On the Importance of the Nature of Hydrogen Bond Donors in Multiple Hydrogen Bond Systems

Abstract

Association constants for the reaction between a fourfold hydrogen bond receptor 4 possessing an AADA hydrogen bond pattern and several complementary partners 5–7 with DDAD and DDA patterns have been determined by NMR titration and by isothermal titration calorimetry (ITC). A variation of one donor site in the DDAD pattern resulted in the following, surprising sequence of stability of the complexes: KAss(6, X = NHCOR) > KAss(7, X = H) > KAss(5, X = NHR). The synthesis of a well soluble DDAD receptor, the amidopyridylurea 6b with a triethylene glycol chain, is described. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Lipophilicity Enhancing Substituents for ADDA Recognition Domains of DAAD·ADDA Heterodimers with Quadruple Hydrogen Bonds

“…Assignments are supported by COSY, HSQC and HMBC experiments. [18] 1 H NMR CIS Titrations: All titration measurements were carried out with a Bruker DRX 500 spectrometer. All chemical shifts are referenced to TMS or to the residual proton or carbon signal of the solvent.…”

“…Saponification of diester 13 afforded diacid 14 in 76 %. [18] Saponification of diester 20 lead to diacid 21, [18] and decarboxylation of the latter afforded monoacid 22. To allow formylation of acid 15 in the α-position, the carboxylic function of 15 was protected as the ethyl ester 16 in 87 % yield by reaction with ethanol in the presence of concentrated sulfuric acid.…”

“…Decarboxylation led to the monoacid 15 in 96 %. [18] From this acid, the respective ethyl ester 23 was prepared in 91 % yield by adding ethanol and concentrated sulfuric acid. For the formylation, lithium diisopropylamide (LDA) was added at -78°C to deprotonate 16 in the α-position.…”

“…Reagents and conditions: [18] tion even after rotation along the heteroaryl-urea bond. Synthesis of the soluble ADDA binding motif 9 with a stabilizing intramolecular hydrogen bond.…”

“…[10,11,18,21] All four nitrogen atoms that take part in the formation of four hydrogen bonds in the desired DAAD·ADDA heterodimers -two as hydrogen-bond acceptors A, two as N-H hydrogen-bond donors D -are fixed in one plane. For the respective folding of an unorganized receptor, for instance by rotation along bonds, entropic penalties have to be paid.…”