Synthesis of rhenium(I) tricarbonyl complexes with carbohydrate-pendant tridentate ligands and their cellular uptake

Article abstract of DOI:10.1002/ejic.201100953

Twelve [Re^IL(CO)₃]ⁿ⁺ complexes with various carbohydrate-pendant ligands L have been prepared and their uptake into HeLa S3 cells were investigated. The ligand library includes: (i) glucose/galactose as the carbohydrate group; (ii) bis(2-pyridylmethyl)amine (DPA), bis(2-quinolylmethyl)amine (DQA), or N-(2-pyridylmethyl)glycine (NPG) as the metal binding component; and (iii) an ethylene chain as a linker between the metal binding site and the O/C-glycosides. Microwave induced plasma mass spectroscopy (MIP-MS) measurements revealed that all complexes were extensively incorporated into the HeLa cells over a 24 h period, and the DQA complexes showed the highest uptake of all the complexes in the series. However, in comparison to the corresponding Re complexes without the pendant carbohydrate functions (prepared with the related ligands L^DPA, L^DQA, and L^NPG), only the NPG complexes exhibited carbohydrate enhanced cellular uptake. Considering their water solubility and cellular uptake properties, the NPG complexes containing an O-glycoside group (L1 and L′1) are the best candidates for enhancing cellular uptake of metal ions. Microscopic analysis with PC-12 cells in the presence of thefluorescent complex [Re(L′7)(CO)₃]Cl, revealed that the complex stays in the cell cytosol and cannot penetrate into the nucleus. Copyright

Full text of DOI:10.1002/ejic.201100953

FULL PAPER
DOI: 10.1002/ejic.201100953
Synthesis of Rhenium(I) Tricarbonyl Complexes with Carbohydrate-Pendant
Tridentate Ligands and Their Cellular Uptake
Yuji Mikata,*[a] Kyoko Takahashi,[b] Yuka Noguchi,[b] Masami Naemura,[b] Anna Ugai,[b]
Saori Itami,[c] Keiko Yasuda,[c] Satoshi Tamotsu,[c] Takashi Matsuo,[d] and Tim Storr[e]
Keywords: Sugar–metal hybrid material / Carbohydrates / Glycosides / Rhenium / Ligand effects
Twelve [ReIL(CO)3]n+ complexes with various carbohydrate-
pendant ligands L have been prepared and their uptake into
HeLa S3 cells were investigated. The ligand library includes:
(i) glucose/galactose as the carbohydrate group; (ii) bis(2-
pyridylmethyl)amine (DPA), bis(2-quinolylmethyl)amine
(DQA), or N-(2-pyridylmethyl)glycine (NPG) as the metal
binding component; and (iii) an ethylene chain as a linker
between the metal binding site and the O/C-glycosides. Mi-
crowave induced plasma mass spectroscopy (MIP-MS) mea-
surements revealed that all complexes were extensively in-
corporated into the HeLa cells over a 24 h period, and the
DQA complexes showed the highest uptake of all the com-
plexes in the series. However, in comparison to the corre-
sponding Re complexes without the pendant carbohydrate
functions (prepared with the related ligands LDPA, LDQA, and
LNPG), only the NPG complexes exhibited carbohydrate en-
hanced cellular uptake. Considering their water solubility
and cellular uptake properties, the NPG complexes contain-
ing an O-glycoside group (L1 and LЈ1) are the best candi-
dates for enhancing cellular uptake of metal ions. Micro-
scopic analysis with PC-12 cells in the presence of the
fluorescent complex [Re(LЈ7)(CO)3]Cl, revealed that the com-
plex stays in the cell cytosol and cannot penetrate into the
nucleus.
