Research Highlights

New dynamic probes for ions interacting with biomolecules


Figure 1. DNA double helix embedded in water (angled small molecules, not to scale). The dark red spheres on the helix surface represent oxygen atoms of the negatively charged PO2- units, the blue spheres positively charged ions in the environment.

Pairs of negatively charged phosphate groups and positive magnesium ions represent a key structural feature of DNA and RNA embedded in water. Vibrations of phosphate groups have now been established as selective probes of such contact pairs and allow for a mapping of interactions and structure on the ultrafast time scales of molecular dynamics.

DNA and RNA are charged polymers that encode genetic information in a double helix structure and act as key player in the biosynthesis of proteins. Their negative charges are located in the molecular backbone, which consists of ionic phosphate (PO2) and of sugar groups (Figure 1). Stabilization of the macromolecular structures of DNA and RNA requires a compensation of strong repulsive electric forces between the equally charged phosphate groups by ions of opposite, i.e., positive charge. In this context, magnesium (Mg2+) ions Mg2+ are particularly relevant as Mg2+ ions not only stabilize the structure but also mediate the recognition of binding partners and act as catalytic centers. Moreover, changes of macromolecular structure via dynamic folding processes are connected with a rearrangement of positive ions embedded in the surrounding water shell.


Figure 2. Top: Molecular structure of a contact ion pair consisting of dimethylphosphate (DMP) and a magnesium ion Mg2+ embedded in water, arrows mark elongations of the asymmetric PO2- stretching vibration. Bottom: Two-dimensional infrared (2D-IR) spectra of the asymmetric PO2- stretching vibration showing a component P1 from DMP molecules without a magnesium ion and the contribution P2 from contact ion pairs.

Positive ions are arranged in different geometries around DNA and RNA: in so-called site-bound or contact-pair geometries, a positive ion is located in direct contact with an oxygen atom of a phosphate group. In contrast, the so-called outer ion atmosphere consists of positive ions separated by at least one layer of water molecules from the phosphate groups. The functional role of the different geometries and the underlying interactions are far from being understood. A deeper insight at the molecular level requires highly sensitive probes which allow for discerning the different ion geometries without disturbing them, and for mapping their dynamics on the ultrafast time scale of molecular motions.

In a recent publication, we demonstrate that vibrations of phosphate groups represent sensitive and noninvasive probes of ion geometries in a water environment. Dimethylphosphate (DMP, (CH3O)2PO2), an established model system for the DNA and RNA backbone, was prepared in liquid water with an excess of Mg2+ ions (Figure 2, top) and studied by nonlinear vibrational spectroscopy in the femtosecond time domain (1 fs = 10-15 s). The experiments make use of two-dimensional infrared (2D-IR) spectroscopy, a most sophisticated method for analyzing the ionic interactions and structures on the intrinsic time scale of fluctuating molecular motions.

The experiments map Mg2+ ions in direct contact with a PO2 group via a distinct feature in the 2D-IR spectrum (Figure 2, bottom). The interaction with the Mg2+ ion shifts the asymmetric PO2 stretching vibration to a frequency which is higher than in absence of Mg2+ ions. The lineshape and the time evolution of this new feature reveal fluctuations of the contact ion pair geometry and the embedding water shell on a time scale of hundreds of femtoseconds while the contact pair itself exists for much longer times (~10-6 s). An in-depth theoretical analysis shows that the subtle balance of attractive electrostatic (Coulomb) forces and repulsive forces due to the quantum-mechanical exchange interaction govern the frequency position of the phosphate vibration.

The ability of 2D-IR spectroscopy to characterize the short-ranged phosphate-ion interaction in solution provides a novel analytical tool that complements currently available structural techniques. An extension of this new approach to DNA and RNA and their ionic environment is most promising and expected to provide new insight in the forces stabilizing equilibrium structures and driving folding processes.

Jakob Schauss, Fabian Dahms, Benjamin P. Fingerhut, Thomas Elsaesser: Phosphate-magnesium ion interactions in water probed by ultrafast two-dimensional infrared spectroscopy. Phys. Chem. Lett. 10, 238-243 (2019).


Dr. Benjamin Fingerhut, Phone +49 30 63921404
Prof. Thomas Elsaesser, Phone +49 30 63921400


Large-amplitude transfer motion of hydrated excess protons mapped by ultrafast 2D IR spectroscopy

our latest work on the solvated excess proton got published as Science First Release paper:

Large-amplitude transfer motion of hydrated excess protons mapped by ultrafast 2D IR spectroscopy

by Fabian Dahms, Benjamin P. Fingerhut, Erik T. J. Nibbering, Ehud Pines, Thomas Elsaesser,

Science DOI: 10.1126/science.aan5144.


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MACGIC-QUAPI method for the treatment of non-Markovian long-time bath memory

our new method got published in J. Chem. Phys.:

Coarse-grained representation of the quasi adiabatic propagator path integral for the treatment of non-Markovian long-time bath memory

by Martin Richter and Benjamin P. Fingerhut

The Journal of Chemical Physics 146, 214101 (2017); doi: 10.1063/1.4984075


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Range, Magnitude, and Ultrafast Dynamics of Electric Fields at the Hydrated DNA Surface

our recent work got published in J. Phys. Chem. Lett.:
Range, Magnitude, and Ultrafast Dynamics of Electric Fields at the Hydrated DNA Surface

by Torsten Siebert, Biswajit Guchhait, Yingliang Liu, Benjamin P. Fingerhut, and Thomas Elsaesser


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Anharmonicities and coherent vibrational dynamics of phosphate ions in bulk H2O

our recent work got published in PCCP:
Anharmonicities and coherent vibrational dynamics of phosphate ions in bulk H2O

by Rene Costard, Tobias Tyborski and Benjamin P. Fingerhut


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Cyclobutane thymine dimer repair mechanism probed by Femtosecond stimulated Raman spectroscopy

our recent work just got accepted in JACS:
Femtosecond stimulated Raman spectroscopy of the cyclobutane thymine dimer repair mechanism: A computational study

by Hideo Ando , Benjamin P. Fingerhut , Konstantin E. Dorfman , Jason D. Biggs , and Shaul Mukamel


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Conical intersection mediated dynamics of uracil monitored by FSRS spectroscopy

the paper got just accepted at J. Chem. Theory Comput.:
Probing the Conical Intersection Dynamics of the RNA Base Uracil by UV-Pump Stimulated-Raman-Probe Signals; Ab Initio Simulations

by Benjamin P. Fingerhut , Konstantin E. Dorfman , and Shaul Mukamel