C O M M U N I C A T I O N S
dependent release rate is consistent with the mechanism of operation
for the MNP system: release of guest molecules depends on the
rate of protonation of the anilinium nitrogen atom, which occurs
more rapidly at more acidic pH levels.
References
(1) (a) Angelos, S.; Yang, Y.-W.; Patel, K.; Stoddart, J. F.; Zink, J. I. Angew.
Chem., Int. Ed. 2008, 47, 2222–2226. (b) Nguyen, T. D.; Leung, K.C.-F.;
Liong, M.; Liu, Y.; Stoddart, J. F.; Zink, J. I. AdV. Funct. Mater. 2007, 14,
2101–2110. (c) Nguyen, T. D.; Liu, Y.; Saha, S.; Leung, K.C.-F.; Stoddart,
J. F.; Zink, J. I. J. Am. Chem. Soc. 2007, 129, 626–634. (d) Nguyen, T. D.;
Leung, K. C.-F.; Liong, M.; Pentecost, C. D.; Stoddart, J. F.; Zink, J. I.
Org. Lett. 2006, 8, 3363–3366. (e) Leung, K.C.-F.; Nguyen, T. D.; Stoddart,
J. F.; Zink, J. I. Chem. Mater. 2006, 18, 5919–5928. (f) Nguyen, T. D.;
Tseng, H.-R.; Celestre, P. C.; Flood, A. H.; Liu, Y.; Stoddart, J. F.; Zink,
J. I. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 10029–10034. (g) Hernandez,
R.; Tseng, H.-R.; Wong, J. W.; Stoddart, J. F.; Zink, J. I. J. Am. Chem.
Soc. 2004, 126, 3370–3371. (h) Ferris, D. P.; Zhao, Y.-L.; Khashab, N. M.;
Khatib, H. A.; Stoddart, J. F.; Zink, J. I. J. Am. Chem. Soc. 2009, 131,
1686–1688. (i) Saha, S.; Leung, K.C.-F.; Nguyen, T. D.; Stoddart, J. F.;
Zink, J. I. AdV. Funct. Mater. 2007, 17, 685–693.
(2) (a) Zhu, Y.; Fujiwara, M. Angew. Chem., Int. Ed. 2007, 46, 2241–2244.
(b) Johansson, E.; Choi, E.; Angelos, S.; Liong, M.; Zink, J. I. J. Sol-Gel
Sci. Technol. 2008, 46, 313–322. (c) Mal, N. K.; Fujiwara, M.; Tanaka, Y.
Nature 2003, 421, 350–353. (d) Patel, K.; Angelos, S.; Dichtel, W. R.;
Coskun, A.; Yang, Y.-W.; Zink, J. I.; Stoddart, J. F. J. Am. Chem. Soc.
2008, 130, 2382–2383. (e) Lai, C.-Y.; Trewyn, B. G.; Jeftinija, D. M.;
Jeftinija, K.; Xu, S.; Jeftinija, S.; Lin, V.S.-Y. J. Am. Chem. Soc. 2003,
125, 4451–4459. (f) Park, C.; Oh, K.; Lee, S. C.; Kim, C. Angew. Chem.,
Int. Ed. 2007, 46, 1455–1457. (g) Giri, S.; Trewyn, B. G.; Stellmaker, M. P.;
Lin, V.S.-Y. Angew. Chem., Int. Ed. 2005, 44, 5038–5044. (h) Slowing,
I.; Trewyn, B. G.; Giri, S.; Lin, V.S.-Y. AdV. Funct. Mater. 2007, 17, 1225–
1236. (i) Liu, R.; Zhao, X.; Wu, T.; Feng, P. J. Am. Chem. Soc. 2008, 130,
14418–14419. (j) Mun˜oz, B.; Ra´mila, A.; Pe´rez-Pariente, J.; D´ıaz, I.; Vallet-
Reg´ı, M. Chem. Mater. 2003, 15, 500–503. (k) Angelos, S.; Johansson,
E.; Stoddart, J. F.; Zink, J. I. AdV. Funct. Mater. 2007, 17, 2261–2271.
By comparing the release profiles for MNP-1 and MNP-2 (Figure
3a and 3b), a difference in the pH-sensitivity of the two systems is
observed. When pH ) 5.0 is used to activate the MNPs, the
response exhibited by MNP-2 is more pronounced than that by
MNP-1. For MNP-2, 50% of the maximum release is obtained after
600 s (Figure 3b), while, for MNP-1, just 13% of the maximum
release is reached after 600 s (Figure 3a). The difference in the
operation of MNP-1 and MNP-2 corresponds to the difference in
the pKa of the nitrogen atom in aniline and p-anisidine. The
difference in the release efficiency at pH 5 demonstrates that the
pH sensitivity of the MNP system can be rationally tuned through
chemical modification of the stalks at position R.
