A thermodynamic, electrochemical and molecular dynamics study on NAD and NADP recognition by 1,4,7,10,13,16,19-heptaazacyclohenicosane ([21]aneN7)†

Abstract

Interaction of the macrocyclic polyamine 1,4,7,10,13,16,19-heptaazacyclohenicosane ([21]aneN₇) in its protonated forms with the dinucleotides NAD⁺ and NADP⁺ has been followed by pH-metric titration, NMR and cyclic voltammetry. Both dinucleotides interact strongly with [21]aneN₇ forming adduct species with protonation degrees varying from 3 to 7 for NAD⁺ and from 3 to 8 for NADP⁺. Plots of the overall amount of complexed species show recognition of NADP⁺ over NAD⁺ throughout a wide pH range. The extra phosphate group attached to the ribose moiety of NADP⁺ seems to be the factor controlling the recognition process as proved by ³¹P NMR studies. Molecular dynamics on the adducts formed between NAD⁺ and NADP⁺ and tetraprotonated [21]aneN₇ confirm the participation of the phosphate appended to the ribose moiety of the adenosine nucleoside in the electrostatic and hydrogen bonding interactions. Cyclic voltammetric measurements denote significant alterations in the electrochemical behaviour of the NAD⁺/NADH or NADP⁺/NADPH couples as a function of the interaction between the dinucleotide and receptor.