Category Archives: Uncategorized

Solvent-specific effects in ultrafast processes

I thought that ion-specific effects on solution structure and thermodynamics of complex solutes (e.g., proteins) are difficult task. Nevertheless, being long in classical MD simulations, I forgot that quantum chemistry offers way more electronic states (not only the ground state) where the system can live (even simultaneously). This opens yet another complexity of the studied systems.-)

Transition metal complexes, such as ReCl(CO)3(bpy) (bpy = 2,2-bipyridine), offer numerous electronic states, which evolution can be well traced by time-resolved spctroscopy techniques. Following the experimental setup and observation (fluorescence and time-resolved IR) we applied computationally demanding hybrid QM/MM nonadiabatic dynamics on spin-mixed potential energy surfaces. We analyzed fluorescence and inter-system crossing kinetics in acetonitrile and dimethylsulfoxide, finding that responsible time constants are solvent specific. Moreover, we found that the faster time constant correlates with geometry relaxation and the slower with solvent reorientation dynamics.

Congratulations to Adam for converting his MSc thesis in this nice paper and thanks to all collaborators for this nice experience. Enjoy the reading!
[1] Šrut, A., Mai, S., Sazanovich, I. V, Heyda, J., Vlček, A., González, L., & Záliš, S. (2022). Nonadiabatic excited-state dynamics of ReCl(CO) 3 (bpy) in two different solvents. Physical Chemistry Chemical Physics.


Protective osmolytes are depleted from protein surface

Theoretical (computational) modelling of complex protein-osmolyte interactions has always been challenging. Nowadays, computational power allows us to obtain numerically exact results for small to mid-size protein denaturation. But, are the current parameterizations of protein-osmolyte interactions reliable? This is difficult to answer without accurate experimental data to which we can benchmark our simulations. Our recent work in Journal of Physical Chemistry Letters, contributed to this important question on thermodynamic means.
We applied dialysis experiments on lysozyme protein and circular-dichroism on TrpCage miniprotein and quantified the depletion of protective osmolytes (TMAO, betaine) from protein surface.
On the computational side, we employed numerous parameterization of TMAO and betaine, which accurately reproduce experimental properties of aqueous solutions. Surprisingly, we have found that impact of stabilizing osmolytes on protein introduced in the solution can be very diverse. We could vaguely say, this stems from our belief that force-fields which perform well piece-wise, will perform well also when combined together. However, without careful readjustment of weak protein-osmolytes interactions, the simulation results can be even qualitatively wrong (i.e., observing protein denaturation).
This important theoretical message along with the urgent need for solid experimental data are presented in our concise letter, which is supported by an extensive SI 🙂

How does solvent escape from the channel solvate?

Some drugs are difficult to crystal in a pure state, but do readily form co-crystals with some solvents. At elevated temperatures these ‘trapped’ solvent molecules may escape and new, ‘dry’, solid is formed . Combining powder X-ray diffraction, solid-state reaction kinetics modeling, and all-atom MD simulations, we traced in very detail, how motion of solvent molecules cooperate with crystal structure fluctuations. link

Can we dissolve only a piece of a molecule?

A basic property of any compound is solubility in water and in aqueous solutions, which determines a compound’s availability and ability to be used in biochemical or industrial applications. Dr. Heyda (UCT Prague, Czechia), together with colleagues from Prof. Cremer’s group (Pennsylvania State University, US), recently published a contribution on this topic in Nature Chemistry.

From our daily kitchen routines, we expect that solubility increases with temperature: sugar dissolves well in hot tea, and salt in hot water. Caffeine solubility grows from 20 g/l at 25°C to 600 g/l in boiling water. In contrast, the solubility of nonpolar compounds, such as oils, decreases as temperature increases. Similarly, in a beaker, we can control the solubility of more complex molecules such as enzymes.

A cell, however, cannot use temperature variation to control the solubility, stability, and function of its enzymes. Instead, nature has developed softer controlling mechanisms, e.g., a variation of the concentration of osmolytes or ions in the enzyme environment. ‘‘There is a tight, over century-long link between the dissolution of enzymes in salt solutions and Prague. Franz Hofmeister, Professor of Pharmacology at the First Faculty of Medicine, conducted the first systematic study on this topic in 1888, in which he ordered ions according to their ability to precipitate egg white proteins. In our study, we focus on the thiocyanate anion (SCN), which increases solubility,’’ Dr. Heyda explains. Prague citizens and visitors can see a plaque commemorating Hofmeister’s work on a wall at the First Faculty of Medicine in U Nemocnice street.

