Philipp Honegger's research while affiliated with University of Vienna and other places

Publications (22)

Article
Full-text available
Dissolution dynamic nuclear polarization (dDNP) is a versatile hyperpolarization technique to boost signal intensities in nuclear magnetic resonance (NMR) spectroscopy. The possibility to dissolve biomolecules in a hyperpolarized aqueous buffer under mild conditions has recently widened the scope of NMR by dDNP. The water-to-target hyperpolarizatio...
Article
We use polarizable molecular dynamics simulations to study the thermal dependence of both structural and dynamic properties of two ionic liquids sharing the same cation (1-ethyl-3-methylimidazolium). The linear temperature trend in the structure is accompanied by an exponential Arrhenius-like behavior of the dynamics. Our parameter-free Voronoi tes...
Article
Full-text available
The nuclear Overhauser effect (NOE) is a powerful tool in molecular structure elucidation, combining the subtle chemical shift of NMR and three-dimensional information independent of chemical connectivity. Its usage for intermolecular studies, however, is fundamentally limited by an unspecific long-ranged interaction behavior. This joint experiment...
Article
Full-text available
To date, only a few instances of S4-symmetric organic molecules exist. In principle, spirobi-(dinaphthoazepin)ium cations can achieve this highly symmetric point group. Heating racemic 2,2′-bis(bromomethyl)-1,1′binaphthyl with aqueous ammonia afforded a mixture of rac- and meso-3,3′,5,5′-tetrahydro-4,4′-spirobi[dinaphtho[2,1-c:1′,2′-e]azepin]-4-ium...
Article
Full-text available
In the course of an ongoing synthetic project on cyclic diferrocenylphosphines, we obtained a group of planar–chiral diferrocenyl compounds useful as precursors for subsequent cyclization. Here we report the crystal structures of two symmetric compounds [(Fc A ) 2 (Ph)P], one of which contains four stereogenic centres (two C chiral and two planar c...
Article
Different types of spectroscopy capture different aspects of dynamics and different ranges of intermolecular contributions. In this article, we investigate the dielectric relaxation spectroscopy (DRS) of collective nature and the time-dependent Stokes shift (TDSS) of disputed nature. Our computational study of unconfined and confined water clearly...
Preprint
Phosphoric acids bound to 3,3’-subsituted 1,1’-binaphthalene-2,2’-diol (BINOL) have found wide application as effective asymmetric catalysts. In this work, we describe our attempt to construct a new binaphthalene-based phosphoric acid 6 . We found that both the key precursor 2 and the desired product 6 decay rapidly and quantitatively to a stable d...
Article
Full-text available
We describe the synthesis of planar-chiral diferrocene compounds 4, 7 and 12, intended as key precursors for a new family of asymmetric catalyst ligands with less complex structures than their popular equivalents. In contrast to conventional 1,2-disubstituted ferrocenes containing center-chiral and planar-chiral elements, these compounds are purely...
Article
Fast-Field cycling relaxometry is a nuclear magnetic resonance method growing in popularity, yet theoretical interpretation is limited to analytical models of uncertain accuracy. We present the first study calculating fast field cycling dipolar coupling directly from a molecular dynamics simulation trajectory. In principle, the frequency-resolved d...
Article
We propose a methodology to capture short-lived but biophysically important contacts of biomacromolecules using the biomolecule-water nuclear Overhauser effect as an indirect microscope. Thus, instead of probing the direct correlation with the foreign biomolecule, we detect its presence by the disturbance it causes in the surrounding water. In addi...
Article
Full-text available
We present a synthesis of the title compound, a homochiral diferroceno cycle intended for use in asymmetric catalysis. We present a hydrovinylation protocol, which allows the production of the title compound in two steps from a known diferrocenyl precursor. We obtained one of two possible diastereomers selectively and propose a plausible regio- and...
Article
Full-text available
Ferrocene-based compounds are powerful asymmetric ligands usable for chemical catalysis. We present the synthesis of six new homochiral diferroceno cycles potentially useful as P,O-, P,N- or P,S-ligands. Due to the stereoconservative nature of the SN1 reaction at carbons adjacent to ferrocene units, we obtained a single diastereomer of the 8-member...
Article
In this computational study, the intermolecular solute-solvent Nuclear Overhauser Effect (NOE) of the model protein ubiquitin in different chemical environments (free, bound to a partner protein and encapsulated) is investigated. Short-ranged NOE observables such as the NOE/ROE ratio reveal hydration phenomena on absolute timescales such as fast hy...
Article
Full-text available
In the course of an ongoing synthetic project, we observed an unprecedented reactivity of N-methyl groups in bis(N,N-dimethylaminoethylferrocenyl)phenylphosphinesulfide upon treatment with manganese dioxide (MnO2). The intramolecular course of this reaction resulted in the formation of an unexpected homochiral diaza macrocycle. The target structure...
Article
Full-text available
The local changes in protein hydration dynamics upon encapsulation of the protein or macromolecular crowding are essential to understand protein function in cellular environments. We were able to obtain a spatially-resolved picture of the influence of confinement and crowding on the hydration dynamics of the protein ubiquitin by analyzing the time-...
Article
This study is based on extensive MD simulations of a protein in a reverse micelle to mimic the effect of confinement on biomolecules. This permits the calculation of measurable quantities appearing in NQR and Nuclear Overhauser-NMR despite of the high computational effort. We address the long-standing debate about the intermolecular NOE showing tha...
Article
Full-text available
The bioprotective nature of monosaccharides and disaccharides is often attributed to their ability to slow down the dynamics of adjacent water molecules. Indeed, solvation dynamics close to sugars is indisputably retarded compared to bulk water. However, further research is needed on the qualitative and quantitative differences between the water dy...
Article
Confinement and macromolecular crowding are acknowledged to be fundamental for the understanding of biomolecular systems. This computational study combines these two phenomena by investigating a multi-protein system encapsulated in a reverse micelle. Contemporary controversies regarding force field accuracy with respect to hydration in such systems...
Article
In this computational study, we investigate the morphology and dynamics of nanostructures formed by the ionic liquid 1‑dodecyl‑3‑methylimidazolium chloride [C12mim]Cl dissolved in water. Recent works emphasize the positive impact of this additive on various catalytic transformations. The assembling process revealed by molecular dynamics simulation...
Article
In this computational study, we investigate the behaviour of a protein in water encapsulated in a zwitterionic/neutral reverse micelle as a cellular mimetic. Addressing the discussion if current force fields are apt to correctly describe crowded/encapsulated environments, we apply an up-scaling of the non-bonded, non-electrostatic interactions of p...
Article
Recent experiments by Weingaertner et al. have given a first hint that dielectric spectroscopy is able to yield a quantitative measure of inter-protein mutual orientation. Therefore, in this computational study, we investigate crowded multi-protein solutions with a special focus on this mutual orientation and its context with dielectric spectroscop...
Article
This computational study deals with the collective structure and dynamics as well as their in- teraction seen from a dielectric viewpoint in zwitterionic reverse micelles for which a force field was designed de novo. For this end, a dualistic strategy is followed: The raw data are generated by extensive microscopic molecular dynamics (MD) simulatio...

