Manfred Friedrich

New aspects on the hydrogen bond donor (HBD) strength of 1-butyl-3-methylimidazolium room temperature ionic liquids

Improved hydrogen bond donor (HBD) strength parameters of 1-butyl-3-methylimidazolium room temperature ionic liquids (RTILs), acceptor number (AN) of Gutmann and α of Kamlet–Taft, have been determined using [Fe(phen)2(CN)2]ClO4 as an original solvatochromic probe. Each of the parameters shows an excellent correlation with the independently determined HBA strength β (Kamlet–Taft) of the anion which demonstrates that empirical polarity parameters of RTILs can be utilized independently of each other.

X-ray induced effects in phosphate glasses

Abstract Optical absorption and paramagnetic resonance spectra of X-ray irradiated (λCuKα=0.154 nm) ultra- and metaphosphate glasses of high purity were studied. Melting of the samples under different redox conditions, investigation of annealing behavior of the irradiated samples and correlation between optical and EPR spectra allowed the resolution of five main paramagnetic radiation-induced defects and associated optical absorption bands. Phosphorus and oxygen related radiation-induced defects were found, with hole centers POHC and OHC absorbing in the visible and electron trapped centers PO2, PO3 and PO4 absorbing in the ultraviolet region.

Heme impairs the ball-and-chain inactivation of potassium channels.

Significance Heme, traditionally viewed as a stable protein cofactor such as in hemoglobin, also serves as an acute signaling molecule and is cytotoxic at high concentrations. Here, we show that free intracellular heme potently enhances A-type potassium channel function. Such channels determine action potential frequency in excitable cells, and their dysfunction often contributes to pathological hyperexcitability, such as in pain and epilepsy. Binding of free heme at nanomolar concentrations to the “ball-and-chain” N terminus of A-type potassium channels, which typically closes the channels, introduces a stable structure in the otherwise disordered region and allows for a greater efflux of potassium ions, thus reducing cellular excitability. Heme therefore could be a powerful negative-feedback regulator in brain and muscle function. Fine-tuned regulation of K+ channel inactivation enables excitable cells to adjust action potential firing. Fast inactivation present in some K+ channels is mediated by the distal N-terminal structure (ball) occluding the ion permeation pathway. Here we show that Kv1.4 K+ channels are potently regulated by intracellular free heme; heme binds to the N-terminal inactivation domain and thereby impairs the inactivation process, thus enhancing the K+ current with an apparent EC50 value of ∼20 nM. Functional studies on channel mutants and structural investigations on recombinant inactivation ball domain peptides encompassing the first 61 residues of Kv1.4 revealed a heme-responsive binding motif involving Cys13:His16 and a secondary histidine at position 35. Heme binding to the N-terminal inactivation domain induces a conformational constraint that prevents it from reaching its receptor site at the vestibule of the channel pore.

Assessment of fluidity of different invasomes by electron spin resonance and differential scanning calorimetry.

The aim of this study was to investigate the influence of membrane-softening components (terpenes/terpene mixtures, ethanol) on fluidity of phospholipid membranes in invasomes, which contain besides phosphatidylcholine and water, also ethanol and terpenes. Also mTHPC was incorporated into invasomes in order to study its molecular interaction with phospholipids in vesicular membranes. Fluidity of bilayers was investigated by electron spin resonance (ESR) using spin labels 5- and 16-doxyl stearic acid and by differential scanning calorimetry (DSC). Addition of 1% of a single terpene/terpene mixture led to significant fluidity increase around the C16 atom of phospholipid acyl chains comprising the vesicles. However, it was not possible to differentiate between the influences of single terpenes or terpene mixtures. Incorporation of mTHPC into the bilayer of vesicles decreased fluidity near the C16 atom of acyl chains, indicating its localization in the inner hydrophobic zone of bilayers. These results are in agreement with DSC measurements, which showed that terpenes increased fluidity of bilayers, while mTHPC decreased fluidity. Thus, invasomes represent vesicles with very high membrane fluidity. However, no direct correlation between fluidity of invasomes and their penetration enhancing ability was found, indicating that besides fluidity also other phenomena might be responsible for improved skin delivery of mTHPC.

31P NMR characterisation of phosphate fragments during dissolution of calcium sodium phosphate glasses

Phosphate glasses in the system P2O5-CaO-Na2O dissolve in aqueous solutions, and their solubility can be varied by changing the glass composition. This makes them of interest for use as controlled release materials, e.g. as degradable implants, devices for the release of trace elements or as fertilizers, but in order to tailor glass solubility to meet specific requirements, we need to further our understanding of their dissolution behaviour and mechanism. The structure of P2O5-CaO-Na2O glasses (P2O5 between 55 and 35 mol%; glass structure analysed by 31P MAS NMR) changed from a network (55 mol% P2O5) to short chains (35 mol%) with decreasing phosphate content. Solubility in Tris buffer showed significant differences with phosphate content and glass structure; dissolution varied between 90% (50 mol% P2O5) and 15% (35 mol%) at 24 h. Glasses with high phosphate contents significantly lowered the pH of the solution, while glasses with low phosphate contents did not. Glasses consisting of a phosphate network dissolved by a mechanism involving P-O-P bond hydrolysis, as no Q3 groups but increasing concentrations of Q0 (orthophosphate) were found in solution by solution 31P NMR. Glasses consisting of chains, by contrast, can dissolve by hydration of entire chains, but hydrolysis also occurred, resulting in formation of Q0 and small ring structures. This occurrence of hydrolysis (and thus formation of P-OH groups, which can be deprotonated) caused the pH decrease and explains the variation in solution pH with structure.

Synthesis of 1,4-Diamino-2,3-di(2-pyridyl)butane and its Dinuclear Zinc(II) Chloride Complex

In a Henry-type reaction nitromethane reacts with N-(2-pyridylmethylidene)-methylamine (1) yielding 1-methylamino-1-(2-pyridyl)-2-nitromethane (2) in nearly quantitative yield. This orange compound decomposes slowly in an inert gas atmosphere and fast in contact with air. Therefore 2 has to be stored at −78 ◦C as a methanol solution. Reduction of 2 with hydrogen in the presence of a Pd/C catalyst leads to the formation of 1,4-dinitro-2,3-di(2-pyridyl)butane (3) in the rather poor yield of 12 %. The major product is the meso-isomer, meso-3, whereas only traces of (R,R)- and (S,S)- isomers of 3 are formed. A conversion of the nitro groups into amino functionalities succeeds with hydrazine hydrate in the presence of a Pd/C catalyst yielding meso-1,4-diamino-2,3-di(2-pyridyl)butane (4). Recrystallization from an aqueous solution gives 4・2H2O. The zinc(II) chloride complex 5 with the metal atoms in distorted tetrahedral environments can be isolated after addition of two equivalents of ZnCl2 to 4. The molecular structures of trimeric 1, meso-3, (R,R)/(S,S)-3, meso-4, and 5 have been determined and are discussed. Graphical Abstract Synthesis of 1,4-Diamino-2,3-di(2-pyridyl)butane and its Dinuclear Zinc(II) Chloride Complex