Convenient isolation from a 99Mo generator justifies the ex-
tensive use of 99mTc in medical imaging methods. 186Re
Introduction
(t1/2 = 3.68 d, β = 1.07 MeV, γ = 137 keV) and 188Re (t1/2
=
Functionalized carbohydrates are of significant interest
as building blocks for high order complex carbohydrate
structures, asymmetric catalysts, and sugar-metal hybrid
materials.[1] The attachment of carbohydrate moieties to
functional molecules provides integrated properties such as
water solubility, chirality, and biological recognition ele-
ments to those materials. The most convenient and inexpen-
sive strategy to access carbohydrate functionalized materi-
als is a pendant approach in which functional molecules are
connected via a linker to commercially available carbo-
hydrates.[2]
16.98 h, β = 2.12 MeV, γ = 155 keV) have potential use in
therapeutic nuclear medicine. The [M(CO)3]+ (M = Tc, Re)
core has received considerable attention due to its small
size, inert d6 low-spin configuration, and simple aqueous
chemistry.[3] Tridentate chelates are well suited for binding
to the [M(CO)3]+ core, providing a high level of stability to
the resultant complexes due to the chelate effect and by
limiting the accessibility of the metal center to endogenous
ligands in vivo. The rational design of ligands for radioiso-
topes with diagnostic/therapeutic properties is highly desir-
able, especially for use in imaging and therapy. Extensive
studies have been accumulated, and several carbohydrate
functionalized complexes have been reported that display
benefits, in addition to those mentioned above, due to their
carbohydrate groups.[2d,4]
The radiopharmaceutical application of group VII met-
als such as 99mTc and 186/188Re is of recent interest. 99mTc
has ideal properties (t1/2 = 6.01 h, γ = 142.7 keV) for use
in single photon emission computed tomography (SPECT).
[a] KYOUSEI Science Center, Nara Women’s University,
Nara 630-8506, Japan
In this article, facile synthetic routes to tridentate carbo-
hydrate-pendant ligands (Scheme 1) are reported. The li-
gand library includes: (i) glucose/galactose as a carbo-
hydrate moiety; (ii) DPA, DQA, or NPG as the metal bind-
ing component; and (iii) an ethylene linker between the
metal binding site and the O/C-glycosides. Attachment of
carbohydrate functions to the ligands, especially glucose an-
alogs, was hypothesized to enhance the water solubility and
more importantly membrane permeability via cellular gluc-
ose transporters (GLUT) of the compounds,[5] although
some carbohydrate-pendant complexes have been reported
Fax: +81-742-203-095
E-mail: mikata@cc.nara-wu.ac.jp
[b] Department of Chemistry, Nara Women’s University,
Nara 630-8506, Japan
[c] Department of Biological Sciences, Nara Women’s University,
Nara 630-8506, Japan
[d] Graduate School of Materials Science, Nara Institute of Science
and Technology (NAIST),
Takayama, Ikoma, Nara 630-0192, Japan
[e] Department of Chemistry, Simon Fraser University,
8888 University Drive, Burnaby, BC, V5A-1S6, Canada
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejic.201100953.
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Y. Mikata et al.
FULL PAPER
Scheme 1.
to have neither recognition nor transportation ability via acted with N-(2-pyridylmethyl)glycine tert-butyl ester,[9]
a
the Glut1 transporter.[6] C-Glycosides are the carbon ana- procedure that was then followed by deprotection of the
logs of naturally occurring O-glycosides and have been ex- carboxylate and sugar hydroxy groups (Scheme 2). The
tensively studied because of their chemical and enzymatic other ligands, L2H, LЈ2H L4–6 and LЈ4–6, were prepared
stability.[7] This paper provides efficient strategies for carbo- by alkylation of carbohydrate-tethered primary amines 7/
hydrate functionalization of rhenium(I) tricarbonyl com- 7Ј (Scheme 3) and 11/11Ј[10] (Scheme 4) with 2 equiv. of an
plexes, and details of the cellular uptake analyses, per- alkylating agent
–
2-(chloromethyl)pyridine, 2-(chlo-
formed with HeLa cells, of these complexes.