Citations

... We attempted to access similar compounds containing oxygen, nitrogen or sulfur at the ethyl side chain. However, we noticed that when replacing phosphorous (R2PPh) with sulfur (R2S) or nitrogen (R2NPh), eliminations yielding vinylferrocenes as decay products become a serious side reaction [29], thereby limiting the practical value of such compounds. In this article, we present two possible synthetic workarounds: ...
... The averages defined by these equations can be calculated with ease from the atomistic information in an MD trajectory. The weighting factors w ij are commonly chosen as 1. 32 However, with this choice, the calculated average distances diverge with increasing cutoff. Thus, for the sake of simplicity, we chose an exponential weighting function, w e ij r ij = . ...
... In order to synthesize further purely planar-chiral diferrocenyl phosphines (Scheme 4), divinyl substituted diferrocenylphosphine 9 was chosen as a key intermediate, easily accessible from diamine (R,R,Sp,Sp)-8 [34] (Scheme 4). To introduce substituents at terminal carbon atoms, hydroboration of the double bond is well established, leading predominantly to anti-Markownikow products. ...
... Some of them are bridged biferrocenyls, e.g., Eberhard et al. [6], Metallinos et al. [7], Tews et al. [8], Santi et al. [9] and Jäkle et al. [10]. In other diferroceno cycles, the two ferrocene units are connected through heteroatoms such as silicon [11], sulfur [12], boron [13][14][15][16] and phosphorous [16][17][18]. Both Schlögl [19] and Köhler [20] described two ferrocene moieties connected by carbon chains. ...
... Based on hydration number, radius of gyration, glycosidic dihedral angles and cluster formation, it was determined that trehalose-water solutions were more homogeneous than sucrose-water solutions [43]. Trehalose's impact on water molecules was also proven by investigation of single-particle and collective rotation and translation of water, in which it was concluded that trehalose had a slightly greater effect on these properties than sucrose [44]. In comparison to sucrose, it was observed that trehalose had a stronger perturbing effect on the water structure and that water molecules interacted slightly differently with the different atomic sites of these two disaccharides [45]. ...
... The effects of macromolecular crowding on enzymes were experimentally determined using concentrated solutions of model "crowding agents" (e.g., poly(ethylene glycol), dextran, Ficoll, bovine serum albumin (BSA), or cellulose derivate) [120]. Having in mind that not all crowders are equal with respect to protein activity due to their specific interactions, the replacement of synthetic agents with a native-like medium composed of natural crowders (e.g., intracellular content) will lead in the future to a more realistic model of crowding and confinement inside cells (Figure 8). ...
... In addition, molecular dynamics simulation 20,31-36 could provide significant assistance in revealing the mechanism of aggregation of ionic liquids at the atomic and molecular levels. Honegger et al. 36 investigated the morphology and dynamics of nanostructures formed by [C 12 mim][Cl] dissolved in water. Anta et al. 35 studied the formation of micelles and predicted the critical micellar concentration by using molecular dynamics simulation for a series of imidazolium ionic liquids. ...
... An overview of all trajectories is given in Table 1 where the applied force-eld scaling, the number of molecules, the box length a, the number of independent replica and the lengths of the equilibration and production runs are listed. Simulations of one UBQ in 45 000 water molecules were reused from ref. 63, as well as single UBQ 64 and ve UBQ molecules 65 in a RM made up of uncharged surfactants. A mixture of the zwitterionic lauryldimethylamine-N-oxide (LDAO) and the neutral monoglyceride 1-decanoyl-rac-glycerol (DMAG) acted as surfactants. ...
... The derivation of the Kivelson-Madden relation involves some approximations, particularly in its simplified form in Eq. (9), and it has remained a conjecture for many years since its introduction. 7 Nevertheless, recent experimental studies by Weingärtner and coworkers 13,14 and molecular dynamics (MD) simulations by Steinhauser and co-workers 15,16 have produced evidence of its accuracy. Here, we use classical molecular dynamics (MD) simulations of force-field water to provide additional tests and to use this result toward the goal of modeling the nonlinear retardation of polar dynamics by the applied electric field. ...