Origin of cooperativity in hydrogen bonding.

The origin of non-additivity in hydrogen bonds (H-bonds), usually termed as H-bond cooperativity, is investigated in H-bonded linear chains. It is shown that H-bond cooperativity originates solely from classical electrostatics. The latter is corroborated by comparing the H-bond cooperativity in infinitely-long H-bonded hydrogen cyanide, 4-pyridone and formamide chains, assessed using density functional theory (DFT), against the strengthening of the dipole-dipole interaction upon the formation of an infinite chain of effective point-dipoles. It is found that the magnitude of these effective point-dipoles is a consequence of mutual polarization and additional effects beyond a polarizable point-dipole model. Nevertheless, the effective point-dipoles are fully determined once a single H-bond is formed, indicating that quantum effects involved in H-bonding are circumscribed to nearest-neighbor interactions only; i.e. in a linear chain of H-bonds, quantum effects do not contribute to the H-bond non-additivity. This finding is verified by estimating cooperativity along the dissociation path of H-bonds in the infinite chains, using two empirical parameters that account for polarizability, together with DFT association energies and molecular dipoles of solely monomers and dimers.

On cooperative effects and aggregation of GNNQQNY and NNQQNY peptides.

Some health disturbances like neurodegenerative diseases are associated to the presence of amyloids. GNNQQNY and NNQQNY peptides are considered as prototypical examples for studying the formation of amyloids. These exhibit quite different aggregation behaviors despite they solely differ in size by one residue. To get insight into the reasons for such difference, we have examined association energies of aggregates (parallel ß-sheets, fibril-spines, and crystal structures) from GNNQQNY and NNQQY using density functional theory. As we found that GNNQQNY tends to form a zwitterion in the crystal structure, we have investigated the energetics of parallel ß-sheets and fibril-spines in the canonical and zwitterionic states. We found that the formation of GNNQQNY aggregates is energetically more favored than the formation of the NNQQNY ones. We show that the latter is connected to the network of hydrogen bonds formed by each aggregate. Moreover, we found that the formation of some NNQQNY aggregates is anticooperative, whereas cooperative with GNNQQNY. These results have interesting implications for deciphering the factors determining peptide aggregation propensities.