romethyl)quinoline, or tert-butyl bromoacetate – followed
by deprotection. The preparation of C-glucosylamine 7 has
been reported previously.[11] The C-galactosylamine 7Ј was
obtained by a procedure similar to the one given in that
report. During the preparation of 7/7Ј, the cyanomethyl
C-glycosides 6/6Ј[11–12] formed as crystals suitable for X-ray
crystallography, and Figures S1 and S2 reveal the molecular
structures of 6 and 6Ј, including the β-configuration of the
carbohydrate groups. It should be mentioned that com-
pounds 8/8Ј were obtained from a one-pot reaction involv-
ing amines 7/7Ј that were reacted with 1 equiv. of 2-chloro-
methylpyridine and 1 equiv. of tert-butyl bromoacetate; 8/8Ј
Results and Discussion
Synthesis of the Ligands
Carbohydrate-pendant ligands L1–6 and LЈ1–6 were syn-
thesized according to Schemes 2–4. The preparations of L3
and LЈ3 have been reported previously.[8] Ligands L1H and
LЈ1H were synthesized from 2-bromoethyl 2,3,4,6-tetra-O-
acetyl-β-d-gluco- or galactopyranoside (1/1Ј)[8] that were re-
Scheme 2. Reagents and conditions: (i) N-(2-pyridylmethyl)glycine tert-butyl ester, DMF; (ii) formic acid; (iii) NaOMe, MeOH; (iv) bis(2-
pyridylmethyl)amine.
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Rhenium(I) Tricarbonyl Complexes
Scheme 3. Reagents and conditions: (i) formic acid; (ii) diisopropylethylamine (DIPEA); (iii) H2, PtO2, CHCl3/EtOH; (iv) 2-(chloromethyl)-
pyridine, tert-butyl bromoacetate, dimethylformamide (DMF); (v) 2-(chloromethyl)pyridine, DMF; (vi) 2-(chloromethyl)quinoline, DMF;
(vii) NaOMe, MeOH.
were obtained in good yields (69–88%) and no significant
The ethylamine derivatives shown in Scheme 5 that con-
1
amount of side products were isolated. The results of H/ tain the same metal binding sites as L1–6/LЈ1–6 but no
13C NMR, ESI-MS, and elemental analyses supported the sugar residues were prepared. LDPA is a known com-
proposed structures for all ligands.
pound,[13] but the other two ligands (LNPGH and LDQA
)
were synthesized for the first time and fully characterized,
details of which are provided in this paper. The crystal
structure of LDQA was also determined (see Supporting In-
formation, Table S1 and Figure S3).
Synthesis of the Rhenium(I) Tricarbonyl Complexes
Ligands L1–6 and LЈ1–6 were refluxed with rhenium
pentacarbonyl chloride to afford [ReL(CO)3] for L1,2/LЈ1,2
or [ReL(CO)3]Cl for L3–6/LЈ3–6 in 31% to quantitative
yield. As represented in the 1H NMR spectrum of
[Re(L4)(CO)3]Cl shown in Figure 1, distinct chemical shift
changes for the protons associated with the metal binding
are observed when the ligand binds to the metal. No signifi-
cant chemical shift changes were observed for the carbo-
hydrate protons. This clearly shows that the rhenium cen-
ters in the present complexes coordinate to the tridentate
metal binding sites via the nitrogen or oxygen atoms, and
confirms that the carbohydrate moieties remain pendant. In
Scheme 4. Reagents and conditions: (i) 2-(chloromethyl)quinoline,
DMF; (ii) NaOMe, MeOH.
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Y. Mikata et al.
FULL PAPER
Figure 1, the py3 signal, which exhibits a clear doublet in
the spectrum of the free ligand, displays further splitting in
the spectrum of the complex, this is likely to be due to the
long-range effect of the carbohydrate chirality within the
more rigid metal chelate. In the NPG complexes, the metal
coordinated nitrogen atoms become chiral centers. In this
study we did not see any further splitting of the NMR sig-
nals, suggesting the exclusive formation of one diastereomer
for each of the NPG complexes. But we could not deter-
mine the absolute configuration of the complexes. The re-
1
sults from H/13C NMR, ESI-MS, and elemental analyses
supported the proposed structures for all complexes.
