Electrostatics at Interfaces and in Condensed Phase

The vibrational Stark effect enables measuring electric fields experimentally using popular probes like C=O or C≡N stretches. Is it possible to use CF, CF₂ and CF₃ groups in aliphatic molecules as electric field probes? It depends…

MD force fields are carefully parameterized against structural and thermodynamic global observables. However, this begs the question, if the underlying local noncovalent interaction are described accurately? Using the vibrational Stark effect of nitriles, we show that H-bonding interactions in proteins are more accurately simulated in the polarizable AMOEBA force field.

The widespread design of covalent drugs has focused on crafting reactive groups of proper electrophilicity and positioning. We found that environmental electric fields projected onto a reactive chemical bond, an overlooked design element, play essential roles in the covalent inhibition of TEM-1 β-lactamase by avibactam. 

We have used electrode-supported model membranes in many previous studies to control the transmembrane potential. Here we quantify the transmembrane electrostatics combining SEIRA spectroscopy and MD simulations.

Vibrational Stark probes like C=O groups are inherently sensitive only to electric along the bond axis and thus one-dimensional probes. Here, we show that the deuterated aldhehyd gives a 2D view using the C=O and C-D modes.

Nitriles are almost ideal electric field probes when utilizing the vibrational Stark effect frequency shift. Almost, because they suffer from the additional H-bonding shift. Here, we show that the IR Intensity does not suffer from such effect and is the true ideal electric field strength indicator.

What are the physical origins of antibiotic resistance? Using experiments and theory we explore the active site electric fields and chemical positioning in β-lactamases.

Photoisomerization in phytochromes leads to a functionally relevant transition of an α-helical segment to a β-sheet. Using nitrile probes on non-natural amino acids reveals electric field changes during this secondary structural change.

Molecular dynamics force fields rely on careful parameterization and experimental methods are required to assure their accuracy. The vibrational Stark effect quantifies local electrostatic interation and is very useful to test and refine force fields.

The CO molecule is a known inhibitor of the reduced heme a3 active site in cytochrom c oxidase. However, even prior to oxidative dissociation, the CO is electrostatically destabilized in its position as ligand.

In order to perform our study (24) on the evolution of electric fields in β-lactamases, we need site-specifically 13C-labeled penicillin G and cefotaxime. To our surprise there are no commercial sources, so we did it ourselves.

In vibrational Stark spectroscopy (VSS) kV-voltages are applied between Ni-coated FTIR windows, leading to photon limitation. Using QCL-based spectrometers the sensitivity of VSS can be improved considerably.

We introduce the non-canonical amino acid cyano-phenylalanine into cytochrome c as a vibrational Stark probe. Using this probe determine the interfacial electric fields at various positions of the protein.

Antimicrobial peptides are the first line of defense after contact of an infectious invader, often acting via interactions with the target membrane. The transmembrane electrostatics can play a major governing role in antimicrobial action. We show, for the first time using SEIRAS, that we can control the large-scale reorientation of AMP helices to form the active ion channel form.

A comprehensive understanding of physical and chemical processes at biological membranes requires the knowledge of the interfacial electric field which is a key parameter for controlling molecular structures and reaction dynamics at electrodes. We utilize the vibrational Stark effect quantify interfacial electric fields.

The voltage-dependent anion channel (VDAC) regulates the transfer of metabolites between the cytosol and the mitochondrium. Opening and partial closing of the channel is known to be driven by the transmembrane potentia. Our results indicate alterations of the inclination angle of the β-strands as crucial molecular events, reflecting an expansion or contraction of the β-barrel pore.