene 9 (300 mg, 0.8465 mmol),
acetone (50 mL), bromide 8 (1.7 g, 5.07 mmol), and K2CO3 (700 mg,
5.07 mmol). Purification: Silicagel column chromatography using 50−
60% EtOAc in hexane. Pure product: 840 mg. Yield: 89%. Sticky
liquid. 1H NMR (CDCl3, 500 MHz): δ 7.68 (s, 3H), 7.65 (d, 6H, J =
8.70 Hz), 7.10 (d, 6H, J = 8.75 Hz), 6.90 (s, 6H), 5.10 (s, 6H), 4.81−
4.77 (m, 18H), 2.52−2.50 (m, 9H). 13C NMR (CDCl3, 125 MHz): δ
158.3, 151.7, 141.8, 136.9, 134.1, 133.1, 128.3, 123.9, 115.2, 107.8,
79.1, 78.4, 75.9, 75.2, 69.9, 60.3, 57.1. IR (neat): 3286, 2926, 2868,
2121, 1606, 1509, 1444, 1386, 1230, 1180, 1110, 1005, 828 cm−1.
MALDI-TOF-MS (m/z): calcd, 1111.19; found, 1134.4 (M+ + Na).
General Procedure for Synthesis of Click Dendrimer. The
alkynyl core and the carboranyl azide 13 were dissolved in THF.
CuSO4, 5H2O, potassium ascorbate, and water were added to it. The
reaction mixture was stirred at room temperature for 16 h. The
mixture was then extracted with dichloromethane, and the organic
layer was washed with aqueous ammonium chloride and water and
dried over anhydrous MgSO4 and evaporated. The residue was
purified by silica gel column chromatography.
Figure 1. Accumulation of dendrimer 16 to SK-Hep1 human
hepatocellular carcinoma cells. Cell pellets were assayed for boron
content by inductively coupled plasma mass spectrometry (ICP-MS),
as described in the Experimental Section. The values indicated on the y
axis were the average of triplicate determinations for each
concentration and are reported as nanograms of boron per 5 × 105
cells.
mmol) and propargyl bromide (80 wt % in toluene, 19.5 mL) were
then added to it. The mixture was refluxed at 80 °C for 20 h, filtered
through a silica pad, and was then concentrated. The organic layer was
dried over MgSO4 and evaporated. Compound 6 was synthesized by
using a similar procedure from methyl-3,4,5-trihydroxybenzoate 5.
Both compounds 2 and 6 were synthesized in quantitative yields and
used for further reaction without purification. LiAlH4 (6.21 g, 163.76
mmol) was suspended in dry THF (200 mL) and cooled to 0 °C. A
solution of 2 (10.0 g, 40.94 mmol) in 30 mL of dry THF was then
added to it at 0 °C. The mixture was stirred at 0 °C for 1 h and then at
room temperature for 5 h. LiAlH4 was quenched with dropwise
addition of water very carefully, and then the reaction mixture was
extracted with dichloromethane. The organic layer was washed with
water, dried over anhydrous MgSO4, and evaporated to get 9.0 g of
pure product 3 in quantitative yield. Without purification, this product
was used for the next reaction. To the solution of 3 (9.0 g, 41.62
mmol) in dichloromethane (150 mL) was added PBr3 (4 mL, 41.62
mmol), and the reaction mixture was stirred at room temperature for
15 h. After the reaction was over, water was added to that reaction
mixture and extracted with dichloromethane. The organic layer was
washed with water, dried over anhydrous MgSO4, and evaporated to
14: The alkynyl core 10 (50 mg, 0.106 mmol), carboranyl azide 13
(154 mg, 0.640 mmol), THF (3 mL), CuSO4, 5H2O (319.71 mg,
1.280 mmol), potassium ascorbate (548.63 mg, 2.561 mmol), and
water (3 mL). Purification: silica gel column chromatography using
50−90% EtOAc in hexane. Pure product: 108 mg. Yield: 85%. mp >
1
230 °C (dec). H NMR (CDCl3, 500 MHz): δ 7.67 (s, 3H), 7.66 (s,
3H), 7.64 (d, 6H, J = 8.7 Hz), 7.10 (d, 6H, J = 8.7 Hz), 5.31 (s, 6H),
4.43 (s, 6H), 2.23 (s, 6H), 2.19 (s, 6H), 1.92 (s, 9H). 13C NMR
(CDCl3, 125 MHz): δ 157.8, 144.6, 141.6, 134.3, 128.4, 123.9, 122.6,
115.1, 76.5, 75.0, 62.0, 49.2, 32.0, 29.9, 23.0. IR (KBr): 3140, 2944,
2580, 1607, 1510, 1467, 1232, 828 cm−1. 11B NMR (proton-
decoupled): −4.0, −5.33, −9.50, −10.20. MALDI-TOF-MS (m/z):
calcd, 1192.57; found, 1192.13 (M+, 100%).
