Measurement of Electric Fields Experienced by Urea Guest Molecules in the 18-Crown-6/Urea (1:5) Host–Guest Complex: An Experimental Reference Point for Electric-Field-Assisted Catalysis

Abstract

High resolution synchrotron and neutron single crystal diffraction data of 18-crown-6:(pentakis)urea measured at 30 K are combined, with the aim to better appreciate the electrostatics associated with intermolecular interactions in condensed matter. With two 18-crown-6 molecules and five different urea molecules in the crystal, this represents the most ambitious combined X-ray/synchrotron and neutron experimental charge density analysis to date on a co-crystal or host-guest system incorporating such a large number of unique molecules. Dipole moments of the five urea guest molecules in the crystal are enhanced considerably compared with values determined for isolated molecules, and 2D maps of the electrostatic potential and electric field show clearly how the urea molecules are oriented with dipole moments aligned along the electric field exerted by their molecular neighbors. Experimental electric fields in the range 10-19 GV m-1 , obtained for the five different urea environments, corroborate independent measurements of electric fields in the active sites of enzymes, and provide an important experimental reference point for recent discussions focused on electric-field-assisted catalysis.

External electric field effects on chemical structure and reactivity

“…In 2014, Boxer and coworkers offered experimental support for this hypothesis by demonstrating a link between charge anisotropy in enzymes and chemical catalysis through the exploitation of the vibrational Stark effect. These findings have recently been corroborated in a more direct manner by Spackman and coworkers . In their study, a combined X‐ray/synchrotron and neutron experimental charge density analysis was performed on a cocrystal of urea and 18‐crown‐6 molecules; a model mimicking the substrate selectivity of enzymes.…”

Electron Density Studies in Materials Research

“…Very recently, also the electric field in a complex co‐crystal of 18‐crown‐6/urea was investigated using the experimental ED, and it was shown that all urea molecules aligned with the electric field exerted by the rest of the structure, and that a significant dipole enhancement of the guest molecules occur . The EF inside the cavities were on the order of 10–19 GV m −1 , similar to those established at active sites in proteins .…”

“…Very recently,a lso the electric field in ac omplex co-crystal of 18-crown-6/urea was investigated using the experimental ED, and it wasshown that all urea molecules aligned with the electric field exerted by the rest of the structure, and that as ignificant dipole enhancement of the guest molecules occur. [96] The EF inside the cavities were on the order of 10-19 GV m À1 ,s imilar to those established at active sites in proteins. [97] These EFs are much larger than the macroscopic fields that can be applied to ac rystal in the laboratory,b efore dielectric breakdown, [98] making inclusion compounds very interesting model systemsf or the response to high local EFs inside proteins and materials.…”

TITAN: A Code for Modeling and Generating Electric Fields—Features and Applications to Enzymatic Reactivity

“…= 51.4 V/Å). The magnitude of this LEF is at the lower end of the range of LEFs usually observed for proteins . Nevertheless, the LEF of the protein matrix in P450 OleT JE has the right orientation to facilitate the studied H‐abstraction reaction, that is, lower the reaction barrier (cf.…”

“…In 2014, Boxer and coworkers offered experimental support for this hypothesis by demonstrating a link between charge anisotropy in enzymes and chemical catalysis through the exploitation of the vibrational Stark effect . Subsequently, these findings were corroborated in a direct manner by Spackman and coworkers . Together, these two landmark experimental studies constitute compelling experimental evidence that electrostatics is indeed an important factor in biochemical catalysis that cannot be neglected.…”