Glucosamine Conjugates of Tricarbonylcyclopentadienyl Rhenium(I) and Technetium(I) Cores

Cara L. Ferreira,†‡ Charles B. Ewart,†‡ Simon R. Bayly,†‡ Brian O. Patrick,† Jennifer Steele,† Michael J. Adam,*‡ and Chris Orvig*†
Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada, and TRIUMF, 4004 Wesbrook Mall, Vancouver, British Columbia, V6T 2A3, Canada
Inorg. Chem., 2006, 45 (17), pp 6979–6987
DOI: 10.1021/ic0605672
Publication Date (Web): July 21, 2006
Copyright © 2006 American Chemical Society
†

 University of British Columbia.

,
‡

 TRIUMF.

,
*

 To whom correspondence should be addressed. E-mail:  adam@triumf.ca (M.J.A.); orvig@chem.ubc.ca (C.O.).

Abstract

Abstract Image

To obtain a 99mTc glucose conjugate for imaging, double-ligand transfer (DLT) and related reactions were examined for the preparation of CpM(CO)3 (Cp = cyclopentadienyl; M = Re, Tc) complexes with pendant carbohydrates at Cp. Tricarbonyl{N-(1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-β-d-glucopyranose)cyclopentadienyl carboxamide}rhenium(I) (1a) and tricarbonyl{N-(2-amino-2-deoxy-β-d-glucopyranose)cyclopentadienyl carboxamide}rhenium(I) (2a) were prepared. The compounds were fully characterized by mass spectrometry, elemental analysis, IR, and NMR spectroscopy. Full assignment of the NMR spectra verified the pendant nature of the glucosamine moieties in the solution state and that 2a exists as both anomers. The solid-state structure of 2a was determined by X-ray crystallography, again confirming the pendant nature of the glucosamine, but differing from the solution state in that the β anomer crystallized preferentially (93%). Compound 2a was determined to be a high-affinity competitive inhibitor (Ki = 330 ± 70 μM) of the glucose metabolism enzyme hexokinase, demonstrating that it retains certain biological activity. The 99mTc analogues 1b and 2b were prepared in moderate radiochemical yields by means of the single-ligand transfer (SLT) route, which is more pertinent to radiopharmaceutical synthesis.

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History

  • Published In Issue August 21, 2006
  • Received April 4, 2006

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