Crystal structure elucidation was successfully performed
for the C-glycoside complex [Re(LЈ4)(CO)3]Cl, and con-
firmed the above mentioned structure (Figure 2). The Re
complex of compound 9 {[Re(9)(CO)3]ClO4} with a OH-
protected C-glucoside group also afforded crystals suitable
for X-ray crystallography (Figure 3). These structures exhi-
bit no significant changes from the corresponding O-glycos-
ide derivatives, indicating the stable coordination of the tri-
dentate N,O-ligands that support the rhenium tricarbonyl
structure.
The analogous rhenium complexes without the pendant
sugar moieties were prepared in a similar way to that em-
ployed for the preparation of the L1–6 and LЈ1–6 com-
plexes detailed above. All complexes were fully charac-
terized by H/13C NMR, ESI-MS, and elemental analyses,
1
and [Re(LNPG)(CO)3]Cl and [Re(LDPA)(CO)3]Cl were also
analyzed by X-ray crystallography (Figures S4 and S5, Sup-
porting Information).
Scheme 5. Reagents and conditions: (i) N-(2-pyridylmethyl)glycine
tert-butyl ester, DMF; (ii) trifluroacetic acid (TFA); (iii) 2-
(chloromethyl)pyridine, acetonitrile; (iv) 2-(chloromethyl)quinoline,
acetonitrile.
Figure 1. Partial 1H NMR spectra for [Re(L4)(CO)3]Cl (top) and L4 (bottom) in CD3OD. Asterisks indicate solvent peaks or those
associated with small amounts of impurities.
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Rhenium(I) Tricarbonyl Complexes
Figure 2. ORTEP diagram of the cationic portion of [Re(LЈ4)(CO)3]-
Cl·0.5CH3CN·0.5C2H5OH (ellipsoids are drawn at the 50% prob-
ability level). The hydrogen atoms, counter anion, and solvent mo-
lecules are omitted for clarity.
Figure 4. Cellular rhenium concentration (mm) after incubation for
24 h of HeLa S3 cells with the ReI tricarbonyl complexes (100 μm)
containing sugar-pendant ligands. Open bars, filled bars, and gray
bars represent nonsugar, O-glycoside, and C-glycoside ligands,
respectively.
The rhenium complexes without pendant carbohydrate
functions exhibit considerable differences in the amount of
cellular uptake when compared to their carbohydrate-
appended analogues. The Re complexes of LDPA and LDQA
exhibit higher uptake values (Figure 4) in comparison to
the carbohydrate-attached complexes, probably because of
their increased hydrophobicity. It is of significant interest
that in the NPG derivatives, for which all complexes have
good water solubility, the pendant O-glycoside in L1/LЈ1
enhances Re incorporation into the cells by a factor of 5–8
compared with the C-glycoside and nonsugar analogues.
This O-glycoside preference was not observed in the DPA
and DQA series. Finally, in all cases no significant differ-
ence between the glucose and galactose derivatives was ob-
served.
Considering the total charge of the complex, the cell
membrane permeability trend would be expected to be as
follows: NPG complexes (neutral chelate) Ͼ DPA and
DQA complexes (cationic metal chelates). However, the
present results show that the overall trend in Re complex
uptake is DQA Ͼ DPA Ͼ NPG and there is little difference
in the uptake of the the C- and O-glycosides. Because the
DQA complexes exhibit poor water solubility, the high
Figure 3. ORTEP diagram of the cationic portion of [Re(9)(CO)3]-
ClO4·H2O (ellipsoids are drawn at the 50% probability level). The
hydrogen atoms, counter anion, and solvent molecule are omitted
for clarity.
