Anal. Chem. 2007, 79, 1890-1896
Molecular Recognition of Protonated Polyamines at Calix[4]Crown-5 Self-Assembled Monolayer Modified Electrodes by Impedance Measurements Jin-Young Park, Byung-Cheol Kim, and Su-Moon Park*
Department of Chemistry and Center for Integrated Molecular Systems, Pohang University of Science and Technology, Pohang, Gyeongbuk 790-784, Korea
Molecular recognition of protonated aliphatic polyamines has been studied at calix[4]crown-5 self-assembled monolayer modified gold electrodes by electrochemical impedance spectroscopic (EIS) experiments. The energy of complex formation between the calix [4]crown-5 molecule and a series of alkyl ammonium ions was shown by molecular modeling and EIS experiments to depend on the number of amine groups in the alkyl chain as well as the number of methylene groups between the amine groups. The structures of complexes formed between the crown ether on the lower rim of calix[4]arene and protonated amines were determined by minimizing the complex formation energies. The adducts thus formed on the SAM rendered the electron transfer from the electrode to the probe (Fe(CN)63-/4- pair) easier or more difficult depending on the number of ammonium groups and their arrangement in linear alkyl chains. Analytical procedures have been developed to detect protonated spermidine (a recognized cancer marker) in simulated urine, blood, erythrocyte, and cerebrospinal fluids. Polyamines are associated with cell growth and differentiation with multiple functions such as antiglycation activity, surrogate roles in cancer cell, radical scavenger, and DNA stabilization in living organisms.1-7 For this reason, clinical biochemists have been interested in detection of polyamines and their analysis in blood, cerebrospinal fluids, erythrocytes, and urine samples.8-12 Investigators have found elevated concentrations of urinary polyamines in breast,13 cervical,14 ovarian,15 and lung cancer, as well as * To whom correspondence should be addressed. E-mail:
[email protected]. Phone: +82-54-279-2102. Fax: +82-54-279-3399. (1) Caldarea, C. M.; Barbiroli, B.; Moruzzi, G. Biochem. J. 1965, 97, 84. (2) Janne, J.; Alhonen, L.; Leinonen, P. Ann. Med. 1991, 23, 241. (3) Russell, D. H. CRC Rev. Clin. Lab. Sci. 1983, 18, 261. (4) Patocka, J.; Kuehn, G. D. Acta Med. 2000, 43, 119. (5) Gugliucci, A.; Menini, T. Life Sci. 2003, 72, 2603. (6) Ha, H. C.; Sirisoma, N. S.; Kuppusamy, P.; Zweier, J. L.; Woster, P. M.; Casero, R. A., Jr. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 11140. (7) Drolet, G.; Dumbroff, E. B.; Legge, R. L.; Thompson, J. E. Phytochemistry 1986, 25, 367. (8) Marton, L. J.; Edward, M. S.; Levin, V. A.; Lubich, W. P.; Wilson, C. B. Cancer Res. 1979, 39, 993. (9) Moulinoux, J. P.; Quemener, V.; Khan, N. A. Cell Mol. Biol. 1991, 37, 773. (10) Russell, D. H. Nature 233, 144. (11) Russell, D. H.; Levy, C. C.; Schimpff, S. C.; Hawk, I. A. Cancer Res. 1971, 31, 1555. (12) Takami, H.; Romsdahl, M.; Nishioka, M. Lancet 1979, 2, 919.
1890 Analytical Chemistry, Vol. 79, No. 5, March 1, 2007
leukemia, patients.16 Many studies have been carried out on whether the polyamines can be used for early detection of cancers and inspection of chemotherapy efficacies.17-21 The polyamine levels can also be elevated in other diseases. Patients suffering from cystic fibrosis,22 muscular dystrophy,23 psoriasis,24 and diabetics25 may have high levels of polyamines even though they have no cancer. However, not all cancer patients show positive results for urinary polyamines during their cancer diagnosis.26 Thus, while use of polyamine levels has some limitations in early screening of cancer, they still have been utilized for predicting success of chemotherapy or surgery and recurrence of cancer, as the high level of polyamine is reduced after the successful cancer treatment. In many cases, an increase in the polyamine level is connected with the recurrence of cancer.9,11,17 Thus, the serial diagnoses about the polyamines can predict the process of tumor growth and suggest the next plan of suitable therapy. For clinical measurements, the polyamines present in red blood cells (5-50 µM), blood serum (
