Macrocyclic polyamines [16]-N3 and [21]-N4: synthesis and study of their ATP complexation by 31P nuclear magnetic resonance spectroscopy

Abstract

The macrocyclic polyamines [16]-N₃, compound 1, and [21]-N₄, compound 2, possessing a hydroxymethyl side-chain have been synthesized. The macrocyclisation was achieved by condensation of lysine ditosate 3b with appropriate components 5 and 6 in the presence of Cs₂CO₃ to obtain 7 and 8 in 33 and 37% yield, respectively. The complexation of polyamines 1 and 2 with ATP was studied by ³¹P NMR spectroscopy, which indicated a specific recognition of γ-phosphorus of ATP (NMe₄ salt) by the polyamines. The binding constant estimates indicated that ATP binds compound 2ca. 35-times stronger than it does compound 1. The binding curves indicated a definite 1 : 1 stoicheiometry for 2 :ATP complex, and not so well defined stoicheiometry for 1 :ATP binding. The mononucleotides, AMP and cAMP, and dinucleotide TpT did not show significant complexation with either compound 1 or 2. The binding of ATP by macrocyclic polyamines 1 and 2 and the presence of a hydroxymethyl side-chain to link with a nucleophile may aid rational design of chemical nucleases.