MIP-MS Evaluation of the Uptake of Re Complexes by
HeLa S3 Cells
Quantification of rhenium metal uptake into HeLa S3 water solubility of the NPG complexes is of significant im-
cells was investigated, allowing for evaluation of the effect portance. Interestingly, the NPG O-glycoside derivatives
of the ligand structure on the uptake process. Fifteen Re (L1/LЈ1) exhibit enhanced uptake in comparison to both
complexes with and without pendant carbohydrate moieties the C-glycoside analogues (L2/LЈ2) and the carbohydrate-
were incubated with the cells at 100 μm concentration in free derivative. The effect of O-glycosylation of the ligands
growth media for 24 h, and the incorporated metal contents in the NPG series causes a deviation from the overall trend
in the cells were quantified by MIP-MS. No detectable cyto- observed for metal complex uptake, and provides a poten-
toxicity of the complexes was observed under the experi- tial starting point for further structural modifications aimed
mental conditions used. The results of this study are shown at enhancing the cellular uptake of rhenium(I) tricarbonyl
in Table 1 and summarized in Figure 4. The cell volume complexes. Increased glucose concentration in media did
(2.27 pL) was calculated from the mean radius (16.3 μm) of not block the uptake of the L1 and LЈ1 complexes (data
the cells measured by microscopic analysis, and with the not shown), suggesting that the uptake mechanism is dif-
assumption that the cells are spherical in shape.
ferent from that for glucose transport.
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Y. Mikata et al.
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Table 1. Details of the uptake of ReI tricarbonyl complexes by HeLa S3 Cells.[a]
Ligand
LNPG
Re [ngL–1], individual
Re [ngL–1], average
Re uptake (nmol/105 cells)
(1.22Ϯ0.20)ϫ10–2
Cellular concentration of Re (mm)[b]
0.054Ϯ0.009
234.5Ϯ37.0
217.0Ϯ30.5
233.0Ϯ42.0
1654.0Ϯ108.5
1797.5Ϯ103.0
1663.0Ϯ98.5
1648.0Ϯ80.5
1771.0Ϯ87.5
1804.0Ϯ127.0
435.5Ϯ50.0
352.0Ϯ46.0
338.5Ϯ47.5
296.0Ϯ34.5
298.5Ϯ34.5
271.0Ϯ33.0
3959.5Ϯ131.5
3612.0Ϯ117.5
3747.5Ϯ122.5
702.0Ϯ49.5
653.5Ϯ53.5
707.5Ϯ61.0
294.0Ϯ36.0
319.0Ϯ24.5
303.0Ϯ38.5
616.9Ϯ59.0
691.5Ϯ61.0
745.5Ϯ63.5
670.5Ϯ65.0
621.0Ϯ55.0
673.0Ϯ48.5
21303.0Ϯ414.0
17067.0Ϯ110.0
14723.0Ϯ303.5
1991.5Ϯ87.5
2080.5Ϯ93.0
2010.0Ϯ115.0
3174.5Ϯ108.0
2373.5Ϯ105.0
2581.0Ϯ100.5
2702.0Ϯ135.5
2863.5Ϯ110.5
2880.0Ϯ137.5
2688.5Ϯ83.5
2574.5Ϯ117.5
2605.0Ϯ115.0
228.0Ϯ36.5
L1
1705.0Ϯ103.0
1741.0Ϯ98.0
375.5Ϯ48.0
(9.16Ϯ0.55)ϫ10–2
(9.35Ϯ0.53)ϫ10–2
(2.02Ϯ0.26)ϫ10–2
(1.55Ϯ0.18)ϫ10–2
(20.26Ϯ0.67)ϫ10–2
(3.69Ϯ0.30)ϫ10–2
(1.64Ϯ0.18)ϫ10–2
(3.68Ϯ0.33)ϫ10–2
(3.52Ϯ0.30)ϫ10–2
(95.04Ϯ1.48)ϫ10–2
(10.74Ϯ0.53)ϫ10–2
(14.55Ϯ0.56)ϫ10–2
(15.12Ϯ0.69)ϫ10–2
(14.08Ϯ0.56)ϫ10–2
0.404Ϯ0.024
0.412Ϯ0.023
0.089Ϯ0.011
0.068Ϯ0.008
0.893Ϯ0.030
0.163Ϯ0.013
0.072Ϯ0.008
0.162Ϯ0.015
0.155Ϯ0.013
4.187Ϯ0.065
0.473Ϯ0.023
0.641Ϯ0.025
0.666Ϯ0.030
0.620Ϯ0.025
LЈ1
L2
LЈ2
LDPA
L3
288.5Ϯ34.0
3773.0Ϯ124.0
687.5Ϯ55.0
LЈ3
L4
305.0Ϯ33.0
684.5Ϯ61.0
LЈ4
LDQA
L5
655.0Ϯ56.0
17698.0Ϯ276.0
2000.5Ϯ98.5
2709.5Ϯ104.5
2815.0Ϯ128.0
2622.5Ϯ105.0
LЈ5
L6
LЈ6
[a] Recorded after 24 h incubation. [b] The average volume of the cells was estimated to be 2.27 pL (see text).
