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

Abstract

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-xylenediamine (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) n NH3 +, 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)H2 2+–cy(px)H2 4−, and 1,688 M−1 for (arg)H2 2+–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. Anionic cyclophanes bearing carboxylate arms have multi-point electrostatic interaction with the methylated basic amino acid dications as well as diaminoalkane dications in aqueous media, to construct ion pairs with intermolecular hydrogen bonding N+–H···O−. The formation constants vary from 31 to 2,884 M−1, depending on the alkyl chain length as well as the cyclophane frame size. The highest stability is found for a complex of lysine ester.