Hydrazide-Based Quadruply Hydrogen-Bonded Heterodimers. Structure, Assembling Selectivity, and Supramolecular Substitution

This paper describes the synthesis, self-assembly, and characterization of a new class of highly
stable hydrazide-based quadruply hydrogen-bonded heterodimers. All of the hydrazide-derived heterodimers
possess the complementary ADDA−DAAD hydrogen-bonding sequences. Hydrazide derivatives 1, which
has two intramolecular S(6) RO···H−N hydrogen bonds, and 2 complex to afford two fastly exchanging
isomeric heterodimers 1·2 and 1·2‘ in chloroform, as a result of two different conformational arrangements
of 2. An average binding constant Kassoc of 4.7 × 104 M-1 was determined for heterodimer 1·2 and 1·2‘ by
1H NMR titration of 1 with changing 2 in chloroform-d. In contrast, 1 binds 11 and 12, both of which are
introduced with two intramolecular S(6) hydrogen bonds, to exclusively afford heterodimers 1·11 and 1·12,
with Kassoc values of 1.8 × 104 and 5.0 × 102 M-1, respectively. Fluorine-containing 19, which has a hydrazide
skeleton identical to that of 1 but two intramolecular S(6) F···H−N hydrogen bonds, can also complex with
2, 11, and 12, to afford heterodimers 19·2, 19·2‘, 19·11, and 19·12, with Kassoc values of of 1.2 × 104
(average value for 19·2 and 19·2‘), 5.4 × 103, and 1.9 × 102 M-1, respectively. The structures of the new
heterodimers have been proven with NOESY, IR, and VPO (for some of the heterodimers) experiments.
Moreover, 1 and 19 can also strongly bind 2,7-dilauroylamido-1,8-naphthyridine 23 to afford dimers 1·23
and 19·23 with Kassoc values of 6.0 × 105 and 1.4 × 105 M-1, respectively. Adding 1 to the 1:1 solution of
23 and 1-octyl-3-(4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl)urea 24 or 1-octyl-3-(4-oxo-1,4-dihydro-pyrimidin-2-yl)urea 25, which had been developed initially by Zimmerman and Meijer, respectively, induces
dimers 23·24 and 23·25 to dissociate, leading to the formation of dimers 1·23 and 24·24 or 25·25,
respectively. The new hydrazide-based hydrogen-bonding modules described are useful building blocks
for self-assembly and open a new avenue to recognition between discrete supramolecular species.