Christian Roth

The Influence of Hydrogen‐Bond Defects on the Properties of Ionic Liquids

Ionic liquids (ILs) are salts with uncommonly low melting points that are formed by a combination of specific cations and anions; they display distinctive properties and can be used in a variety of applications. The working temperature range of an ionic liquid is set by the melting point and the boiling or decomposition point. In particular, the melting point (Tm) varies substantially between different ILs for reasons presently not fully understood, but which we explore herein. We show that the melting points of imidazolium ionic liquids can be decreased by about 100 K if an extended ionic and hydrogen-bond network is disrupted by localized interactions, which can also be hydrogen bonds. Evidence for the presence of ion–ion interactions through hydrogen bonds was reported by Dymek et al., Avent et al., and Elaiwi et al. some time ago. It is reasonable to assume that the interesting features of the melting points must be related to the formation of structures in the solid and the liquid phases of the ILs. Extended hydrogen-bond networks in the liquid phase were reported with possible implications for both the structure and solvent properties of the ILs. Dupont et al. described pure imidazolium ILs as hydrogenbonded polymeric supramolecules. Antonietti et al. suggested that these supramolecular solvent structures represent an interesting molecular basis of molecular recognition and self-organization processes. However, in all of these examples it is suggested that hydrogen bonds strengthen the structure of ILs leading to properties similar to those of molecular liquids. This idea is also the basis of most of the structure– property relations discussed in the literature including quantitative structure–property relationships (QSPR) methods to correlate the melting points of ILs based on “molecular descriptors” derived from quantum chemical calculations. Such empirical correlations suffer from the fact that large experimental data sets are required and that the statistical methods used are rather complex. In addition, no interpretation of these fundamental physical properties at the molecular level is provided. Krossing et al. have developed a simple predictive framework to calculate the melting point of a given ionic liquid based on lattice and solvation free energies. They showed that ILs are liquid under standard ambient conditions because the liquid state is thermodynamically favorable, owing to the large size and conformational flexibility of the ions involved. This leads to small lattice enthalpies and large entropy changes that favor the liquid state. For such studies substituted imidazolium, pyrrolidinium, pyridinium, and ammonium cations have been used along with fluorometalate, triflate, and bis(trifluoromethylsulfonyl)imide anions. Unfortunately, Krossing s results do not correlate with experimentally obtained melting points for protic ionic liquids (PILs) reported byMarkusson et al. The reason for the large deviations of the predicted from the experimental melting points is probably related to the general trend of increasing Tm with the increasing size of the anions. We do not intend to present another framework for predicting ionic liquid properties here. Instead we want to demonstrate that in addition to the large size and conformational flexibility of the ions, local defects such as directional hydrogen bonds can significantly decrease the melting points of ionic liquids. For eight imidazolium-based ionic liquids we show that these defects can increase their working temperature range by up to 100 K and thus expand the spectrum of potential applications. This was suggested previously by Fumino et al. based on spectroscopic measurements and DFT calculations on IL aggregates. They assumed that local and directional types of interactions present defects in the Coulomb system which may lower the melting points, viscosities, and enthalpies of vaporization. In contrast, based on quantum chemical calculations, Hunt claimed that an increase in the melting points and viscosities upon methylation at C(2) stem from reduced entropy. Noack et al. showed very recently that neither the “defect hypothesis” of Fumino et al. nor the “entropy hypothesis” of Hunt alone can explain the changes in the physicochemical properties. However, in all these studies the data base was not sufficiently large and other effects such as volume changes could not be excluded for the ILs under investigation. [*] Dipl.-Chem. C. Roth, Dr. K. Fumino, Dr. D. Paschek, Prof. Dr. R. Ludwig Universit t Rostock, Institut f r Chemie Abteilung f r Physikalische Chemie Dr. Lorenz Weg 1, 18059 Rostock (Germany) Fax: (+49)381-498-6517 E-mail: ralf.ludwig@uni-rostock.de

Structural and functional studies on a thermostable polyethylene terephthalate degrading hydrolase from Thermobifida fusca

Bacterial cutinases are promising catalysts for the modification and degradation of the widely used plastic polyethylene terephthalate (PET). The improvement of the enzyme for industrial purposes is limited due to the lack of structural information for cutinases of bacterial origin. We have crystallized and structurally characterized a cutinase from Thermobifida fusca KW3 (TfCut2) in free as well as in inhibitor-bound form. Together with our analysis of the thermal stability and modelling studies, we suggest possible reasons for the outstanding thermostability in comparison to the less thermostable homolog from Thermobifida alba AHK119 and propose a model for the binding of the enzyme towards its polymeric substrate. The TfCut2 structure is the basis for the rational design of catalytically more efficient enzyme variants for the hydrolysis of PET and other synthetic polyesters.