15: The alkynyl core 11 (70 mg, 0.073 mmol), carboranyl azide 13
(213 mg, 0.885 mmol), THF (4 mL), CuSO4, 5H2O (437 mg, 1.752
mmol), potassium ascorbate (750 mg, 3.504 mmol), and water (4
mL). Purification: silica gel column chromatography using 50−90%
EtOAc in hexane. Pure product: 136 mg. Yield: 78%. Colorless solid.
1
get 11.2 g of pure product 4. Yield: 96%. H NMR (CDCl3, 500
MHz): δ 6.67 (d, 2H, J = 2.0 Hz), 6.58 (t, 1H, J = 2.0 Hz), 4.70 (d,
4H, J = 2.5 Hz), 4.44 (s, 2H), 2.57 (t, 2H, J = 2.5 Hz). 13C NMR
(CDCl3, 125 MHz): δ 158.7, 139.9, 108.7, 102.4, 78.1, 75.8, 56.0, 33.2.
ES-MS (m/z): Calcd, 279.13; found, 279.0 (M+, 100%). Compound 8
was synthesized from 5 by employing a procedure described
elsewhere.10
General Procedure for Synthesis of Alkynyl Core. 1,3,5-
Tris(4-hydroxyphenyl)benzene 9 was solubilized in acetone. To this
solution, the alkynyl bromo compound and K2CO3 were added, and
the reaction mixture was refluxed at 60−70 °C up to 24 h. The mixture
was filtered through a cotton plug, and the solvent was evaporated and
then purified by silica gel column chromatography.
10: 1,3,5-Tris(4-hydroxyphenyl)benzene 9 (140 mg, 0.395 mmol),
acetone (20 mL), propargyl bromide (0.3 mL), and K2CO3 (327 mg,
2.37 mmol). Purification: Silicagel column chromatography using 20−
30% EtOAc in hexane. Pure product: 176 mg. Yield: 95%. mp: 120−
122 °C. 1H NMR (CDCl3, 500 MHz): δ 7.69 (s, 3H), 7.66 (d, 6H, J =
8.0 Hz), 7.11 (d, 6H, J = 8.0 Hz), 4.78 (s, 6H), 2.58 (s, 3H). 13C NMR
(CDCl3, 125 MHz): δ 157.2, 141.7, 134.6, 128.3, 124.0, 115.2, 78.5,
75.6, 55.9. IR (KBr): 3283, 2918, 2114, 1672, 1606, 1510, 1444, 1222,
1037, 921, 834 cm−1. ES-MS (m/z): calcd, 468.5; found, 469.2 (M+ +
1, 100%).
1
mp > 260 °C. H NMR (CDCl3, 500 MHz): δ 7.68 (s, 3H), 7.65 (s,
3H), 7.63 (s, 9H), 7.07 (d, 6H, J = 8.50 Hz), 6.75 (s, 6H), 6.61 (s,
3H), 5.23 (s, 6H), 5.10 (s, 12H), 4.39 (s, 12H), 2.23−2.21 (m, 36H),
1.92 (s, 18H). 13C NMR (CDCl3, 125 MHz): δ 159.5, 158.3, 144.3,
141.7, 139.8, 133.9, 128.3, 123.7, 122.7, 115.2, 106.5, 101.4, 76.4, 75.0,
69.7, 61.9, 49.2, 32.0, 29.9, 23.0. 11B NMR (proton-decoupled): −3.99,
−5.61, −9.65, −10.38. IR (KBr): 2961, 2927, 2586, 2361, 2099, 1710,
1591, 1454, 1384, 1261, 1161, 1041, 803 cm−1. MALDI-TOF-MS (m/
z): calcd, 2397.12; found, 2397.58 (M+, 100%).
16: The alkynyl core 12 (125 mg, 0.112 mmol), carboranyl azide 13
(489 mg, 2.030 mmol), THF (6 mL), CuSO4, 5H2O (1.01 g, 4.05
mmol), potassium ascorbate (1.73 g, 8.114 mmol), and water (6 mL).
