A R T I C L E S
Liu et al.
Experimental Section
product was purified by alumina column (dichloromethane/methanol,
9
5:5) to give the final product as a yellow oil (1.90 g, 60%). ESI-MS:
Materials and Analysis. All chemicals unless indicated were
obtained from Sigma Aldrich and used as received. Air-sensitive
materials were handled in an Omni-Lab VAC glove box under dry
nitrogen atmosphere with oxygen levels <0.2 ppm. All solvents were
spectrophotometric grade and purchased from EMD Biosciences.
Amine-bearing compounds were visualized on thin layer chromatog-
raphy (TLC) plates using a ninhydrin solution. All other TLC plates
were visualized by iodine staining. NMR spectra were recorded on a
Bruker DRX 401 NMR Spectrometer. ESI-MS was measured on an
Applied Biosystems QTrap mass spectrometer. Samples were dissolved
in a solution of acetonitrile, water, and acetic acid (50:50:0.01 v/v) at
a concentration of 2.5 pmol/µL and introduced via syringe pump at a
flow rate of 10 µL/min. UV-vis absorbance spectra were taken using
an HP 8453 diode array spectrophotometer. Photoluminescence spectra
were recorded with a SPEX FluoroMax-3 spectrofluorimeter. The
absorbance of all solutions was kept below 0.1 OD to avoid inner-
filter effects. Commercial QD605’s were obtained from Invitrogen (cat.
no. Q22041, component A).
+
1
m/z 601 [M + H] . H NMR (400 MHz, CDCl
2
2
-
3
): δ (ppm) 3.63 (m,
6H), 3.52 (t, J ) 5.2 Hz, 2H), 3.47 (t, J ) 5.2 Hz, 2H) 3.10 (m, 2H),
.86 (t, J ) 5.2 Hz, 2H), 2.40 (m, 1H), 2.17 (t, J ) 6.5 Hz, 2H), 1.99
1.46 (m, 7H).
Compound 3 (aminoPEG). To a solution of 2 (1.50 g, 2.50 mmol)
in 4:1 water/ethanol (20 mL) at 4 °C was slowly added 4 equiv of
sodium borohydride over a 30 min period. The solution was stirred for
2
h at 4 °C, acidified to pH 2 with 3 M HCl, and extracted with
chloroform (3 × 15 mL). The combined organics were dried over
MgSO
4
and filtered. The solvent was removed in vacuo to yield the
+
product as a colorless oil (1.37 g, 91%). ESI-MS: m/z 603 [M + H] .
1
H NMR (400 MHz, CDCl ): δ (ppm) 3.84 (m, 2H), 3.61 (m, 36H),
3
3
1
.52 (m, 4H), 3.13 (m, 2H), 2.84 (m, 2H), 2.62 (m, 2H), 2.19 (m, 2H),
.99 - 1.46 (m, 9H).
Compound 5 (LA-PEG-CO H). Into a solution of 2 (1.90 g, 3.16
2
mmol) and triethylamine (0.320 g, 3.16 mmol) in dichloromethane (30
mL) was dripped slowly a solution of methylmalonylchloride (0.475
g, 3.48 mmol) in dichloromethane (10 mL) at 4 °C. The solution was
stirred at RT for 4 h and the solvent removed in vacuo. The crude
product was purified by silica column (dichloromethane/methanol, 95:
Compound 1 (Diamino-PEG). Neat PEG
20.0 g, 48.3 mmol) was degassed at 80 °C for 1 h with stirring to
remove traces of water. The flask was back-filled with N and cooled
8
(average MW 400 g/mol)
(
2
5
(
3
) and the solvent evaporated to give the pure product as a yellow oil
1.97 g, 89%). Methylester deprotection was achieved by stirring with
.5 equiv of NaOH in methanol for 5 h at 60 °C. The solvent was
on an ice bath before thionyl chloride (10.5 mL, 145.0 mmol) was
slowly added. The solution was warmed to 25 °C and stirred for 2 h.
The conversion was monitored by the disappearance of the broad O-H
removed in vacuo after neutralizing to pH 7 with 3 M HCl. The product
was dissolved in water, acidified to pH 2, and extracted with chloroform
-1
-1
stretch at 3500 cm and the appearance of a C-Cl stretch at 730 cm
in the IR spectrum. The product was diluted with DMF (20 mL) and
the solvent removed under reduced pressure. This was repeated three
times to remove all residual traces of thionyl chloride. The sample was
dissolved in a solution of sodium azide (9.42 g, 145.0 mmol) in 250
mL of DMF and stirred overnight at 85 °C. The solvent was removed
under reduced pressure, and 200 mL of dichloromethane was added.
