title: Torsional and Electronic Factors Control the C-H⋅⋅⋅O Interaction.
abstract: The precise role of non-conventional hydrogen bonds such as the C-H⋅⋅⋅O interaction in influencing the conformation of small molecules remains unresolved. Here we survey a series of β-turn mimetics using X-ray crystallography and NMR spectroscopy in conjunction with quantum calculation, and conclude that favourable torsional and electronic effects are important for the population of states with conformationally influential C-H⋅⋅⋅O interactions. Our results also highlight the challenge in attempting to deconvolute a myriad of interdependent noncovalent interactions in order to focus on the contribution of a single one. Within a small molecule that is designed to resemble the complexity of the environment within peptides and proteins, the interplay of different steric burdens, hydrogen-acceptor/-donor properties and rotational profiles illustrate why unambiguous conclusions based solely on NMR chemical shift data are extremely challenging to rationalize.
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Russell W
authors.initials: RW
authors.lastname: Driver
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Timothy D W
authors.initials: TD
authors.lastname: Claridge
authors.affiliation: Department of Chemistry and Biochemistry, Utah State University, Logan, Utah, 84322-0300, USA. steve.scheiner@usu.edu.
authors.forename: Steve
authors.initials: S
authors.lastname: Scheiner
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK. martin.smith@chem.ox.ac.uk.
authors.forename: Martin D
authors.identifier: http://orcid.org/0000-0002-8849-488X
authors.initials: MD
authors.lastname: Smith
keywords: NMR spectroscopy; crystallography; density functional calculations; foldamers; hydrogen bonds