AJAC  Vol.4 No.6 , June 2013
Use of Cucurbit [6] Uril as a Modifier in the Electrochemical Determination of Antitumor Platinum (II) Complex: Trans-[PtCl2(Dimethylamine) (Isopropylamine)]. Application to Biological Samples

A square wave voltammetry (DPV) method for trans-Pt[Cl2(Dimethylamine)(isopropylamine)] determination is developed. To this end, all the chemical and instrumental variables affecting the determination of trans-Pt[Cl2(Dimethylamine) (isopropylamine)] are optimized. From studies of the mechanisms governing the electrochemical response of trans-Pt[Cl2(Dimethylamine)(isopropylamine)], it was concluded that it was an electrochemically reversible system with an adsorptive oxidation phenomenon. Under optimal conditions, the variation of analytical signal (Ip) with trans-Pt[Cl2(Dimethylamine)(isopropylamine)] concentration was linear in the 0.05 μg·mL-1 to 10 μg·mL-1 range, with a LOD 91 μg·mL-1 of and a LOQ of 303 μg·mL-1, a RSD 1.10% and Er 0.72%. The optimized method was applied to the determination of trans-Pt[Cl2(Dimethylamine)(isopropylamine)] in biological fluids, in human urine and synthetic urine.

Cite this paper: C. Domínguez and P. Hernández, "Use of Cucurbit [6] Uril as a Modifier in the Electrochemical Determination of Antitumor Platinum (II) Complex: Trans-[PtCl2(Dimethylamine) (Isopropylamine)]. Application to Biological Samples," American Journal of Analytical Chemistry, Vol. 4 No. 6, 2013, pp. 314-322. doi: 10.4236/ajac.2013.46040.

[1]   B. Lippert, “Cisplatin: Chemistry and Biochemistry of Leading Anticancer Drug,” Wiley-VCH, Weinheim, 1999. doi:10.1002/9783906390420

[2]   E. Wong and C. M. Giandomenico, “Current Status of Platinum-Based Antitumor Drugs,” Chemical Reviews, Vol. 99, No. 9, 1999, pp. 2451-2466. doi:10.1021/cr980420v

[3]   L. Kelland, “The Resurgence of Platinum-Based Cancer Chemotherapy,” Natural Reviews on Cancer, Vol. 7, 2007, pp. 573-584. doi:10.1038/nrc2167

[4]   N. J. Wheate and J. G. Collins, “Multi-Nuclear Platinum Complexes as Anti-Cancer Drugs,” Coordination Chemistry Reviews, Vol. 241, No. 1-2, 2003, pp. 133-145. doi:10.1016/S0010-8545(03)00050-X

[5]   N. J. Wheate and J. G. Collins, “Multi-Nuclear Platinum Drugs: A New Paradigm in Chemotherapy,” Current Medicinal Chemistry-Anti-Cancer Agents, Vol. 5, No. 3, 2005, pp. 267-279. doi:10.2174/1568011053765994

[6]   T. Dragovich, D. Mendelson, S. Kurtin, K. Richardson, D. Von Hoff and A. Hoos, “A Phase 2 Trial of the Liposomal DACH Platinum L-NDDP in Patients with Therapy- Refractory Advanced Colorectal Cancer,” Cancer Chemotherapy and Pharmacology, Vol. 58, No. 6, 2006, pp. 759-764. doi:10.1007/s00280-006-0235-4

[7]   C. Lu, R. Pérez-Soler, B. Piperdi, G. L. Walsh, S. G. Swisher, W. R. Smythe, H. J. Shin, J. Y. Ro, L. Feng, M. Truong, A. Yalamanchili, G. Lópes-Berestein, W. K. Hong, A. R. Khokhar and D. M. Shin, Journal of Clinical Oncology, Vol. 23, No. 15, 2005, pp. 3495-3501. doi:10.1200/JCO.2005.00.802

[8]   J. R. Rice, J. L. Gerberich, D. P. Nowotnik and S. B. Howell, “Preclinical Efficacy and Pharmacokinetics of AP5346, A Novel Diaminocyclohexane-Platinum Tumor- Targeting Drug Delivery System,” Clinical Cancer Research, Vol. 12, 2006, pp. 2248-2254. doi:10.1158/1078-0432.CCR-05-2169

[9]   M. Campone, J. M. Rademaker-Lakhai, J. Bennouna, S. B. Howell, D. P. Nowotnik, J. H. Beijnen and J. H. M. Schellens, “Phase I and Pharmacokinetic Trial of AP5346, a DACH-Platinum-Polymer Conjugate, Administered Weekly for Three out of Every 4 Weeks to Advanced Solid Tumor Patients,” Cancer Chemotherapy and Pharmacology, Vol. 60, No. 4, 2007, pp. 523-533. doi:10.1007/s00280-006-0397-0

