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Addressing Association Entropy by Reconstructing Guanidinium Anchor Groups for Anion Binding: Design, Synthesis, and Host–Guest Binding Studies in Polar and Protic Solutions
Author(s) -
Jadhav Vinod D.,
Herdtweck Eberhardt,
Schmidtchen Franz P.
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200702036
Subject(s) - isothermal titration calorimetry , chemistry , hydrogen bond , affinities , guanidine , solvent , selectivity , hydrophobic effect , cationic polymerization , stereochemistry , crystallography , combinatorial chemistry , organic chemistry , molecule , catalysis
The bicyclic hexahydropyrimidino[1,2 a ]pyrimidine cationic scaffold has a well‐known capacity to bind a variety of oxoanions (phosphates, carboxylates, squarates, phosphinates). Based on this feature, the parent host was supplemented with sec ‐carboxamido substituents to generate compounds 1 – 3 in an effort to improve the anion‐binding affinity and selectivity and to learn about the role and magnitude of entropic factors. Bicyclic guanidinium compounds were prepared by a convergent strategy via the corresponding tetraester 22 followed by catalytic amidation. Host–guest binding studies with isothermal titration calorimetry in acetonitrile probed the behavior of artificial hosts 1 – 3 in comparison with the tetraallylguanidinium compound 4 on binding p ‐nitrobenzoate, dihydrogenphosphate, and 2,2′‐bisphenolcyclophosphate guests that showed enhanced affinities in the 10 5 –10 6 M −1 range. Contrary to expectation, better binding emerges from more positive association entropies rather than from stronger enthalpic interactions (hydrogen bonding). In an NMR spectroscopy titration in DMSO, o ‐phthalate was sufficiently basic to abstract a proton from the guanidinium function, as confirmed by an X‐ray crystal structure of the product. The novel carboxamide‐appended anchor groups also bind carboxylates and phosphates, but not hydrogen sulfate in methanol with affinities in excess of 10 4 M −1 . The energetic signature of the complexation in methanol is inverted with respect to acetonitrile solvent and shows a pattern of general ion pairing with strong positive entropies overcompensating endothermic binding enthalpies. This study provides an example of the fact that bona fide decoration of a parent guanidinium anchor function with an additional binding functionality may provide the desired enhancement of the host–guest affinity, yet for a different reason than that implemented by design as guided by standard molecular modeling.