Gold Glyconanoparticles
1909 1921
1H; H-5'), 4.37 (dd, J 12.0, 3.0 Hz, 1H; H-6), 4.24 (dd, J 12.0, 4.5 Hz,
1H; H-6), 4.11 4.06 (m, 2H; H-6, H-5), 3.85 (m, 1H; CH2O), 3.46 (m, 1H;
CH2O), 2.81 (t, J 7.5 Hz, 2H; CH2S), 2.32 (t, 3H; SAc), 1.70 0.92 ppm
(m, 18H; 9 CH2); 13C NMR (125 MHz, CDCl3): d 196.0 (COS), 165.6,
165.0 (Bz), 133.3, 133.2, 133.0, 129.9, 129.8, 129.7, 129.5, 128.9, 128.5, 128.3,
gave the disulfide 4 (0.97 g, 1.84 mmol, 80%). [a]2D0 57.3 (c 1 in
1
MeOH); H NMR (500 MHz, MeOD): d 5.13 (d, J 3.5 Hz, 1H; H-1'),
4.24 (d, J 8.0 Hz, 1H; H-1), 3.41 (dd, J 9.5, 3.5 Hz, 1H; H-2'), 3.20 (t,
J 9.2 Hz, 1H; H-2), 2.65 (t, J 7.5 Hz, 2H; CH2S), 1.66 1.57 (m, 4H;
2CH2), 1.38 1.29 ppm (m, 14H; 7CH2); 13C NMR (125 MHz, MeOD):
d 101.0, 99.6 (C-1, C-1'), 78.0, 74.5, 73.3, 71.4, 70.8, 68.2, 67.7, 59.4, 58.9 (C-
6, C-6'), 27.5, 27.3, 27.0, 26.2, 26.1, 23.8 ppm; MALDI-TOF: m/z: 1077
128.1, 128.0 (CH CH) 100.7, 96.3, (C-1, C-1'), 75.0, 73.2, 72.3, 70.8, 70.1,
69.9, 69.0, 63.5, 62.5 (C-6, C-6'), 30.6 (CH2O), 29.3, 29.1, 29.0, 28.7 ppm
(CH2CH2); MALDI-TOF: m/z: 1320 [MNa]
[MNa] , 595; elemental analysis calcd (%) for (C23H43O11S)2 ¥ 5H2O
(1144): C 48.4, H 8.3; found: C 48.4, H 7.8.
11-Thioacetyl-3,6,9-trioxaundecanyl-2,3,4,6-tetra-O-benzoyl-b-d-glucopy-
ranoside (35): Reaction of trichloroacetimidate 34 (1.3 g, 1.8 mmol) and the
acceptor 8 (0.33 g, 1.3 mmol) gave 34. Column chromatography (hexane/
AcOEt 3:2) gave 34 as an amorphous solid (0.8 g, 1 mmol, 75%). 1H NMR
(300 MHz, CDCl3): d 8.10 7.80 (m, 8H; Bz), 7.60 7.20 (m, 12H; Bz),
5.90 (t, J 9.6 Hz, 1H; H-3), 5.68 (t, J 9.9 Hz, 1H), 5.52 (t, J 8.7 Hz,
1H), 4.97 (d, J 7.8 Hz, 1H; H-1), 4.64 (dd, J 12.3, 3.3 Hz, 1H), 4.49 (dd
J 12.0, 5.1 Hz, 1H), 4.20 4.18 (m, 3H), 4.05 3.95 (m, 1H; H-6a) 3.90
3.75 (m, 1H; H6b), 3.70 3.35 (m, 12H; OCH2CH2O), 3.08 (t, J 6.5 Hz,
2H; CH2S), 2.32 ppm (s, 3H; SAc).
