Detection and Verification of a Key Intermediate in an Enantioselective Peptide Catalyzed Acylation Reaction

Until now, the intermediate responsible for the acyl transfer of a highly enantioselective tetrapeptide organocatalyst for the kinetic resolution of trans-cycloalkane-1,2-diols has never been directly observed. It was proposed computationally that a π-methylhistidine moiety is acylated as an intermediate step in the catalytic cycle. In this study we set out to investigate whether we can detect and characterize this key intermediate using NMR-spectroscopy and mass spectrometry. Different mass spectrometric experiments using a nano-ElectroSpray Ionization (ESI) source and tandem MS-techniques allowed the identification of tetrapeptide acylium ions using different acylation reagents. The complexes of trans-cyclohexane-1,2-diols with the tetrapeptide were also detected. Additionally, we were able to detect acylated tetrapeptides in solution using NMR-spectroscopy and monitor the acetylation reaction of a trans-cyclohexane-1,2-diol. These findings are important steps towards the understanding of this highly enantioselective organocatalyst.     

The Influence of the Halide in the Crystal Structures of 1-(2,3,5,6-Tetrafluoro-4-pyridyl)-3-benzylimidazolium Halides

The crystal structures of 1-(2,3,5,6-tetrafluoro-4-pyridyl)-3-benzylimidazolium chloride (1) and iodide (3) have been determined by single crystal X-ray diffraction. The crystal structure of 1 is similar to that of the bromide salt (2), possessing anion···C₅F₅N···C₆H₅ motifs, whilst that of 3 contains columns of alternating iodide anions and parallel tetrafluoropyridyl rings. All three crystal structures possess C(1)–H∙∙∙X⁻ and C(2)–H∙∙∙X⁻ hydrogen bonding. DFT calculations reveal that the strengths of the hydrogen bonding interactions lie in the order C(1)–H···X⁻ > C(3)–H···X⁻ > C(2)–H···X⁻ for the same halide (X⁻) and Cl⁻ > Br⁻ > I⁻ for each position. It is suggested that salt 3 adopts a different structure to salts 1 and 2 because of the larger size of iodide.     

Study of the mesomorphic behaviour through the structure modification of azo and acetylene pyridinium and imidazolium-based ionic liquid crystals

ABSTRACT

In this work, 14 pyridinium and imidazolium-based ionic liquid crystal (ILC) with azo (N=N) and acetylene (C≡C) as linking group were synthesised in high yields and completely characterised. The structure of the molecules were planned in order to allow a complete investigation on how modifications such as presence and position of charges, linking group, number of alkoxy chains and their length affect the thermal stability and liquid crystalline behaviour. All compounds were thoroughly investigated using polarised optical microscopy (POM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) measurements and thermogravimetric analysis (TGA). While the presence of charges favoured a liquid crystalline behaviour, especially SmA (and SmA₂) phase, a decrease of thermal stability was noticed. A strong dependence of the charge position and a preference for monolayer or bilayer molecular organisation was observed. On the other hand, it was demonstrated that the addition of a second alkoxy chain promoted layer distortions in some molecules, resulting in the formation of Smà and Cub phases. Also a direct comparison between the N=N and C≡C linking groups was realised, along with further comparison with literature data. The structure–properties are investigated in detail.     

Synthesis of di(Imdazolium) and di(Pyrazolium) Salts as Precursors for N-heterocyclic Dicarbene Complexes

Alpha,omega-bis(pyrazol-1-yl)alkanes and alpha,omega-bis(imidazol-1-yl)alkanes with spacers consisting of four to ten methylene groups have been prepared from pyrazole, 3,5-dimethylpyrazole or imidazole and corresponding dibromoalkanes in a superbasic medium KOH-DMSO. The proposed method of synthesis allowed the preparation of new flexible bidentate ligands without the need to use toxic solvents and tedious workup procedures. Bis(pyrazol-1-yl)alkanes were further functionalized for their use as precursors for “non-classical” mesoionic N-heterocyclic carbene ligands. One the first step, iodine atoms were introduced to positions 4 of pyrazole rings by oxidative iodination using I₂-HIO₃ system. On the next step, nitrogen atoms in positions 2 of pyrazole rings were alkylated using several agents. Reaction with methyliodide unexpectedly led to the formation of only mono-alkylated products even after 7 days of refluxing in a neat alkyliodide. Methylation by trimethyloxonium tetrafluoroborate or methyltriflate led to dimethylated products in high yields. Bis(imidazol-1-yl)alkanes were easily alkylated by methyliodide to give di(imidazolium) salts – precursors to “classic” N-heterocyclic dicarbenes.     

Crystal structure of 1,3-dialkyldiazolium bromides

Systematic X-ray diffraction study of the crystal structures of 1,3-dialkylimidazole-based ionic liquids containing the Br⁻ anion was performed. Analysis of the influence of the nature of the cation on the formation of a hydrogen bond system and the supramolecular arrangement of ions demonstrated that not only CH⋯Br contacts but also anion—π-system and CH—π-system interactions exist in the crystalline state. Conclusions were drawn on the character of changes in the melting point in a series of bromide ionic liquids containing the imidazolium cation. Dedicated to Academician O. M. Nefedov on the occasion of his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1916–1925, November, 2006.     