Microheterogeneities in Ionic-Liquid-Methanol Solutions Studied by FTIR Spectroscopy, DFT Calculations and Molecular Dynamics Simulations

The interest in ionic liquids (ILs) is steadily increasing because of their fascinating physicochemical properties and because of their broad range of applications in synthesis, separation, catalysis and electrochemistry. However, the multiplicity of their uses strongly depends on a molecular understanding of their exceptional properties. One key to a better understanding of their unique properties are spectroscopic studies of ionic liquids in conventional organic solvents in combination with DFT calculations and molecular dynamics simulations. Therefore we investigated the mixtures of the imidazolium-based ionic liquid [C(2)mim][NTf(2)] with methanol. Caused by the amphiphilic character of methanol both liquids are miscible over the whole mixture range. The scope of this work is to study the changes in the IL network upon dilution and to investigate the formation of methanol clusters embedded in the IL matrix. The mixtures were studied by FTIR spectroscopy in the mid-infrared region. The formation of methanol clusters was studied from the OD stretching vibrational bands between 2300 and 2800 cm(-1). The cluster populations of methanol could be derived from molecular dynamics simulations for the same mixtures. Weighting the DFT calculated frequencies by the cluster populations we could reproduce the measured spectra in the OD stretching region up to X(MeOH)=0.5. Above X(MeOH)=0.8, strong formation of self-methanol clusters takes place resulting in increasing diffusion coefficients related to decreasing dynamical heterogeneities. Thus we obtained a deep understanding of the solute-solvent and solute-solute interactions as well as information about the presence of microheterogeneities in the mixtures.

An isomorphous series of cubic, copper-based triazolyl isophthalate MOFs: linker substitution and adsorption properties.

An isomorphous series of 10 microporous copper-based metal-organic frameworks (MOFs) with the general formulas (∞)(3)[{Cu(3)(μ(3)-OH)(X)}(4){Cu(2)(H(2)O)(2)}(3)(H-R-trz-ia)(12)] (R = H, CH(3), Ph; X(2-) = SO(4)(2-), SeO(4)(2-), 2 NO(3)(2-) (1-8)) and (∞)(3)[{Cu(3)(μ(3)-OH)(X)}(8){Cu(2)(H(2)O)(2)}(6)(H-3py-trz-ia)(24)Cu(6)]X(3) (R = 3py; X(2-) = SO(4)(2-), SeO(4)(2-) (9, 10)) is presented together with the closely related compounds (∞)(3)[Cu(6)(μ(4)-O)(μ(3)-OH)(2)(H-Metrz-ia)(4)][Cu(H(2)O)(6)](NO(3))(2)·10H(2)O (11) and (∞)(3)[Cu(2)(H-3py-trz-ia)(2)(H(2)O)(3)] (12(Cu)), which are obtained under similar reaction conditions. The porosity of the series of cubic MOFs with twf-d topology reaches up to 66%. While the diameters of the spherical pores remain unaffected, adsorption measurements show that the pore volume can be fine-tuned by the substituents of the triazolyl isophthalate ligand and choice of the respective copper salt, that is, copper sulfate, selenate, or nitrate.

The Dissolution of Polyols in Salt Solutions and Ionic Liquids at Molecular Level: Ions, Counter Ions, and Hofmeister Effects

The dissolving process of polyols in salt solutions (TBAF, TBAC, TBAB, TBAI, TMAF) and imidazolium-based ionic liquids ([C2 mim][OAc], [C2 mim][Et2 PO4 ], [C2 mim][EtSO4 ], [C2 mim][SCN]) is exemplarily studied by IR spectroscopy. Vibrational bands and their shifts in the OH stretch region reveal crucial information for the dissolved polyol interacting with the anions of the salt solutions and ionic liquids. The well-chosen set of ionic solutions confirms the linear relation between the OH-stretch frequencies and the solubility capacity of the salt solutions. Likewise, it also provides an explanation of the dissolving process at molecular level. Notably, the solubility capacities of the anions in the salt solutions follow the well-known Hofmeister series. This phenomenon can be understood on the basis of the disruption power of the anions and the specific size ratio of the anion/cation combinations.