11,11'-Dithiobis(3,6,9-trioxaundecanyl-b-d-glucopyranoside) (5): This
compound was prepared from 35 (0.8 g, 1 mmol). The product precipitated
as a white solid that, after washing with cold ethanol, gave the disulfide 5
(0.37 g, 2.14 mmol, quantitative). [a]2D0 À4.0 (c 0.7 in MeOH); 1H NMR
(500 MHz, CD3OD): d 4.28 (d, J 7.5 Hz, 1H; H-1), 4.04 4.00 (m, 1H;
H-5), 3.84 (d, J 13.5 Hz, 1H), 3.75 3.60 (m, 14H; OCH2CH2), 3.37 3.20
(m, 6H), 3.17 (t, J 8.7 Hz, 1H), 2.89 ppm (t, J 6.5 Hz, 2H; CH2S);
13C NMR (125 MHz, CD3OD): d 102.7 (C-1), 76.2, 76.1, 73.3, 69.8, 69.7,
69.7, 69.5, 68.7, 67.9, 61.0, 37.9 ppm; MALDI-TOF: m/z: 765.1 [MNa] ,
781.8 [MK] , 395.1 [M/2Na] .
General procedure for debenzoylations
General procedure for preparation of glyconanoparticles
Synthesis of compounds 1, 2, 3, 4 and 5: A solution of 25, 26, 27, 31 or 35
(1 equiv) in dry MeOH (25 mL) was treated with 1n methanolic solution of
NaOMe. The reaction was stirred under an argon atmosphere. The reaction
mixture was left for 24 h, without the argon atmosphere, to complete the
oxidation of the thiol group. After 24 h, TLC (CH2Cl2/MeOH 35%)
showed the appearance of a new product (Rf 0.5). The reaction was
neutralised with Amberlist IR-120 resin, filtered and evaporated to
dryness. The residue was washed with diethyl ether (15 mL) to remove
methyl benzoate.
Synthesis of compounds 1-Au, 2-Au, 3-Au, 4-Au, 5-Au, 6-Au and 10-Au: A
solution of disulfide (0.012 M, 5.5 equiv) in MeOH was added to a solution
of tetrachloroauric acid (0.025 M, 1 equiv) in water. NaBH4 (1m, 22 equiv)
in water was then added in small portions with rapid shaking. The black
suspension formed was shaken for an additional 2 h and the solvent was
then removed. The residue (20 50 mg of crude product) was dissolved in
10 mL of NANOPURE water and was purified by centrifugal filtering
(CENTRIPLUS Mr 30000, 1 h, 3000 xg). The process was repeated until
the nanoparticles were free of salts and starting material (absence of signals
11,11'-Dithiobis[undecanyl(b-d-galactopyranosyl)(1 ! 4)-b-d-glucopyran-
oside] (1): This compound was prepared from 25 (3 g, 2.31 mmol). The
product precipitated as a white solid that, after washing with cold ethanol,
gave the disulfide 1 (0.97 g, 1.84 mmol, 80%). [a]2D0 À5.38 (c 0.9 in
MeOH); 1H NMR (500 MHz, MeOD): d 4.35 (d, J 7.5 Hz, 1H; H-1),
4.27 (d, J 8.0 Hz, 1H; H-1'), 3.90 3.86 (m, 2H), 3.83 (dd, 1H), 3.80 (dd,
J 3.5, 0.5 Hz, 1H; H-4'), 3.76 (dd, J 11.5, 8.0 Hz, 1H; H-6), 3.68 (dd, J
11.5, 5.0 Hz, 1H; H-6'), 3.38 (m, 1H; H-5), 3.22 (dd, J 8.9, 8.0 Hz, 1H;
H-4), 2.57 (t, J 7.5 Hz, 2H; CH2S), 1.64 1.28 ppm (m, 19H; CH2);
13C NMR (125 MHz, MeOD): d 105.9, 105.1 (C-1, C-1'), 81.5, 77.9, 77.3,
75.6, 73.4, 71.8, 71.2, 63.4, 62.9, 56.6, 32.7, 31.9, 31.5, 31.1, 30.7, 28.0 ppm;
due to disulfide and Na in 1H NMR and 23Na NMR spectra). The residue
in the centriplus filter was dissolved in water (2 mL) and lyophilised. The
molecular formula of the nanoparticles was calculated, based on the
average diameter obtained by TEM[32], and confirmed by elemental
analysis.
