Strong Short‐Range Cooperativity in Hydrogen‐Bond Chains

Abstract

Chains of hydrogen bonds such as those found in water and proteins are often presumed to be more stable than the sum of the individual Hbonds.However,the energetics of cooperativity are complicated by solvent effects and the dynamics of intermolecular interactions,m eaning that information on cooperativity typically is derived from theory or indirect structural data. Herein, we present direct measurements of energetic cooperativity in an experimental system in which the geometry and the number of Hbonds in achain were systematically controlled. Strikingly,w ef ound that adding asecond H-bond donor to form achain can almost double the strength of the terminal Hbond, while further extensions have little effect. The experimental observations add weight to computations whichh ave suggested that strong, but shortrange cooperative effects mayo ccur in H-bond chains.Chainsofhydrogenbondsareprevalentstructural motifs in supramolecular and biological systems. Hbonds are widely proposed to exhibit positive cooperativity, [1] which may be manifested by acombination of conformational [1,2] and electronic effects that may make ac hain more stable than the sum of its parts.[3] Such cooperative effects have been shown to influence reactivity, [4] to contribute to the structure,i nteractions,a nd properties of biomolecules and materials, [5] and to facilitate the communication of chemical information.[6] Hbonded water clusters and chains have been isolated in the solid state [7] and studied experimentally in both liquid and gas phases.[8] Although many nanoscale and bulk properties may be influenced by the cooperativity of H-bond networks,itisnot possible to directly quantify interaction energies from structural or vibrational characteristics.I na ddition, discussion of the relative contributions of electrostatics,p olarization, and covalencyi nHbond cooperativity [5b, 9] is further exacerbated by the challenge of considering the influence of the surrounding solvent.Herein, we have employed synthetic molecular balances [10] to directly measure the effect of H-bond-chain length on the strength of H-bonding interactions in solution. At the outset of our investigation we identified the series of phenol, catechol, and pyrogallol ( Figure 1B)a sapertinent model system for examining cooperativity in H-bond chains.Indeed, H-bond chains have previously been proposed to contribute to the supramolecular properties of catechol and pyrogallol derivatives. [3b, 11] We reasoned that the pre-organization and proximity of the intramolecular H-bond donors and acceptors in this series of compounds would minimize conformational entropic effects to allow examination of cooperative electronic influences.I nitially we measured the experimental complexation Gibbs energies of phenol, catechol, and pyrogallol with the strong H-bond acceptor tri-n-butylphosphine oxide using 31 PNMR spectroscopy.T he binding energies became more favorable as the number of OH groups was increased ( Figure 1A). Such atrend could be rationalized by cooperative e...

The Origin of Chalcogen-Bonding Interactions

“…31 The lack of solvent dependence in the present investigation is particularly surprising considering that the conformational free energies of similar formamide molecular balances hosting H-bonding and aromatic interactions were found to be strongly dependent on the H-bond donor and acceptor abilities of the solvent. 42,68 These findings indicate that the chalcogen-bonding interactions in the present investigation do not have a substantial solvophobic, electrostatic or dipolar origin (Table S18). Although, the balances in the present investigation were not soluble in water, given the apparent universality of the observed solvent independence, it might be reasonable to expect similar conformational preferences in aqueous solution.…”

“…Such conformational preferences are comparable to those of OH to OC H-bonds measured in structurally related molecular balances. 68 Varying the thiophene substituent had a substantial influence on the preference for O•••S contacts, following the trend Me < H < Cl < COOMe < COMe < CHO (Figure 2, left). Interestingly, the O•••Se contact in compound 1c was slightly more favorable than the O•••S contact in compound 1a-CHO, despite the increased steric bulk and the lack of an electron-withdrawing group on the selenophene ring.…”

“…62−67 More specifically, the molecular balances shown in Figure 1 are derived from previous investigations of solvent effects and hydrogen bonding interactions. 42,47,68 The new designs in Figure 1 host chalcogen-bonding interactions in the closed conformers (Figure 1A,D, right) that are absent in the open conformation (Figure 1A,D, left). Since rotation about the (thio)formamide is slow on the NMR time scale at room temperature, integration of the discrete 19 F NMR resonances corresponding to each conformer provides direct access to the conformational equilibrium constant K and, therefore, the conformational free energy difference, ΔG EXP = −RT ln K.…”

Quantifying Interactions and Solvent Effects Using Molecular Balances and Model Complexes

“…33 Formamide-based molecular balances have also been used to examine the cooperativity of hydrogen bonds. 34 The molecular balances shown in Figure 5A can form an internal hydrogen bond between the phenolic hydroxyl group and the formamide carbonyl. The corresponding catechol (1H, green) and pyrogallol (2H, blue) derivatives afford chains of one and two hydrogen bonds, respectively.…”

Competing Hydrogen-Bond Polarities in a Dynamic Oligourea Foldamer: A Molecular Spring Torsion Balance

“…Importantly, the overall P screw sense preference of 11 is retained. This suggests that the geometry (and maybe cooperativity 29 ) of the intramolecular hydrogen bonds still favours their contribution to the overall hydrogenbond network, even in competition with an alternative intermolecular hydrogen bond at the urea N terminus of 11 in its less favoured conformation. Addition of chloride did reduce the conformational preference of 11, with the CD suggesting unfolding of the helix with chloride in 10-fold excess.…”