C. Lang, X. Zhang, Q. Luo, Z. Dong, J. Xu, J. Liu
FULL PAPER
122.1, 120.0, 116.2, 43.4, 29.4 ppm. HRMS (ESI): calcd. for
C22H18F12N4S3 [M + H]+ 663.0575; found 663.0349.
Calculations: Free representative transporters 1F2, 2F2, 3F2, and
their complexes with chloride ions were subjected to theoretical
calculations by using ab initio methods by means of the
Gaussian 09 program (Hartree–Fock, 6-31+G* basis set, im-
plemented within Spartan’06).
Preparation of Compound 3N: Bis(2-aminoethyl) selenide
(0.6 mmol) and 4-nitrophenyl isothiocyanate (1.3 mmol) were sus-
pended in anhydrous THF (5 mL) and stirred under N2 at room
temperature for 16 h. The mixture was then concentrated under
reduced pressure. The residue was washed with cold CH2Cl2 and
MeOH. The obtained solid was then dried under high vacuum to
yield the product as a yellow solid. Yield: 40%. 1H NMR ([D6]-
DMSO): δ = 10.26 (s, 2 H), 8.41 (s, 2 H), 8.18 (d, J = 9.2 Hz, 4
H), 7.81 (d, J = 9.2 Hz, 4 H), 3.79 (d, J = 5.5 Hz, 4 H), 2.85 (t, J
= 7.2 Hz, 4 H) ppm. 13C NMR ([D6]DMSO): δ = 179.9, 146.5,
141.9, 124.5, 120.6, 44.3, 21.5 ppm. HRMS (ESI): calcd. for
C18H20N6O4S2Se [M + H]+ 529.0225; found 529.0104.
–
Procedure for Anion-Transport Experiments: In the Cl–/NO3 anti-
port experiment, a typical procedure was as follows: EYPC (9 mg,
or 5.2 mg with 1.9 mg of cholesterol) was first dissolved in CHCl3
(3 mL) and concentrated under reduced pressure. The resultant
thin film was then dried under high vacuum for 3 h. The lipid was
hydrated with NaNO3 (200 mm) solution that contained lucigenin
(1 mm) at 40 °C for 2 h followed by 10 freeze-thaw cycles with li-
quid nitrogen and a thermostat-regulated water bath. The resulting
suspension was then extruded through a polycarbonate membrane
(0.22 μm) before purification by Sephadex G-75 to remove the extra
vesicular dye by using an NaNO3 (200 mm) solution as elute. The
obtained vesicles were stored below 4 °C. Then NaNO3 (1.94 mL,
200 mm) solution was added before transferring the vesicle solution
(60 μL) into a fluorometric cell. The fluorescence emission was con-
tinuously monitored at 503 nm (excited at 372 nm), and then meth-
anol (10 μl) solution of the carrier was added with gentle stirring.
Finally, a Triton X-100 water solution (10 μL, 50%) was added to
achieve complete lysis of the vesicles. By using E0 and Eϱ to repre-
sent the initial and final emission intensity, the collected data of
the fluorescence time course was normalized in accordance to the
equation (E0 – Et)/(E0 – Eϱ). The injection of additive parts during
the fluorescence experiment of the spectrum was subtracted for
clarity.
Preparation of Compound 3F: Bis(2-aminoethyl) selenide (0.8 mmol)
and 4-(trifluoromethyl)phenyl isothiocyanate (1.64 mmol) were
suspended in anhydrous THF (5 mL) and stirred under N2 at room
temperature for 16 h. The mixture was then concentrated under
reduced pressure. The residue was then purified by column
chromatography on silica gel to yield the product as a white solid.
Yield: 62%. 1H NMR ([D6]DMSO): δ = 9.98 (s, 2 H), 8.19 (s, 2
H), 7.70 (d, J = 8.6 Hz, 4 H), 7.65 (d, J = 8.8 Hz, 4 H), 3.78 (s, 4
H), 2.83 (t, J = 7.3 Hz, 4 H) ppm. 13C NMR ([D6]DMSO): δ =
180.3, 143.2, 127.6, 125.7, 123.3, 121.9, 44.3, 21.6 ppm. HRMS
(ESI): calcd. for C20H20F6N4S2Se [M + H]+ 575.0272; found
575.0313.
Preparation of Compound 3F2: Bis(2-aminoethyl) selenide
(0.7 mmol) and 3,5-bis(trifluoromethyl)phenyl isothiocyanate
(1.44 mmol) were suspended in anhydrous THF (5 mL) and stirred
under N2 at room temperature for 16 h. The mixture was then con-
centrated under reduced pressure. The residue was then purified by
column chromatography on silica gel to yield the product as a white
Acknowledgments
This work was supported by the Natural Science Foundation of
China (nos. 21234004, 21420102007, 21221063, 21474038), the
111 Project (B06009), and the Chang Jiang Scholars Program of
China.
