Highly Stable Self-Assembly in Water: Ion Pair Driven Dimerization of a Guanidiniocarbonyl Pyrrole Carboxylate Zwitterion

The synthesis of a novel water-soluble guanidiniocarbonyl pyrrole carboxylate zwitterion 2 is
described, and its self-association in aqueous solutions is studied. Zwitterion 2 forms extremely stable 1:1
dimers which are held together by an extensive hydrogen bonding network in combination with two mutual
interacting ion pairs as could be shown by ESI MS and X-ray structure determination. NMR dilution studies
in different highly polar solvents showed that dimerization is fast on the NMR time scale with association
constants ranging from an estimated 1010 M-1 in DMSO to a surprisingly high 170 M-1 in water. Hence,
zwitterion 2 belongs to the most efficient self-assembling systems solely on the basis of electrostatic
interactions reported so far. Furthermore, an amidopyridine pyrrole carboxylic acid 10 was developed as
a neutral analogue of zwitterion 2, which also dimerizes with an essentially identical hydrogen bonding
pattern (according to ESI MS and X-ray structure determination) but lacking the ionic interactions. NMR
binding studies demonstrated that the solely hydrogen-bonded neutral dimer of 10 is stable only in organic
solvents of low polarity (K > 104 M-1 in CDCl3 but <10 M-1 in 5% DMSO in CDCl3). The comparison of
both systems impressively underlines the importance of ion pair interactions for stable self-association of
such H-bonded binding motifs in water.