Direct Measurements of Electric Fields in Weak OH 3 3 3π Hydrogen Bonds

Hydrogen bonding is of fundamental importance for structure, function, and dynamics in a vast number of chemical and biological systems. 6 In conventional hydrogen bonds, X H 3 3 3A, a hydrogen atom bridges the proton donor X and proton acceptor A. The donor is usually very electronegative, for example, O or N, whereas the acceptor is an electronegative atom with at least one lone pair of electrons. Hydrogen bonds vary enormously in bond energy from∼15 40 kcal/mol for the strongest interactions to less than 4 kcal/mol for the weakest. It is proposed, largely based on calculations, that strong hydrogen bonds have more covalent character, whereas electrostatics are more important for weak hydrogen bonds, but the precise contribution of electrostatics to hydrogen bonding is widely debated. In this work, we consider a class of hydrogen bonds that are important in noncovalent aromatic interactions, where πelectrons play the role of the proton acceptor, which are a very common phenomenon in chemistry and biology. They play an important role in the structures of proteins andDNA, as well as in drug receptor binding and catalysis. For example, edge-toface interactions between the partially positively charged hydrogen of one aromatic system and the partially negative π-cloud of another aromatic system contribute to the stereoselectivity of organic reactions and to self-assembly in crystals of benzene and are widespread in proteins. Another important class of these interactions is the cation π interaction, where cations, such as the charged side chains of arginines and lysines, interact with the π-cloud of an aromatic system such as tyrosine, phenylalanine, and tryptophan. These interactions are ubiquitous in proteins and are believed to be important for their structures, but as yet no experimental measurements of electric fields have been made to determine the extent to which these interactions are dictated by classical electrostatics as opposed to other effects (e.g., van der Waals, charge-transfer, etc.). Here we present the first experimental measurements of the magnitude of electric fields in aromatic edge-to-face interactions using a model system consisting of phenol and a series of substituted benzene derivatives. We used the OH (or OD) stretch modes of phenol as vibrational probes of the change in electric field upon complex formation, where shifts in the IR spectra are directly related to electric field changes through the vibrational Stark effect. We chose this system based on the elegant studies of Fayer and co-workers on hydrogen bond exchange dynamics for phenol and benzene, which form an edge-to-face (or OH 3 3 3π hydrogen bonding) complex in solution. The structure of this complex has been studied by DFT calculations in the gas phase and by MD simulations in solution. The calculations suggest that the hydroxyl group of phenol is pointing toward the center of one C C bond of the benzene ring and interacts with the favorable electrostatic potential of the benzene π-system in a weak OH 3 3 3π hydrogen bond (strength <4 kcal/mol). As shown in the following, the electrostatic potential can be systematically manipulated by using substituted benzene derivatives to tune the charge density of the π-cloud by adding either methyl substituents as electron-donating groups or chlorine substituents as electron-withdrawing groups. The effect of this systematic variation of the electric field experienced by the OH (or OD) group was detected using the vibrational absorption of the OH (or OD). These small model complexes enable