Molecular Recognition via Base Pairing: Amine-Containing, Cytosine-Based Ditopic Receptors That Complex Guanosine Monophosphate

Hiroyuki Furuta, Darren Magda, Jonathan L. Sessler

Research output: Contribution to journalArticlepeer-review

108 Citations (Scopus)

Abstract

The synthesis and binding properties of two types of amine-containing, cytosine-based ditopic receptors, 4-amino-1 -[4-[N,N-bis[2-(N,N-diethylamino)ethyl]amino]butyl]-2( 1H)-pyrimidinone (1) and 4-amino-1 -[4-(N,N-diethyl-amino)butyl]-2(1H)-pyrimidinone (2a), 4-amino-1-[5-(N,N-diethylamino)pentyl]-2(1H)-pyrimidinone (2b), and 4-amino-1-[6-(N,N-diethylamino)hexyl]-2(1H)-pyrimidinone (2c), are described. These systems were prepared by the functionalization of the trityl-protected iodoalkyl-substituted cytosine derivatives of general structure 9, with the appropriate secondary amines [bis(diethylaminoethyl)amine and diethylamine, in the cases of 1 and 2a−c, respectively] and subsequent deprotection with trifluoroacetic acid. The nitrogen-free cytosine derivative, 4-amino-1-(5-ethylheptyl)-2(1H)-pyrimidinone (3), was synthesized directly from the sodium salt of cytosine by reaction with 5-ethyl-1-iodoheptane in DMF. The four cytosine derivatives 1 and 2a−c contain both base pairing and ammonium electrostatic binding subunits. As such, they were expected to act as efficient ditopic receptors for the complexation of guanosine 5′-monophosphate (GMP), a prototypical purine-derived substrate. Quantitative binding studies carried out in DMSO-d6 indicate that compounds 1, 2a, 2b, and 2c in their neutral forms bind GMP free acid with first association constants, K11, of 26000 ± 3900, 820 ± 120, 1000 ± 150, and 1300 ± 200 M−1 and second association constants, K12 (for 1) and K21 (for 2a−c), of 1500 ± 230, 660 ± 100, 720 ± 110, and 1200 ± 180 M−1 respectively (where K11, K21, and K12 represent the formation of 1:1, 2:1, and 1:2 receptor-to-GMP complexes, respectively), whereas the ammonium-free system 3 was found to bind this same substrate as a 1:1 complex with a K11 of only 5 ± 2 M−1. The greater binding affinity of receptor 1, relative to that of 2a−c (and 3), is ascribed to the additional electrostatic interactions possible in the supramolecular GMP-receptor complex derived from this more precisely elaborated system.

Original languageEnglish
Pages (from-to)978-985
Number of pages8
JournalJournal of the American Chemical Society
Volume113
Issue number3
DOIs
Publication statusPublished - Jan 1 1991
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint Dive into the research topics of 'Molecular Recognition via Base Pairing: Amine-Containing, Cytosine-Based Ditopic Receptors That Complex Guanosine Monophosphate'. Together they form a unique fingerprint.

Cite this