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 H bonds. However, the energetics of cooperativity are complicated by solvent effects and the dynamics of intermolecular interactions, meaning 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 H bonds in a chain were systematically controlled. Strikingly, we found that adding a second H‐bond donor to form a chain can almost double the strength of the terminal H bond, while further extensions have little effect. The experimental observations add weight to computations which have suggested that strong, but short‐range cooperative effects may occur in H‐bond chains.

While the protein composition of various yeast 60S ribosomal subunit assembly intermediates has been studied in detail, little is known about ribosomal RNA (rRNA) structural rearrangements that take place during early 60S assembly steps. Using a high-throughput RNA structure probing method, we provide nucleotide resolution insights into rRNA structural rearrangements during nucleolar 60S assembly. Our results suggest that many rRNA-folding steps, such as folding of 5.8S rRNA, occur at a very specific stage of assembly, and propose that downstream nuclear assembly events can only continue once 5.8S folding has been completed. Our maps of nucleotide flexibility enable making predictions about the establishment of protein–rRNA interactions, providing intriguing insights into the temporal order of protein–rRNA as well as long-range inter-domain rRNA interactions. These data argue that many distant domains in the rRNA can assemble simultaneously during early 60S assembly and underscore the enormous complexity of 60S synthesis.

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...

Crystallographic and computational studies suggest the occurrence of favourable interactions between polarizable arenes and halogen atoms. However, the systematic experimental quantification of halogen⋅⋅⋅arene interactions in solution has been hindered by the large variance in the steric demands of the halogens. Here we have synthesized molecular balances to quantify halogen⋅⋅⋅arene contacts in 17 solvents and solvent mixtures using 1H NMR spectroscopy. Calculations indicate that favourable halogen⋅⋅⋅arene interactions arise from London dispersion in the gas phase. In contrast, comparison of our experimental measurements with partitioned SAPT0 energies indicate that dispersion is sufficiently attenuated by the solvent that the halogen⋅⋅⋅arene interaction trend was instead aligned with increasing exchange repulsion as the halogen increased in size (ΔGX⋅⋅⋅Ph=0 to +1.5 kJ mol−1). Halogen⋅⋅⋅arene contacts were slightly less disfavoured in solvents with higher solvophobicities and lower polarizabilities, but strikingly, were always less favoured than CH3⋅⋅⋅arene contacts (ΔGMe⋅⋅⋅Ph=0 to −1.4 kJ mol−1).

Crystallographic and computational studies suggest the occurrence of favourable interactions between polarizable arenes and halogen atoms. However, the systematic experimental quantification of halogen⋅⋅⋅arene interactions in solution has been hindered by the large variance in the steric demands of the halogens. Here we have synthesized molecular balances to quantify halogen⋅⋅⋅arene contacts in 17 solvents and solvent mixtures using 1H NMR spectroscopy. Calculations indicate that favourable halogen⋅⋅⋅arene interactions arise from London dispersion in the gas phase. In contrast, comparison of our experimental measurements with partitioned SAPT0 energies indicate that dispersion is sufficiently attenuated by the solvent that the halogen⋅⋅⋅arene interaction trend was instead aligned with increasing exchange repulsion as the halogen increased in size (ΔGX⋅⋅⋅Ph=0 to +1.5 kJ mol−1). Halogen⋅⋅⋅arene contacts were slightly less disfavoured in solvents with higher solvophobicities and lower polarizabilities, but strikingly, were always less favoured than CH3⋅⋅⋅arene contacts (ΔGMe⋅⋅⋅Ph=0 to −1.4 kJ mol−1).