Aqueous Solutions of Ionic Liquids: Microscopic Assembly

Aqueous solutions of ionic liquids are of special interest, due to the distinctive properties of ionic liquids, in particular, their amphiphilic character. A better understanding of the structure–property relationships of such systems is hence desirable. One of the crucial molecular‐level interactions that influences the macroscopic behavior is hydrogen bonding. In this work, we conduct molecular dynamics simulations to investigate the effects of ionic liquids on the hydrogen‐bond network of water in dilute aqueous solutions of ionic liquids with various combinations of cations and anions. Calculations are performed for imidazolium‐based cations with alkyl chains of different lengths and for a variety of anions, namely, [Br]^?, [NO₃]^?, [SCN]^?, [BF₄]^?, [PF₆]^?, and [Tf₂N]^?. The structure of water and the water–ionic liquid interactions involved in the formation of a heterogeneous network are analyzed by using radial distribution functions and hydrogen‐bond statistics. To this end, we employ the geometric criterion of the hydrogen‐bond definition and it is shown that the structure of water is sensitive to the amount of ionic liquid and to the anion type. In particular, [SCN]^? and [Tf₂N]^? were found to be the most hydrophilic and hydrophobic anions, respectively. Conversely, the cation chain length did not influence the results.     

Ionic Liquids Containing Silsesquioxane and Cyclic Siloxane Frameworks

This paper describes the author's recent work on the preparation and properties of thermally stable ionic liquids (ILs) containing siloxane frameworks. Quaternary ammonium and imidazolium salt-type ILs containing random oligosilsesquioxane frameworks were successfully prepared via the hydrolytic condensation of the corresponding organotrialkoxysilanes by using an aqueous superacid bis(trifluoromethanesulfonyl)imide (HNTf₂) solution as a catalyst and solvent. Imidazolium salt-type ILs containing polyhedral oligomeric silsesquioxane (POSS) frameworks were also prepared through a reaction similar to that described above by using a water/methanol mixed solution of HNTf₂. In addition, amorphous POSSs with two types of ionic groups randomly distributed in the side chain were prepared. These POSSs were ILs exhibiting fluidity at relatively low temperatures. Furthermore, imidazolium and ammonium salt-type ILs containing cyclic oligosiloxane frameworks were prepared through a reaction similar to that of the corresponding organodialkoxysilanes. The thermal decomposition temperatures of the above ILs containing siloxane frameworks were higher than those of general ILs.     

Study of complexation between perrhenate ion and N-methyl-N-vinylacetamide and N-methyl-N-vinylamine copolymers in aqueous solutions by fast monolith high-performance liquid chromatography (HPLC)

Complexation between perrhenate ion and N-methyl-N-vinylacetamide and N-methyl-N-vinylamine copolymers in aqueous solutions was studied by high-performance liquid chromatography on monolith ultrashort columns. It was demonstrated that complexation has slow kinetics and strongly depends on the length of alkyl substituent.     

Synthesis of novel chiral imidazolium stationary phases and their enantioseparation evaluation by high-performance liquid chromatography

Two novel chiral stationary phases (CSPs) were prepared by bonding chiral imidazoliums on the surface of silica gel. The chiral imidazoles were derivatized from chiral amines, 1-phenylethylamine and 1-(1-naphthyl)ethylamine. The obtained CSPs were characterized by Fourier Transform Infrared (FT-IR) spectroscopy and elemental analysis (EA), demonstrating the bonding densities of CSP 1 and CSP 2 were 0.43 mmol g⁻¹ and 0.40 mmol g⁻¹, respectively. These two CSPs could be used to availably separate 8 pharmaceuticals, 7 mandelic acid/its derivatives, 2 1-phenylethylamine derivatives, 1 1,1′-bi-2-naphthol, and 1 camphorsulfonic acid in high-performance liquid chromatography (HPLC). It is found that CSP 1 could effectively enantioseparate most chiral analytes, especially the acidic components, while CSP 2 could enantiorecognize all chiral analytes, although a number of components did not achieve baseline separation. Additionally, the effects of mobile phase composition, mobile phase pH and salt content, chiral selector structures, and analyte structures on the enantiorecognitions of the two CSPs were investigated. It is found that high acetonitrile content in mobile phases was conducive to enantiorecognition. Mobile phase pH and salt content could alter the retention behaviors of different enantiomers of the same chiral compound, resulting in better enantioresolution. Moreover, both chiral selector structures and substituted groups of analytes played a significant role in the separation of chiral solutes.     

The search for formal electrostatic effects on molecular conformation and crystal packing: crystal structure of 2,2′′‐disubstituted (H versus PPh2) 1,1′‐(1,2‐phenylene)bis(3‐methyl‐1H‐imidazol‐3‐ium) bis(trifluoromethanesulfonate)

Electrostatic interactions between localized integral charges make the stability and structure of highly charged small and rigid organics intriguing. Can σ/π‐electron delocalization compensate reduced conformational freedom by lowering the repulsion between identical charges? The crystal structure of the title salt, C₁₄H₁₆N₄²⁺·2CF₃SO₃⁻, (2), is described and compared with that of the 2,2′′‐bis(diphenylphosphanyl) derivative, (4). The conformations of the dications and their interactions with neighbouring trifluoromethanesulfonate anions are first analyzed from the standpoint of formal electrostatic effects. Neither cation exhibits any geometrical strain induced by the intrinsic repulsion between the positive charges. In contrast, the relative orientation of the imidazolium rings [i.e. anti for (2) and syn for (4)] is controlled by different configurations of the interactions with the closest trifluoromethanesulfonate anions. The long‐range arrangement is also found to be specific: beyond the formal electrostatic packing, C—H…O and C—H…F contacts have no definite `hydrogen‐bond' character but allow the delineation of layers, which are either pleated or flat in the packing of (2) or (4), respectively.