Even after a century, the investigation of ion effects on solubility is leading to novel, unexpected findings. Joint experimental and theoretical collaboration of teams from Pennsylvania State University and UCT Prague has revealed the paradoxical behavior of polyethylene oxide. While the solubility of the polymer increases in the presence of sodium thiocyanate (NaSCN), the solubility of the monomer in the presence of the same salt decreases.

In order for this work to succeed, the connection of computer simulations with two types of experiments was essential,’’ Dr. Heyda notes. “In the first experiment, we monitored the strength of the binding of the thiocyanate anion to every single monomer unit [-CH2-CH2-O-]. In the other experiment, the averaged water structure in the vicinity of polyethylene oxide molecule was measured. Employing computer simulations, we were able to refine this information again to the level of individual monomer units.”

With this information in hand, we have proven that the thiocyanate anion is depleted from the regions with well-ordered water structures (terminal groups), while the anion is attracted to regions where a water structure is perturbed. Such behavior is depicted in the figure below. This explains why sodium thiocyanate lowers the solubility of dimethoxyethane (monomer), slightly increases the solubility of the dimer, and significantly increases the solubility of longer polyethylene oxides. Importantly, an analogous behavior was also observed for chemically more complex acrylamide-based polymers, which are chemically close to peptides.


Rogers, B.A., Okur, H.I., Yan, C. et al. Weakly hydrated anions bind to polymers but not monomers in aqueous solutionsNat. Chem. (2021).

Solvent dynamics and electrostatic field fluctuations affect electron hoping dynamics

Our recent work in PNAS ‘Photoinduced hole hopping through tryptophans in proteins‘ presents a thorough investigation of water dynamics and electrostatic field fluctuations on the electron (hole) hopping dynamics in two rhenium-modified azurins. The research was done in collaboration with our excellent colleagues at Caltech, Queen Mary University of London, and Heyrovsky Institute of Czech Academy of Sciences.
We have employed QM/MM/MD TD-DFT dynamics on ps-timescales, which were complemented by advanced QM-analysis in the vicinity of electronic state crossing points. Accounting for explicit (MM) solvent we have described that the local hydration of key residues and ligands, which are involved in electron transport, fluctuates in time. Our results revealed that the electron hopping occurs, when the intrinsic hydration of TRP residue is not optimal for the initial electronic state, and instead resembles the hydration of the final state. Consequently, when the electron hop is attempted, the solvent environment is ready to stabilize it. In more generalized view, the electrostatic field fluctuations are good measures to judge if the system is approaching the electronic state crossing region.

Enjoy reading of our manuscript and if you are really interested check also our extensive SI.-)

Thermodynamic insight in the hydration of a single guanidinium cation

Schematic temperature and pressure response of guanidinium cation hydration to increased temperatures and pressures.

We have employed extensive densimetry measurements of guanidinium chloride at UCT Prague, and performed MD simulations at UCT Prague, IOCB Prague, and at Ruđer Bošković Institute, Zagreb. We have collected data on temperature and pressure response of guanidinium chloride hydration, allowing us to determine volumetric properties at infinite dilution, i.e., at single ion limit.
We have clearly demonstrated this response is anomalous, on the half way between ordinary ions (e.g. sodium) and hydrophobic molecules (e.g. benzene). Employing directional analysis and Kirkwood-Buff theory, MD simulations point to hydrophobe-like hydration of quasi-aromatic faces and ion-like hydration of in-plane NH2 moieties. Enjoy the reading of our paper in the ‘Battino and Wilhelm’ Special Issue of the Journal of Chemical Thermodynamics. link

Congratulations to Jakub to 3 Spring publications

We researched the NIPAM/water solution by means of molecular dynamics, osmometry, densimetry and ITC-calorimetry. Employing Kirkwood-Buff inversion, we gathered improved force-field and provided consistent micro- and macroscopic insight. link

Within the collaboration with Darmstadt simulation group (prof. Nico van der Vegt) we have investigated the generic stabilizing effect of TMAO on pentaalanine and other uncharged peptides. TMAO effect at both ambient and deep-ocean conditions was studied and peptide-length and chain-termination challenges were resolved. link

Finally, we were happy to experimentally support our Santa Barbara and Darmstadt colleagues, in their review article on thermodynamic effect of TMAO and urea mixtures with implications on protein denaturation/protection. Complete Kirkwood-Buff description is available over very broad range of concentrations. link