Understanding the Dissolution of Polyols by Ionic Liquids Using the Example of a Well‐Defined Model Compound

Cellulose is the most abundant natural polymer in our environment and the most obvious renewable resource for producing biocomposites. It has been an enormous challenge to find suitable solvents for its dissolution. The traditional dissolution processes suffered from the environmental toxicity or from insufficient solvation power of the solvents. In 2002 Swatloski et al. reported the use of ionic liquids as solvents for cellulose both for the regeneration of cellulose and for the modification of the polysaccharide. 2] Ionic liquids (ILs) are salts with uncommonly low melting temperatures that are formed by a combination of specific cations and anions leading to distinctive properties and a variety of applications. 11] Although the dissolution process of cellulose has been widely studied since, the understanding is far from being complete. Usually it is quoted that “suitable solvents must be able to disrupt effectively the strong hydrogen bond network in cellulose”. Following this argument, the solvent–cellulose interactions must successfully compete with the cellulose–cellulose hydrogen bonds. For a better understanding of the hydrogen bond mechanism causing the insolubility of cellulose other substances such as dextran, glucose and cellulose derivatives were investigated. Obviously, beside the cellulose–solvent interaction also the cellulose–cellulose and solvent–solvent interactions have to be taken into account. However, a mechanistic understanding of solubility is difficult for cellulose because of its strong hydrogen bond network resulting in a stable solid state structure and the formation of extended crystalline regions in solution. Moreover, the OH stretch frequencies, which act as good indicators for the interaction strength, merge into a broad and unspecific vibrational band making any assignment nearly impossible. Thus, we tried to find a simple model compound with similar properties as cellulose, but which is welldefined with respect to structure and frequencies. A good candidate for such a model compound is 2,2-bis(hydroxymethyl)1,3-propanediol (pentaerythritol, C5H12O4), a quite familiar polyol, whose properties have already been discussed in the “hydrogen bond” chapter of Linus Pauling’s famous textbook “The nature of the chemical bond”. The molecules form tetragonal crystals in which they are bound into layers by strong hydrogen bonds, resulting in a very high melting point temperature of 262 8C. Interestingly, pentaerythritol (PET) also shares with cellulose its unfavourable solubility in water, which is apparently related to the unusually high stability of its crystalline form. An important structural motif of crystalline PET is that hydrogen bonds tie the oxygen atoms together into square groups (see Figure 1), as also known for the meth-

Discovery of Selective Small-Molecule Activators of a Bacterial Glycoside Hydrolase.

Fragment-based approaches are used routinely to discover enzyme inhibitors as cellular tools and potential therapeutic agents. There have been few reports, however, of the discovery of small-molecule enzyme activators. Herein, we describe the discovery and characterization of small-molecule activators of a glycoside hydrolase (a bacterial O-GlcNAc hydrolase). A ligand-observed NMR screen of a library of commercially available fragments identified an enzyme activator which yielded an approximate 90 % increase in kcat/KM values (kcat=catalytic rate constant; KM=Michaelis constant). This compound binds to the enzyme in close proximity to the catalytic center. Evolution of the initial hits led to improved compounds that behave as nonessential activators effecting both KM and Vmax values (Vmax=maximum rate of reaction). The compounds appear to stabilize an active “closed” form of the enzyme. Such activators could offer an orthogonal alternative to enzyme inhibitors for perturbation of enzyme activity in vivo, and could also be used for glycoside hydrolase activation in many industrial processes.

Three-dimensional structure of a Streptomyces sviceus GNAT acetyltransferase with similarity to the C-terminal domain of the human GH84 O-GlcNAcase

The crystal structure of a bacterial acetyltransferase with 27% sequence identity to the C-terminal domain of human O-GlcNAcase has been solved at 1.5 Å resolution. This S. sviceus protein is compared with known GCN5-related acetyltransferases, adding to the diversity observed in this superfamily.

Structural and functional insight into human O-GlcNAcase

O-GlcNAc hydrolase, OGA, removes O-linked N-acetylglucosamine (O-GlcNAc) from myriad nucleocytoplasmic proteins. Through co-expression and assembly of OGA fragments we determined the 3-D structure of human OGA, revealing an unusual helix exchanged dimer that lays a structural foundation for an improved understanding of substrate recognition and regulation of OGA. Structures of OGA in complex with a series of inhibitors define a precise blueprint for the design of inhibitors having clinical value.

A Convenient Approach to Stereoisomeric Iminocyclitols: Generation of Potent Brain‐Permeable OGA Inhibitors

Pyrrolidine-based iminocyclitols are a promising class of glycosidase inhibitors. Reported herein is a convenient epimerization strategy that provides direct access to a range of stereoisomeric iminocyclitol inhibitors of O-GlcNAcase (OGA), the enzyme responsible for catalyzing removal of O-GlcNAc from nucleocytoplasmic proteins. Structural details regarding the binding of these inhibitors to a bacterial homologue of OGA reveal the basis for potency. These compounds are orally available and permeate into rodent brain to increase O-GlcNAc, and should prove useful tools for studying the role of OGA in health and disease.