lacto-C11SAu (1-Au): Reaction of disulfide 1 (200 mg, 0.19 mmol) and
HAuCl4 (25 mg, 0.073 mmol) gave nanoparticle 1-Au (17 mg, 2.22 Â
10À4 mmol) as a dark brown powder. Average diameter and number of
gold atoms: 1.8 nm, 201; 1H NMR (500 MHz, D2O): d 4.50 4.42 (m, 2H;
H-1, H-1'), 4.10 3.30 (m, 11H), 2.00 1.10 ppm (m, 12H); 1H NMR
(500 MHz, [D6]DMSO): d 5.04 (m, 2H), 4.73 (d, J 4.5 Hz, 1H), 4.60 (m,
2H), 4.50 4.46 (m, 2H), 4.15 (d, J 6.5 Hz, 1H; H-1), 4.12 (d, J 8.0 Hz,
1H; H-1'), 3.70 (m, 2H), 3.56 (m, 2H), 3.49 3.26 (m, 5H), 2.95 (m, 1H;
H-5), 2.64 (t, J 7.0 Hz, 1.2H), 2.52 (t, J 7.0 Hz, 0.7H; CH2S), 1.58 1.45
(m, 4H, CH2CH2), 1.25 ppm (m, 16H; CH2CH2); UV/Vis (H2O): l
520 nm (surface plasmon band); IR (KBr): nÄ 3414, 2921, 2850, 2360,
1639, 1425, 1065 cmÀ1; elemental analysis calcd (%) for (C23H44O11S)70Au201
(76594): C 25.2, H 4.05; found C 25.1 H 4.40
MALDI-TOF: m/z: 1096 [MK] , 597.3; elemental analysis calcd (%) for
(C23H43O11S)2 (1054): C 52.0, H 8.3; found: C 51.7, H 8.3.
11,11'-Dithiobis[3,6,9-trioxaundecanyl(b-d-galactopyranosyl)(1 ! 4)-b-d-
glucopyranoside] (2): This compound was prepared from 26 (3 g,
2.68 mmol). The product precipitated as a white solid that, after washing
with cold ethanol, gave the disulfide 2 (1.14 g, 2.14 mmol, 80%). [a]D20
À4.08 (c 0.7 in MeOH); 1H NMR (300 MHz, D2O): d 4.51 (d, J
8.1 Hz, 1H; H-1'), 4.45 (d, J 7.8 Hz, 1H; H-1), 4.04 4.00 (m, 1H; H-5),
3.98 (m, 1H; H-6), 3.92 (d, J 3.0 Hz, 1H; H-4), 3.38 3.20 (m, 1H; H-5'),
2.98 2.71 ppm (m, 2H; CH2S); 13C NMR (125 MHz, MeOD): d 105.9,
105.1 (C-1, C-1'), 81.5 (C-4), 77.9, 77.3, 77.1, 75.7, 75.6, 73.4 (C-2'), 72.8, 72.4,
72.1, 70.6 (CH2O), 63.3, 62.8 ppm (C-6', C-6); MALDI-TOF: m/z: 1089
lacto-EG4SAu (2-Au): Reaction of the disulfide 2 (100 mg, 0.09 mmol) and
HAuCl4 (13.6 mg, 0.04 mmol) gave 2-Au (8 mg, 1.09 Â 10À4 mmol) as a dark
brown powder. Average diameter and number of gold atoms: 1.8 nm, 201.
1H NMR (300 MHz, D2O): d 4.50 4.30 (brm, 2H; H-1, H-1'), 4.10 3.35
(brm, 21H), 3.26 ppm (brm, 2H); 1H NMR (500 MHz, [D6]DMSO): d
5.06 (brm, 2H), 4.75 (brm, 1H), 4.65 (m, 2H), 4.18 (brm, 2H; H-1, H-1'),
3.86 (m, 2H), 3.58 3.37 (m, 18H), 3.01 (brm, 1H), 2.61 ppm (t, J 4.5 Hz;
CH2S); UV (H2O): l 520 nm (surface plasmon band); elemental analysis
calcd (%) for (C20H37O14S)63Au201 (73203): C 20.6, H 3.2; found C 20.7 H 3.6
[MNa] , 601; elemental analysis calcd (%) for (C20H38O14S)2 ¥ H2O
(1084): C 44.2 H: 7.2; found: C 44.0 H 7.7
29,29'-Dithiobis[3,6,9,12,15,18-hexaoxaundecanyl(b-d-galactopyranosyl)-
(1 ! 4)-b-d-glucopyranoside] (3): This compound was prepared from 27
(0.8 g, 0.5 mmol). The product precipitated as a white solid that, after
washing with cold ethanol, gave the disulfide 3 (0.34 g, 0.42 mmol, 85%).