Purification: silica gel column chromatography using 20% methanol in
ethyl acetate. Pure product: 280 mg. Yield: 76%. Colorless solid. mp >
230 °C. 1H NMR (DMSO-d6, 500 MHz): δ 8.26 (s, 3H), 8.14 (s, 6H),
7.82 (d, 6H, J = 8.50 Hz), 7.16 (d, 6H, J = 8.50 Hz), 7.0 (s, 9H), 5.19
(s, 6H), 4.44−4.37 (m, 18H), 4.0 (s, 18H), 2.51 (s, 18H), 2.36−2.29
(m, 18H), 1.98 (s, 27H). 13C NMR (CDCl3, 125 MHz): δ 158.6,
152.2, 144.1, 143.3, 141.5, 136.9, 133.3, 133.2, 128.6, 124.9, 115.7,
107.8, 78.7, 76.6, 69.8, 66.0, 62.6, 48.8, 31.5, 30.3, 22.8. 11B NMR
(proton-decoupled): −4.85, −6.23, −9.89, −10.92. IR (KBr): 3139,
2973, 2874, 2583, 1731, 1641, 1511, 1433, 1385, 1223, 1106, 1046,
11: 1,3,5-Tris(4-hydroxyphenyl)benzene 9 (140 mg, 0.395 mmol),
acetone (20 mL), bromide 4 (661 mg, 2.37 mmol), and K2CO3 (327
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827 cm−1. MALDI-TOF-MS (m/z): calcd, 3299.6; found, 3345.05 (M+
+ 2Na).
(7) (a) Dash, B. P.; Satapathy, R.; Maguire, J. A.; Hosmane, N. S.
Chem. Commun. 2009, 3267−3269. (b) Nunez, R.; Gonzalez-Campo,
A.; Laromaine, A.; Teixidor, F.; Sillanpaa, R.; Kivekas, R.; Vinas, C.
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Angew. Chem., Int. Ed. Engl. 1994, 33, 666−668.
ASSOCIATED CONTENT
■
S
* Supporting Information
Figures giving NMR spectra and MALDI-TOF spectra of
compounds prepared in this paper. This material is available
free of charge via the Internet at http://pubs.acs.org.
(8) (a) Djeda, R.; Ruiz, J.; Astruc, D.; Satapathy, R.; Dash, B. P.;
Hosmane, N. S. Inorg. Chem. 2010, 49, 10702−10709. (b) Rostovtsev,
V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed.
2002, 41, 2596−2600. (c) Tornøe, C. W.; Christensen, C.; Meldal, M.
J. Org. Chem. 2002, 67, 3057−3064. (d) Meldal, M.; Tornøe, C. W.
Chem. Rev. 2008, 108, 2952−3015. (e) Kolb, H. C.; Finn, M. G.;
Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004−2021.
(9) (a) Dash, B. P.; Satapathy, R.; Gaillard, E. R.; Norton, K. M.;
Maguire, J. A.; Hosmane, N. S. Inorg. Chem. 2011, 50, 5485−5493.
(b) Dash, B. P.; Satapathy, R.; Maguire, J. A.; Hosmane, N. S. Org. Lett.
2008, 10, 2247−2250. (c) Dash, B. P.; Satapathy, R.; Gaillard, E. R.;
Maguire, J. A.; Hosmane, N. S. J. Am. Chem. Soc. 2010, 132, 6578−
6587.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: hosmane@niu.edu.
Present Address
⊥Department of Chemistry, Ravenshaw University, Cuttack
753003, India.
ACKNOWLEDGMENTS
■
This work was supported by grants from the National Science
Foundation (CHE-0906179 and CHE-0840504). N.S.H. also
acknowledges the Inaugural Board of Trustees Professorship
from Northern Illinois University and the Alexander von
Humboldt Foundation’s Research Prize for Senior Scientists.
We acknowledge the technical skill of Anthony Lutton in the
ICP-MS analyses at the Ohio State University Trace Element
Research Laboratory.
(10) Camponovo, J.; Ruiz, J.; Cloutet, E.; Astruc, D. Chem.Eur. J.
2009, 15, 2990−3002.
(11) Dash, B. P.; Satapathy, R.; Maguire, J. A.; Hosmane, N. S.
Organometallics 2010, 29, 5230−5235.
(12) (a) Bode, B. P.; Fuchs, B. C.; Hurley, B. P.; Conroy, J. L.;
Suetterlin, J. E.; Tanabe, K. K.; Rhoads, D. B.; Abcouwer, S. F.; Souba,
W. W. Am. J. Physiol.: Gastrointest. Liver Physiol. 2002, 283, G1062−
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Kinashi, Y.; Nagata, K.; Maruhashi, A.; Kudo, M.; Ono, K. Jpn. J. Clin.
Oncol. 2007, 37, 376−381.
DEDICATION
■
∥Dedicated to the memory of Professor F. Gordon A. Stone.
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