Highly Stable Self-Association of 5-(Guanidiniocarbonyl)-1H-pyrrole-2-carboxylate in DMSO – The Importance of Electrostatic Interactions

The zwitterionic compound 5-(guanidiniocarbonyl)-1H-pyrrole-2-carboxylate (1) self-assembles to form dimers, which are completely stable in DMSO even at 170 °C or at concentrations of 0.001 mM. This high stability stems from a combination of multiple weak interactions. NMR titrations of 1H-pyrrole-2-carboxylate (5) with (1H-pyrrole-2-carbonyl)guanidinium (6) and [5-(methoxycarbonyl)-1H-pyrrole-2-carbonyl]guanidinium (8) led to binding constants of K ≈ 106 mol–1 in DMSO and K ≈ 103 mol–1 in 40% water/DMSO for carboxylate binding by the 2-(guanidiniocarbonyl)pyrrole moiety. The stability constant for the dimer 12 in DMSO could therefore be estimated as K ≈ 1012 mol–1. In solution, the self-association process of 1 can be completely disrupted by protonation of the carboxylate group. In the solid state, however, the hydrochloride salt 1+ also exists as a similar but only very weakly hydrogen-bonded dimer.