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Structural Chemistry

, Volume 22, Issue 3, pp 649–659 | Cite as

Tyrosine alkyl esters as prodrug: the structure and intermolecular interactions of l-tyrosine methyl ester compared to l-tyrosine and its ethyl and n-butyl esters

  • Béatrice Nicolaï
  • Nathalie Mahé
  • René Céolin
  • Ivo B. Rietveld
  • Maria Barrio
  • Josep-Lluis Tamarit
Original Research

Abstract

l-Tyrosine alkyl esters are used as prodrugs for l-tyrosine. Although prodrugs are often designed for their behavior in solution, understanding their solid-state properties is the first step in mastering drug delivery. The crystal structure of l-tyrosine methyl ester has been determined and compared to published structures of l-tyrosine and its ethyl and n-butyl esters. It is almost isostructural with the other esters: it crystallizes in the orthorhombic chiral space group P212121, a = 5.7634(15) Å, b = 12.111(2) Å, c = 14.3713(19) Å, V = 1003.1(4) Å3 with Z′ = 1. Their main packing motif is a C(9) infinite hydrogen-bond chain, but the conformation of l-tyrosine methyl ester is different from the other two: eclipsed versus U-shaped, respectively. The published structure of the ethyl ester, which was incomplete, has been confirmed by X-ray powder diffraction data. Because l-tyrosine methyl ester is very stable (28 years stored at room temperature), and its hydrolysis rate is relatively low, it should be one of the better prodrugs among the alkyl esters of tyrosine.

Keywords

Prodrugs Crystal structure Thermal analysis Solid state stability Structure property relationship Amino acid Thermal expansion Hirshfeld surface Molecular conformation Tyrosine methyl ester 

Notes

Acknowledgments

The authors thank Philippe Bénas (Université Paris Descartes) and M. Marsal (Universitat Politècnica de Catalunya) for assistance with single-crystal X-ray diffraction data collection and SEM examinations, respectively. The authors thank the late Nestor Veglio for the powder diffraction data collection. Part of this study was supported by the Spanish grant FIS2008-00837 and by the Catalan government (2008SGR-1251). RC thanks the Generalitat de Catalunya (2007PIV00011) for an invited position at the Universitat Politècnica de Catalunya.

Supplementary material

11224_2010_9723_MOESM1_ESM.doc (80 kb)
Supplementary material 1 (DOC 80 kb)
11224_2010_9723_MOESM2_ESM.zip (6.9 mb)
Supplementary material 2 (ZIP 7043 kb)

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Béatrice Nicolaï
    • 1
  • Nathalie Mahé
    • 1
  • René Céolin
    • 1
    • 2
  • Ivo B. Rietveld
    • 1
  • Maria Barrio
    • 2
  • Josep-Lluis Tamarit
    • 2
  1. 1.Laboratoire de Chimie Physique, EAD Physico-chimie Industrielle du Médicament (former EA4066), Faculté de PharmacieUniversité Paris DescartesParisFrance
  2. 2.Grup de Caracterització de Materials (GCM), Departament de Física i Enginyeria NuclearUniversitat Politècnica de Catalunya, ETSEIBBarcelonaSpain

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