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

Abstract

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 10(10) 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 > 10(4) 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.

Modularly Designed Organocatalytic Assemblies for Direct Nitro‐Michael Addition Reactions

“…Our hypothesis is shown in Equation (1) with proline as the reaction-center module. When proline and a tertiary amine carrying a thiourea moiety (the stereocontrolling module) [7] are mixed, an acid-base reaction between the carboxylic acid and the tertiary amine groups should lead to an ammonium salt.[8] Ionic interactions between the ammonium and the carboxylate should cause these two modules to self-assemble, [9] forming a potential organocatalyst incorporating both the proline reaction center and a stereocontrolling moiety. Michael addition is one of the most important CÀC bondforming reactions in organic synthesis, [10] and many proline derivatives [11] have been developed as catalysts for the direct addition of ketones/aldehydes to nitroalkenes since the proline-catalyzed direct nitro-Michael addition was discovered.…”

Noncovalent Catch and Release of Carboxylates in Water

“…[34][35][36]38,39 While there have been numerous studies of receptors that can bind to carboxylates, 13,40−46 there are fewer examples that retain strong complex affinities in water that rely on electrostatic interactions because these interactions are diminished by competitive interactions with solvent. 18,19,47−49 However, rigid molecules bearing a guanidinium moiety have been shown to bind carboxylates even in polar solutions, 17,19,50,51 but associations strong enough to mimic those in biology are far from realized for these particular systems.…”

Phosphoramidates: Molecular Packing and Hydrogen Bond Strength in Compounds Having a P(O)(N)n(O)3-n (n = 1, 2, 3) Skeleton

“…The single crystal X-ray determinations were performed for [R 1 R 2 N] = NHCH 3 (KABVAL) [93], N(CH 3 ) 2 (POTJAJ) [94], NHC(CH 3 ) 3 (KABVEP) [93], NHC 6 H 5 (KEQLUO) [95], NHCH 2 C 6 H 5 (TOKXIB) [96] and NHC 6 H 4 (4-OCH 3 ) (WAWNIS) [97] and also for the substituents shown in Scheme 17 [98][99][100][101][102][103][104][105]. Moreover, a few other phosphoramide compounds which each contains a triamido moiety (like for example compounds with refcodes EDEVAK [106] and NUVSEC [107] (Schemes 18 and 19) and some co-crystal compounds (for example BARHMP [108] and VAFRIE [109], see Schemes 20 and 21) were reported. 1 There is the hydrogen-bonded amide molecule in the structure, i.e.…”