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Facile synthesis and detailed characterization of a new ferrocenyl uracil peptide nucleic acid monomer.

Authors
  • Gasser, Gilles
  • Belousoff, Matthew J
  • Bond, Alan M
  • Spiccia, Leone
Type
Published Article
Journal
The Journal of organic chemistry
Publication Date
Sep 29, 2006
Volume
71
Issue
20
Pages
7565–7573
Identifiers
PMID: 16995660
Source
Medline
License
Unknown

Abstract

A new ferrocenyl uracil peptide nucleic acid (PNA) monomer, tert-butyl-2-(N-(2-(((9H-floren-9-yl)methoxy)carbonylamino)ethyl)-2-(5-(N-ferrocenylmethylbenzamido)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetate (1), has been successfully prepared in good yield by a procedure involving the one-pot reaction of the key synthon, 5-(ferrocenylmethylamino)pyrimidine-2,4(1H,3H)-dione (4), itself prepared from the reaction of (ferrocenylmethyl)trimethylammonium iodide and 5-aminouracil, with benzoyl chloride followed by ethyl bromoacetate. After hydrolysis of the ester, the acid was coupled with a protected PNA backbone to generate 1. NMR spectroscopy showed that 1 hydrogen bonds 9-ethyladenine (EA) in a 1:1 mixture of CD3CN:CDCl3 with an association constant Ka of 70 M(-1) at 30 degrees C. This value is comparable with those observed for model receptors and shows that the ferrocenyl moiety of 1 does not hinder the hydrogen bonding of our new PNA monomer to the complementary DNA base or if it does, not significantly. 1 is oxidized to 1+ with a reversible potential of +538 mV vs the DMFc(0/+) (decamethylferrocene) couple under voltammetric conditions in a 1:1 mixture of CH3CN:CHCl3 (0.1 M Bu4NPF6). For this reversible process, a slightly larger diffusion coefficient of 4.2 x 10(-6) cm(2).s(-1) than usually found for these compounds was determined from these electrochemical studies, which should be analytically useful as it will readily afford submicromolar voltammetric detection limits.

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