Substituent Effects in Double‐Helical Hydrogen‐Bonded AAA‐DDD Complexes

Abstract

Two series of DDD and AAA hydrogen-bond arrays were synthesized that form triply-hydrogen-bonded double-helical complexes when combined in CDCl(3) solution. Derivatization of the DDD arrays with electron-withdrawing groups increases the complex association constants by up to a factor of 30 in those arrays examined. Derivatization of the AAA arrays with electron donating substituents reveals a similar magnitude effect on the complex stabilities. The effect of substitution on both types of arrays are modeled quite satisfactorily (R(2) > 0.96 in all cases) as free energy relationships with respect to the sums of their Hammett substituent constants. In all, the complex stabilities can be manipulated over more than three orders of magnitude (>20 kJ mol(-1)) using this type of modification.

Synthesis and Self‐Association of Double‐Helical AADD Arrays

“…In fact, the δ max (NH a ) calculated for self‐association of 14 b and 14 c from the dilution data (9.90 and 10.16 ppm, respectively) are very similar to the value for 14 a ; lending further support for this conclusion. Addition of a moderately electron‐withdrawing substituent (R 4 =COOEt) to the indole ring in 14 c increased the dimer stability by a modest amount in comparison to 14 b (ΔΔ G =−3.5 kJ mol −1 ) and with a similar magnitude to that observed in a related system that we have recently reported 10c. Through‐space contacts observed in a NOESY experiment with 14 c also corroborated a solution‐state structure similar to that observed in the solid state (see the Supporting Information).…”

“…Similarly, the installation of a trimethylene tether between the two donor heterocycles (R 3 ) was anticipated to improve dimerization as a result of its preorganizing effect on the array’s conformation. The installation of electron‐donating R 1 (CH 3 ) and electron‐withdrawing R 4 (CO 2 Et, NO 2 ) group were expected to improve the acceptor and donor character of their respective heterocycles 10c…”

“…The dimerization constant exhibited by this array in CDCl 3 is comparable to the most stable examples of neutral AADD dimers reported in the literature to date. Given the limited increases in dimer stability expected from the incorporation of the electron withdrawing (R 4 =NO 2 ) and donating (R 1 =CH 3 ) groups to the underlying skeleton,10c a large proportion of this remarkable increase in stability (ΔΔ G ≥−22.3 kJ mol −1 in comparison to 14 c ) must originate from preorganization by the trimethylene tether. Moreover, it raises the question of what further increases in K dimer might be realized in this system, if either or both of the two other interplanar degrees of freedom were restrained in a similar manner.…”

Substituent effects in hydrogen bonding: DFT and QTAIM studies on acids and carboxylates complexes with formamide

“…The ability to tune the properties of molecules by changing the substituent comes from the basic research by Hammett [15]. However, in supramolecular chemistry there are several possibilities to tune the non-covalent interactions [16, 17]. These are the electronic substituent effect [18–20, 17], steric effect [21–24], and intermolecular electronic repulsion [25] to mention a few.…”

“…However, in supramolecular chemistry there are several possibilities to tune the non-covalent interactions [16, 17]. These are the electronic substituent effect [18–20, 17], steric effect [21–24], and intermolecular electronic repulsion [25] to mention a few. Although very good reviews on tuning the molecular properties and thus influence on their interactions has been published there are still not so many extensive works in the topic of pure substituent effect in simple associates.…”