[10]   Y. J. Jun, J. I. Kim, M. J. Jun and Y. S. Sohn, “Selective Tumor Targeting by Enhanced Permeability and Retention Effect. Synthesis and Antitumor Activity of Polyphosphazene-Platinum (II) Conjugates,” Journal of Inorganic Biochemistry, Vol. 99, No. 8, 2005, pp. 1593-1601. doi:10.1016/j.jinorgbio.2005.04.019

[11]   P. Sood, K. B. Thurmond, J. E. Jacob, L. K. Waller, G. O. Silva, D. R. Stewart and D. P. Nowotnik, “Synthesis and Characterization of AP5346, a Novel Polymer-Linked Diaminocyclohexyl Platinum Chemotherapeutic Agent,” Bioconjuate Chemistry, Vol. 17, No. 5, 2006, pp. 1270- 1279. doi:10.1021/bc0600517

[12]   F. Kratz, I. A. Müller, C. Ryppa and A. Warnecke, “Prodrug Strategies in Anticancer Chemotherapy,” Chem- MedChem, Vol. 3, No. 1, 2008, pp. 20-53. doi:10.1002/cmdc.200700159

[13]   K. Uekama, F. Hirayama, H. Arima and J. Incl, “Recent Aspect of Cyclodextrin-Based Drug Delivery System,” Journal of Inclusion Phenomena and Macrocyclic Chemistry, Vol. 56, No. 1-2, 2006, pp. 3-8. doi:10.1007/s10847-006-9052-y

[14]   R. Behrend, E. Meyer and F. Rusche, “I. Ueber Condensationsproducte aus Glycoluril und Formaldehyd,” Justus Liebigs Annalen der Chemie, Vol. 339, No. 1, 1905, pp. 1-37. doi:10.1002/jlac.19053390102

[15]   W. A. Freeman, W. L. Mock and N.-Y. Shih, “Cucurbituril,” Journal of the American Chemical Society, Vol. 103, No. 24, 1981, pp. 7367-7368. doi:10.1021/ja00414a070

[16]   J. Kim, I. S. Jung, S. Y. Kim, E. Lee, J. K. Kang, S. Sakamoto, K. Yamaguchi and K. Kim, “New Cucurbituril Homologues: Syntheses, Isolation, Characterization, and X-Ray Crystal Structures of Cucurbit[n]uril (n = 5, 7, and 8),” Journal of the American Chemical Society, Vol. 122, No. 3, 2000, pp. 540-541. doi:10.1021/ja993376p

[17]   S. Liu, P. Y. Zavalij and L. Isaacs, “Cucurbit[10]uril,” Journal of the American Chemical Society, Vol. 127, No. 48, 2005, pp. 16798-16799. doi:10.1021/ja056287n

[18]   N. J. Wheate, “Cucurbit[n]uril: A New Molecule in Host- Guest Chemistry,” Australian Journal of Chemistry, Vol. 59, No. 5, 2006, p. 354. doi:10.1071/CH06066

[19]   J. Lagona, P. Mukhopadhyay, S. Chakrabarti and L. Isaacs, “The Cucurbit[n]uril Family,” Angewandte Chemie International Edition, Vol. 44, No. 31, 2005, pp. 4844-4870. doi:10.1002/anie.200460675

[20]   K. Kim, N. Selvapalam, Y. H. Ko, K. M. Park and D. Kim, “Functionalized Cucurbiturils and Their Applications,” Chemical Society Reviews, Vol. 36, No. 2, 2007, pp. 267-279. doi:10.1039/b603088m

[21]   A. P. Day, R. J. Arnold, B. Blanch and J. Snushall, “Controlling Factors in the Synthesis of Cucurbituril and Its Homologues,” The Journal of Organic Chemistry, Vol. 66, No. 24, 2001, pp. 8094-8100. doi:10.1021/jo015897c

[22]   D. Whang, J. Heo, J. H. Park and K. Kim, “A Molecular Bowl with Metal Ion as Bottom: Reversible Inclusion of Organic Molecules in Cesium Ion Complexed Cucurbituril,” Angewandte Chemie International Edition, Vol. 37, No. 1-2, 1998, pp. 78-80. doi:10.1002/(SICI)1521-3773(19980202)37:1/2<78::AID-ANIE78>3.0.CO;2-9

[23]   H.-J. Buschmann, E. Cleve, E. Schollemeyer, “Cucurbituril as a Ligand for the Complexation of Cations in Aqueous Solutions,” Inorganica Chimica Acta, Vol. 193, No. 1, 1992, pp. 93-97. doi:10.1016/S0020-1693(00)83800-1

[24]   Y. M. Jeon, H. Kim, D. Whang and K. Kim, Journal of Physical Chemistry Society, Vol. 118, No. 40, 1996, pp. 9790-9791.