[a]2D0 À6.48 (c 0.7 in MeOH); 1H NMR (500 MHz, D2O): d 4.47(d,
J 8.0 Hz, 1H; H-1'), 4.41 (d, J 7.5 Hz, 1H; H-1), 4.03 (m, 1H), 3.94 (m,
1H; H-6), 3.90 (d, J 3.0 Hz, 1H; H-4'), 3.82 3.62 (m, 30H), 3.57 3.50
(m, 4H), 3.46 3.43 (m, 2H), 3.32 (t, J 8.5 Hz, 1H; H-4), 2.60 2.55 (m,
2H; CH2S), 1.60 1.55 (m, 4H), 1.38 1.30 ppm (m, 14H); 13C NMR
(125 MHz, D2O): d 102.6, 101.8 (C-1, C-1'), 78.1, 75.0, 74.9, 74.4, 74.0,
72.4, 72.2, 70.7, 70.6, 69.6, 69.5, 69.4, 69.3, 68.3, 68.2, 60.6, 59.8 (C-6, C-6'),
30.5, 29.5, 29.3, 29.2, 29.0, 28.9, 28.5, 25.8, 25.7 ppm; MALDI-TOF: m/z:
lacto-EG6C11SAu (3-Au): Reaction of the disulfide 3 (70 mg, 0.088 mmol)
and HAuCl4 (5.42 mg, 0.016 mmol) gave 3-Au (9 mg, 8.11 Â 10À5 mmol) as
a black powder. Average diameter and number of gold atoms: 2.2 nm, 201.
1H NMR (500 MHz, D2O): d 4.47 (d, J 7.5 Hz, 1H; H-1), 4.42 (d, J
7.5 Hz, 1H; H-1'), 4.05 3.89 (m, 3H), 3.82 3.46 (m, 35H), 3.34 3.31 (m,
1H), 2.73 2.67 (m, 0.8H), 1.72 1.04 ppm (m, 16H); UV (H2O): l
520 nm (surface plasmon band); elemental analysis calcd (%) for
(C35H67O17S)90Au202 (110984): C 34.0, H 5.43; found C 33.40 H 5.6.
malto-C11SAu (4-Au): Reaction of the disulfide 4 (50 mg, 0.1 mmol) and
HAuCl4 (6.16 mg, 0.018 mmol) gave 4-Au (12 mg, 2.09 Â 10À4 mmol) as a
brown powder. Average diameter and number of gold atoms: <1.3 nm,
<79. 1H NMR(500 MHz, D2O): d 5.33 (brs, 1H; H-1'), 4.37(brs, 1H;
H-1), 3.87 3.33 (m, 15H); 2.70 (brs, 2H; CH2S), 1.65 1.33 ppm (brm,
19H); 1H NMR (500 MHz, [D6]DMSO): d 5.44 (s, 1H), 4.39 (d, J
1620 [MK] , 860; elemental analysis calcd (%) for (C35H67O17S)2 ¥ H2O
(1600): C 51.9 H: 8.5; found: C 51.8 H 8.9.
11,11'-Dithiobis[undecanyl(a-d-glucopyranosyl)(1 ! 4)-b-d-glucopyrano-
side] (4): This compound was prepared from 31 (3 g, 2.31 mmol). The
product precipitated as a white solid that, after washing with cold ethanol,
Chem. Eur. J. 2003, 9, 1909 1921
¹ 2003 Wiley-VCH Verlag GmbH &Co. KGaA, Weinheim
1919