The precipitate was removed by vacuum filtration and the solvent
evaporated in vacuo to yield the intermediate diazide. The conversion
(
3 × 20 mL) to yield the pure product in quantitative yield. ESI-MS:
m/z 731 [M + H] . H NMR (400 MHz, CDCl ): δ (ppm) 3.70-3.52
m, 36 H), 3.51-3.35 (m, 6H), 3.14 (m, 2H), 2.45 (m, 1H), 2.20 (t, J
7.3 Hz, 2H), 1.96-1.36 (m, 7H).
Compound 6 (carboxyPEG). To a solution of 2 (1.50 g, 2.06 mmol)
in 0.25 M sodium bicarbonate buffer (20 mL) at 4 °C was slowly added
equiv of sodium borohydride over a 30 min period. The solution
+
1
3
(
)
4
was stirred for 2 h at 4 °C, acidified to pH 2 with 3 M HCl, and
extracted with chloroform (3 × 15 mL). The combined organics were
-
1
was confirmed by the appearance of a sharp azide stretch at 2100 cm
and the disappearance of the C-Cl stretch at 730 cm-1 in the IR
4
dried over MgSO and filtered. The solvent was removed in vacuo to
spectrum. The sample was dissolved in 300 mL of tetrahydrofuran
+
1
yield the product as a colorless oil. ESI-MS: m/z 733 [M + H] . H
NMR (400 MHz, CDCl ): δ (ppm) 3.70-3.52 (m, 36 H), 3.51-3.35
m, 6H), 2.87 (m, 1H), 2.65 (m, 2H), 2.18 (t, J ) 7.3 Hz, 2H), 1.96-
.36 (m, 9H).
Synthesis of CdSe(Zn
(THF), and triphenylphosphine (27.9 g, 106 mmol) was added. The
3
solution was stirred at 25 °C for 4 h before adding 4 mL of water and
stirring overnight. The THF was removed in vacuo, and 100 mL of
water was added. The precipitate was removed by vacuum filtration
and the filtrate washed with toluene (3 × 50 mL). The water was
removed in vacuo to yield the pure product as light-yellow oil (17.8 g,
(
1
x
Cd1-xS) core(shell) QDs. CdSe cores were
39
synthesized according to previously reported procedures. Overcoating
with an alloyed shell was carried out via modifications to previously
reported procedures. Briefly, CdSe cores precipitated from growth
solution by the addition of methanol were redispersed in hexane and
injected into a degassed solution of 10 g of 99% trioctylphosphine oxide
+
1
8
9%). ESI-MS: m/z 457 [M + H] . H NMR (400 MHz, CDCl
3
): δ
(ppm) 3.53 (m, 28 H), 3.39 (t, J ) 5.2 Hz, 4H), 2.74 (t, J ) 5.2 Hz,
4
H), 1.27 (s, 4H).
Lipoic Acid NHS-Ester (LA-NHS). To a solution of lipoic acid
(TOPO) and 0.4 g n-hexylphosphonic acid. After removing the hexane
(LA, 5.00 g, 24.23 mmol) and N-hydroxysuccinimide (NHS, 3.35 g,
under reduced pressure at 80 °C, the flask was back-filled with dry N
and the temperature increased to 130 °C before adding 0.25 mL of
decylamine and stirring for 30 min. Precursor solutions of diethylzinc
2
2
9.1 mmol) in 150 mL of tetrahydrofuran at 4 °C was added slowly a
solution of dicyclohexylcarbodiimide (6.00 g, 29.1 mmol) in 10 mL
of tetrahydrofuran. The mixture was warmed to room temperature and
stirred for 5 h. The precipitate was removed by vacuum filtration and
the solvent evaporated in vacuo. The crude product was redissolved in
(
ZnEt
2
), dimethylcadmium (CdMe
2
), and hexamethyldisilathiane
[(TMS)
2
S] were prepared by dissolving the appropriate amounts of each
in 4 mL of TOP and loading them into two separate syringes for metal
and sulfur under inert atmosphere. The molar quantity of ZnEt required
to achieve the desired shell thickness (typically 5 monolayers) was
calculated according to the methods of Leatherdale.51 For an alloyed
1
00 mL of ethyl acetate and filtered once more by vacuum filtration.
2
The product was recrystallized from a solution of hot ethyl acetate/
1
hexane (1:1 v/v) as a pale-yellow solid (5.88 g, 80%). H NMR (400
MHz, CDCl
t, J ) 7.1 Hz, 2H)), 2.50 (m, 1H), 1.99-1.46 (m, 7H).
Compound 2 (LA-PEG-Amine). To a solution of compound 1 (12
3
): δ (ppm) 3.58 (m, 1H), 3.13 (m, 2H), 2.84 (s, 4H), 2.63
shell, an appropriate mole fraction ZnEt
2
was replaced by CdMe2. A
(
2-fold molar excess of (TMS) S was used. The precursor solutions were
2
injected simultaneously into the 130 °C bath at a rate of 4 mL/h. The
sample was annealed overnight at 80 °C, and 4 mL of butanol was
added. The QDs were stored in growth solution under ambient
conditions and centrifuged once more before use. Typical fluorescence
quantum yields were 68% for QD605 in hexane.
g, 29.1 mmol) and sodium bicarbonate (2.44 g, 29.1 mmol) in
dimethylformamide/water (100 mL, 50:50 v/v) at 4 °C was added
dropwise a solution of LA-NHS (1.60 g, 5.27 mmol) in 10 mL of
dimethylformamide over 1 h. The solution was warmed to RT, stirred
overnight, and extracted with chloroform (3 × 30 mL). The combined
organic extracts were washed with water (3 × 30 mL), dried over
sodium sulfate, and filtered, and the solvent was evaporated. The crude
(51) Leatherdale, C. A.; Woo, W. K.; Mikulec, F. V.; Bawendi, M. G. J. Phys.
Chem. B 2002, 106, 7619-7622.
1282 J. AM. CHEM. SOC.
9
VOL. 130, NO. 4, 2008
Liu, Wenhao