Evaluation by Fluorescent Microscopy of the Uptake of Re
Complexes by PC-12 Cells
Upon excitation at 330 nm, [Re(LЈ7)(CO)3]Cl exhibited
a moderately intense fluorescence signal at around 420 nm
(Figure S6), which can be viewed by a fluorescent micro-
The distribution of a representative Re complex inside PC- scope (excitation 330–385 nm, detection Ͼ 420 nm). The
12 cells was investigated by a fluorescent microscopy mea- fluorescent microscopic analysis was performed with PC-
surement[14] performed with a methoxy substituted DQA 12 rat adrenal pheochromocytoma. Increased fluorescence
O-galactoside complex, [Re(LЈ7)(CO)3]Cl (Scheme 6), for from the cells was observed after incubation with
which superior cell uptake and fluorescence detection was [Re(LЈ7)(CO)3]Cl (50 μm) for 4 h (Figure 5, b). From this
expected. Introduction of the methoxy group on to the picture we can conclude that the complex penetrates into
quinoline ring enhances the fluorescent intensity and shifts the cell because the fluorescence was observed from whole
the excitation/emission wavelengths of the ligand relative to cell and not localized in the cell membrane. The fluorescent
the signals for the corresponding ligand devoid of such a nuclear stain DAPI (4Ј,6-diamino-2-phenylindole dihydro-
group.[15] Considering the “O-glycoside effect” observed for chloride) was added during the microscopic analysis and
the L1/LЈ1 complexes, the O-glycoside linker was chosen selectively accumulates in the cell nucleus (Figure 5, c).
for use in this study.
Interestingly, overlaying of parts b and s of Figure 5 demon-
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Rhenium(I) Tricarbonyl Complexes
cent quinoline derivative [Re(LЈ7)(CO)3]Cl reveals that the
complex stays in the cytosol and does not penetrate into
the nucleus. The water soluble NPG complexes exhibited
carbohydrate enhanced cell uptake; however, no carbo-
hydrate dependent uptake was observed in this study. The
NPG complexes with pendant O-glycoside groups, L1 and
LЈ1, displayed increased uptake in comparison to both the
C-glycoside analogues (L2/LЈ2) and the carbohydrate-free
derivative. This result provides a potential starting point for
further structural modifications aimed at enhancing the
cellular uptake of rhenium(I) tricarbonyl complexes. We are
currently investigating the cellular uptake of the Re com-
plexes in a variety of cell lines to determine the generality
of this approach. Biodistribution studies employing radio-
active 99mTc complexes are also currently underway.
Scheme 6. Reagents and conditions: (i) 2-(chloromethyl)-6-methoxy-
quinoline, DMF; (ii) NaOMe, MeOH.
Experimental Section
General: All reagents and solvents for the syntheses were obtained
from commercial sources and used as received. 1H NMR
(300.07 MHz) and 13C NMR (75.00 MHz) spectra were recorded
on a Varian GEMINI 2000 spectrometer and referenced to internal
tetramethylsilane (TMS) or solvent signals. Elemental analyses
were recorded on a J-Science JM-10 Micro Corder. The synthetic
and characterization details for all new compounds are described
in the Supporting Information.
strates that [Re(LЈ7)(CO)3]Cl is localized in the cytosol and
does not penetrate into the nucleus (Figure 5, d). This study
clearly demonstrates the cell permeability of [Re(LЈ7)(CO)3]-
Cl and also the localization of the complex in PC-12 cells.
