Ion-pairing of anionic DTPA-based cyclophanes with diaminoalkanes and methylated amino acids, lysine and arginine, in their dicationic form

Complex formation of three anionic cyclophanes with the dications of diaminoalkanes and basic amino acid esters was studied by ¹H NMR titrations in aqueous media. Every cyclophane bearing six CH₂CO₂^- arms consists of two diethylenetriaminepentaacetic (DTPA) units linked by two aromatic diamine units through amide bonds; the interlinking amine is p-xylen-ediamine (abbreviated as px), 4,4′-methylenedianiline (ma) or 4,4′-diaminobibenzyl (dab). The cyclophanes that exist in the anionic form cyH₂^4- (with two acidic protons) have multi-point electrostatic interaction with diaminoalkane dications ⁺H₃N(CH₂)_nNH₃⁺, so as to construct ion pairs stabilized by hydrogen-bonding between CH₂CO₂^- and NH₃⁺. The formation constants vary from 31 to 2,477 M^-1 depending on the cation-anion combinations; the highest stability is found for the complex of the px-derived cyclophane, cy(px)H₂^4-, with diaminobutane, and the lowest for diaminobutane-cy(dab)H₂^4- pair. The stability is correlated with the chain length of the diaminoalkanes as well as the size of the cyclophanes. These geometrical factors are also crucial for ion-pairing with the dications of methylated lysine and arginine; the formation constant is 2,884 M^-1 for (lys)H₂²⁺-cy(px)H₂^4-, and 1,688 M^-1 for (arg)H₂²⁺-cy(px)H₂^4-, while the constants of the cy(ma)H₂^4- and cy(dab)H₂^4- complexes are in a much smaller range of 39-230 M^-1.