1
solid. Yield: 60%. H NMR ([D6]DMSO): δ = 10.19 (s, 2 H), 8.35
(s, 2 H), 8.24 (s, 4 H), 7.74 (s, 2 H), 3.79 (s, 4 H), 2.84 (t, J =
7.2 Hz, 4 H) ppm. 13C NMR ([D6]DMSO): δ = 180.5, 141.8, 126.5,
124.3, 122.1, 120.0, 116.2, 44.3, 21.5 ppm. HRMS (ESI): calcd. for
C22H18F12N4S2Se [M + H]+ 711.0019; found 710.9779.
[1] T. M. Fyles, Chem. Soc. Rev. 2007, 36, 335; N. Sakai, S. Matile,
Langmuir 2013, 29, 9031; G. W. Gokel, R. Ferdani, J. Liu, R.
Pajewski, H. Shabany, P. Uetrecht, Chem. Eur. J. 2001, 7, 33;
N. Madhavan, E. C. Robert, M. S. Gin, Angew. Chem. Int. Ed.
2005, 44, 7584; Angew. Chem. 2005, 117, 7756; M. S. Kaucher,
W. A. Harrell Jr., J. T. Davis, J. Am. Chem. Soc. 2006, 128, 38;
W. Si, L. Chen, X. B. Hu, G. F. Tang, Z. X. Chen, J. L. Hou,
Z. T. Li, Angew. Chem. Int. Ed. 2011, 50, 12564; Angew. Chem.
2011, 123, 12772; X. B. Zhou, G. Liu, K. Yamato, Y. Shen, R.
Cheng, X. Wei, W. Bai, Y. Gao, H. Li, Y. Liu, F. Liu, D. M.
Czajkowsky, J. Wang, M. J. Dabney, Z. Cai, J. Hu, F. V. Bright,
L. He, X. C. Zeng, Z. F. Shao, B. Gong, Nat. Commun. 2012,
3, 949; C. Han, H. Su, Z. Sun, L. Wen, D. Tian, K. Xu, J. Hu,
A. Wang, H. Li, L. Jiang, Chem. Eur. J. 2013, 19, 9388; M.
Vidal, A. Schmitzer, Chem. Eur. J. 2014, 20, 9998.
[2] H. Valkenier, L. W. Judd, H. Li, S. Hussain, D. N. Sheppard,
A. P. Davis, J. Am. Chem. Soc. 2014, 136, 12507; S. J. Brooks,
J. Shang, W. Si, W. Zhao, Y. Che, J. L. Hou, H. Jiang, Org.
Lett. 2014, 16, 4008; L. Adriaenssens, C. Estarellas, A. V.
Jentzsch, M. M. Belmonte, S. Matile, P. Ballester, J. Am. Chem.
Soc. 2013, 135, 8324; N. Busschaert, I. L. Kirby, S. Young, S. J.
Coles, P. N. Horton, M. E. Light, P. A. Gale, Angew. Chem.
Int. Ed. 2012, 51, 4426; Angew. Chem. 2012, 124, 4502; A. V.
Jentzsch, D. Emery, J. Mareda, S. K. Nayak, P. Metrangolo, G.
Resnati, N. Sakai, S. Matile, Nat. Commun. 2012, 3, 905; I.
Park, J. Yoo, B. Kim, S. Adhikari, S. K. Kim, Y. Yeon, C. J. E.
Haynes, J. L. Sutton, C. C. Tong, V. M. Lynch, J. L. Sessler,
P. A. Gale, C. Lee, Chem. Eur. J. 2012, 18, 2514; N. Busschaert,
HPLC Measurements: To assess the hydrophobicity of receptors,
their retention times were measured by reverse-phase HPLC. The
mobile phase was prepared with HCOOH, acetonitrile and water.
Samples under test were prepared as DMSO solutions at a concen-
tration of 0.1 mg/mL. Samples were injected (2 μL) directly onto
an Agilent SB C-18 column (2.1 mmϫ50 mm 1.8 μm particle size)
and separated by using acetonitrile (50%) and HCOOH (0.1%) in
water over 5 min. UV data were recorded at 19–600 nm, and mass
spectra were recorded by using positive-ion electrospray ionization
to assign retention times to respective receptors. clogP values were
calculated relative to the VCC Laboratory online calculator
ALOGPS 2.14.[19]
Anion-Binding Affinities: Chloride binding affinities were investi-
1
gated by using H NMR spectroscopic titration in [D6]DMSO/5%
H2O. TBAC (100 mm) in a solution of receptor (1 mm) in [D6]-
DMSO/5% H2O was prepared as the guest solution. Receptor
(1 mm) in [D6]DMSO/5% H2O was prepared as the host solution.
To perform the titration experiment, aliquots of the guest and host
solutions in a total volume of 500 μL were mixed (the volume of
the guest solution was initially 0 μL, then 5–450 μL, and finally
500 μL). Binding constants were obtained by fitting the change in
chemical shift of the thiourea NH signal to a 1:1 model by using
the WinEQ NMR 2 computer program.[20] In this study, both NH
signals were considered.
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