The response of MNP-1 to high pH conditions (Figure 3c)
illustrates that the MNP system can be operated through an
alternative base-driven mechanism. When the pH is adjusted to 10
such that all of the ammonium groups on the stalk are deprotonated,
the ion-dipole interactions between the CB[6] ring and the stalk
are disrupted, resulting in dethreading of the ring and release of
the encapsulated guests. As shown in the release profile, the rate
of the base-driven release is rapid: 50% of the maximum release
occurs at 400 s, just ∼100 s after the base is added.
(3) Lu, J.; Choi, E.; Tamanoi, F.; Zink, J. I. Small 2008, 4, 421–426.
(4) (a) Lu, J.; Liong, M.; Zink, J. I.; Tamanoi, F. Small 2007, 3, 1341–1346.
(b) Lu, J.; Liong, M.; Sherman, S.; Xia, T.; Kovochich, M.; Nel, A. E.;
Zink, J. I. Nanobiotechnology 2007, 3, 89–95. (c) Lin, Y.-S.; Wu, S.-H.;
Hung, Y.; Chou, Y.-H.; Chang, C.; Lin, M.-L.; Tsai, C.-P.; Mou, C.-Y.
Chem. Mater. 2006, 18, 5170–5172.
(5) (a) Behrend, R.; Meyer, E.; Rusche, F. Liebigs Ann. Chem. 1905, 339,
1–37. (b) Freeman, W. A.; Mock, W. L.; Shih, N.-Y. J. Am. Chem. Soc.
1981, 103, 7367–7368. (c) Mock, W. L.; Shih, N.-Y. J. Am. Chem. Soc.
1989, 111, 2697–2699. (d) Tuncel, D.; Steinke, J. H. G. Chem Commun.
2001, 253–254. (e) Kim, K. Chem. Soc. ReV. 2002, 31, 96–107. (f) Lee,
J. W.; Samal, S.; Selvapalam, N.; Kim, H.-J.; Kim, K. Acc. Chem. Res.
2003, 36, 621–630. (g) Ma´rquez, C.; Hudgins, R. R.; Nau, W. M. J. Am.
Chem. Soc. 2004, 126, 5806–5816. (h) Lagona, J.; Mukhopadhyay, P.;
Chakrabarti, S.; Issacs, L. Angew. Chem., Int. Ed. 2005, 44, 4844–4870.
In conclusion, we have designed and synthesized a novel MNP
system. Luminescence spectroscopy has been used to demonstrate
that the MNPs are able to keep guest molecules encapsulated at
neutral pH but release them when the pH is lowered. Furthermore,
the pH at which the MNP system responds can be tuned through
rational chemical modification of the stalk. For biological applica-
tions, the ability to fine-tune the system for optimal response
enhances the versatility of this MNP system for use in a wide range
of different tissues with different pH values. Efforts are now
underway to explore the applications of these MNPs by testing their
delivery capabilities with various types of human cancer cells with
varying lysosomal pH levels.
(6) (a) Lee, J. W.; Kim, K.; Kim, K. Chem. Commun. 2001, 1042–1043. (b)
Tuncel, D.; Steinke, J. H. G. Chem. Commun. 2002, 496–497. (c) Jun,
S. I.; Lee, J. W.; Sakamoto, S.; Yamaguchi, K.; Kim, K. Tetrahedron Lett.
2000, 41, 471–475. (d) Tuncel, D.; Katterle, M. Chem.sEur. J. 2008, 14,
4110–4116.
(7) Mock, W. L.; Pierpont, J. J. Chem. Soc., Chem. Commun. 1990, 1509–
1511.
Acknowledgment. This work was supported by the US DOD
(HDTRA1-08-1-0041) and the National Science Foundation (CHE
0809384).
(8) Weast, R. C. CRC Handbook of Chemistry and Physics, 54th ed.; CRC
Press: Cleveland, OH, 1973.
(9) Kresge, C. T.; Leonowicz, M. E.; Roth, W. J.; Vartuli, J. C.; Beck, J. S.
Nature 1992, 359, 710–712.
(10) Huh, S.; Wiench, J. W.; Yoo, J. C.; Pruski, M.; Lin, V.S.-Y. Chem. Mater.
2003, 15, 4247–4256.
Supporting Information Available: Synthetic procedures and
spectral characterization data. This material is available free of charge
JA9010157
9
12914 J. AM. CHEM. SOC. VOL. 131, NO. 36, 2009