X-ray Crystallography: Single crystals of 6, 6Ј, LDQA, [Re(LЈ4)-
(CO)3]Cl, [Re(9)(CO)3]ClO4, [Re(LNPG)(CO)3]Cl, and [Re(LDPA)-
(CO)3]Cl were covered by Paraton-N oil and mounted on glass fi-
bers. All data were collected at 123 or 223 K on a Rigaku Mercury
charge coupled device (CCD) detector, with monochromatic
Mo-Kα radiation generated from an X-ray tube operating at 50 kV/
40 mA. Data were processed on a PC with the CrystalClear Soft-
ware (Rigaku). Structures were solved by direct methods (SIR-92)
Table 2. Crystallographic data for [Re(LЈ4)(CO)3]Cl·0.5CH3CN·
0.5C2H5OH and [Re(9)(CO)3]ClO4·H2O.
[Re(LЈ4)(CO)3]Cl·
[Re(9)(CO)3]ClO4·H2O
0.5CH3CN·0.5C2H5OH
Formula
FW
Crystal system
Space group
a [Å]
C25H31.5ClN3.5O8.5Re
738.70
monoclinic
C2
36.4467(14)
9.2658(4)
16.1508(7)
95.546(2)
5428.7(12)
8
C31H37ClN3O17Re
945.30
monoclinic
P21
14.271(2)
7.3184(9)
19.286(3)
111.1690(12)
1878.4(4)
2
Figure 5. Differential interference contrast and fluorescent micro-
graphs of cultured PC-12 rat adrenal cells incubated in the presence
of [Re(LЈ7)(CO)3]Cl (50 μm) for 4 h: (a) differential interference
contrast; (b) fluorescent micrograph; (c) fluorescent micrograph in
the presence of DAPI; (d) image formed from the merging of
images (b) and (c).
b [Å]
c [Å]
β [deg]
V [Å3]
Z
Dcalcd. [gcm–3]
μ [cm–1]
2θmax [deg]
Temperature [K]
1.807
46.335
55.0
123
1.671
33.838
55.0
Conclusions
223
Reflections collected 21484
14746
8649
Glucose- and galactose-pendant ligands containing
DPA, DQA, and NPG as metal binding sites have been pre-
pared. The structures of rhenium(I) tricarbonyl complexes
with these ligands were characterized and their uptake into
HeLa S3 cells studied. MIP-MS measurements reveal that
the DQA complexes show the highest uptake of all the com-
Reflections used
Rint
11713
0.0322
712
0.0224
506
0.0307
0.0659
1.047
Parameters
Final R1[a] [I Ͼ 2θ(I)] 0.0399
wR2[a] (all data)
0.0806
1.067
GOF
plexes in the series. Microscopic analysis with the fluores- [a] R1 = (Σ||Fo| – |Fc||)/(Σ|Fo|). wR2 = {[Σw(Fo – Fc2)2]/[Σw(Fo ) ]}1/2
.
2
2 2
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223

Y. Mikata et al.
FULL PAPER
and refined by full-matrix least-squares methods on F2 (SHELXL-
97). Crystal data for carbohydrate-pendant rhenium(I) tricarbonyl
complexes [Re(LЈ4)(CO)3]Cl and [Re(9)(CO)3]ClO4 are summa-
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CCDC-825160 {for [Re(9)(CO)3]ClO4}, -825161 {for [Re(LЈ4)-
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Acknowledgments
This work was supported by the Nara Women’s University Intra-
mural Grant for Project Research, Grant-in Aid for Scientific Re-
search from the Ministry of Education, Culture, Sports, Science
and Technology (MEXT), Japan, and the Research for Promoting
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Received: September 8, 2011
Published Online: December 7, 2011
Eur. J. Inorg. Chem. 2012, 217–225
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