[25]   N. J. Wheate, P. G. A. Kumar, A. M. Torres, J. R. Aldrich-Wringht and W. S. Price, “Examination of Cucurbit [7]uril and Its Host-Guest Complexes by Diffusion Nuclear Magnetic Resonance,” Journal of Physical Chemistry B, Vol. 112, No. 8, 2008, pp. 2311-2314. doi:10.1021/jp709847p

[26]   K. B. Tarmyshov and F. Muller-Plathe, “Ion Binding to Cucurbit[6]uril: Structure and Dynamics,” Journal of Physical Chemistry B, Vol. 110, No. 29, 2006, pp. 14463- 14468. doi:10.1021/jp0622637

[27]   Osaka, M. Kondou, N. Selvaplan, S. Samal, K. Kim, M. V. Rekharsky, Y. Inoue and R. Arakawa, “Characterization of Host-Guest Complexes of Cucurbit[n]uril (n = 6, 7) by Electrospray Ionization Mass Spectrometry,” Journal of Mass Spectrometry, Vol. 41, No. 2, 2006, pp. 202-207. doi:10.1002/jms.978

[28]   W.-H. huang, P. Y. Zavalij and L. Isaacs, “Chiral Recognition inside a Chiral Cucurbituril,” Angewandte Chemie International Edition, Vol. 46, No. 39, 2007, pp. 7425- 7427. doi:10.1002/anie.200702189

[29]   Q. An, G. Li, C. Tao, Y. Li, Y. Wu and W. Zang, “A General and Efficient Method to Form Self-Assembled Cucurbit[N]Uril Monolayers on Gold Surfaces,” Chemical Communications, No. 17, 2008, pp. 1989-1991. doi:10.1039/b719927a

[30]   N. J. Wheate, D. P. Buck, A. I. Day and J. G. Collins, “Cucurbit[n]uril Binding of Platinum Anticancer Complexes,” Dalton Transactions, Vol. 17, No. 3, 2006, pp. 451- 458. doi:10.1039/b513197a

[31]   S. Kemp, N. J. Wheate, S. Wang, J. G. Collins, S. F. Ralph, A. I. Day, V. J. Higgings and J. R. Aldrich-Wright, “Encapsulation of Platinum(II)-Based DNA Intercalators within Cucurbit[6,7,8]urils,” Journal of Biological Inorganic Chemistry, Vol. 12, No. 7, 2007, pp. 969-979. doi:10.1007/s00775-007-0269-z

[32]   N. J. Wheate, R. I. Taleb, A. M. Krause-Heuer, R. L. Cook, S. Wang, V. J. Higgings and J. R. Aldrich-Wright, Dalton Transactions, 2007, pp. 505-5064.

[33]   J. M. Perez, L. R. Kelland, E. I. Montero, F. E. Boxal, M. Fuertes, C. Alonso and C. Navarro-Ranninger, “Antitumor and Cellular Pharmacological Properties of a Novel Platinum (IV) Complex: Trans-[PtCl2(OH)2(Dimethylamine)(Isopropylamine)],” Molecular Pharmacology, Vol. 63, No. 4, 2003, pp. 903-944. doi:10.1124/mol.63.4.933

[34]   J. M. Perez, E. I. Montero, A. G. Quiroga, M. A. Fuertes, C. Alonso and C. Navarro-Ranninger, “Cellular Uptake, DNA Binding and Apoptosis Induction of Citotoxic Trans- [PtCl2(N,N-Dimethylamine)(Isopropylamine)] in A2780cisR Ovarian Tumor Cells,” Metal Based Drugs, Vol. 8, No. 1, 2001, pp. 29-37. doi:10.1155/MBD.2001.29

[35]   J. M. Perez, E. I. Montero, A. M. González, A. Alvarez- Valdés, C. Alonso and C. Navarro-Ranninger, “Apoptosis Induction and Inhibition of H-Ras Overexpresion by Novel Trans-[PtCl2)(Isopropylamine)(amine’)] Complexes,” Journal of Inorganic Biochemistry, Vol. 77, No. 1, 1999, pp. 37-42.

[36]   E. I. Montero, J. M. Perez, A. Schwartz, M. A. Fuertes, J. M. Maligne, C. Alonso, M. Leng and C. Navarro-Ranninger, “Apoptosis Induction and DNA Interstrand Cross- Link Formation by Citotoxic Trans- [PtCl2(NH(CH3)2(NH2(CH(CH3)2]: Cross-Linking between d(G) and Complementary d(G) within Oligonucleotide Duplexes,” Biochemistry (Chemical Biology), Vol. 3, No. 1, 2002, pp. 101-107. doi:10.1002/1439-7633(20020104)3:1<61::AID-CBIC61>3.0.CO;2-I

[37]   B. J. Stevens, “Clinical Analysis by Atomic Absorption,” Department of Pathology. The Royal Children’s Hospital, Melbourne, 1970.