Abstract
The crystal and molecular structure of Tirofiban [N-(n-butanesulfonyl)-O-(4-(4-piperidinyl)-butyl)-(S)-tyrosine] is here reported. In the solid state the carboxylic group is in the anionic form while the piperidine molecule appear in the protonated form. By H NMR spectroscopy and potentiometric study three pKa are found: pKaCOOH=3.1(1), pKaNHPIP=11.6(1) and pKaNHSO2=13.8(1). The complexing ability of Tirofiban towards various metal ions (Cu(II), Ni(II), Co(II), Cd(II), Pb(II), Zn(II) and Ca(II)) is also determined by means of potentiometric studies. The prevailing species are [M(TirH)2]2+ where the ligand coordinates the metal ion through carboxylic group, while the piperidine nitrogen is still protonated. The great stability of these complexes may be due to the presence of hydrogen bond interactions, as well as the formation of stacking interactions involving the phenyl ring of the tyrosine residue.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Altomare A, Burla MC, Cavalli M, Cascarano GL, Giacovazzo C, Gagliardi A, Moliterni AGG, Polidori G, Spagna R. 1999 SIR97: A new tool for crystal structure determination and refinement. J Appl Cryst 32 115-119.
Battistuzzi G, Borsari M, Menabue L, Saladini M, Sola M. 1996 Amide group coordination to the Pb2+ ion. Inorg Chem 35, 4239-4246.
Bax A, Griffey RH, Hawkins BL. 1983 Correlation of proton and nitrogen-15 chemical shifts by multiple quantum NMR*. J Magn Reson 55, 301-315.
Bax A, Summers MF. 1986 Proton and carbon-13 assignments from sensitivity-enhanced detection of heteronuclear multiple-bond connectivity by 2D multiple quantum NMR. J Am Chem Soc 108, 2093-2094.
Bax A, Subramanian S. 1986 Sensitivity-enhanced two-dimensional heteronuclear shift correlation NMR spectroscopy. J Magn Reson 67, 565-569.
Bellamy LJ. 1975 The infrared Spectra of Complex Molecules. London: Chapman and Hall.
Borsari M, Menabue L, Saladini M. 1999 Coordination properties of N-p-tolylsulfonyl-L-glutamic acid toward metal(II). Part 2. Solution study on binary and ternary 2,2′-bipyridine containing systems. Polyhedron 18, 1983-1989.
Colthrum NB, Daly LH, Wiberley SE. 1964 Introduction to Infrared and Raman Spectroscopy. New York: Academic Press.
Chung JYL, Zhao D, Hunghes DL, Grabowski EJJ 1993 A practical synthesis of fibrogen receptor antagonist MK-383. Selective functionalization of (S)-tyrosine. Tetrahedron 49, 5767-5776.
Farrugia LJ. 1999 WinGX suite for small-molecule single-crystal crystallography. J Appl Cryst 32, 837-838.
Ferguson JJ, Lau TK 1998 New antiplatelet agents for acute coronary syndromes. Am Heart 135, S194-200.
Frassineti C, Ghelli S, Gans P, Sabatini A, Moruzzi MS, Vacca A. 1995 Nuclear magnetic resonance as a tool for determining protonation constants of natural polyprotic bases in solution. Anal Biochem 231, 374-382.
Gans P, Sabatini A, Vacca A. 1996 Investigation of equilibria in solution. Determination of equilibrium constants with the HYPERQUAD suite of programs. Talanta 43, 1739-1753.
Kazunao K, Kazuo U. 2002 Clinical Pharmacokinetics of Tirofiban, a Nonpeptide Glycoprotein IIb/IIIa Receptor Antagonist: Comparison with the Monoclonal Antibody Abciximab. {Review} Clin Pharmacok 41(3) 187-195.
Kereiakes DJ, Lorenz T, Young JJ, Kukielka G, Mueller MN, Nanniazzi-Alaimo L, Phillips DR 2001 Differential effects of citrate versus PPACK anticoagulation on measured platelet inhibition by Abciximab, Eptifibatide and Tirofiban. J Thromb Thrombolys 12, 123-127.
Iacopino D, Menabue L, Saladini M. 1999 Crystallographic study on metal(II) complexes with N-(2-Nitrophenylsulfonyl)glycine. Aust J Chem 52, 741-748.
McClellan KJ, Goa KL 1998 Tirofiban: A review of its use in acute coronary syndromes. Drugs 56, 1067-1080.
Menabue L, Saladini M, Bavoso A, Ostuni A. 1998 Investigation on coordination ability of N-chloro-acetylglycine towards Cu(II) in solid and solution state. Inorg Chim Acta 268, 205-210.
Mousa SA, Bozarth JM, Forsythe MS, Slee A. 2000 Differential antiplatelet efficacy for various GPIIb/IIIa antagonists: role of plasma calcium levels. Cardiov Res 47, 819-826.
Nagayama, K, Kumar A, Wuethrich K, Ernst RR. 1980 Experimental techniques of two-dimensional correlated spectroscopy. J Magn Reson 40, 321-334
NIST Standard Reference database 46, Critically selected Stability Constants, Version 5, webbook.nist.gov.
North AC, Phillips DC, Mathews FS. 1968 A semi-empirical method of absorption correction Acta Crystallogr Sect A 24, 351-359.
Perrin DD, Dempsey B. 1979 Buffers for pH and Metal Ion Control. London: Chapman and Hall.
Saladini M, Iacopino D, Menabue L. 2000 Metal(II) binding ability of a novel N-protected amino acid. Solution state investigation on binary and ternary complexes with 2,2′-bipyridine. J Inorg Biochem 78 355-361 and ref. therein.
Saladini M, Menabue L, Ferrari E, Iacopino D. 2001 Amide group coordination to the Hg2+ ion. Potentiometric, 1H-NMR and structural study on Hg2+-N-protected amino acids systems. J Chem Soc Dalton Trans 1513-1519.
Saladini M, Menabue L, Ferrari E. 2001 Sugar complexes with metal2+ ions: thermodynamic parameters of associations of Ca2+, Mg2+ and Zn2+ with galactaric acid. Carbohydr Res 336 55-61.
Sheldrick GM. 1998 SHELX97 Programs for Crystal Structure Analysis Institute fÜr Anorganische Chemie der Universitat, Gottingen, Germany.
Van de Werf F. 1997 Clinical trials with glycoprotein IIb/IIIa receptor antagonists in acute coronary syndromes. Tromb Haemost 78, 210-213.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ferrari, E., Menabue, L. & Saladini, M. Characterization and metal affinity of Tirofiban, a pharmaceutical compound used in acute coronary syndromes. Biometals 17, 145–155 (2004). https://doi.org/10.1023/B:BIOM.0000018376.52169.40
Issue Date:
DOI: https://doi.org/10.1023/B:BIOM.0000018376.52169.40